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Catalisano G, Ippolito M, Blanda A, Meessen J, Giarratano A, Todesco N, Bonato V, Restuccia F, Montomoli J, Fiore G, Grasselli G, Caironi P, Latini R, Cortegiani A. Effects of hyperoxemia in patients with sepsis - A post-hoc analysis of a multicentre randomized clinical trial. Pulmonology 2025; 31:2416784. [PMID: 36907813 DOI: 10.1016/j.pulmoe.2023.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 02/09/2023] [Accepted: 02/10/2023] [Indexed: 03/14/2023] Open
Abstract
BACKGROUND Administration of supplemental oxygen is a life-saving treatment in critically ill patients. Still, optimal dosing remains unclear during sepsis. The aim of this post-hoc analysis was to assess the association between hyperoxemia and 90-day mortality in a large cohort of septic patients. METHODS This is a post-hoc analysis of the Albumin Italian Outcome Sepsis (ALBIOS) randomized controlled trial (RCT). Patients with sepsis who survived the first 48 h since randomization were included and stratified into two groups according to their average PaO2 levels during the first 48 h (PaO2 0-48 h). The cut-off value was established at 100 mmHg (average PaO2 0-48 h >100 mmHg: hyperoxemia group; PaO2 0-48h≤100: normoxemia group). The primary outcome was 90-day mortality. RESULTS 1632 patients were included in this analysis (661 patients in the hyperoxemia group, 971 patients in the normoxemia group). Concerning the primary outcome, 344 (35.4%) patients in the hyperoxemia group vs. 236 (35.7%) in the normoxemia group had died within 90 days from randomization (p = 0.909). No association was found after adjusting for confounders (HR 0.87; CI [95%] 0.736-1.028, p = 0.102) or after excluding patients with hypoxemia at enrollment, patients with lung infection or including post-surgical patients only. Conversely, we found an association between lower risk of 90-day mortality and hyperoxemia in the subgroup including patients who had the lung as primary site of infection (HR 0.72; CI [95%] 0.565-0.918). Mortality at 28 days, ICU mortality, incidence of acute kidney injury, use of renal replacement therapy, days to suspension of vasopressor or inotropic agents, and resolution of primary and secondary infections did not differ significantly. Duration of mechanical ventilation and length of stay in ICU were significantly longer in patients with hyperoxemia. CONCLUSIONS In a post-hoc analysis of a RCT enrolling septic patients, hyperoxemia as average PaO2>100 mmHg during the first 48 h was not associated with patients' survival.
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Affiliation(s)
- G Catalisano
- Department of Surgical, Oncological and Oral Science (Di.Chir.On.S.), University of Palermo, Italy
| | - M Ippolito
- Department of Surgical, Oncological and Oral Science (Di.Chir.On.S.), University of Palermo, Italy
- Department of Anaesthesia, Intensive Care and Emergency, University Hospital Policlinico Paolo Giaccone, Italy
| | - A Blanda
- Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri - IRCCS, Italy
| | - J Meessen
- Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri - IRCCS, Italy
| | - A Giarratano
- Department of Surgical, Oncological and Oral Science (Di.Chir.On.S.), University of Palermo, Italy
- Department of Anaesthesia, Intensive Care and Emergency, University Hospital Policlinico Paolo Giaccone, Italy
| | - N Todesco
- Servizio di Anestesia, Rianimazione e Terapie Intensive, Azienda Sanitaria Friuli Occidentale, P.O. Santa Maria degli Angeli, Pordenone, Italy
| | - V Bonato
- S.C. Anestesia e Rianimazione, Ospedale SS. Arrigo e Biagio, Alessandria, Italy
| | - F Restuccia
- Department of Anesthesiology and Critical Care Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - J Montomoli
- Department of Anesthesia and Intensive Care, Infermi Hospital, AUSL Romagna, Rimini, Italy
| | - G Fiore
- S.C. Anestesia e Rianimazione Moncalieri-Carmagnola (TO), Dipartimento Area Chirurgica, ASLTO5, Italy
| | - G Grasselli
- Department of Anesthesia, Intensive Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Italy
| | - P Caironi
- Department of Anaesthesia and Critical Care, AOU S. Luigi Gonzaga, Department of Oncology, University of Turin, Italy
| | - R Latini
- Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri - IRCCS, Italy
| | - A Cortegiani
- Department of Surgical, Oncological and Oral Science (Di.Chir.On.S.), University of Palermo, Italy
- Department of Anaesthesia, Intensive Care and Emergency, University Hospital Policlinico Paolo Giaccone, Italy
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Bolger-Chen M, Lopera Higuita M, Pendexter CA, Mojoudi M, Uygun K, Tessier SN. Enhancing outcomes in Langendorff-perfused rodent hearts through perfusion parameter optimization. Sci Rep 2025; 15:15935. [PMID: 40335499 PMCID: PMC12059170 DOI: 10.1038/s41598-025-00159-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Accepted: 04/25/2025] [Indexed: 05/09/2025] Open
Abstract
Despite important advancements in addressing cardiovascular diseases (CVDs), there has been an overall lack of progress in the field, leading to a slower decline in the rate of CVDs related deaths, and even an increase for some risk groups (e.g. increase in stroke mortality) exacerbated by an aging and obese population. While a multi-faceted problem, this deceleration may be influenced by the preferred model systems utilized in translation research. Cardiac cell lines, although easier to handle, lack biological accuracy due to the unnatural modifications required for successful culture and may not recapitulate complex 3-dimensional structural and environmental factors. At the same time, whole animal experimentation provides unwanted complexity during initial scientific development. Alternatively, ex vivo perfusion of isolated rodent hearts provides the needed biological accuracy with decreased organismal complexity. This platform facilitates the evaluation of the isolated heart, without neuro-reflexes and/or humoral contributions, unveiling the direct effects of stimuli in heart function/homeostasis. This manuscript leverages the wide array of perfusion parameters (i.e. perfusate, flow rate, coronary pressures), to demonstrate the capability of ex vivo heart perfusion protocols to accommodate a large range of experimental needs. Through this work, it was determined that the use of physiological perfusion pressures leads to increased left ventricular (LV) pressures but results in a loss of function over time, making it ideal conditions for organ assessment. Conversely, lower-than-physiological perfusion pressures lead to decreased LV pressures but prevent loss of function over time, which is preferable when longer perfusion times are relevant to experimental needs. Similarly, the use of adenosine as a pharmacological intervention was found to decrease both edema formation and inflammatory responses. In contrast, the use of packed red blood cells as oxygen carriers appears to induce a pro-inflammatory response and cause greater cardiac damage, particularly when combined with low perfusion pressures.
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Affiliation(s)
- Maya Bolger-Chen
- Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, and Shriners Children's Boston, Boston, MA, USA
| | - Manuela Lopera Higuita
- Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, and Shriners Children's Boston, Boston, MA, USA
| | - Casie A Pendexter
- Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, and Shriners Children's Boston, Boston, MA, USA
| | - Mohammadreza Mojoudi
- Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, and Shriners Children's Boston, Boston, MA, USA
| | - Korkut Uygun
- Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, and Shriners Children's Boston, Boston, MA, USA
| | - Shannon N Tessier
- Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, and Shriners Children's Boston, Boston, MA, USA.
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Chen D, Xing ZX, Li SP, Lu T, Wang JX, Wu YX, Pang QF. Preconception maternal hyperoxia exposure causes cardiac insufficiency through induction of mitochondrial toxicity in mice offspring. Reprod Toxicol 2025; 133:108864. [PMID: 39988061 DOI: 10.1016/j.reprotox.2025.108864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 01/22/2025] [Accepted: 02/20/2025] [Indexed: 02/25/2025]
Abstract
Although essential, excessive oxygen is toxic. The adverse effects of maternal hyperoxygenation have recently garnered attention. However, the potential toxicity of maternal hyperoxia exposure before pregnancy and its effects on offspring development remain unclear. This study aims to investigate the cardiac developmental toxicity of maternal pre-pregnancy hyperoxia exposure on the offspring. Our findings reveal that preconception maternal hyperoxia exposure leads to growth retardation, cardiac insufficiency, and remodeling in both male and female offspring. Additionally, maternal pre-pregnancy hyperoxia exposure induces mitochondrial damage characterized by reduced oxidative phosphorylation, inhibited tricarboxylic acid (TCA) cycle, and decreased ATP production in the cardiac tissues of offspring mice. Supplementation of sodium propionate during lactation significantly improves growth retardation, mitigates metabolic remodeling, and partially restores cardiac function in hyperoxia-exposed offspring. In conclusion, our study suggests that maternal hyperoxia exposure before pregnancy leads to cardiac insufficiency in murine offspring. These findings may have important implications for mitigating maternal high oxygen toxicity on offspring development and disease risk, especially the cardiotoxic effects of hyperoxia on offspring development.
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Affiliation(s)
- Dan Chen
- A Department of physiopathology, Wuxi School of Medicine, Jiangnan university, Wuxi, Jiangsu Province 214122, China.
| | - Zhi-Xuan Xing
- A Department of physiopathology, Wuxi School of Medicine, Jiangnan university, Wuxi, Jiangsu Province 214122, China
| | - Sheng-Peng Li
- A Department of physiopathology, Wuxi School of Medicine, Jiangnan university, Wuxi, Jiangsu Province 214122, China
| | - Tao Lu
- A Department of physiopathology, Wuxi School of Medicine, Jiangnan university, Wuxi, Jiangsu Province 214122, China
| | - Jia-Xin Wang
- A Department of physiopathology, Wuxi School of Medicine, Jiangnan university, Wuxi, Jiangsu Province 214122, China
| | - Ya-Xian Wu
- A Department of physiopathology, Wuxi School of Medicine, Jiangnan university, Wuxi, Jiangsu Province 214122, China
| | - Qing-Feng Pang
- A Department of physiopathology, Wuxi School of Medicine, Jiangnan university, Wuxi, Jiangsu Province 214122, China.
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Wu M, Chang L, Sun L, Dai Z, Bo J, Xu X. Effects of high vs. low perioperative inspired oxygen fraction on length of hospital stay and postoperative complications: a systematic review, meta-analysis, and trial sequential analysis. Minerva Anestesiol 2025; 91:201-213. [PMID: 40207837 DOI: 10.23736/s0375-9393.25.18649-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/11/2025]
Abstract
INTRODUCTION Prolonged length of hospital stay (LOS) and postoperative complications in surgical patients are major public health issues worldwide. Perioperative hyperoxia may increase LOS, and the incidence of cardiac, cerebral, renal, and pulmonary injury; however, the supporting clinical evidence is controversial. Therefore, the current meta-analysis included all relevant randomized controlled trials (RCTs) to investigate the effect of high and low inspired oxygen fraction (FiO2) on LOS, according to postoperative complications. EVIDENCE ACQUISITION Standard published RCTs were searched from bibliographic databases to identify all evidence reporting perioperative FiO2 for patients undergoing surgeries. The primary outcome was LOS, and the secondary outcomes were postoperative organ complications, surgical site infection (SSI), and postoperative mortality. The relative risk (RR) and Peto-odds ratio (Peto-OR) for dichotomous outcomes and the mean difference (MD) and standardized mean difference (SMD) for continuous outcomes were estimated using a random-effects model. Trial sequential analysis (TSA) was performed in the meta-analysis to evaluate the required information sizes and assess whether the primary outcome in our meta-analysis was conclusive. EVIDENCE SYNTHESIS Thirty-one RCTs with 10506 participants undergoing different surgeries were included. The LOS in the high FiO2 group did not differ significantly from that in the low FiO2 group (MD -0.01, 95% CI -0.10 to 0.08, P=0.81). Moreover, we found no meaningful evidence of subgroup differences in the primary outcome, in comparisons of FiO2, RCT type, surgery type, duration of oxygen inhalation or timing of oxygen inhalation. TSA results further suggested that the number of included studies was sufficient for the primary outcome. There was also no significant difference in postoperative organ complications (cardiac, cerebral, renal, and pulmonary), SSI (rate of SSI, ASEPSIS score, and ASEPSIS score > 20 cases), or postoperative mortality. For postoperative atelectasis, sensitivity analysis showed that after exclusion of one study, "Myles 2007," high FiO2 was associated with increased postoperative atelectasis. CONCLUSIONS The use of low FiO2 has no effect on LOS, or the incidence of cardiac, cerebral, and renal injury or postoperative mortality. Compared with low FiO2, high FiO2 did not reduce SSI which was contrary to the guidelines. Meanwhile, high FiO2 may increase postoperative atelectasis in surgical patients.
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Affiliation(s)
- Mimi Wu
- Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Lanlan Chang
- Department of Anesthesiology, Jinan Seventh People's Hospital, Jinan, China
| | - Leying Sun
- Department of Anesthesiology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
| | - Zhao Dai
- Department of Anesthesiology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
| | - Jinhua Bo
- Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Xin Xu
- Department of Anesthesiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China -
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Gu WJ, Shi R, Cen Y, Ye YY, Xie XD, Yin HY. Association Between Arterial Hyperoxia and Mortality in Pediatric and Adult Patients Undergoing Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis. Anesth Analg 2024:00000539-990000000-01086. [PMID: 39705180 DOI: 10.1213/ane.0000000000007348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2024]
Abstract
BACKGROUND In patients receiving extracorporeal membrane oxygenation (ECMO) support, the association between arterial hyperoxia and outcomes is unclear. We performed a systematic review and meta-analysis to determine the association between arterial Po2 (Pao2) and mortality in patients with ECMO. METHODS The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement and registered in International Prospective Register of Systematic Reviews (PROSPERO; CRD42023467361). We systematically searched PubMed and Embase databases up to September 2023 for randomized trials or observational studies that investigated the association between Pao2 and mortality in pediatric and adult patients receiving venovenous ECMO (VV-ECMO), venoarterial ECMO (VA-ECMO), and extracorporeal cardiopulmonary resuscitation (ECPR). The predefined outcome was 28-day mortality. We synthesized the data using a random-effects model, calculating odds ratios (OR) and corresponding 95% confidence intervals (CI). RESULTS Thirteen cohort studies (17,766 participants) were included. All studies used categorical Pao2 cutoff, with varying thresholds ranging from ≥100 mm Hg to ≥300 mm Hg. When compared with patients with normoxia, elevated Pao2 levels at all studied thresholds were consistently associated with increased mortality (≥300 mm Hg: OR 1.56, 95% CI, 1.31-1.85, P < .01; ≥200 mm Hg: OR 1.43, 95% CI, 1.10-1.87, P < .01; ≥150 mm Hg: OR 1.51, 95% CI, 1.15-1.98, P < .01; and ≥100 mm Hg: OR 1.44, 95% CI, 1.03-2.02, P = .03). A sensitivity analysis focusing on studies reporting adjusted OR yielded similar results. We observed this association in both adult and pediatric populations. CONCLUSIONS In critically ill patients on VV- or VA-ECMO, increased Pao2 values were associated with increased 28-day mortality in ECMO patients. Our results should be interpreted with caution given observational nature of included studies. Further randomized trials are warranted to validate these results.
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Affiliation(s)
- Wan-Jie Gu
- From the Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Rui Shi
- Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yun Cen
- From the Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Ying-Ying Ye
- From the Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Xu-Dong Xie
- From the Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Hai-Yan Yin
- From the Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
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Ghazaly HF, Aly AAA, Tammam AS, Hassan MM, Hammad SS, Mahmoud NM, Hemaida TS. Influence of liberal versus conservative oxygen therapies on the hemodynamic parameters of mechanically ventilated patients with sepsis: a randomized clinical trial. BMC Anesthesiol 2024; 24:469. [PMID: 39707209 PMCID: PMC11660434 DOI: 10.1186/s12871-024-02838-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Accepted: 11/27/2024] [Indexed: 12/23/2024] Open
Abstract
BACKGROUND There is no significant evidence verifying the efficacy of liberal versus conservative oxygen therapy on hemodynamics in patients with sepsis. We investigated how liberal and conservative oxygen therapy influenced stroke volume, cardiac output, and vasopressor needs in patients with sepsis undergoing mechanical ventilation. METHODS This randomized clinical trial included 106 patients with an admission diagnosis of infection, a Sequential Organ Failure Assessment (SOFA) score of two points or higher and required invasive mechanical ventilation for at least 72 h. Patients were randomly assigned to one of two oxygenation strategies: liberal (n = 53) with a target SpO2 of ≥ 96% or conservative (n = 53) with a target SpO2 of 88-92%. Transthoracic Doppler echocardiography was done twice to measure stroke volume and cardiac output, initially upon enrollment in the trial and then 72 h later. The primary outcome was stroke volume. Secondary outcomes were cardiac output, vasopressor use, mechanical ventilation duration, ICU stay length, and adverse events. RESULTS Stroke volume and cardiac output measurements did not differ significantly between research groups after 72 h of oxygenation treatment (p = 0.459 and 0.637, respectively). Forty-five patients (84.9%) in the conservative oxygen therapy group needed vasopressors to maintain their mean arterial pressure above 65 mmHg, whereas 35 patients (66.0%) in the liberal group did (p = 0.024). A multivariate logistic regression analysis of the independent variables for vasopressor requirements revealed that patients in the conservative oxygen group were 3.83 times more likely to require vasopressors (AOR = 3.83, 95% CI: 1.31-11.18, p = 0.014) than those in the liberal group. Older patients (AOR = 1.03, 95% CI: 1.01-1.07, p = 0.038) and those with higher SOFA scores (AOR = 1.36, CI: 1.09-1.68, P = 0.005) were significantly more likely to need vasopressors. CONCLUSIONS Liberal or conservative oxygen therapy did not influence stroke volume or cardiac output measurements in mechanically ventilated patients with sepsis. Patients in the conservative oxygen group were more likely to require vasopressors than those in the liberal group. TRIAL REGISTRATION This study was approved by the Ethics Committee of Aswan University Hospital (approval number: Aswu/460/5/20) (registration date: 05/05/2020) and registered on ClinicalTrials.gov (NCT04824703) (03/30/2021).
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Affiliation(s)
- Huda F Ghazaly
- Anesthesia and Surgical Intensive Care Department, Faculty of Medicine, Aswan University, Aswan, Egypt.
| | - Ahmed Alsaied A Aly
- Anesthesia and Surgical Intensive Care Department, Faculty of Medicine, Aswan University, Aswan, Egypt
| | - Ahmed S Tammam
- Anesthesia and Surgical Intensive Care Department, Faculty of Medicine, Aswan University, Aswan, Egypt
| | - Mahmoud M Hassan
- Anesthesia and Surgical Intensive Care Department, Faculty of Medicine, Aswan University, Aswan, Egypt
| | - Soudy S Hammad
- Anesthesia and Surgical Intensive Care Department, Faculty of Medicine, Aswan University, Aswan, Egypt
| | - Naggeh M Mahmoud
- Cardiology Department, Faculty of Medicine, Aswan University, Aswan, Egypt
| | - Tarek S Hemaida
- Anesthesia and Surgical Intensive Care Department, Faculty of Medicine, Aswan University, Aswan, Egypt
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Müller J, Lichtblau M, Saxer S, Schmucki M, Furian M, Schneider SR, Herzig JJ, Bauer M, Saragoni D, Schwarz EI, Cajamarca E, Hoyos R, Ulrich S. The acute effect of high-dose supplemental oxygen on haemodynamics assessed by echocardiography in patients with pulmonary vascular disease living in Quito at 2850 m: a randomized, single-blind, placebo-controlled crossover trial. EUROPEAN HEART JOURNAL OPEN 2024; 4:oeae097. [PMID: 39698150 PMCID: PMC11653896 DOI: 10.1093/ehjopen/oeae097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 11/18/2024] [Accepted: 11/21/2024] [Indexed: 12/20/2024]
Abstract
Aims More than 220 Mio people live at altitudes above 2000 m, many of whom have pre-existing chronic diseases, including pulmonary vascular diseases (PVDs) such as pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH). We investigated the acute effects of high-dose supplemental oxygen on pulmonary haemodynamics assessed by echocardiography in patients with PVD permanently living at 2850 m. Methods and results In a randomized, single-blind, placebo-controlled crossover trial, patients with PVD diagnosed with PAH or CTEPH were allocated to receive 10 L/min supplemental oxygen (FiO2 ≈ 95%) and placebo air administered via a facial mask with reservoir near their living altitude in Quito at 2850 m (FiO20.21, PiO2 ≈ 60% of sea level) in random order with a washout period of >2 h. After >15 min of breathing the respective FiO2, systolic pulmonary artery pressure (sPAP), cardiac output (CO), and other parameters were assessed by echocardiography. Furthermore, radial arterial blood gases were analysed. Twenty-eight patients with PVD (24 females, 26 PAH, age 45 ± 12 years) treated with phosphodiesterase-5 inhibitors (n = 28) and endothelin receptor antagonists (n = 9) were included. With oxygen vs. placebo air, sPAP was 57 ± 23 vs. 68 ± 24 mmHg, mean difference -11 mmHg (-15 to -6 mmHg, P < 0.001), CO was 3.2 ± 0.9 vs. 3.9 ± 1.1 L/min; -0.7 L/min (-0.9 to -0.4 L/min, P < 0.001), while sPAP/CO was unchanged, and the right ventriculo-arterial coupling was increased. PaO2 was 22.5 ± 9.7 vs. 7.6 ± 1.5 kPa; 14.9 kPa (11.4-18.4 kPa, P < 0.001). Conclusion High-dose oxygen therapy in prevalent patients with PVD living near 2850 m significantly lowered sPAP but also CO by a reduced heart rate, resulting in an unchanged pulmonary resistance. Whether longer-term oxygen therapy would improve pulmonary vascular resistance requires further investigation. Registration NCT06084559 URL: https://clinicaltrials.gov/study/NCT06084559.
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Affiliation(s)
- Julian Müller
- Department of Pulmonology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Pestalozzistrasse 3, 8032 Zurich, Switzerland
| | - Mona Lichtblau
- Department of Pulmonology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Pestalozzistrasse 3, 8032 Zurich, Switzerland
| | - Stéphanie Saxer
- Department of Pulmonology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
- Department of Health, Eastern Swiss University of Applied Sciences, Rosenbergstrasse 59, 9000 St. Gallen, Switzerland
| | - Mirjam Schmucki
- Department of Pulmonology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Pestalozzistrasse 3, 8032 Zurich, Switzerland
| | - Michael Furian
- Department of Pulmonology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
| | - Simon R Schneider
- Department of Pulmonology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
| | - Joël J Herzig
- Department of Pulmonology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
| | - Meret Bauer
- Department of Pulmonology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
| | - Diego Saragoni
- Department of Pulmonology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Pestalozzistrasse 3, 8032 Zurich, Switzerland
| | - Esther I Schwarz
- Department of Pulmonology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Pestalozzistrasse 3, 8032 Zurich, Switzerland
| | - Elizabeth Cajamarca
- Pneumology Unit, Carlos Andrade Marín Hospital, Av. Universitaria, 170103 Quito, Ecuador
| | - Rodrigo Hoyos
- Pneumology Unit, Carlos Andrade Marín Hospital, Av. Universitaria, 170103 Quito, Ecuador
| | - Silvia Ulrich
- Department of Pulmonology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Pestalozzistrasse 3, 8032 Zurich, Switzerland
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Amesz JH, Langmuur SJ, Bierhuizen MF, Dumay D, van de Woestijne PC, Sjatskig J, Sluijter LE, Duncker DJ, Manintveld OC, Taverne YJ. Myocardial oxygen handling and metabolic function of ex-situ perfused human hearts from circulatory death donors. JHLT OPEN 2024; 6:100159. [PMID: 40145048 PMCID: PMC11935508 DOI: 10.1016/j.jhlto.2024.100159] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 03/28/2025]
Abstract
Background This study investigated oxygen handling of human hearts donated after circulatory death (DCD) on normothermic ex-situ heart perfusion (ESHP) and evaluated oxygen handling markers as adjuncts to cardiac viability assessment. Methods This single-center retrospective study included human DCD heart transplantation procedures using ESHP. Lactate concentrations, blood gas, myocardial oxygen consumption (MVO2), delivery (MDO2), and extraction (MEO2), coronary blood flow (CBF), coronary vascular resistance (CVR), and adenosine infusion were reported over time. Correlation between parameters was assessed, and statistical testing compared patients who did and did not require extracorporeal membrane oxygenation (ECMO) support after transplantation. Results Lactate concentrations decreased during ESHP in all transplanted hearts (n = 25) and increased in 1 rejected heart. Arterial partial pressure of oxygen (PO2) was 75.2 ± 2.9 kPa, with an arteriovenous ΔPO2 of 44.8 ± 10.4 kPa. Oxygen saturation was 100% in most arterial and venous samples. Average MVO2 was 2.7 ± 0.6 ml/min/100 g myocardium, MDO2 98.5 ± 20.4 ml/min, and MEO2 8.6 ± 1.8%. Average CVR was 0.025 ± 0.006 mm Hg min/ml/100 g and increased over time. ΔPO2 correlated strongly with MVO2 (R = 0.797, p < 0.001) and lactate trend (R = 0.799, p < 0.001) in transplanted hearts, without differences compared to the rejected heart with increasing lactate. Adenosine infusion on ESHP was significantly higher in patients requiring ECMO post-transplantation vs non-ECMO cases (11.7 (4.5-21.0) vs 2.2 (1.5-6.7) ml/h, p = 0.039). Conclusions Hearts on normothermic ESHP receive excessive MDO2, due to high PO2 and CBF, while the MVO2 is relatively low. Thus, CBF and PO2 can potentially be lowered. Furthermore, ΔPO2 could serve as additional marker of metabolic function under these hyperoxic circumstances. The adenosine infusion rate might predict post-transplantation ECMO requirement.
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Affiliation(s)
- Jorik H. Amesz
- Translational Cardiothoracic Surgery Research Lab, Department of Cardiothoracic Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands
- Department of Cardiothoracic Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Sanne J.J. Langmuur
- Translational Cardiothoracic Surgery Research Lab, Department of Cardiothoracic Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands
- Department of Cardiothoracic Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands
- Erasmus MC Transplant Institute, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Mark F.A. Bierhuizen
- Translational Cardiothoracic Surgery Research Lab, Department of Cardiothoracic Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands
- Department of Cardiothoracic Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands
- Department of Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Dwight Dumay
- Clinical Perfusion, Department of Cardiothoracic Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands
| | | | - Jelena Sjatskig
- Department of Cardiothoracic Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Lisa E. Sluijter
- Clinical Perfusion, Department of Cardiothoracic Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Dirk J. Duncker
- Division of Experimental Cardiology, Department of Cardiology, Erasmus MC Cardiovascular Institute, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Olivier C. Manintveld
- Erasmus MC Transplant Institute, Erasmus University Medical Center, Rotterdam, the Netherlands
- Department of Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Yannick J.H.J. Taverne
- Translational Cardiothoracic Surgery Research Lab, Department of Cardiothoracic Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands
- Department of Cardiothoracic Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands
- Erasmus MC Transplant Institute, Erasmus University Medical Center, Rotterdam, the Netherlands
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9
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Jha AK. Role of Supplemental Oxygen in Intermediate Risk Pulmonary Embolism. Chest 2024; 166:e99. [PMID: 39260957 DOI: 10.1016/j.chest.2024.04.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 04/10/2024] [Accepted: 04/11/2024] [Indexed: 09/13/2024] Open
Affiliation(s)
- Ajay Kumar Jha
- Department of Anaesthesiology and Critical Care, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India.
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10
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Billings FT, McIlroy DR, Shotwell MS, Lopez MG, Vaughn MT, Morse JL, Hennessey CJ, Wanderer JP, Semler MW, Rice TW, Wunsch H, Kheterpal S. Determinants and Practice Variability of Oxygen Administration during Surgery in the United States: A Retrospective Cohort Study. Anesthesiology 2024; 141:511-523. [PMID: 38759157 PMCID: PMC11321923 DOI: 10.1097/aln.0000000000005078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/19/2024]
Abstract
BACKGROUND The best approaches to supplemental oxygen administration during surgery remain unclear, which may contribute to variation in practice. This study aimed to assess determinants of oxygen administration and its variability during surgery. METHODS Using multivariable linear mixed-effects regression, the study measured the associations between intraoperative fraction of inspired oxygen and patient, procedure, medical center, anesthesiologist, and in-room anesthesia provider factors in surgical cases of 120 min or longer in adult patients who received general anesthesia with tracheal intubation and were admitted to the hospital after surgery between January 2016 and January 2019 at 42 medical centers across the United States participating in the Multicenter Perioperative Outcomes Group data registry. RESULTS The sample included 367,841 cases (median [25th, 75th] age, 59 [47, 69] yr; 51.1% women; 26.1% treated with nitrous oxide) managed by 3,836 anesthesiologists and 15,381 in-room anesthesia providers. Median (25th, 75th) fraction of inspired oxygen was 0.55 (0.48, 0.61), with 6.9% of cases less than 0.40 and 8.7% greater than 0.90. Numerous patient and procedure factors were statistically associated with increased inspired oxygen, notably advanced American Society of Anesthesiologists classification, heart disease, emergency surgery, and cardiac surgery, but most factors had little clinical significance (less than 1% inspired oxygen change). Overall, patient factors only explained 3.5% (95% CI, 3.5 to 3.5%) of the variability in oxygen administration, and procedure factors 4.4% (95% CI, 4.2 to 4.6%). Anesthesiologist explained 7.7% (95% CI, 7.2 to 8.2%) of the variability in oxygen administration, in-room anesthesia provider 8.1% (95% CI, 7.8 to 8.4%), medical center 23.3% (95% CI, 22.4 to 24.2%), and 53.0% (95% CI, 52.4 to 53.6%) was unexplained. CONCLUSIONS Among adults undergoing surgery with anesthesia and tracheal intubation, supplemental oxygen administration was variable and appeared arbitrary. Most patient and procedure factors had statistical but minor clinical associations with oxygen administration. Medical center and anesthesia provider explained significantly more variability in oxygen administration than patient or procedure factors. EDITOR’S PERSPECTIVE
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Affiliation(s)
- Frederic T Billings
- Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - David R McIlroy
- Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Matthew S Shotwell
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Marcos G Lopez
- Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Michelle T Vaughn
- Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan
| | - Jennifer L Morse
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Cassandra J Hennessey
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Jonathan P Wanderer
- Departments of Anesthesiology and Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Matthew W Semler
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Todd W Rice
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Hannah Wunsch
- Department of Anesthesiology, New York-Presbyterian Hospital/Weill Cornell Medicine, New York, New York
| | - Sachin Kheterpal
- Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan
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11
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Sigg AA, Zivkovic V, Bartussek J, Schuepbach RA, Ince C, Hilty MP. The physiological basis for individualized oxygenation targets in critically ill patients with circulatory shock. Intensive Care Med Exp 2024; 12:72. [PMID: 39174691 PMCID: PMC11341514 DOI: 10.1186/s40635-024-00651-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 07/21/2024] [Indexed: 08/24/2024] Open
Abstract
BACKGROUND Circulatory shock, defined as decreased tissue perfusion, leading to inadequate oxygen delivery to meet cellular metabolic demands, remains a common condition with high morbidity and mortality. Rapid restitution and restoration of adequate tissue perfusion are the main treatment goals. To achieve this, current hemodynamic strategies focus on adjusting global physiological variables such as cardiac output (CO), hemoglobin (Hb) concentration, and arterial hemoglobin oxygen saturation (SaO2). However, it remains a challenge to identify optimal targets for these global variables that best support microcirculatory function. Weighting up the risks and benefits is especially difficult for choosing the amount of oxygen supplementation in critically ill patients. This review assesses the physiological basis for oxygen delivery to the tissue and provides an overview of the relevant literature to emphasize the importance of considering risks and benefits and support decision making at the bedside. PHYSIOLOGICAL PREMISES Oxygen must reach the tissue to enable oxidative phosphorylation. The human body timely detects hypoxia via different mechanisms aiming to maintain adequate tissue oxygenation. In contrast to the pulmonary circulation, where the main response to hypoxia is arteriolar vasoconstriction, the regulatory mechanisms of the systemic circulation aim to optimize oxygen availability in the tissues. This is achieved by increasing the capillary density in the microcirculation and the capillary hematocrit thereby increasing the capacity of oxygen diffusion from the red blood cells to the tissue. Hyperoxia, on the other hand, is associated with oxygen radical production, promoting cell death. CURRENT STATE OF RESEARCH Clinical trials in critically ill patients have primarily focused on comparing macrocirculatory endpoints and outcomes based on stroke volume and oxygenation targets. Some earlier studies have indicated potential benefits of conservative oxygenation. Recent trials show contradictory results regarding mortality, organ dysfunction, and ventilatory-free days. Empirical studies comparing various targets for SaO2, or partial pressure of oxygen indicate a U-shaped curve balancing positive and negative effects of oxygen supplementation. CONCLUSION AND FUTURE DIRECTIONS To optimize risk-benefit ratio of resuscitation measures in critically ill patients with circulatory shock in addition to individual targets for CO and Hb concentration, a primary aim should be to restore tissue perfusion and avoid hyperoxia. In the future, an individualized approach with microcirculatory targets will become increasingly relevant. Further studies are needed to define optimal targets.
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Affiliation(s)
- Anne-Aylin Sigg
- Institute of Intensive Care Medicine, University Hospital of Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.
| | - Vanja Zivkovic
- Institute of Intensive Care Medicine, University Hospital of Zurich, Raemistrasse 100, 8091, Zurich, Switzerland
| | - Jan Bartussek
- Institute of Intensive Care Medicine, University Hospital of Zurich, Raemistrasse 100, 8091, Zurich, Switzerland
| | - Reto A Schuepbach
- Institute of Intensive Care Medicine, University Hospital of Zurich, Raemistrasse 100, 8091, Zurich, Switzerland
| | - Can Ince
- Department of Intensive Care, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Matthias P Hilty
- Institute of Intensive Care Medicine, University Hospital of Zurich, Raemistrasse 100, 8091, Zurich, Switzerland
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12
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Ayalasomayajula Y, Hesaraghatta A, Dantuluri N, Yassine J, Saleem F, Mansour H, Chayawatto C, Rangarajan N, Rangarajan S, Krishnan S, Panguluri SK. Influence of age and sex on physical, cardiac electrical and functional alterations in progressive hyperoxia treatment: A time course study in a murine model. Exp Gerontol 2024; 191:112435. [PMID: 38636569 PMCID: PMC11495054 DOI: 10.1016/j.exger.2024.112435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 03/29/2024] [Accepted: 04/15/2024] [Indexed: 04/20/2024]
Abstract
Oxygen supplementation is a widely used treatment for ICU patients. However, it can lead to hyperoxia, which in turn can result in oxidative stress, cardiac remodeling, and even mortality. This paper expands upon previous research conducted by our lab to establish time-dependent cardiac changes under hyperoxia. In this study, both young and aged mice (male and female) underwent 72 h of hyperoxia exposure and were monitored at 24-hour intervals for cardiac electrophysiological and functional parameters using ECG and electrocardiogram data. Our analysis showed that young male mice experienced significant weight loss as well as significant lung edema by 48 h. Although young male mice were highly susceptible to physical changes, they were resistant to early cardiac functional and electrophysiological changes compared to the other groups. Both young and aged female and aged males developed functional impairments by 24 h of hyperoxia exposure. Furthermore, sex and age differences were noted in the onset of electrophysiological changes. While some groups could resist early cardiac remodeling, our data suggests that 72 h of hyperoxia exposure is sufficient to induce significant cardiac remodeling across all age and sex groups. Our data establishes that time-dependent cardiac changes due to oxygen supplementation can have devastating consequences even with short exposure periods. These findings can aid in developing clinical practices for individuals admitted to the ICU by elucidating the impact of aging, sex, and length of stay under mechanical ventilation to limit hyperoxia-induced cardiac remodeling.
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Affiliation(s)
- Yashwant Ayalasomayajula
- Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA
| | - Anagha Hesaraghatta
- Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA
| | - Neha Dantuluri
- Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA
| | - Jenna Yassine
- Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA
| | - Faizan Saleem
- Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA
| | - Hussein Mansour
- Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA
| | - Chayapatou Chayawatto
- Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA
| | - Nishank Rangarajan
- Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA
| | - Sashank Rangarajan
- Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA
| | - Smrithi Krishnan
- Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA
| | - Siva Kumar Panguluri
- Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA; Cell Biology, Microbiology and Molecular Biology, College of Arts and Sciences, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA.
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13
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Kelava M, Milam AJ, Mi J, Alfirevic A, Grady P, Unai S, Elgharably H, McCurry K, Koprivanac M, Duncan A. Arterial Hyperoxemia During Cardiopulmonary Bypass Was Not Associated With Worse Postoperative Pulmonary Function: A Retrospective Cohort Study. Anesth Analg 2024; 138:1003-1010. [PMID: 37733624 PMCID: PMC10994185 DOI: 10.1213/ane.0000000000006627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/02/2023] [Indexed: 09/23/2023]
Abstract
BACKGROUND Arterial hyperoxemia may cause end-organ damage secondary to the increased formation of free oxygen radicals. The clinical evidence on postoperative lung toxicity from arterial hyperoxemia during cardiopulmonary bypass (CPB) is scarce, and the effect of arterial partial pressure of oxygen (Pa o2 ) during cardiac surgery on lung injury has been underinvestigated. Thus, we aimed to examine the relationship between Pa o2 during CPB and postoperative lung injury. Secondarily, we examined the relationship between Pa o2 and global (lactate), and regional tissue malperfusion (acute kidney injury). We further explored the association with regional tissue malperfusion by examining markers of cardiac (troponin) and liver injury (bilirubin). METHODS This was a retrospective cohort study including patients who underwent elective cardiac surgeries (coronary artery bypass, valve, aortic, or combined) requiring CPB between April 2015 and December 2021 at a large quaternary medical center. The primary outcome was postoperative lung function defined as the ratio of Pa o2 to fractional inspired oxygen concentration (F io2 ); P/F ratio 6 hours following surgery or before extubation. The association between CPB in-line sample monitor Pa o2 and primary, secondary, and exploratory outcomes was evaluated using linear or logistic regression models adjusting for available baseline confounders. RESULTS A total of 9141 patients met inclusion and exclusion criteria, and 8429 (92.2%) patients had complete baseline variables available and were included in the analysis. The mean age of the sample was 64 (SD = 13), and 68% were men (n = 6208). The time-weighted average (TWA) of in-line sample monitor Pa o2 during CPB was weakly positively associated with the postoperative P/F ratio. With a 100-unit increase in Pa o2 , the estimated increase in postoperative P/F ratio was 4.61 (95% CI, 0.71-8.50; P = .02). Our secondary analysis showed no significant association between Pa o2 with peak lactate 6 hours post CPB (geometric mean ratio [GMR], 1.01; 98.3% CI, 0.98-1.03; P = .55), average lactate 6 hours post CPB (GMR, 1.00; 98.3% CI, 0.97-1.03; P = .93), or acute kidney injury by Kidney Disease Improving Global Outcomes (KDIGO) criteria (odds ratio, 0.91; 98.3% CI, 0.75-1.10; P = .23). CONCLUSIONS Our investigation found no clinically significant association between Pa o2 during CPB and postoperative lung function. Similarly, there was no association between Pa o2 during CPB and lactate levels, postoperative renal function, or other exploratory outcomes.
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Affiliation(s)
- Marta Kelava
- From the Departments of Cardiothoracic Anesthesiology
- Outcomes Research, Cleveland Clinic, Cleveland, Ohio
| | - Adam J. Milam
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Phoenix, Arizona
| | - Junhui Mi
- Departments of Quantitative Health Sciences
| | | | | | - Shinya Unai
- Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio
| | | | - Kenneth McCurry
- Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio
| | | | - Andra Duncan
- From the Departments of Cardiothoracic Anesthesiology
- Outcomes Research, Cleveland Clinic, Cleveland, Ohio
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14
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Hilderink BN, Crane RF, van den Bogaard B, Pillay J, Juffermans NP. Hyperoxemia and hypoxemia impair cellular oxygenation: a study in healthy volunteers. Intensive Care Med Exp 2024; 12:37. [PMID: 38619625 PMCID: PMC11018572 DOI: 10.1186/s40635-024-00619-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 03/28/2024] [Indexed: 04/16/2024] Open
Abstract
INTRODUCTION Administration of oxygen therapy is common, yet there is a lack of knowledge on its ability to prevent cellular hypoxia as well as on its potential toxicity. Consequently, the optimal oxygenation targets in clinical practice remain unresolved. The novel PpIX technique measures the mitochondrial oxygen tension in the skin (mitoPO2) which allows for non-invasive investigation on the effect of hypoxemia and hyperoxemia on cellular oxygen availability. RESULTS During hypoxemia, SpO2 was 80 (77-83)% and PaO2 45(38-50) mmHg for 15 min. MitoPO2 decreased from 42(35-51) at baseline to 6(4.3-9)mmHg (p < 0.001), despite 16(12-16)% increase in cardiac output which maintained global oxygen delivery (DO2). During hyperoxic breathing, an FiO2 of 40% decreased mitoPO2 to 20 (9-27) mmHg. Cardiac output was unaltered during hyperoxia, but perfused De Backer density was reduced by one-third (p < 0.01). A PaO2 < 100 mmHg and > 200 mmHg were both associated with a reduction in mitoPO2. CONCLUSIONS Hypoxemia decreases mitoPO2 profoundly, despite complete compensation of global oxygen delivery. In addition, hyperoxemia also decreases mitoPO2, accompanied by a reduction in microcirculatory perfusion. These results suggest that mitoPO2 can be used to titrate oxygen support.
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Affiliation(s)
- Bashar N Hilderink
- Department of Intensive Care, OLVG Hospital, Amsterdam, The Netherlands.
| | - Reinier F Crane
- Department of Intensive Care, OLVG Hospital, Amsterdam, The Netherlands
| | | | - Janesh Pillay
- Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Nicole P Juffermans
- Department of Intensive Care, OLVG Hospital, Amsterdam, The Netherlands
- Laboratory of Translational Intensive Care, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
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15
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Simon Machado R, Mathias K, Joaquim L, de Quadros RW, Rezin GT, Petronilho F. Hyperoxia and brain: the link between necessity and injury from a molecular perspective. Neurotox Res 2024; 42:25. [PMID: 38619632 DOI: 10.1007/s12640-024-00702-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Revised: 11/15/2023] [Accepted: 03/25/2024] [Indexed: 04/16/2024]
Abstract
Oxygen (O2) supplementation is commonly used to treat hypoxia in patients with respiratory failure. However, indiscriminate use can lead to hyperoxia, a condition detrimental to living tissues, particularly the brain. The brain is sensitive to reactive oxygen species (ROS) and inflammation caused by high concentrations of O2, which can result in brain damage and mitochondrial dysfunction, common features of neurodegenerative disorders. Hyperoxia leads to increased production of ROS, causing oxidative stress, an imbalance between oxidants and antioxidants, which can damage tissues. The brain is particularly vulnerable to oxidative stress due to its lipid composition, high O2 consumption rate, and low levels of antioxidant enzymes. Moreover, hyperoxia can cause vasoconstriction and decreased O2 supply to the brain, posing a challenge to redox balance and neurodegenerative processes. Studies have shown that the severity of hyperoxia-induced brain damage varies with inspired O2 concentration and duration of exposure. Therefore, careful evaluation of the balance between benefits and risks of O2 supplementation, especially in clinical settings, is crucial.
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Affiliation(s)
- Richard Simon Machado
- Laboratory of Experimental Neurology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciuma, SC, Brazil.
- Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate Program in Health Sciences, Health Sciences Unit, University of South Santa Catarina, Tubarão, SC, Brazil.
| | - Khiany Mathias
- Laboratory of Experimental Neurology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciuma, SC, Brazil
| | - Larissa Joaquim
- Laboratory of Experimental Neurology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciuma, SC, Brazil
| | | | - Gislaine Tezza Rezin
- Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate Program in Health Sciences, Health Sciences Unit, University of South Santa Catarina, Tubarão, SC, Brazil
| | - Fabricia Petronilho
- Laboratory of Experimental Neurology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciuma, SC, Brazil
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16
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Young DA, Jones PAT, Matenchuk BA, Sivak A, Davenport MH, Steinback CD. The effect of hyperoxia on muscle sympathetic nerve activity: a systematic review and meta-analysis. Clin Auton Res 2024; 34:233-252. [PMID: 38709357 DOI: 10.1007/s10286-024-01033-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Accepted: 04/09/2024] [Indexed: 05/07/2024]
Abstract
PURPOSE We conducted a meta-analysis to determine the effect of hyperoxia on muscle sympathetic nerve activity in healthy individuals and those with cardio-metabolic diseases. METHODS A comprehensive search of electronic databases was performed until August 2022. All study designs (except reviews) were included: population (humans; apparently healthy or with at least one chronic disease); exposures (muscle sympathetic nerve activity during hyperoxia or hyperbaria); comparators (hyperoxia or hyperbaria vs. normoxia); and outcomes (muscle sympathetic nerve activity, heart rate, blood pressure, minute ventilation). Forty-nine studies were ultimately included in the meta-analysis. RESULTS In healthy individuals, hyperoxia had no effect on sympathetic burst frequency (mean difference [MD] - 1.07 bursts/min; 95% confidence interval [CI] - 2.17, 0.04bursts/min; P = 0.06), burst incidence (MD 0.27 bursts/100 heartbeats [hb]; 95% CI - 2.10, 2.64 bursts/100 hb; P = 0.82), burst amplitude (P = 0.85), or total activity (P = 0.31). In those with chronic diseases, hyperoxia decreased burst frequency (MD - 5.57 bursts/min; 95% CI - 7.48, - 3.67 bursts/min; P < 0.001) and burst incidence (MD - 4.44 bursts/100 hb; 95% CI - 7.94, - 0.94 bursts/100 hb; P = 0.01), but had no effect on burst amplitude (P = 0.36) or total activity (P = 0.90). Our meta-regression analyses identified an inverse relationship between normoxic burst frequency and change in burst frequency with hyperoxia. In both groups, hyperoxia decreased heart rate but had no effect on any measure of blood pressure. CONCLUSION Hyperoxia does not change sympathetic activity in healthy humans. Conversely, in those with chronic diseases, hyperoxia decreases sympathetic activity. Regardless of disease status, resting sympathetic burst frequency predicts the degree of change in burst frequency, with larger decreases for those with higher resting activity.
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Affiliation(s)
- Desmond A Young
- Neurovascular Health Lab, Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, AB, Canada
| | - Paris A T Jones
- Neurovascular Health Lab, Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, AB, Canada
| | - Brittany A Matenchuk
- Neurovascular Health Lab, Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, AB, Canada
- Program for Pregnancy and Postpartum Health, Faculty of Kinesiology, Sport, and Recreation, Women and Children's Health Research Institute, Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada
| | - Allison Sivak
- Geoffrey and Robyn Sperber Health Sciences Library, University of Alberta, Edmonton, AB, Canada
| | - Margie H Davenport
- Neurovascular Health Lab, Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, AB, Canada
- Program for Pregnancy and Postpartum Health, Faculty of Kinesiology, Sport, and Recreation, Women and Children's Health Research Institute, Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada
| | - Craig D Steinback
- Neurovascular Health Lab, Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, AB, Canada.
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17
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Vezzoli A, Mrakic-Sposta S, Brizzolari A, Balestra C, Camporesi EM, Bosco G. Oxy-Inflammation in Humans during Underwater Activities. Int J Mol Sci 2024; 25:3060. [PMID: 38474303 DOI: 10.3390/ijms25053060] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2024] [Revised: 02/22/2024] [Accepted: 03/01/2024] [Indexed: 03/14/2024] Open
Abstract
Underwater activities are characterized by an imbalance between reactive oxygen/nitrogen species (RONS) and antioxidant mechanisms, which can be associated with an inflammatory response, depending on O2 availability. This review explores the oxidative stress mechanisms and related inflammation status (Oxy-Inflammation) in underwater activities such as breath-hold (BH) diving, Self-Contained Underwater Breathing Apparatus (SCUBA) and Closed-Circuit Rebreather (CCR) diving, and saturation diving. Divers are exposed to hypoxic and hyperoxic conditions, amplified by environmental conditions, hyperbaric pressure, cold water, different types of breathing gases, and air/non-air mixtures. The "diving response", including physiological adaptation, cardiovascular stress, increased arterial blood pressure, peripheral vasoconstriction, altered blood gas values, and risk of bubble formation during decompression, are reported.
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Affiliation(s)
- Alessandra Vezzoli
- Institute of Clinical Physiology-National Research Council (CNR-IFC), 20142 Milano, Italy
- Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy
| | - Simona Mrakic-Sposta
- Institute of Clinical Physiology-National Research Council (CNR-IFC), 20142 Milano, Italy
| | - Andrea Brizzolari
- Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy
| | - Costantino Balestra
- Environmental, Occupational, Aging (Integrative) Physiology Laboratory, Haute Ecole Bruxelles-Brabant (HE2B), 1160 Brussels, Belgium
- Physical Activity Teaching Unit, Motor Sciences Department, Université Libre de Bruxelles (ULB), 1050 Brussels, Belgium
- DAN Europe Research Division (Roseto-Brussels), 1160 Brussels, Belgium
| | | | - Gerardo Bosco
- Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy
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18
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Nemzek JA, Hakenjos JM, Hoenerhoff MJ, Fry CD. Isoflurane and Pentobarbital Anesthesia for Pulmonary Studies Requiring Prolonged Mechanical Ventilation in Mice. JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE : JAALAS 2024; 63:41-48. [PMID: 38065567 PMCID: PMC10844742 DOI: 10.30802/aalas-jaalas-23-000014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 03/27/2023] [Accepted: 05/31/2023] [Indexed: 02/08/2024]
Abstract
Mechanical ventilation can be used in mice to support high-risk anesthesia or to create clinically relevant, intensive care models. However, the choice of anesthetic and inspired oxygen concentration for prolonged procedures may affect basic physiology and lung inflammation. To characterize the effects of anesthetics and oxygen concentration in mice experiencing mechanical ventilation, mice were anesthetized with either isoflurane or pentobarbital for tracheostomy followed by mechanical ventilation with either 100% or 21% oxygen. Body temperature, oxygen saturation, and pulse rate were monitored continuously. After 6 h, mice were euthanized for collection of blood and bronchoalveolar lavage fluid for evaluation of biomarkers of inflammation and lung injury, including cell counts and cytokine levels. Overall, both isoflurane and pentobarbital provided suitable anesthesia for 6 h of mechanical ventilation with either 21% or 100% oxygen. We found no differences in lung inflammation biomarkers attributable to either oxygen concentration or the anesthetic. However, the combination of pentobarbital and 100% oxygen resulted in a significantly higher concentration of a biomarker for lung epithelial cell injury. This study demonstrates that the combination of anesthetic agent, mechanical ventilation, and inspired oxygen concentrations can alter vital signs and lung injury biomarkers during prolonged procedures. Their combined impact may influence model development and the interpretation of research results, warranting the need for preliminary evaluation to establish the baseline effects.
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Affiliation(s)
- Jean A Nemzek
- Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan; and
| | | | - Mark J Hoenerhoff
- Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan; and
| | - Christopher D Fry
- Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan; and
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Lie SL, Hisdal J, Rehn M, Høiseth LØ. Hemodynamic effects of supplemental oxygen versus air in simulated blood loss in healthy volunteers: a randomized, controlled, double-blind, crossover trial. Intensive Care Med Exp 2023; 11:76. [PMID: 37947905 PMCID: PMC10638149 DOI: 10.1186/s40635-023-00561-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 11/01/2023] [Indexed: 11/12/2023] Open
Abstract
BACKGROUND Trauma patients frequently receive supplemental oxygen, but its hemodynamic effects in blood loss are poorly understood. We studied the effects of oxygen on the hemodynamic response and tolerance to simulated blood loss in healthy volunteers. METHODS Fifteen healthy volunteers were exposed to simulated blood loss by lower body negative pressure (LBNP) on two separate visits at least 24 h apart. They were randomized to inhale 100% oxygen or medical air on visit 1, while inhaling the other on visit 2. To simulate progressive blood loss LBNP was increased every 3 min in levels of 10 mmHg from 0 to 80 mmHg or until hemodynamic decompensation. Oxygen and air were delivered on a reservoired face mask at 15 L/min. The effect of oxygen compared to air on the changes in cardiac output, stroke volume and middle cerebral artery blood velocity (MCAV) was examined with mixed regression to account for repeated measurements within subjects. The effect of oxygen compared to air on the tolerance to blood loss was measured as the time to hemodynamic decompensation in a shared frailty model. Cardiac output was the primary outcome variable. RESULTS Oxygen had no statistically significant effect on the changes in cardiac output (0.031 L/min/LBNP level, 95% confidence interval (CI): - 0.015 to 0.077, P = 0.188), stroke volume (0.39 mL/LBNP level, 95% CI: - 0.39 to 1.2, P = 0.383), or MCAV (0.25 cm/s/LBNP level, 95% CI: - 0.11 to 0.61, P = 0.176). Four subjects exhibited hemodynamic decompensation when inhaling oxygen compared to 10 when inhaling air (proportional hazard ratio 0.24, 95% CI: 0.065 to 0.85, P = 0.027). CONCLUSIONS We found no effect of oxygen compared to air on the changes in cardiac output, stroke volume or MCAV during simulated blood loss in healthy volunteers. However, oxygen had a favorable effect on the tolerance to simulated blood loss with fewer hemodynamic decompensations. Our findings suggest that supplemental oxygen does not adversely affect the hemodynamic response to simulated blood loss. Trial registration This trial was registered in ClinicalTrials.gov (NCT05150418) December 9, 2021.
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Affiliation(s)
- Sole Lindvåg Lie
- Department of Research and Development, Norwegian Air Ambulance Foundation, Oslo, Norway.
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
- Section of Vascular Investigations, Oslo University Hospital, Oslo, Norway.
| | - Jonny Hisdal
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Section of Vascular Investigations, Oslo University Hospital, Oslo, Norway
| | - Marius Rehn
- Department of Research and Development, Norwegian Air Ambulance Foundation, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Air Ambulance Department, Division of Prehospital Services, Oslo University Hospital, Oslo, Norway
| | - Lars Øivind Høiseth
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Anesthesia and Intensive Care Medicine, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway
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Begashvili I, Kiladze M, Ejibishvili C, Grigolia G. Minimal fixed flow anesthesia for off-pump coronary artery bypass surgery: A parallel randomized trail. Heliyon 2023; 9:e22181. [PMID: 38034715 PMCID: PMC10685267 DOI: 10.1016/j.heliyon.2023.e22181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 09/23/2023] [Accepted: 11/06/2023] [Indexed: 12/02/2023] Open
Abstract
Objectives The aim of the present study was to test a safety of a fixed minimal (0.5 l/min) fresh gas flow (FGF) anesthesia as a method ensuring adequate oxygenation during off-pump coronary artery bypass grafting operations. Design A randomized, prospective study. Setting Single-center clinical hospital affiliated with a university. Participants 208 patients underwent off-pump coronary artery bypass surgery. Interventions All patients received endotracheal inhalational anesthesia with fixed minimal FGF. Half of them were anesthetized by sevoflurane and another half by isoflurane. The fresh (carrier) gas was pure oxygen in the control groups and a mixture of medical air and oxygen (FiO2 0.8) in the trial groups. Measurements and main results In the control groups inhaled oxygen concentration changed minimally during the operation. In the trial groups in 28.8 % of cases inhaled oxygen concentration dropped below preliminary margin (0.4). Body surface area (BSA) (B = 38.7; p = 0.002) and patient's age (B = -0.47; p = 0.004) were retained into final logistic regression model as independent predictors. We divided BSA into subcategories and analyzed data by survival cox regression with Forward LR method. Patients with BSA>2.3 (Exp.B = 183) and BSA [2.2-2.3] (Exp.B = 59) had high chance to get less than 0.4 of inhaled oxygen concentration compared to the patients with BSA <2.0 (p < 0.001).Exp(B) or OR for the patients' age as independent predictor tested in multiple logistic regression was 0.628 In other words, for every year less the patient had 1/0.628 = 1.6 times more chance to reach the preliminary low margin (0.4) of oxygenation. Conclusions Fixed minimal FGF 0.5 l/min with FiO2 0.8 may not be sufficient for the younger patients with BSA >2.0 to maintain inhaled oxygen concentration above 0.4. Using pure oxygen as a carrier gas during fixed minimal flow long term anesthesia is much safer and more reliable.
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Affiliation(s)
- Ioseb Begashvili
- Tbilisi 5th clinical hospital, Department of cardiac anesthesia and intensive care. PhD student of Ivane Javakhishvili Tbilisi state university. Address: Temqa - XI, I Quarter, 5th clinical hospital “Open Heart”, 0102 Tbilisi, Georgia
| | - Merab Kiladze
- Professor of Ivane Javakhishvili Tbilisi state university, Chief of the department of surgery at American hospital Tbilisi, Georgia
| | - Christina Ejibishvili
- Tbilisi 5th clinical hospital, Department of cardiac anesthesia and intensive care, PhD student of Ivane Javakhishvili Tbilisi state university, Georgia
| | - George Grigolia
- Tbilisi 5th clinical hospital, Head of the department of cardiac anesthesia and intensive care, Georgia
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Singh S, Rout A, Chaudhary R, Garg A, Tantry US, Gurbel PA. Oxygen Targets After Cardiac Arrest: A Meta-analysis of Randomized Controlled Trials. Am J Ther 2023; 30:e509-e518. [PMID: 37921678 PMCID: PMC10809880 DOI: 10.1097/mjt.0000000000001636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2023]
Abstract
BACKGROUND Optimal oxygen saturation target in patients resuscitated after cardiac arrest is unknown. Previous randomized controlled trials (RCTs) comparing restrictive oxygen therapy with liberal therapy have shown conflicting results. STUDY QUESTION We performed a meta-analysis of available RCTs to consolidate the contrasting findings regarding the oxygen targets after cardiac arrest. DATA SOURCES We searched electronic databases for RCTs comparing restrictive versus liberal oxygen targets in patients resuscitated after cardiac arrest. STUDY DESIGN End points of interest were mortality, unfavorable neurological outcomes, and rearrests. Random-effects meta-analysis was performed to estimate the risk ratio (RR) with a 95% confidence interval (CI). RESULTS Eight RCTs with 1641 patients (restrictive n = 833, liberal n = 808) were included in the analysis. The oxygen targets were defined by either saturation, partial pressure (PaO2), or supplementation rates. The mean age and male percentage were 63 years and 80%, respectively. There was no significant difference observed in the 2 groups for overall mortality (RR = 0.91, 95% CI = 0.75-1.10, P = 0.33), unfavorable neurological outcomes (RR = 0.93, 95% CI = 0.74-1.18, P = 0.56), and rearrests (RR = 0.67, 95% CI = 0.22-1.98, P = 0.47). CONCLUSIONS Overall, this meta-analysis shows no significant difference in mortality, unfavorable neurological outcomes, and rearrests when using restrictive or liberal oxygen targets in patients after cardiac arrest. The limitations in the newer trials should be kept in mind while interpreting the overall results.
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Affiliation(s)
- Sahib Singh
- Department of Medicine, Sinai Hospital of Baltimore, Baltimore, MD
| | - Amit Rout
- Division of Cardiology, University of Louisville, Louisville, KY
| | - Rahul Chaudhary
- Division of Cardiology, University of Pittsburgh, Pittsburgh, PA
| | - Aakash Garg
- Cardiology Associates of Schenectady, St. Peter’s Health Partners, Albany, NY
| | - Udaya S. Tantry
- Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, MD
| | - Paul A. Gurbel
- Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, MD
- Division of Cardiology, Sinai Hospital of Baltimore, Baltimore, MD
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Chuai F, Dong T, Liu Y, Jiang W, Zhang L, Chen L, Chuai Y, Zhou Y. The effect of intrapartum prolonged oxygen exposure on fetal metabolic status: secondary analysis from a randomized controlled trial. Front Endocrinol (Lausanne) 2023; 14:1204956. [PMID: 37441500 PMCID: PMC10335765 DOI: 10.3389/fendo.2023.1204956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 05/15/2023] [Indexed: 07/15/2023] Open
Abstract
Objective The aim of the study is to assess the effect of maternal prolonged oxygen exposure during labor on fetal acid-base status, fetal heart rate tracings, and umbilical cord arterial metabolites. Design The study was conducted as a secondary analysis. Settings The study was set in three tertiary teaching hospitals in Beijing, China. Participants Approximately 140 women in the latent phase of labor with no complications participated in the study. Intervention Participants were randomly allocated in a 1:1 ratio to receive either 10 L of oxygen per minute in a tight-fitting simple facemask until delivery or room air only. Main outcome measures The primary outcome was the umbilical cord arterial lactate. Results Baseline demographics and labor outcomes were similar between the oxygen and room air groups; the time from randomization to delivery was 322 ± 147 min. There were no differences between the two groups in the umbilical cord arterial lactate (mean difference 0.3 mmol/L, 95% confidence interval -0.2 to 0.9), the number of participants with high-risk category II fetal heart rate tracings (relative risk 0.94, 95% confidence interval 0.68 to 1.32), or the duration of those high-risk tracings (mean difference 3.6 min, 95% confidence interval -9.3 to 16.4). Prolonged oxygen exposure significantly altered 91 umbilical cord arterial metabolites, and these alterations did not appear to be related to oxidative stress. Conclusion Maternal prolonged oxygen exposure during labor did not affect either the umbilical cord arterial lactate or high-risk category II fetal heart rate tracings but might result in alterations to the umbilical cord arterial metabolic profile. Clinical trial registration www.clinicaltrials.gov, identifier NCT03764696.
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Affiliation(s)
- Fang Chuai
- Department of Obstetrics and Gynaecology, Sixth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Tong Dong
- Department of Obstetrics and Gynaecology, Sixth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yuan Liu
- Department of Obstetrics and Gynaecology, Sixth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Wen Jiang
- Department of Obstetrics and Gynaecology, Seventh Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Lanmei Zhang
- Department of Obstetrics and Gynecology, PLA Strategic Support Force Characteristic Medical Center, Beijing, China
| | - Lei Chen
- Department of Obstetrics and Gynaecology, Sixth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yunhai Chuai
- Department of Obstetrics and Gynaecology, Sixth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yuhang Zhou
- Department of Day Treatment, Sixth Medical Center, Chinese PLA General Hospital, Beijing, China
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Brat K, Chovanec Z, Mitas L, Sramek V, Olson LJ, Cundrle I. Hyperoxemia post thoracic surgery - Does it matter? Heliyon 2023; 9:e17606. [PMID: 37416669 PMCID: PMC10320252 DOI: 10.1016/j.heliyon.2023.e17606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Revised: 06/19/2023] [Accepted: 06/22/2023] [Indexed: 07/08/2023] Open
Abstract
Introduction Post-operative oxygen therapy is used to prevent hypoxemia and surgical site infection. However, with improvements of anesthesia techniques, post-operative hypoxemia incidence is declining and the benefits of oxygen on surgical site infection have been questioned. Moreover, hyperoxemia might have adverse effects on the pulmonary and cardiovascular systems. We hypothesized hyperoxemia post thoracic surgery is associated with post-operative pulmonary and cardiovascular complications. Methods Consecutive lung resection patients were included in this post-hoc analysis. Post-operative pulmonary and cardiovascular complications were prospectively assessed during the first 30 post-operative days, or hospital stay. Arterial blood gases were analyzed at 1, 6 and 12 h after surgery. Hyperoxemia was defined as arterial partial pressure of oxygen (PaO2)>100 mmHg. Patients with hyperoxemia duration in at least two adjacent time points were considered as hyperoxemic. Student t-test, Mann-Whitney U test and two-tailed Fisher exact test were used for group comparison. P values < 0.05 were considered statistically significant. Results Three hundred sixty-three consecutive patients were included in this post-hoc analysis. Two hundred five patients (57%), were considered hyperoxemic and included in the hyperoxemia group. Patients in the hyperoxemia group had significantly higher PaO2 at 1, 6 and 12 h after surgery (p < 0.05). Otherwise, there was no significant difference in age, sex, comorbidities, pulmonary function tests parameters, lung surgery procedure, incidence of post-operative pulmonary and cardiovascular complications, intensive care unit and hospital length of stay and 30-day mortality. Conclusion Hyperoxemia after lung resection surgery is common and not associated with post-operative complications or 30-day mortality.
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Affiliation(s)
- Kristian Brat
- Department of Respiratory Diseases, University Hospital Brno, Czech Republic
- Faculty of Medicine, Masaryk University, Brno, Czech Republic
- International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic
| | - Zdenek Chovanec
- Faculty of Medicine, Masaryk University, Brno, Czech Republic
- First Department of Surgery, St. Anne's University Hospital, Brno, Czech Republic
| | - Ladislav Mitas
- Faculty of Medicine, Masaryk University, Brno, Czech Republic
- Department of Surgery, University Hospital Brno, Czech Republic
| | - Vladimir Sramek
- Faculty of Medicine, Masaryk University, Brno, Czech Republic
- International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic
- Department of Anesthesiology and Intensive Care, St. Anne's University Hospital Brno, Brno, Czech Republic
| | - Lyle J. Olson
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA
| | - Ivan Cundrle
- Faculty of Medicine, Masaryk University, Brno, Czech Republic
- International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic
- Department of Anesthesiology and Intensive Care, St. Anne's University Hospital Brno, Brno, Czech Republic
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Friess JO, Mikasi J, Baumann R, Ranjan R, Fischer K, Levis A, Terbeck S, Hirschi T, Gerber D, Erdoes G, Schoenhoff FS, Carrel TP, Madhkour R, Eberle B, Guensch DP. Hyperoxia-induced deterioration of diastolic function in anaesthetised patients with coronary artery disease - Randomised crossover trial. BJA OPEN 2023; 6:100135. [PMID: 37588173 PMCID: PMC10430862 DOI: 10.1016/j.bjao.2023.100135] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 03/07/2023] [Accepted: 03/17/2023] [Indexed: 08/18/2023]
Abstract
Background There are no current recommendations for oxygen titration in patients with stable coronary artery disease. This study investigates the effect of iatrogenic hyperoxia on cardiac function in patients with coronary artery disease undergoing general anaesthesia. Methods Patients scheduled for elective coronary artery bypass graft surgery were prospectively recruited into this randomised crossover clinical trial. All patients were exposed to inspired oxygen fractions of 0.3 (normoxaemia) and 0.8 (hyperoxia) in randomised order. A transoesophageal echocardiographic imaging protocol was performed during each exposure. Primary analysis investigated changes in 3D peak strain, whereas secondary analyses investigated other systolic and diastolic responses. Results There was no statistical difference in systolic function between normoxaemia and hyperoxia. However, the response in systolic function to hyperoxia was dependent on ventricular function at normoxaemia. Patients with a normoxaemic left ventricular (LV) global longitudinal strain (GLS) poorer than the derived cut-off (>-15.4%) improved with hyperoxia (P<0.01), whereas in patients with normoxaemic LV-GLS <-15.4%, LV-GLS worsened with transition to hyperoxia (P<0.01). The same was seen for right ventricular GLS with a cut-off at -24.1%. Diastolic function worsened during hyperoxia indicated by a significant increase of averaged E/e' (8.6 [2.6]. vs 8.2 [2.4], P=0.01) and E/A ratio (1.4 (0.4) vs 1.3 (0.4), P=0.01). Conclusions Although the response of biventricular systolic variables is dependent on systolic function at normoxaemia, diastolic function consistently worsens under hyperoxia. In coronary artery disease, intraoperative strain analysis may offer guidance for oxygen titration. Clinical trial registration NCT04424433.
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Affiliation(s)
- Jan O. Friess
- Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Jan Mikasi
- Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Rico Baumann
- Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Rajevan Ranjan
- Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Kady Fischer
- Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Anja Levis
- Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Sandra Terbeck
- Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Trevor Hirschi
- Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Daniel Gerber
- Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Gabor Erdoes
- Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Florian S. Schoenhoff
- Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Thierry P. Carrel
- Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Raouf Madhkour
- Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Balthasar Eberle
- Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Dominik P. Guensch
- Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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Reiterer C, Fleischmann E, Kabon B, Taschner A, Kurz A, Adamowitsch N, von Sonnenburg MF, Fraunschiel M, Graf A. Hemodynamic effects of intraoperative 30% versus 80% oxygen concentrations: an exploratory analysis. Front Med (Lausanne) 2023; 10:1200223. [PMID: 37324125 PMCID: PMC10265637 DOI: 10.3389/fmed.2023.1200223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 05/05/2023] [Indexed: 06/17/2023] Open
Abstract
Background Supplemental oxygen leads to an increase in peripheral vascular resistance which finally increases systemic blood pressure in healthy subjects and patients with coronary artery disease, heart failure, undergoing heart surgery, and with sepsis. However, it is unknown whether this effect can also be observed in anesthetized patients having surgery. Thus, we evaluated in this exploratory analysis of a randomized controlled trial the effect of 80% versus 30% oxygen on intraoperative blood pressure and heart rate. Methods We present data from a previous study including 258 patients, who were randomized to a perioperative inspiratory FiO2 of 0.8 (128 patients) versus 0.3 (130 patients) for major abdominal surgery. Continuous arterial blood pressure values were recorded every three seconds and were exported from the electronic anesthesia record system. We calculated time-weighted average (TWA) and Average Real Variability (ARV) of mean arterial blood pressure and of heart rate. Results There was no significant difference in TWA of mean arterial pressure between the 80% (80 mmHg [76, 85]) and 30% (81 mmHg [77, 86]) oxygen group (effect estimate -0.16 mmHg, CI -1.83 to 1.51; p = 0.85). There was also no significant difference in TWA of heart rate between the 80 and 30% oxygen group (median TWA of heart rate in the 80% oxygen group: 65 beats.min-1 [58, 72], and in the 30% oxygen group: 64 beats.min-1 [58; 70]; effect estimate: 0.12 beats.min-1, CI -2.55 to 2.8, p = 0.94). Also for ARV values, no significant differences between groups could be detected. Conclusion In contrast to previous results, we did not observe a significant increase in blood pressure or a significant decrease in heart rate in patients, who received 80% oxygen as compared to patients, who received 30% oxygen during surgery and for the first two postoperative hours. Thus, hemodynamic effects of supplemental oxygen might play a negligible role in anesthetized patients. Clinical Trail Registration https://clinicaltrials.gov/ct2/show/NCT03366857?term=vienna&cond=oxygen&draw=2&rank=1.
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Affiliation(s)
- Christian Reiterer
- Department of Anesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria
- Outcome Research Consortium, Cleveland, OH, United States
| | - Edith Fleischmann
- Department of Anesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria
- Outcome Research Consortium, Cleveland, OH, United States
| | - Barbara Kabon
- Department of Anesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria
- Outcome Research Consortium, Cleveland, OH, United States
| | - Alexander Taschner
- Department of Anesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria
- Outcome Research Consortium, Cleveland, OH, United States
| | - Andrea Kurz
- Outcome Research Consortium, Cleveland, OH, United States
- Department of General Anesthesiology, Cleveland Clinic, Anesthesia Institute, Cleveland, OH, United States
- Department of General Anesthesiology, Emergency Medicine and Intensive Care Medicine, Medical University of Graz, Graz, Austria
| | - Nikolas Adamowitsch
- Department of Anesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria
| | | | - Melanie Fraunschiel
- IT Systems and Communications, Medical University of Vienna, Vienna, Austria
| | - Alexandra Graf
- Center for Medical Data Science, Medical University of Vienna, Vienna, Austria
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Jentzer JC, Miller PE, Alviar C, Yalamuri S, Bohman JK, Tonna JE. Exposure to Arterial Hyperoxia During Extracorporeal Membrane Oxygenator Support and Mortality in Patients With Cardiogenic Shock. Circ Heart Fail 2023; 16:e010328. [PMID: 36871240 PMCID: PMC10121893 DOI: 10.1161/circheartfailure.122.010328] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 03/01/2023] [Indexed: 03/06/2023]
Abstract
BACKGROUND Exposure to hyperoxia, a high arterial partial pressure of oxygen (PaO2), may be associated with worse outcomes in patients receiving extracorporeal membrane oxygenator (ECMO) support. We examined hyperoxia in the Extracorporeal Life Support Organization Registry among patients receiving venoarterial ECMO for cardiogenic shock. METHODS We included Extracorporeal Life Support Organization Registry patients from 2010 to 2020 who received venoarterial ECMO for cardiogenic shock, excluding extracorporeal CPR. Patients were grouped based on PaO2 after 24 hours of ECMO: normoxia (PaO2 60-150 mmHg), mild hyperoxia (PaO2 151-300 mmHg), and severe hyperoxia (PaO2 >300 mmHg). In-hospital mortality was evaluated using multivariable logistic regression. RESULTS Among 9959 patients, 3005 (30.2%) patients had mild hyperoxia and 1972 (19.8%) had severe hyperoxia. In-hospital mortality increased across groups: normoxia, 47.8%; mild hyperoxia, 55.6% (adjusted odds ratio, 1.37 [95% CI, 1.23-1.53]; P<0.001); severe hyperoxia, 65.4% (adjusted odds ratio, 2.20 [95% CI, 1.92-2.52]; P<0.001). A higher PaO2 was incrementally associated with increased in-hospital mortality (adjusted odds ratio, 1.14 per 50 mmHg higher [95% CI, 1.12-1.16]; P<0.001). Patients with a higher PaO2 had increased in-hospital mortality in each subgroup and when stratified by ventilator settings, airway pressures, acid-base status, and other clinical variables. In the random forest model, PaO2 was the second strongest predictor of in-hospital mortality, after older age. CONCLUSIONS Exposure to hyperoxia during venoarterial ECMO support for cardiogenic shock is strongly associated with increased in-hospital mortality, independent from hemodynamic and ventilatory status. Until clinical trial data are available, we suggest targeting a normal PaO2 and avoiding hyperoxia in CS patients receiving venoarterial ECMO.
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Affiliation(s)
- Jacob C. Jentzer
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | - P. Elliott Miller
- Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT
| | - Carlos Alviar
- Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, New York
| | - Suraj Yalamuri
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - J. Kyle Bohman
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Joseph E. Tonna
- Divisions of Cardiothoracic Surgery and Emergency Medicine, University of Utah Health and School of Medicine, Salt Lake City, UT
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Rossaint R, Afshari A, Bouillon B, Cerny V, Cimpoesu D, Curry N, Duranteau J, Filipescu D, Grottke O, Grønlykke L, Harrois A, Hunt BJ, Kaserer A, Komadina R, Madsen MH, Maegele M, Mora L, Riddez L, Romero CS, Samama CM, Vincent JL, Wiberg S, Spahn DR. The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition. Crit Care 2023; 27:80. [PMID: 36859355 PMCID: PMC9977110 DOI: 10.1186/s13054-023-04327-7] [Citation(s) in RCA: 264] [Impact Index Per Article: 132.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 01/20/2023] [Indexed: 03/03/2023] Open
Abstract
BACKGROUND Severe trauma represents a major global public health burden and the management of post-traumatic bleeding continues to challenge healthcare systems around the world. Post-traumatic bleeding and associated traumatic coagulopathy remain leading causes of potentially preventable multiorgan failure and death if not diagnosed and managed in an appropriate and timely manner. This sixth edition of the European guideline on the management of major bleeding and coagulopathy following traumatic injury aims to advise clinicians who care for the bleeding trauma patient during the initial diagnostic and therapeutic phases of patient management. METHODS The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma included representatives from six European professional societies and convened to assess and update the previous version of this guideline using a structured, evidence-based consensus approach. Structured literature searches covered the period since the last edition of the guideline, but considered evidence cited previously. The format of this edition has been adjusted to reflect the trend towards concise guideline documents that cite only the highest-quality studies and most relevant literature rather than attempting to provide a comprehensive literature review to accompany each recommendation. RESULTS This guideline comprises 39 clinical practice recommendations that follow an approximate temporal path for management of the bleeding trauma patient, with recommendations grouped behind key decision points. While approximately one-third of patients who have experienced severe trauma arrive in hospital in a coagulopathic state, a systematic diagnostic and therapeutic approach has been shown to reduce the number of preventable deaths attributable to traumatic injury. CONCLUSION A multidisciplinary approach and adherence to evidence-based guidelines are pillars of best practice in the management of severely injured trauma patients. Further improvement in outcomes will be achieved by optimising and standardising trauma care in line with the available evidence across Europe and beyond.
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Affiliation(s)
- Rolf Rossaint
- Department of Anaesthesiology, University Hospital Aachen, RWTH, Aachen University, Pauwelsstrasse 30, D-52074, Aachen, Germany.
| | - Arash Afshari
- grid.5254.60000 0001 0674 042XDepartment of Paediatric and Obstetric Anaesthesia, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
| | - Bertil Bouillon
- grid.412581.b0000 0000 9024 6397Department of Trauma and Orthopaedic Surgery, Cologne-Merheim Medical Centre (CMMC), University of Witten/Herdecke, Ostmerheimer Strasse 200, D-51109 Cologne, Germany
| | - Vladimir Cerny
- grid.424917.d0000 0001 1379 0994Department of Anaesthesiology, Perioperative Medicine and Intensive Care, Masaryk Hospital, J.E. Purkinje University, Socialni pece 3316/12A, CZ-40113 Usti nad Labem, Czech Republic ,grid.4491.80000 0004 1937 116XDepartment of Anaesthesiology and Intensive Care Medicine, Charles University Faculty of Medicine, Simkova 870, CZ-50003 Hradec Králové, Czech Republic
| | - Diana Cimpoesu
- grid.411038.f0000 0001 0685 1605Department of Emergency Medicine, Emergency County Hospital “Sf. Spiridon” Iasi, University of Medicine and Pharmacy ”Grigore T. Popa” Iasi, Blvd. Independentei 1, RO-700111 Iasi, Romania
| | - Nicola Curry
- grid.410556.30000 0001 0440 1440Oxford Haemophilia and Thrombosis Centre, Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Trust, Windmill Road, Oxford, OX3 7HE UK ,grid.4991.50000 0004 1936 8948Radcliffe Department of Medicine, Oxford University, Oxford, UK
| | - Jacques Duranteau
- grid.460789.40000 0004 4910 6535Department of Anesthesiology, Intensive Care and Perioperative Medicine, Assistance Publique Hôpitaux de Paris, Paris Saclay University, 78 rue du Général Leclerc, F-94275 Le Kremlin-Bicêtre Cedex, France
| | - Daniela Filipescu
- grid.8194.40000 0000 9828 7548Department of Cardiac Anaesthesia and Intensive Care, “Prof. Dr. C. C. Iliescu” Emergency Institute of Cardiovascular Diseases, Carol Davila University of Medicine and Pharmacy, Sos Fundeni 256-258, RO-022328 Bucharest, Romania
| | - Oliver Grottke
- grid.1957.a0000 0001 0728 696XDepartment of Anaesthesiology, University Hospital Aachen, RWTH, Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany
| | - Lars Grønlykke
- grid.5254.60000 0001 0674 042XDepartment of Thoracic Anaesthesiology, The Heart Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
| | - Anatole Harrois
- grid.460789.40000 0004 4910 6535Department of Anesthesiology, Intensive Care and Perioperative Medicine, Assistance Publique Hôpitaux de Paris, Paris Saclay University, 78 rue du Général Leclerc, F-94275 Le Kremlin-Bicêtre Cedex, France
| | - Beverley J. Hunt
- grid.420545.20000 0004 0489 3985Thrombosis and Haemophilia Centre, Guy’s and St Thomas’ NHS Foundation Trust, Westminster Bridge Road, London, SE1 7EH UK
| | - Alexander Kaserer
- grid.412004.30000 0004 0478 9977Institute of Anaesthesiology, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland
| | - Radko Komadina
- grid.8954.00000 0001 0721 6013Department of Traumatology, General and Teaching Hospital Celje, Medical Faculty, Ljubljana University, Oblakova ulica 5, SI-3000 Celje, Slovenia
| | - Mikkel Herold Madsen
- grid.5254.60000 0001 0674 042XDepartment of Paediatric and Obstetric Anaesthesia, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
| | - Marc Maegele
- grid.412581.b0000 0000 9024 6397Department of Trauma and Orthopaedic Surgery, Cologne-Merheim Medical Centre (CMMC), Institute for Research in Operative Medicine (IFOM), University of Witten/Herdecke, Ostmerheimer Strasse 200, D-51109 Cologne, Germany
| | - Lidia Mora
- grid.7080.f0000 0001 2296 0625Department of Anaesthesiology, Intensive Care and Pain Clinic, Vall d’Hebron Trauma, Rehabilitation and Burns Hospital, Autonomous University of Barcelona, Passeig de la Vall d’Hebron 119-129, ES-08035 Barcelona, Spain
| | - Louis Riddez
- grid.24381.3c0000 0000 9241 5705Department of Surgery and Trauma, Karolinska University Hospital, S-171 76 Solna, Sweden
| | - Carolina S. Romero
- grid.106023.60000 0004 1770 977XDepartment of Anaesthesia, Intensive Care and Pain Therapy, Consorcio Hospital General Universitario de Valencia, Universidad Europea of Valencia Methodology Research Department, Avenida Tres Cruces 2, ES-46014 Valencia, Spain
| | - Charles-Marc Samama
- Department of Anaesthesia, Intensive Care and Perioperative Medicine, GHU AP-HP Centre - Université Paris Cité - Cochin Hospital, 27 rue du Faubourg St. Jacques, F-75014 Paris, France
| | - Jean-Louis Vincent
- grid.4989.c0000 0001 2348 0746Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Route de Lennik 808, B-1070 Brussels, Belgium
| | - Sebastian Wiberg
- grid.5254.60000 0001 0674 042XDepartment of Thoracic Anaesthesiology, The Heart Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
| | - Donat R. Spahn
- grid.412004.30000 0004 0478 9977Institute of Anaesthesiology, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland
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Ho CM, Sun HY. Oxygen "therapy" for infection in liver transplant surgery: less is more, enough is enough. BMC Med 2023; 21:52. [PMID: 36782244 PMCID: PMC9924852 DOI: 10.1186/s12916-023-02767-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 02/02/2023] [Indexed: 02/15/2023] Open
Affiliation(s)
- Cheng-Maw Ho
- Department of Surgery, National Taiwan University Hospital and College of Medicine, 7 Chung-Shan South Road, Taipei, 100 Taiwan
| | - Hsin-Yun Sun
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
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Hyperoxia exposure upregulates Dvl-1 and activates Wnt/β-catenin signaling pathway in newborn rat lung. BMC Mol Cell Biol 2023; 24:4. [PMID: 36726071 PMCID: PMC9893620 DOI: 10.1186/s12860-023-00465-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 01/30/2023] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Bronchopulmonary dysplasia is a serious and lifelong pulmonary disease in premature neonates that influences around one-quarter of premature newborns. The wingless-related integration site /β-catenin signaling pathway, which is abnormally activated in the lungs with pulmonary fibrosis, affects cell differentiation and lung development. METHODS Newborn rats were subjected to hyperoxia exposure. Histopathological changes to the lungs were evaluated through immunohistochemistry, and the activation of disheveled and Wnt /β-catenin signaling pathway components was assessed by Western blotting and real-time PCR. The abilities of proliferation, apoptosis and migration were detected by Cell Counting Kit-8, flow cytometry and scratch wound assay, respectively. RESULTS Contrasting with normoxic lungs, hyperoxia-exposed lungs demonstrated larger alveoli, fewer alveoli and thicker alveolar septa. Superoxide dismutase activity was significantly decreased (7th day: P < 0.05; 14th day: P < 0.01) and malondialdehyde significantly increased (7th day: P < 0.05; 14th day: P < 0.01) after hyperoxia exposure. Protein and mRNA expression levels of β-catenin, Dvl-1, CTNNBL1 and cyclin D1 were significantly upregulated by hyperoxia exposure on 7th day (P < 0.01) and 14th day (P < 0.01). In hyperoxic conditions, Dvl-l downregulation and Dvl-l downregulation + MSAB treatment significantly increased the proliferation rates, decreased the apoptosis rates and improved the ability of cell migration. In hyperoxic conditions, Dvl-l downregulation could decrease the mRNA expression levels of GSK3β, β-catenin, CTNNBL1 and cyclin D1 and decrease the protein relative expression levels of GSK3β, p-GSK3β, β-catenin, CTNNBL1 and cyclin D1. CONCLUSIONS We confirmed the positive role of Dvl-1 and the Wnt/β-catenin signaling pathway in promoting BPD in hyperoxia conditions and provided a promising therapeutic target.
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Kelley EF, Carlson AR, Wentz RJ, Ziegler BL, Johnson BD. Influence of rapidly oscillating inspired O 2 and N 2 concentrations on pulmonary vascular function and lung fluid balance in healthy adults. Front Physiol 2022; 13:1018057. [PMID: 36569769 PMCID: PMC9768664 DOI: 10.3389/fphys.2022.1018057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 11/15/2022] [Indexed: 12/12/2022] Open
Abstract
Introduction: Aircrew may experience rapidly oscillating inspired O2/N2 ratios owing to fluctuations in the on-board oxygen delivery systems (OBOG). Recent investigations suggest these oscillations may contribute to the constellation of physiologic events in aircrew of high-performance aircraft. Therefore, the purpose of this study was to determine whether these "operationally-relevant" environmental challenges may cause decrements in measures of pulmonary vascular physiology. Methods: Thirty healthy participants (Age: 29 ± 5 years) were recruited and assigned to one of the three exposures. Participants were instrumented for physiologic monitoring and underwent baseline cardiopulmonary physiology testing (ground level) consisting of a rebreathe method for quantifying pulmonary blood flow (Qc), pulmonary capillary blood volume (Vc) and alveolar-capillary conductance (Dm). Ultrasound was used to quantify "comet tails" (measure of lung fluid balance). After baseline testing, the participants had two 45 min exposures to an altitude of 8,000 ft where they breathed from gas mixtures alternating between 80/20 and 30/70 O2/N2 ratios at the required frequency (30 s, 60 s, or 120 s), separated by repeat baseline measure. Immediately and 45 min after the second exposure, baseline measures were repeated. Results: We observed no changes in Qc, Dm or Vc during the 60 s exposures. In response to the 30 s oscillation exposure, there was a significantly reduced Qc and Vc at the post-testing period (p = 0.03). Additionally, exposure to the 120 s oscillations resulted in a significant decrease in Vc at the recovery testing period and an increase in the Dm/Vc ratio at both the post and recovery period (p < 0.01). Additionally, we observed no changes in the number of comet tails. Conclusion: These data suggest "operationally-relevant" changes in inspired gas concentrations may cause an acute, albeit mild pulmonary vascular derecruitment, reduced distention and/or mild pulmonary-capillary vasoconstriction, without significant changes in lung fluid balance or respiratory gas exchange. The operational relevance remains less clear, particularly in the setting of additional environmental stressors common during flight (e.g., g forces).
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Affiliation(s)
- Eli F. Kelley
- AFRL, 711HPW, WPAFB, Dayton, OH, United States,*Correspondence: Eli F. Kelley,
| | - Alex R. Carlson
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, United States
| | - Robert J. Wentz
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, United States
| | - Briana L. Ziegler
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, United States
| | - Bruce D. Johnson
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, United States
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31
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A Methodological Perspective on the Function and Assessment of Peripheral Chemoreceptors in Heart Failure: A Review of Data from Clinical Trials. Biomolecules 2022; 12:biom12121758. [PMID: 36551186 PMCID: PMC9775522 DOI: 10.3390/biom12121758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 11/22/2022] [Accepted: 11/24/2022] [Indexed: 11/29/2022] Open
Abstract
Augmented peripheral chemoreceptor sensitivity (PChS) is a common feature of many sympathetically mediated diseases, among others, and it is an important mechanism of the pathophysiology of heart failure (HF). It is related not only to the greater severity of symptoms, especially to dyspnea and lower exercise tolerance but also to a greater prevalence of complications and poor prognosis. The causes, mechanisms, and impact of the enhanced activity of peripheral chemoreceptors (PChR) in the HF population are subject to intense research. Several methodologies have been established and utilized to assess the PChR function. Each of them presents certain advantages and limitations. Furthermore, numerous factors could influence and modulate the response from PChR in studied subjects. Nevertheless, even with the impressive number of studies conducted in this field, there are still some gaps in knowledge that require further research. We performed a review of all clinical trials in HF human patients, in which the function of PChR was evaluated. This review provides an extensive synthesis of studies evaluating PChR function in the HF human population, including methods used, factors potentially influencing the results, and predictors of increased PChS.
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32
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Burtscher J, Mallet RT, Pialoux V, Millet GP, Burtscher M. Adaptive Responses to Hypoxia and/or Hyperoxia in Humans. Antioxid Redox Signal 2022; 37:887-912. [PMID: 35102747 DOI: 10.1089/ars.2021.0280] [Citation(s) in RCA: 79] [Impact Index Per Article: 26.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Significance: Oxygen is indispensable for aerobic life, but its utilization exposes cells and tissues to oxidative stress; thus, tight regulation of cellular, tissue, and systemic oxygen concentrations is crucial. Here, we review the current understanding of how the human organism (mal-)adapts to low (hypoxia) and high (hyperoxia) oxygen levels and how these adaptations may be harnessed as therapeutic or performance enhancing strategies at the systemic level. Recent Advances: Hyperbaric oxygen therapy is already a cornerstone of modern medicine, and the application of mild hypoxia, that is, hypoxia conditioning (HC), to strengthen the resilience of organs or the whole body to severe hypoxic insults is an important preparation for high-altitude sojourns or to protect the cardiovascular system from hypoxic/ischemic damage. Many other applications of adaptations to hypo- and/or hyperoxia are only just emerging. HC-sometimes in combination with hyperoxic interventions-is gaining traction for the treatment of chronic diseases, including numerous neurological disorders, and for performance enhancement. Critical Issues: The dose- and intensity-dependent effects of varying oxygen concentrations render hypoxia- and/or hyperoxia-based interventions potentially highly beneficial, yet hazardous, although the risks versus benefits are as yet ill-defined. Future Directions: The field of low and high oxygen conditioning is expanding rapidly, and novel applications are increasingly recognized, for example, the modulation of aging processes, mood disorders, or metabolic diseases. To advance hypoxia/hyperoxia conditioning to clinical applications, more research on the effects of the intensity, duration, and frequency of altered oxygen concentrations, as well as on individual vulnerabilities to such interventions, is paramount. Antioxid. Redox Signal. 37, 887-912.
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Affiliation(s)
- Johannes Burtscher
- Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.,Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland
| | - Robert T Mallet
- Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, Texas, USA
| | - Vincent Pialoux
- Inter-University Laboratory of Human Movement Biology EA7424, University Claude Bernard Lyon 1, University of Lyon, Lyon, France
| | - Grégoire P Millet
- Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.,Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland
| | - Martin Burtscher
- Department of Sport Science, University of Innsbruck, Innsbruck, Austria
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Siwicka-Gieroba D, Robba C, Gołacki J, Badenes R, Dabrowski W. Cerebral Oxygen Delivery and Consumption in Brain-Injured Patients. J Pers Med 2022; 12:1763. [PMID: 36573716 PMCID: PMC9698645 DOI: 10.3390/jpm12111763] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Revised: 10/12/2022] [Accepted: 10/17/2022] [Indexed: 12/30/2022] Open
Abstract
Organism survival depends on oxygen delivery and utilization to maintain the balance of energy and toxic oxidants production. This regulation is crucial to the brain, especially after acute injuries. Secondary insults after brain damage may include impaired cerebral metabolism, ischemia, intracranial hypertension and oxygen concentration disturbances such as hypoxia or hyperoxia. Recent data highlight the important role of clinical protocols in improving oxygen delivery and resulting in lower mortality in brain-injured patients. Clinical protocols guide the rules for oxygen supplementation based on physiological processes such as elevation of oxygen supply (by mean arterial pressure (MAP) and intracranial pressure (ICP) modulation, cerebral vasoreactivity, oxygen capacity) and reduction of oxygen demand (by pharmacological sedation and coma or hypothermia). The aim of this review is to discuss oxygen metabolism in the brain under different conditions.
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Affiliation(s)
- Dorota Siwicka-Gieroba
- Department of Anaesthesiology and Intensive Care, Medical University in Lublin, 20-954 Lublin, Poland
| | - Chiara Robba
- Department of Anesthesiology and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, 16132 Genoa, Italy
- Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, 16132 Genoa, Italy
| | - Jakub Gołacki
- Department of Anaesthesiology and Intensive Care, Medical University in Lublin, 20-954 Lublin, Poland
| | - Rafael Badenes
- Department of Anesthesiology and Surgical-Trauma Intensive Care, Hospital Clinic Universitari, University of Valencia, 46010 Valencia, Spain
| | - Wojciech Dabrowski
- Department of Anaesthesiology and Intensive Care, Medical University in Lublin, 20-954 Lublin, Poland
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Alva R, Mirza M, Baiton A, Lazuran L, Samokysh L, Bobinski A, Cowan C, Jaimon A, Obioru D, Al Makhoul T, Stuart JA. Oxygen toxicity: cellular mechanisms in normobaric hyperoxia. Cell Biol Toxicol 2022; 39:111-143. [PMID: 36112262 PMCID: PMC9483325 DOI: 10.1007/s10565-022-09773-7] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 09/07/2022] [Indexed: 12/15/2022]
Abstract
In clinical settings, oxygen therapy is administered to preterm neonates and to adults with acute and chronic conditions such as COVID-19, pulmonary fibrosis, sepsis, cardiac arrest, carbon monoxide poisoning, and acute heart failure. In non-clinical settings, divers and astronauts may also receive supplemental oxygen. In addition, under current standard cell culture practices, cells are maintained in atmospheric oxygen, which is several times higher than what most cells experience in vivo. In all the above scenarios, the elevated oxygen levels (hyperoxia) can lead to increased production of reactive oxygen species from mitochondria, NADPH oxidases, and other sources. This can cause cell dysfunction or death. Acute hyperoxia injury impairs various cellular functions, manifesting ultimately as physiological deficits. Chronic hyperoxia, particularly in the neonate, can disrupt development, leading to permanent deficiencies. In this review, we discuss the cellular activities and pathways affected by hyperoxia, as well as strategies that have been developed to ameliorate injury.
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Affiliation(s)
- Ricardo Alva
- Department of Biological Sciences, Brock University, St. Catharines, ON, L2S 3A1, Canada
| | - Maha Mirza
- Department of Biological Sciences, Brock University, St. Catharines, ON, L2S 3A1, Canada
| | - Adam Baiton
- Department of Biological Sciences, Brock University, St. Catharines, ON, L2S 3A1, Canada
| | - Lucas Lazuran
- Department of Biological Sciences, Brock University, St. Catharines, ON, L2S 3A1, Canada
| | - Lyuda Samokysh
- Department of Biological Sciences, Brock University, St. Catharines, ON, L2S 3A1, Canada
| | - Ava Bobinski
- Department of Biological Sciences, Brock University, St. Catharines, ON, L2S 3A1, Canada
| | - Cale Cowan
- Department of Biological Sciences, Brock University, St. Catharines, ON, L2S 3A1, Canada
| | - Alvin Jaimon
- Department of Biological Sciences, Brock University, St. Catharines, ON, L2S 3A1, Canada
| | - Dede Obioru
- Department of Biological Sciences, Brock University, St. Catharines, ON, L2S 3A1, Canada
| | - Tala Al Makhoul
- Department of Biological Sciences, Brock University, St. Catharines, ON, L2S 3A1, Canada
| | - Jeffrey A Stuart
- Department of Biological Sciences, Brock University, St. Catharines, ON, L2S 3A1, Canada.
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Zhu Z, Zhou M, Wei Y, Chen H. Time-varying intensity of oxygen exposure is associated with mortality in critically ill patients with mechanical ventilation. Crit Care 2022; 26:239. [PMID: 35932009 PMCID: PMC9356484 DOI: 10.1186/s13054-022-04114-w] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Accepted: 07/29/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND There is no consensus exists regarding the association between oxygen exposure (arterial oxygen tension or fraction of inspired oxygen) and outcomes for patients with mechanical ventilation. Additionally, whether the association remains persistent over time is unknown. We aimed to explore the association between exposure to different intensities of oxygen exposure over time and 28-day mortality in patients with mechanical ventilation. METHODS We obtained data from the Medical Information Mart for Intensive Care IV (MIMIC-IV), which included adult (≥ 18 years) patients who received invasive mechanical ventilation for at least 48 h. We excluded patients who received extracorporeal membrane oxygenation (ECMO) or who initiated ventilation more than 24 h after ICU admission. The primary outcome was 28-day mortality. Piece-wise exponential additive mixed models were employed to estimate the strength of associations over time. RESULTS A total of 7784 patients were included in the final analysis. Patients had a median duration of invasive mechanical ventilation of 8.1 days (IQR: 3.8-28 days), and the overall 28-day mortality rate was 26.3%. After adjustment for baseline and time-dependent confounders, both daily time-weighted average (TWA) arterial oxygen tension (PaO2) and fraction of inspired oxygen (FiO2) were associated with increased 28-day mortality, and the strength of the association manifested predominantly in the early-middle course of illness. A significant increase in the hazard of death was found to be associated with daily exposure to TWA-PaO2 ≥ 120 mmHg (Hazard ratio 1.166, 95% CI 1.059-1.284) or TWA-FiO2 ≥ 0.5 (Hazard ratio 1.496, 95% CI 1.363-1.641) during the entire course. A cumulative effect of harmful exposure (TWA-PaO2 ≥ 120 mmHg or TWA-FiO2 ≥ 0.5) was also observed. CONCLUSION PaO2 and FiO2 should be carefully monitored in patients with mechanical ventilation, especially during the early-middle course after ICU admission. Cumulative exposure to higher intensities of oxygen exposure was associated with an increased risk of death.
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Affiliation(s)
- Zhu Zhu
- Department of General Surgery, Suzhou Science & Technology Town Hospital, Suzhou, 215153 Jiangsu People’s Republic of China
| | - Mingqin Zhou
- Department of Critical Care Medicine, Cancer Hospital of Shantou University Medical College, No.7 Raoping Road, Shantou, 515100 Guangdong People’s Republic of China
| | - Yao Wei
- Department of Critical Care Medicine, The First Affiliated Hospital of Soochow University, Soochow University, No. 899 Pinghai Road, Suzhou, 215000 People’s Republic of China
| | - Hui Chen
- Department of Critical Care Medicine, The First Affiliated Hospital of Soochow University, Soochow University, No. 899 Pinghai Road, Suzhou, 215000 People’s Republic of China
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Thomas A, van Diepen S, Beekman R, Sinha SS, Brusca SB, Alviar CL, Jentzer J, Bohula EA, Katz JN, Shahu A, Barnett C, Morrow DA, Gilmore EJ, Solomon MA, Miller PE. Oxygen Supplementation and Hyperoxia in Critically Ill Cardiac Patients: From Pathophysiology to Clinical Practice. JACC. ADVANCES 2022; 1:100065. [PMID: 36238193 PMCID: PMC9555075 DOI: 10.1016/j.jacadv.2022.100065] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Oxygen supplementation has been a mainstay in the management of patients with acute cardiac disease. While hypoxia is known to be detrimental, the adverse effects of artificially high oxygen levels (hyperoxia) have only recently been recognized. Hyperoxia may induce harmful hemodynamic effects, including peripheral and coronary vasoconstriction, and direct cellular toxicity through the production of reactive oxygen species. In addition, emerging evidence has shown that hyperoxia is associated with adverse clinical outcomes. Thus, it is essential for the cardiac intensive care unit (CICU) clinician to understand the available evidence and titrate oxygen therapies to specific goals. This review summarizes the pathophysiology of oxygen within the cardiovascular system and the association between supplemental oxygen and hyperoxia in patients with common CICU diagnoses, including acute myocardial infarction, heart failure, shock, cardiac arrest, pulmonary hypertension, and respiratory failure. Finally, we highlight lessons learned from available trials, gaps in knowledge, and future directions.
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Affiliation(s)
- Alexander Thomas
- Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT
| | - Sean van Diepen
- Department of Critical Care and Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Canada
| | - Rachel Beekman
- Department of Neurology, Yale University School of Medicine, New Haven, CT
| | - Shashank S. Sinha
- Inova Heart and Vascular Institute, Inova Fairfax Medical Center, Falls Church, VA
| | - Samuel B. Brusca
- Division of Cardiology, University of California San Francisco, San Francisco, CA
| | - Carlos L. Alviar
- Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, New York
| | - Jacob Jentzer
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | - Erin A. Bohula
- TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - Jason N. Katz
- Division of Cardiology, Duke University Medical Center, Durham, NC
| | - Andi Shahu
- Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT
| | - Christopher Barnett
- Division of Cardiology, University of California San Francisco, San Francisco, CA
| | - David A. Morrow
- TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - Emily J. Gilmore
- Department of Neurology, Yale University School of Medicine, New Haven, CT
| | - Michael A. Solomon
- Critical Care Medicine Department, National Institutes of Health Clinical Center and Cardiovascular Branch, National Heart, Lung, and Blood Institute, of the National Institutes of Health, Bethesda, MD
| | - P. Elliott Miller
- Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT
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Dong N, Zhou PP, Li D, Zhu HS, Liu LH, Ma HX, Shi Q, Ju XL. Intratracheal administration of umbilical cord-derived mesenchymal stem cells attenuates hyperoxia-induced multi-organ injury via heme oxygenase-1 and JAK/STAT pathways. World J Stem Cells 2022; 14:556-576. [PMID: 36157523 PMCID: PMC9350625 DOI: 10.4252/wjsc.v14.i7.556] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 05/04/2022] [Accepted: 06/20/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Bronchopulmonary dysplasia (BPD) is not merely a chronic lung disease, but a systemic condition with multiple organs implications predominantly associated with hyperoxia exposure. Despite advances in current management strategies, limited progress has been made in reducing the BPD-related systemic damage. Meanwhile, although the protective effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) or their exosomes on hyperoxia-induced lung injury have been explored by many researchers, the underlying mechanism has not been addressed in detail, and few studies have focused on the therapeutic effect on systemic multiple organ injury.
AIM To investigate whether hUC-MSC intratracheal administration could attenuate hyperoxia-induced lung, heart, and kidney injuries and the underlying regulatory mechanisms.
METHODS Neonatal rats were exposed to hyperoxia (80% O2), treated with hUC-MSCs intratracheal (iT) or intraperitoneal (iP) on postnatal day 7, and harvested on postnatal day 21. The tissue sections of the lung, heart, and kidney were analyzed morphometrically. Protein contents of the bronchoalveolar lavage fluid (BALF), myeloperoxidase (MPO) expression, and malondialdehyde (MDA) levels were examined. Pulmonary inflammatory cytokines were measured via enzyme-linked immunosorbent assay. A comparative transcriptomic analysis of differentially expressed genes (DEGs) in lung tissue was conducted via RNA-sequencing. Subsequently, we performed reverse transcription-quantitative polymerase chain reaction and western blot analysis to explore the expression of target mRNA and proteins related to inflammatory and oxidative responses.
RESULTS iT hUC-MSCs administration improved pulmonary alveolarization and angiogenesis (P < 0.01, P < 0.01, P < 0.001, and P < 0.05 for mean linear intercept, septal counts, vascular medial thickness index, and microvessel density respectively). Meanwhile, treatment with hUC-MSCs iT ameliorated right ventricular hypertrophy (for Fulton’s index, P < 0.01), and relieved reduced nephrogenic zone width (P < 0.01) and glomerular diameter (P < 0.001) in kidneys. Among the beneficial effects, a reduction of BALF protein, MPO, and MDA was observed in hUC-MSCs groups (P < 0.01, P < 0.001, and P < 0.05 respectively). Increased pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-1β, and IL-6 expression observed in the hyperoxia group were significantly attenuated by hUC-MSCs administration (P < 0.01, P < 0.001, and P < 0.05 respectively). In addition, we observed an increase in anti-inflammatory cytokine IL-10 expression in rats that received hUC-MSCs iT compared with rats reared in hyperoxia (P < 0.05). Transcriptomic analysis showed that the DEGs in lung tissues induced by hyperoxia were enriched in pathways related to inflammatory responses, epithelial cell proliferation, and vasculature development. hUC-MSCs administration blunted these hyperoxia-induced dysregulated genes and resulted in a shift in the gene expression pattern toward the normoxia group. hUC-MSCs increased heme oxygenase-1 (HO-1), JAK2, and STAT3 expression, and their phosphorylation in the lung, heart, and kidney (P < 0.05). Remarkably, no significant difference was observed between the iT and iP administration.
CONCLUSION iT hUC-MSCs administration ameliorates hyperoxia-induced lung, heart, and kidney injuries by activating HO-1 expression and JAK/STAT signaling. The therapeutic benefits of local iT and iP administration are equivalent.
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Affiliation(s)
- Na Dong
- Department of Pediatrics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Pan-Pan Zhou
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Dong Li
- Stem Cell and Regenerative Medicine Research Center, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Hua-Su Zhu
- Department of Pediatrics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Ling-Hong Liu
- Stem Cell and Regenerative Medicine Research Center, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Hui-Xian Ma
- Stem Cell and Regenerative Medicine Research Center, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Qing Shi
- Stem Cell and Regenerative Medicine Research Center, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Xiu-Li Ju
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
- Stem Cell and Regenerative Medicine Research Center, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
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Lindvåg Lie S, Hisdal J, Rehn M, Høiseth LØ. Effects of supplemental oxygen on systemic and cerebral hemodynamics in experimental hypovolemia: Protocol for a randomized, double blinded crossover study. PLoS One 2022; 17:e0270598. [PMID: 35749486 PMCID: PMC9231698 DOI: 10.1371/journal.pone.0270598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 05/04/2022] [Indexed: 11/18/2022] Open
Abstract
Supplemental oxygen is widely administered in trauma patients, often leading to hyperoxia. However, the clinical evidence for providing supplemental oxygen in all trauma patients is scarce, and hyperoxia has been found to increase mortality in some patient populations. Hypovolemia is a common finding in trauma patients, which affects many hemodynamic parameters, but little is known about how supplemental oxygen affects systemic and cerebral hemodynamics during hypovolemia. We therefore plan to conduct an experimental, randomized, double blinded crossover study to investigate the effect of 100% oxygen compared to room air delivered by a face mask with reservoir on systemic and cerebral hemodynamics during simulated hypovolemia in the lower body negative pressure model in 15 healthy volunteers. We will measure cardiac output, stroke volume, blood pressure, middle cerebral artery velocity and tolerance to hypovolemia continuously in all subjects at two visits to investigate whether oxygen affects the cardiovascular response to simulated hypovolemia. The effect of oxygen on the outcome variables will be analyzed with mixed linear regression. Trial registration: The study is registered in the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT, registration number 2021-003238-35).
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Affiliation(s)
- Sole Lindvåg Lie
- Department of Research and Development, Norwegian Air Ambulance Foundation, Oslo, Norway
- Faculty of Medicine, University of Oslo, Oslo, Norway
- Section of Vascular Investigations, Oslo University Hospital, Oslo, Norway
- * E-mail:
| | - Jonny Hisdal
- Faculty of Medicine, University of Oslo, Oslo, Norway
- Section of Vascular Investigations, Oslo University Hospital, Oslo, Norway
| | - Marius Rehn
- Department of Research and Development, Norwegian Air Ambulance Foundation, Oslo, Norway
- Division of Prehospital Services, Air Ambulance Department, Oslo University Hospital, Oslo, Norway
- Faculty of Health Sciences, University of Stavanger, Stavanger, Norway
| | - Lars Øivind Høiseth
- Department of Research and Development, Norwegian Air Ambulance Foundation, Oslo, Norway
- Division of Emergencies and Critical Care, Department of Anesthesiology, Oslo University Hospital, Oslo, Norway
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Chuai Y, Jiang W, Zhang L, Chuai F, Sun X, Peng K, Gao J, Dong T, Chen L, Yao Y. Effect of long-duration oxygen vs room air during labor on umbilical cord venous partial pressure of oxygen: a randomized controlled trial. Am J Obstet Gynecol 2022; 227:629.e1-629.e16. [PMID: 35580635 DOI: 10.1016/j.ajog.2022.05.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 05/06/2022] [Accepted: 05/11/2022] [Indexed: 11/01/2022]
Abstract
BACKGROUND There are limited data to guide the duration and dose of oxygen supplementation for pregnant women undergoing labor. OBJECTIVE To assess the effect of maternal long-duration high-concentration oxygen administration during labor on umbilical cord venous partial pressure of oxygen. STUDY DESIGN This randomized clinical trial was conducted between January and October of 2021 in the obstetrics wards of 3 tertiary teaching hospitals in Beijing, China. Women undergoing the latent phase of labor with no existing medical conditions or obstetrical complications who were admitted for delivery were eligible. The women who met inclusion criteria with category I fetal heart rate tracings in labor were randomized in a 1:1 ratio to oxygen or room air. The oxygen group received 10 L of oxygen per minute by simple, tight-fitting face mask until delivery. The room-air group received room air only, without a face mask. The primary outcome was the umbilical cord venous partial pressure of oxygen. RESULTS A total of 661 women were screened, and 521 were excluded; 140 participants with category I fetal heart rate tracings were enrolled and randomized to oxygen (N=70) or room air (N=70). A total of 135 women with valid paired umbilical cord venous and arterial gas values were included in the umbilical cord venous partial pressure of oxygen and arterial pH analyses. All 140 women were included in the fetal heart rate tracings analysis. Baseline characteristics were similar between the oxygen and room-air groups. The duration of oxygen exposure was approximately 322±147 minutes. There were no differences between the oxygen and room-air groups in the umbilical cord venous partial pressure of oxygen (mean difference, 1.1 mm Hg; 95% confidence interval, -1.0 to 3.2; P=.318) or the proportion of participants with category II fetal heart rate tracings (81.4% vs 78.6%; relative risk, 1.04; 95% confidence interval, 0.88-1.22; P=.672). However, the umbilical cord arterial pH was significantly lower in the oxygen group than in the room-air group (median, 7.23; interquartile range, 7.20-7.27 vs median 7.27; interquartile range, 7.20-7.30; P=.005). CONCLUSION Maternal long-duration high-concentration oxygen administration during labor did not affect either the umbilical cord venous partial pressure of oxygen or fetal heart rate pattern distribution but resulted in a deterioration of the umbilical cord arterial pH at birth.
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Kraus AC, De Miguel C. Hyperoxia and Acute Kidney Injury: A Tale of Oxygen and the Kidney. Semin Nephrol 2022; 42:151282. [PMID: 36404211 PMCID: PMC9825666 DOI: 10.1016/j.semnephrol.2022.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Although oxygen supplementation is beneficial to support life in the clinic, excessive oxygen therapy also has been linked to damage to organs such as the lung or the eye. However, there is a lack of understanding of whether high oxygen therapy directly affects the kidney, leading to acute kidney injury, and what molecular mechanisms may be involved in this process. In this review, we revise our current understanding of the mechanisms by which hyperoxia leads to organ damage and highlight possible areas of investigation for the scientific community interested in novel mechanisms of kidney disease. Overall, we found a significant need for both animal and clinical studies evaluating the role of hyperoxia in inducing kidney damage. Thus, we urge the research community to further investigate oxygen therapy and its impact on kidney health with the goal of optimizing oxygen therapy guidelines and improving patient care.
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Affiliation(s)
- Abigayle C Kraus
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
| | - Carmen De Miguel
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.
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Li T, Zhou D, Zhao D, Lin Q, Wang D, Wang C, Zhang R. Impact of Oxygen Saturation on Mortality in Obese and Non-obese Critically Ill Patients With Mechanical Ventilation: A Retrospective Observational Study. Front Med (Lausanne) 2022; 9:839787. [PMID: 35492310 PMCID: PMC9051400 DOI: 10.3389/fmed.2022.839787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 03/25/2022] [Indexed: 11/17/2022] Open
Abstract
Background The main aim of this study was to evaluate the effect of oxygen saturation on mortality in critically ill patients with mechanical ventilation according to obesity status. Methods We conducted an observational study in mechanically ventilated patients admitted to the ICU retrospectively. Demographic, arterial blood gas, ventilator setting, interventions, and peripheral oxygen saturation (Spo2) during the first 24 h were recorded and analyzed between non-obese and obese patients. The main exposure included Spo2, time-weighted mean Spo2 (TWM-Spo2), and proportion of time spent in different Spo2 (PTS-Spo2) levels. The primary outcome was hospital mortality. We used multivariable logistic regression models to assess the relationship between Spo2 and mortality, as well as the interaction between PTS-Spo2 and obesity status. Results A total of 25,100 patients were included, of which 10,564 (42%) were obese patients. After adjusting for confounders, compared with TWM-Spo2 of 94–98%, TWM-Spo2 of < =88% (OR 3.572; CI [2.343, 5.455]; p < 0.001) and of 89–93% (OR 1.514; CI [1.343, 1.706]; p < 0.001) were both associated with higher risk of mortality. PTS-Spo2 of 99–100% was associated with increased risk of mortality for obese patients (OR 1.028; 95% CI 1.010–1.046; p = 0.002; Pinteraction = 0.001), while PTS-Spo2 of 89–93% was associated with increased risk of mortality (OR 1.089; 95% CI 1.051–1.128; p < 0.001; Pinteraction = 0.001) for non-obese patients. Conclusions For obese and non-obese critically ill patients with mechanical ventilation, the impact of oxygen saturation on hospital mortality is different.
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Perioperative Supplemental Oxygen and Plasma Catecholamine Concentrations after Major Abdominal Surgery-Secondary Analysis of a Randomized Clinical Trial. J Clin Med 2022; 11:jcm11071767. [PMID: 35407374 PMCID: PMC9000182 DOI: 10.3390/jcm11071767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 03/15/2022] [Accepted: 03/21/2022] [Indexed: 11/30/2022] Open
Abstract
Perioperative stress is associated with increased sympathetic activity that leads to increases in heart rate and blood pressure, which are associated with the development of perioperative myocardial ischemia. In healthy volunteers, it was shown that the administration of supplemental oxygen attenuated sympathetic nerve activity and subsequently led to lower plasma catecholamine concentrations. We therefore tested the hypothesis that perioperative supplemental oxygen attenuates sympathetic nerve in patients at risk for cardiovascular complications undergoing major abdominal surgery. We randomly assigned 81 patients to receive either 80% or 30% inspired oxygen concentration throughout surgery and the first two postoperative hours. We assessed noradrenaline, adrenaline, and dopamine plasma concentrations before the induction of anesthesia, two hours after surgery and on the third postoperative day. There was no significant difference in postoperative noradrenaline (effect estimated: −41.5 ng·L−1, 95%CI −134.3, 51.2; p = 0.38), adrenaline (effect estimated: 11.2 ng·L−1, 95%CI −7.6, 30.1; p = 0.24), and dopamine (effect estimated: −1.61 ng·L−1, 95%CI −7.2, 3.9; p = 0.57) concentrations between both groups. Based on our results, it seems unlikely that supplemental oxygen influences endogenous catecholamine release in the perioperative setting.
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Santiago-Fuentes LM, Charleston-Villalobos S, González-Camarena R, Voss A, Mejía-Avila ME, Buendía-Roldan I, Reulecke S, Aljama-Corrales T. Effects of Supplemental Oxygen on Cardiovascular and Respiratory Interactions by Extended Partial Directed Coherence in Idiopathic Pulmonary Fibrosis. FRONTIERS IN NETWORK PHYSIOLOGY 2022; 2:834056. [PMID: 36926096 PMCID: PMC10013060 DOI: 10.3389/fnetp.2022.834056] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 02/07/2022] [Indexed: 11/13/2022]
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic and restrictive disease characterized by fibrosis and inflammatory changes in lung tissue producing a reduction in diffusion capacity and leading to exertional chronic arterial hypoxemia and dyspnea. Furthermore, clinically, supplemental oxygen (SupplO2) has been prescribed to IPF patients to improve symptoms. However, the evidence about the benefits or disadvantages of oxygen supplementation is not conclusive. In addition, the impact of SupplO2 on the autonomic nervous system (ANS) regulation in respiratory diseases needs to be evaluated. In this study the interactions between cardiovascular and respiratory systems in IPF patients, during ambient air (AA) and SupplO2 breathing, are compared to those from a matched healthy group. Interactions were estimated by time series of successive beat-to-beat intervals (BBI), respiratory amplitude (RESP) at BBI onset, arterial systolic (SYS) and diastolic (DIA) blood pressures. The paper explores the Granger causality (GC) between systems in the frequency domain by the extended partial directed coherence (ePDC), considering instantaneous effects. Also, traditional linear and nonlinear markers as power in low (LF) and high frequency (HF) bands, symbolic dynamic indices as well as arterial baroreflex, were calculated. The results showed that for IPF during AA phase: 1) mean BBI and power of BBI-HF band, as well as mean respiratory frequency were significantly lower (p < 0.05) and higher (p < 0.001), respectively, indicating a strong sympathetic influence, and 2) the RESP → SYS interaction was characterized by Mayer waves and diminished RESP → BBI, i.e., decreased respiratory sinus arrhythmia. In contrast, during short-term SupplO2 phase: 1) oxygen might produce a negative influence on the systolic blood pressure variability, 2) the arterial baroreflex reduced significantly (p < 0.01) and 3) reduction of RSA reflected by RESP → BBI with simultaneous increase of Traube-Hering waves in RESP → SYS (p < 0.001), reflected increased sympathetic modulation to the vessels. The results gathered in this study may be helpful in the management of the administration of SupplO2.
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Affiliation(s)
| | | | | | - Andreas Voss
- Institute of Biomedical Engineering and Informatics, University of Technology Ilmenau, Ilmenau, Germany
| | | | | | - Sina Reulecke
- Electrical Engineering Department, Universidad Autónoma Metropolitana, Mexico City, Mexico
| | - Tomás Aljama-Corrales
- Electrical Engineering Department, Universidad Autónoma Metropolitana, Mexico City, Mexico
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Singer M, Young PJ, Laffey JG, Asfar P, Taccone FS, Skrifvars MB, Meyhoff CS, Radermacher P. Dangers of hyperoxia. Crit Care 2021; 25:440. [PMID: 34924022 PMCID: PMC8686263 DOI: 10.1186/s13054-021-03815-y] [Citation(s) in RCA: 141] [Impact Index Per Article: 35.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 11/04/2021] [Indexed: 01/27/2023] Open
Abstract
Oxygen (O2) toxicity remains a concern, particularly to the lung. This is mainly related to excessive production of reactive oxygen species (ROS). Supplemental O2, i.e. inspiratory O2 concentrations (FIO2) > 0.21 may cause hyperoxaemia (i.e. arterial (a) PO2 > 100 mmHg) and, subsequently, hyperoxia (increased tissue O2 concentration), thereby enhancing ROS formation. Here, we review the pathophysiology of O2 toxicity and the potential harms of supplemental O2 in various ICU conditions. The current evidence base suggests that PaO2 > 300 mmHg (40 kPa) should be avoided, but it remains uncertain whether there is an "optimal level" which may vary for given clinical conditions. Since even moderately supra-physiological PaO2 may be associated with deleterious side effects, it seems advisable at present to titrate O2 to maintain PaO2 within the normal range, avoiding both hypoxaemia and excess hyperoxaemia.
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Affiliation(s)
- Mervyn Singer
- Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, London, UK
| | - Paul J Young
- Medical Research Institute of New Zealand, and Intensive Care Unit, Wellington Hospital, Wellington, Wellington, New Zealand
- Australian and New Zealand Intensive Care Research Centre, Department of Critical Care Medicine, University of Melbourne, Melbourne, VIC, Australia
| | - John G Laffey
- Department of Anaesthesia and Intensive Care Medicine, Galway University Hospitals, and School of Medicine, National University of Ireland, Galway, Ireland
| | - Pierre Asfar
- Département de Médecine Intensive - Réanimation Et Médecine Hyperbare, Centre Hospitalier Universitaire d'Angers, Angers, France
| | - Fabio Silvio Taccone
- Department of Intensive Care, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Markus B Skrifvars
- Department of Emergency Care and Services, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Christian S Meyhoff
- Department of Anaesthesia and Intensive Care, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Peter Radermacher
- Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Helmholtzstrasse 8-1, 89081, Ulm, Germany.
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Busani S, Sarti M, Serra F, Gelmini R, Venturelli S, Munari E, Girardis M. Revisited Hyperoxia Pathophysiology in the Perioperative Setting: A Narrative Review. Front Med (Lausanne) 2021; 8:689450. [PMID: 34746165 PMCID: PMC8569225 DOI: 10.3389/fmed.2021.689450] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 09/22/2021] [Indexed: 01/05/2023] Open
Abstract
The widespread use of high-dose oxygen, to avoid perioperative hypoxemia along with WHO-recommended intraoperative hyperoxia to reduce surgical site infections, is an established clinical practice. However, growing pathophysiological evidence has demonstrated that hyperoxia exerts deleterious effects on many organs, mainly mediated by reactive oxygen species. The purpose of this narrative review was to present the pathophysiology of perioperative hyperoxia on surgical wound healing, on systemic macro and microcirculation, on the lungs, heart, brain, kidneys, gut, coagulation, and infections. We reported here that a high systemic oxygen supply could induce oxidative stress with inflammation, vasoconstriction, impaired microcirculation, activation of hemostasis, acute and chronic lung injury, coronary blood flow disturbances, cerebral ischemia, surgical anastomosis impairment, gut dysbiosis, and altered antibiotics susceptibility. Clinical studies have provided rather conflicting results on the definitions and outcomes of hyperoxic patients, often not speculating on the biological basis of their results, while this review highlighted what happens when supranormal PaO2 values are reached in the surgical setting. Based on the assumptions analyzed in this study, we may suggest that the maintenance of PaO2 within physiological ranges, avoiding unnecessary oxygen administration, may be the basis for good clinical practice.
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Affiliation(s)
- Stefano Busani
- Cattedra e Servizio di Anestesia e Rianimazione, Azienda Universitaria Policlinico di Modena, Modena, Italy
| | - Marco Sarti
- Cattedra e Servizio di Anestesia e Rianimazione, Azienda Universitaria Policlinico di Modena, Modena, Italy
| | - Francesco Serra
- Chirurgia Generale d'Urgenza e Oncologica, Azienda Universitaria Policlinico di Modena, Modena, Italy
| | - Roberta Gelmini
- Chirurgia Generale d'Urgenza e Oncologica, Azienda Universitaria Policlinico di Modena, Modena, Italy
| | - Sophie Venturelli
- Cattedra e Servizio di Anestesia e Rianimazione, Azienda Universitaria Policlinico di Modena, Modena, Italy
| | - Elena Munari
- Chirurgia Generale d'Urgenza e Oncologica, Azienda Universitaria Policlinico di Modena, Modena, Italy
| | - Massimo Girardis
- Cattedra e Servizio di Anestesia e Rianimazione, Azienda Universitaria Policlinico di Modena, Modena, Italy
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Tubek S, Niewinski P, Paleczny B, Langner-Hetmanczuk A, Banasiak W, Ponikowski P. Acute hyperoxia reveals tonic influence of peripheral chemoreceptors on systemic vascular resistance in heart failure patients. Sci Rep 2021; 11:20823. [PMID: 34675332 PMCID: PMC8531381 DOI: 10.1038/s41598-021-99159-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Accepted: 09/09/2021] [Indexed: 01/08/2023] Open
Abstract
Peripheral chemoreceptors’ (PCh) hyperactivity increases sympathetic tone. An augmented acute ventilatory response to hypoxia, being a marker of PCh oversensitivity, was also identified as a marker of poor prognosis in HF. However, not much is known about the tonic (chronic) influence of PCh on cardio-respiratory parameters. In our study 30 HF patients and 30 healthy individuals were exposed to 100% oxygen for 1 min during which minute ventilation and hemodynamic parameters were non-invasively recorded. Systemic vascular resistance (SVR) and mean arterial pressure (MAP) responses to acute hyperoxia differed substantially between HF and control. In HF hyperoxia caused a significant drop in SVR in early stages with subsequent normalization, while increase in SVR was observed in controls. MAP increased in controls, but remained unchanged in HF. Bilateral carotid bodies excision performed in two HF subjects changed the response to hyperoxia towards the course seen in healthy individuals. These differences may be explained by the domination of early vascular reaction to hyperoxia in HF by vasodilation due to the inhibition of augmented tonic activity of PCh. Otherwise, in healthy subjects the vasoconstrictive action of oxygen remains unopposed. The magnitude of SVR change during acute hyperoxia may be used as a novel method for tonic PCh activity assessment.
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Affiliation(s)
- Stanislaw Tubek
- Institute of Heart Diseases, Wroclaw Medical University, Borowska 213, 50-556, Wrocław, Poland. .,Institute of Heart Diseases, University Hospital, Wrocław, Poland.
| | - Piotr Niewinski
- Institute of Heart Diseases, Wroclaw Medical University, Borowska 213, 50-556, Wrocław, Poland.,Institute of Heart Diseases, University Hospital, Wrocław, Poland
| | | | - Anna Langner-Hetmanczuk
- Institute of Heart Diseases, Wroclaw Medical University, Borowska 213, 50-556, Wrocław, Poland.,Institute of Heart Diseases, University Hospital, Wrocław, Poland
| | - Waldemar Banasiak
- Department of Cardiology, Centre for Heart Diseases, 4th Military Hospital, Wrocław, Poland
| | - Piotr Ponikowski
- Institute of Heart Diseases, Wroclaw Medical University, Borowska 213, 50-556, Wrocław, Poland.,Institute of Heart Diseases, University Hospital, Wrocław, Poland
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Kimlinger MJ, Mace EH, Harris RC, Zhang MZ, Barajas MB, Hernandez A, Billings FT. Impact of Inhaled Oxygen on Reactive Oxygen Species Production and Oxidative Damage during Spontaneous Ventilation in a Murine Model of Acute Renal Ischemia and Reperfusion. MEDICAL RESEARCH ARCHIVES 2021; 9:2575. [PMID: 35419490 PMCID: PMC9005066 DOI: 10.18103/mra.v9i10.2575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Introduction Acute kidney injury (AKI) affects 10% of patients following major surgery and is independently associated with extra-renal organ injury, development of chronic kidney disease, and death. Perioperative renal ischemia and reperfusion (IR) contributes to AKI by, in part, increasing production of reactive oxygen species (ROS) and leading to oxidative damage. Variations in inhaled oxygen may mediate some aspects of IR injury by affecting tissue oxygenation, ROS production, and oxidative damage. We tested the hypothesis that provision of air (normoxia) compared to 100% oxygen (hyperoxia) during murine renal IR affects renal ROS production and oxidative damage. Methods We administered 100% oxygen or 21% oxygen (air) to 8-9 week-old FVB/N mice and performed dorsal unilateral nephrectomy with contralateral renal ischemia/reperfusion surgery while mice spontaneously ventilated. We subjected mice to 30 minutes of ischemia and 30 minutes of reperfusion prior to sacrifice. We obtained an arterial blood gas (ABG) by performing sternotomy and left cardiac puncture. We stained the kidney with pimonidazole, a marker of tissue hypoxia; 4-HNE, a marker of ROS-production; and we measured F2-isoprostanes in homogenized tissue to quantify oxidative damage. Results Hyperoxia during IR increased arterial oxygen content compared to normoxia, but both groups of mice were hypoventilating at the time of ABG sampling. Renal tissue hypoxia following reperfusion was similar in both treatment groups. ROS production was similar in the cortex of mice (3.8% area in hyperoxia vs. 3.1% in normoxia, P=0.19) but increased in the medulla of hyperoxia-treated animals (6.3% area in hyperoxia vs. 4.5% in nomoxia, P=0.02). Renal F2-isoprostanes were similar in treatment groups (2.2 pg/mg kidney in hyperoxia vs. 2.1 pg/mg in normoxia, P=0.40). Conclusions Hyperoxia during spontaneous ventilation in murine renal IR did not appear to affect renal hypoxia following reperfusion, but hyperoxia increased medullary ROS production compared to normoxia.
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Affiliation(s)
- Melissa J Kimlinger
- Vanderbilt University School of Medicine (MJK), the Department Surgery (EM), the Department of Medicine (RCH, MZ), and the Department of Anesthesiology (MBB, AH, FTB), Vanderbilt University Medical Center, Nashville, TN
| | - Eric H Mace
- Vanderbilt University School of Medicine (MJK), the Department Surgery (EM), the Department of Medicine (RCH, MZ), and the Department of Anesthesiology (MBB, AH, FTB), Vanderbilt University Medical Center, Nashville, TN
| | - Raymond C Harris
- Vanderbilt University School of Medicine (MJK), the Department Surgery (EM), the Department of Medicine (RCH, MZ), and the Department of Anesthesiology (MBB, AH, FTB), Vanderbilt University Medical Center, Nashville, TN
| | - Ming-Zhi Zhang
- Vanderbilt University School of Medicine (MJK), the Department Surgery (EM), the Department of Medicine (RCH, MZ), and the Department of Anesthesiology (MBB, AH, FTB), Vanderbilt University Medical Center, Nashville, TN
| | - Matthew B Barajas
- Vanderbilt University School of Medicine (MJK), the Department Surgery (EM), the Department of Medicine (RCH, MZ), and the Department of Anesthesiology (MBB, AH, FTB), Vanderbilt University Medical Center, Nashville, TN
| | - Antonio Hernandez
- Vanderbilt University School of Medicine (MJK), the Department Surgery (EM), the Department of Medicine (RCH, MZ), and the Department of Anesthesiology (MBB, AH, FTB), Vanderbilt University Medical Center, Nashville, TN
| | - Frederic T Billings
- Vanderbilt University School of Medicine (MJK), the Department Surgery (EM), the Department of Medicine (RCH, MZ), and the Department of Anesthesiology (MBB, AH, FTB), Vanderbilt University Medical Center, Nashville, TN
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Ristescu AI, Tiron CE, Tiron A, Grigoras I. Exploring Hyperoxia Effects in Cancer-From Perioperative Clinical Data to Potential Molecular Mechanisms. Biomedicines 2021; 9:1213. [PMID: 34572400 PMCID: PMC8470547 DOI: 10.3390/biomedicines9091213] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 09/06/2021] [Accepted: 09/10/2021] [Indexed: 12/15/2022] Open
Abstract
Increased inspiratory oxygen concentration is constantly used during the perioperative period of cancer patients to prevent the potential development of hypoxemia and to provide an adequate oxygen transport to the organs, tissues and cells. Although the primary tumours are surgically removed, the effects of perioperative hyperoxia exposure on distal micro-metastases and on circulating cancer cells can potentially play a role in cancer progression or recurrence. In clinical trials, hyperoxia seems to increase the rate of postoperative complications and, by delaying postoperative recovery, it can alter the return to intended oncological treatment. The effects of supplemental oxygen on the long-term mortality of surgical cancer patients offer, at this point, conflicting results. In experimental studies, hyperoxia effects on cancer biology were explored following multiple pathways. In cancer cell cultures and animal models, hyperoxia increases the production of reactive oxygen species (ROS) and increases the oxidative stress. These can be followed by the induction of the expression of Brain-derived neurotrophic factor (BDNF) and other molecules involved in angiogenesis and by the promotion of various degrees of epithelial mesenchymal transition (EMT).
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Affiliation(s)
- Anca Irina Ristescu
- Department of Anaesthesia and Intensive Care, School of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.I.R.); (I.G.)
- Department of Anaesthesia and Intensive Care, Regional Institute of Oncology, 700483 Iasi, Romania
| | - Crina Elena Tiron
- TRANSCEND Research Centre, Regional Institute of Oncology, 700483 Iasi, Romania;
| | - Adrian Tiron
- TRANSCEND Research Centre, Regional Institute of Oncology, 700483 Iasi, Romania;
| | - Ioana Grigoras
- Department of Anaesthesia and Intensive Care, School of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.I.R.); (I.G.)
- Department of Anaesthesia and Intensive Care, Regional Institute of Oncology, 700483 Iasi, Romania
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Yu Y, Yao RQ, Zhang YF, Wang SY, Xi W, Wang JN, Huang XY, Yao YM, Wang ZN. Is oxygen therapy beneficial for normoxemic patients with acute heart failure? A propensity score matched study. Mil Med Res 2021; 8:38. [PMID: 34238369 PMCID: PMC8268364 DOI: 10.1186/s40779-021-00330-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 06/01/2021] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND The clinical efficiency of routine oxygen therapy is uncertain in patients with acute heart failure (AHF) who do not have hypoxemia. The aim of this study was to investigate the association between oxygen therapy and clinical outcomes in normoxemic patients hospitalized with AHF using real-world data. METHODS Normoxemic patients diagnosed with AHF on ICU admission from the electronic ICU (eICU) Collaborative Research Database were included in the current study, in which the study population was divided into the oxygen therapy group and the ambient-air group. Propensity score matching (PSM) was applied to create a balanced covariate distribution between patients receiving supplemental oxygen and those exposed to ambient air. Linear regression and logistic regression models were performed to assess the associations between oxygen therapy and length of stay (LOS), and all-cause in-hospital as well as ICU mortality rates, respectively. A series of sensitivity and subgroup analyses were conducted to further validate the robustness of our findings. RESULTS A total of 2922 normoxemic patients with AHF were finally included in the analysis. Overall, 42.1% (1230/2922) patients were exposed to oxygen therapy, and 57.9% (1692/2922) patients did not receive oxygen therapy (defined as the ambient-air group). After PSM analysis, 1122 pairs of patients were matched: each patient receiving oxygen therapy was matched with a patient without receiving supplemental oxygen. The multivariable logistic model showed that there was no significant interaction between the ambient air and oxygen group for all-cause in-hospital mortality [odds ratio (OR) 1.30; 95% confidence interval (CI) 0.92-1.82; P = 0.138] or ICU mortality (OR 1.39; 95% CI 0.83-2.32; P = 0.206) in the post-PSM cohorts. In addition, linear regression analysis revealed that oxygen therapy was associated with prolonged ICU LOS (OR 1.11; 95% CI 1.06-1.15; P < 0.001) and hospital LOS (OR 1.06; 95% CI 1.01-1.10; P = 0.009) after PSM. Furthermore, the absence of an effect of supplemental oxygen on mortality was consistent in all subgroups. CONCLUSION Routine use of supplemental oxygen in AHF patients without hypoxemia was not found to reduce all-cause in-hospital mortality or ICU mortality.
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Affiliation(s)
- Yue Yu
- Department of Cardiothoracic Surgery, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Huangpu District, Shanghai, 200003, China
| | - Ren-Qi Yao
- Trauma Research Center, Fourth Medical Center and Medical Innovation Research Department of the Chinese PLA General Hospital, 51 Fucheng Road, Haidian District, Beijing, 100048, China.,Department of Burn Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China
| | - Yu-Feng Zhang
- Department of Cardiothoracic Surgery, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Huangpu District, Shanghai, 200003, China
| | - Su-Yu Wang
- Department of Cardiothoracic Surgery, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Huangpu District, Shanghai, 200003, China
| | - Wang Xi
- Department of Cardiothoracic Surgery, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Huangpu District, Shanghai, 200003, China
| | - Jun-Nan Wang
- Department of Cardiothoracic Surgery, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Huangpu District, Shanghai, 200003, China.,Medical Research Center of War Injuries and Trauma, Changzheng Hospital, Naval Medical University, Shanghai, 200003, China
| | - Xiao-Yi Huang
- Department of Pathology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China
| | - Yong-Ming Yao
- Trauma Research Center, Fourth Medical Center and Medical Innovation Research Department of the Chinese PLA General Hospital, 51 Fucheng Road, Haidian District, Beijing, 100048, China.
| | - Zhi-Nong Wang
- Department of Cardiothoracic Surgery, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Huangpu District, Shanghai, 200003, China.
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Fogagnolo A, Montanaro F, Al-Husinat L, Turrini C, Rauseo M, Mirabella L, Ragazzi R, Ottaviani I, Cinnella G, Volta CA, Spadaro S. Management of Intraoperative Mechanical Ventilation to Prevent Postoperative Complications after General Anesthesia: A Narrative Review. J Clin Med 2021; 10:jcm10122656. [PMID: 34208699 PMCID: PMC8234365 DOI: 10.3390/jcm10122656] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 06/09/2021] [Accepted: 06/15/2021] [Indexed: 01/02/2023] Open
Abstract
Mechanical ventilation (MV) is still necessary in many surgical procedures; nonetheless, intraoperative MV is not free from harmful effects. Protective ventilation strategies, which include the combination of low tidal volume and adequate positive end expiratory pressure (PEEP) levels, are usually adopted to minimize the ventilation-induced lung injury and to avoid post-operative pulmonary complications (PPCs). Even so, volutrauma and atelectrauma may co-exist at different levels of tidal volume and PEEP, and therefore, the physiological response to the MV settings should be monitored in each patient. A personalized perioperative approach is gaining relevance in the field of intraoperative MV; in particular, many efforts have been made to individualize PEEP, giving more emphasis on physiological and functional status to the whole body. In this review, we summarized the latest findings about the optimization of PEEP and intraoperative MV in different surgical settings. Starting from a physiological point of view, we described how to approach the individualized MV and monitor the effects of MV on lung function.
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Affiliation(s)
- Alberto Fogagnolo
- Department of Translation Medicine and for Romagna, Section of Anesthesia and Intensive Care, University of Ferrara, 44121 Ferrara, Italy; (F.M.); (C.T.); (R.R.); (I.O.); (C.A.V.); (S.S.)
- Correspondence:
| | - Federica Montanaro
- Department of Translation Medicine and for Romagna, Section of Anesthesia and Intensive Care, University of Ferrara, 44121 Ferrara, Italy; (F.M.); (C.T.); (R.R.); (I.O.); (C.A.V.); (S.S.)
| | - Lou’i Al-Husinat
- Department of Clinical Sciences, Faculty of Medicine, Yarmouk University, Irbid 21163, Jordan;
| | - Cecilia Turrini
- Department of Translation Medicine and for Romagna, Section of Anesthesia and Intensive Care, University of Ferrara, 44121 Ferrara, Italy; (F.M.); (C.T.); (R.R.); (I.O.); (C.A.V.); (S.S.)
| | - Michela Rauseo
- Department of Anesthesia and Intensive Care, University of Foggia, 71122 Foggia, Italy; (M.R.); (L.M.); (G.C.)
| | - Lucia Mirabella
- Department of Anesthesia and Intensive Care, University of Foggia, 71122 Foggia, Italy; (M.R.); (L.M.); (G.C.)
| | - Riccardo Ragazzi
- Department of Translation Medicine and for Romagna, Section of Anesthesia and Intensive Care, University of Ferrara, 44121 Ferrara, Italy; (F.M.); (C.T.); (R.R.); (I.O.); (C.A.V.); (S.S.)
| | - Irene Ottaviani
- Department of Translation Medicine and for Romagna, Section of Anesthesia and Intensive Care, University of Ferrara, 44121 Ferrara, Italy; (F.M.); (C.T.); (R.R.); (I.O.); (C.A.V.); (S.S.)
| | - Gilda Cinnella
- Department of Anesthesia and Intensive Care, University of Foggia, 71122 Foggia, Italy; (M.R.); (L.M.); (G.C.)
| | - Carlo Alberto Volta
- Department of Translation Medicine and for Romagna, Section of Anesthesia and Intensive Care, University of Ferrara, 44121 Ferrara, Italy; (F.M.); (C.T.); (R.R.); (I.O.); (C.A.V.); (S.S.)
| | - Savino Spadaro
- Department of Translation Medicine and for Romagna, Section of Anesthesia and Intensive Care, University of Ferrara, 44121 Ferrara, Italy; (F.M.); (C.T.); (R.R.); (I.O.); (C.A.V.); (S.S.)
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