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Sauter PK, Steblaj B, Kästner SBR, Söbbeler FJ, Reiners JK, Kutter APN, Bautitsta AJG, Neudeck S. Changes in microcirculation variables in an acute endotoxaemic equine model. Equine Vet J 2025. [PMID: 39844573 DOI: 10.1111/evj.14473] [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: 06/22/2024] [Accepted: 12/19/2024] [Indexed: 01/24/2025]
Abstract
BACKGROUND Microcirculation is the essential link between macrocirculation and cellular metabolism. OBJECTIVES To test our hypotheses that microcirculation variables will show a heterogeneous flow pattern during experimental endotoxaemia, and that fluid therapy and noradrenaline (NA) infusion will normalise altered microcirculation variables. STUDY DESIGN In vivo experiments. METHODS Six healthy adult horses were anaesthetised with dexmedetomidine, ketamine, and diazepam and were mechanically ventilated under isoflurane anaesthesia. Endotoxaemia was induced with 30 ng kg-1 Escherichia coli lipopolysaccharide intravenously. One hundred and twenty minutes later fluid bolus and noradrenaline (NA) infusion were administered to produce normotension. Pulse rate (PR) and mean arterial blood pressure (MAP) were measured and microcirculation variables were obtained by side-stream darkfield technique (de Backer density (DBD), perfused de Backer density (PDBD), proportion of perfused vessels, microvascular flow index (MFI), heterogeneity index (HI)), laser Doppler flowmetry (blood flow) and white light spectrometry (tissue oxygen saturation (tSO2)) in sublingual, jejunal and genital area. Measurements were obtained at baseline, after endotoxin, at 60 and 120 min and during the normotensive phase. Data were analysed by mixed model variance analysis and Tukey-Kramer. RESULTS The PPV decreased significantly over time by 30% (p < 0.001) at the jejunum. MFI decreased from baseline to ET60 and from baseline to ET120 in sublingual and genital mucosa (2.9 vs. 1.4, p < 0.001 and 2.8 vs. 1.9, p < 0.01), respectively. The sublingual HI increased from baseline to ET60, ET120 and NA (0.1 vs. 0.9, p = 0.02; vs. 0.6, p = 0.01; vs. 0.3, p = 0.01), respectively. The genital HI increased from baseline to ET120 (0.2 vs. 1.1, p ≤ 0.01) and NA (0.16 vs. 0.53, p < 0.05, respectively). Moderate agreement between observers for MFI assessment was present (kappa = 0.4). The PR significantly increased, and MAP significantly decreased from baseline over time. MAIN LIMITATIONS The obtained data could be influenced by secretions, pressure artefacts, the experience of the examiner and the sampling location. Blood flow was not quantified and there was no control group. CONCLUSIONS Overall, short-term experimental endotoxaemia did negatively alter MFI and HI; however, it did not alter tSO2, blood flow, DBD, PDBD or proportion of perfused vessels. Intravenous fluid therapy and NA did not restore MFI and HI to baseline values.
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Affiliation(s)
- Philipp K Sauter
- Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany
| | - Barbara Steblaj
- Section of Anaesthesiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
| | - Sabine B R Kästner
- Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany
- Clinic for Small Animals, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany
| | - Franz J Söbbeler
- Clinic for Small Animals, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany
| | - Julia K Reiners
- Tierärztliche Klinik für Kleintiere am Kaiserberg, Duisburg, Germany
| | - Annette P N Kutter
- Section of Anaesthesiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
| | | | - Stephan Neudeck
- Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany
- Clinic for Small Animals, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany
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Tang A, Shi Y, Dong Q, Wang S, Ge Y, Wang C, Gong Z, Zhang W, Chen W. Prognostic Value of Sublingual Microcirculation in Sepsis: A Systematic Review and Meta-analysis. J Intensive Care Med 2024; 39:1221-1230. [PMID: 38748542 DOI: 10.1177/08850666241253800] [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] [Indexed: 12/06/2024]
Abstract
Objectives: To investigate the relationship between sublingual microcirculation and the prognosis of sepsis. Data sources: The PubMed, Web of Science, Embase, and China National Knowledge Infrastructure (CNKI) databases were searched to identify studies published from January 2003 to November 2023. Study selection: Clinical studies examining sublingual microcirculation and the prognosis of sepsis were included. Data extraction: Sublingual microcirculation indices included the microvascular blood index (MFI), total vascular density (TVD), perfusion vascular density (PVD), perfusion vascular vessel (PPV), and heterogeneity index (HI). Prognostic outcomes included mortality and severity. Funnel plots and Egger's test were used to detect publication bias. The ability of the small vessel PPV (PPVs) to predict sepsis-related mortality was analyzed based on the summary receiver operating characteristic (SROC) curve, pooled sensitivity, and pooled specificity. Data synthesis: Twenty-five studies involving 1750 subjects were included. The TVD (95% CI 0.11-0.39), PVD (95% CI 0.42-0.88), PPV (95% CI 6.63-13.83), and MFI (95% CI 0.13-0.6) of the survival group were greater than those of the nonsurvival group. The HI in the survival group was lower than that in the nonsurvival group (95% CI -0.49 to -0.03). The TVD (95% CI 0.41-0.83), PVD (95% CI 0.83-1.17), PPV (95% CI 14.49-24.9), and MFI (95% CI 0.25-0.66) of the nonsevere group were greater than those of the severe group. Subgroup analysis revealed no significant difference in TVD between the survival group and the nonsurvival group in the small vessel subgroup. The area under the SROC curve (AUC) was 0.88. Conclusions: Sublingual microcirculation was worse among patients who died and patients with severe sepsis than among patients who survived and patients with nonsevere sepsis. PPV has a good predictive value for the mortality of sepsis patients. This study was recorded in PROSPERO (registration number: CRD42023486349).
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Affiliation(s)
- Aling Tang
- Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yi Shi
- Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Qingqing Dong
- Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Sihui Wang
- Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yao Ge
- Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Chenyan Wang
- Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zhimin Gong
- Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Weizhen Zhang
- Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Wei Chen
- Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Klibus M, Smirnova D, Marcinkevics Z, Rubins U, Grabovskis A, Vanags I, Sabelnikovs O. Quantitative Evaluation of Microcirculatory Alterations in Patients with COVID-19 and Bacterial Septic Shock through Remote Photoplethysmography and Automated Capillary Refill Time Analysis. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1680. [PMID: 39459467 PMCID: PMC11509756 DOI: 10.3390/medicina60101680] [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: 08/15/2024] [Revised: 09/26/2024] [Accepted: 10/08/2024] [Indexed: 10/28/2024]
Abstract
Background and Objectives: Sepsis, a leading global health challenge, accounts for around 20% of deaths worldwide. The complexity of sepsis, especially the difference between bacterial and viral etiologies, requires an effective assessment of microcirculation during resuscitation. This study aimed to evaluate the impact of infusion therapy on microcirculation in patients with sepsis, focusing on bacterial- and COVID-19-associated sepsis using remote photoplethysmography (rPPG) and the automated capillary refill time (aCRT). Materials and Methods: This single-center prospective study was conducted in the ICU of Pauls Stradins Clinical University Hospital, including 20 patients with sepsis/septic shock. The patients were selected based on hemodynamic instability and divided into COVID-19 and Bacterial Septic Shock groups. Fluid responsiveness was assessed using the Passive Leg Raising Test (PLRT). Systemic hemodynamics and microcirculation were monitored through MAP CRT, rPPG, and serum lactate levels. Statistical analyses compared responses within and between the groups across different stages of the protocol. Results: The Bacterial group exhibited higher initial serum lactate levels and more pronounced microcirculatory dysfunction than the COVID-19 group. rPPG was more sensitive in detecting perfusion changes, showing significant differences between the groups. The automated CRT demonstrated greater sensitivity compared to the manual CRT, revealing significant differences during PLRT stages between bacterial- and COVID-19-associated sepsis. Both groups had a transient hemodynamic response to PLRT, with subsequent stabilization upon fluid infusion. Conclusions: When managing patients with sepsis in intensive care, monitoring microcirculation is of paramount importance in infusion therapy. Our study highlights the potential of rPPG and aCRT as tools for this purpose. These techniques can be used in conjunction with routine parameters, such as lactate levels and systemic hemodynamic parameters, to provide a comprehensive assessment of a patient's condition.
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Affiliation(s)
- Mara Klibus
- Department of Clinical Skills and Medical Technology, Rīga Stradiņš University, LV-1007 Riga, Latvia; (M.K.); (D.S.)
- Department of Anaesthesiology and Reanimatology, Rīga Stradiņš University, LV-1007 Riga, Latvia;
- Department of Anaesthesiology and Reanimatology, Pauls Stradins CUH, LV-1002 Riga, Latvia
| | - Darja Smirnova
- Department of Clinical Skills and Medical Technology, Rīga Stradiņš University, LV-1007 Riga, Latvia; (M.K.); (D.S.)
- Department of Anaesthesiology and Reanimatology, Pauls Stradins CUH, LV-1002 Riga, Latvia
| | | | - Uldis Rubins
- Faculty of Science and Technology, University of Latvia, LV-1063 Riga, Latvia; (U.R.); (A.G.)
| | - Andris Grabovskis
- Faculty of Science and Technology, University of Latvia, LV-1063 Riga, Latvia; (U.R.); (A.G.)
| | - Indulis Vanags
- Department of Anaesthesiology and Reanimatology, Rīga Stradiņš University, LV-1007 Riga, Latvia;
| | - Olegs Sabelnikovs
- Department of Clinical Skills and Medical Technology, Rīga Stradiņš University, LV-1007 Riga, Latvia; (M.K.); (D.S.)
- Department of Anaesthesiology and Reanimatology, Rīga Stradiņš University, LV-1007 Riga, Latvia;
- Department of Anaesthesiology and Reanimatology, Pauls Stradins CUH, LV-1002 Riga, Latvia
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Kosmach A, Sveeggen TM, Bagher P. Sublingual microcirculatory function as a prognostic indicator of general microvascular health. Am J Physiol Heart Circ Physiol 2024; 327:H311-H314. [PMID: 38874617 DOI: 10.1152/ajpheart.00390.2024] [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: 06/11/2024] [Revised: 06/12/2024] [Accepted: 06/12/2024] [Indexed: 06/15/2024]
Affiliation(s)
- Anna Kosmach
- Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, United States
| | - Timothy M Sveeggen
- Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, United States
| | - Pooneh Bagher
- Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, United States
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Mirsajadi A, Erickson D, Alias S, Froese L, Singh Sainbhi A, Gomez A, Majumdar R, Herath I, Wilson M, Zarychanski R, Zeiler FA, Mendelson AA. Microvascular Autoregulation in Skeletal Muscle Using Near-Infrared Spectroscopy and Derivation of Optimal Mean Arterial Pressure in the ICU: Pilot Study and Comparison With Cerebral Near-Infrared Spectroscopy. Crit Care Explor 2024; 6:e1111. [PMID: 38904977 PMCID: PMC11196085 DOI: 10.1097/cce.0000000000001111] [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: 06/22/2024] Open
Abstract
IMPORTANCE Microvascular autoregulation (MA) maintains adequate tissue perfusion over a range of arterial blood pressure (ABP) and is frequently impaired in critical illness. MA has been studied in the brain to derive personalized hemodynamic targets after brain injury. The ability to measure MA in other organs is not known, which may inform individualized management during shock. OBJECTIVES This study determines the feasibility of measuring MA in skeletal muscle using near-infrared spectroscopy (NIRS) as a marker of tissue perfusion, the derivation of optimal mean arterial pressure (MAPopt), and comparison with indices from the brain. DESIGN Prospective observational study. SETTING Medical and surgical ICU in a tertiary academic hospital. PARTICIPANTS Adult critically ill patients requiring vasoactive support on the first day of ICU admission. MAIN OUTCOMES AND MEASURES Fifteen critically ill patients were enrolled. NIRS was applied simultaneously to skeletal muscle (brachioradialis) and brain (frontal cortex) while ABP was measured continuously via invasive catheter. MA correlation indices were calculated between ABP and NIRS from skeletal muscle total hemoglobin (MVx), muscle tissue saturation index (MOx), brain total hemoglobin (THx), and brain tissue saturation index (COx). Curve fitting algorithms derive the MAP with the lowest correlation index value, which is the MAPopt. RESULTS MAPopt values were successfully calculated for each correlation index for all patients and were frequently (77%) above 65 mm Hg. For all correlation indices, median time was substantially above impaired MA threshold (24.5-34.9%) and below target MAPopt (9.0-78.6%). Muscle and brain MAPopt show moderate correlation (MVx-THx r = 0.76, p < 0.001; MOx-COx r = 0.69, p = 0.005), with a median difference of -1.27 mm Hg (-9.85 to -0.18 mm Hg) and 0.05 mm Hg (-7.05 to 2.68 mm Hg). CONCLUSIONS AND RELEVANCE This study demonstrates, for the first time, the feasibility of calculating MA indices and MAPopt in skeletal muscle using NIRS. Future studies should explore the association between impaired skeletal muscle MA, ICU outcomes, and organ-specific differences in MA and MAPopt thresholds.
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Affiliation(s)
- Amirali Mirsajadi
- Department of Biomedical Engineering, Faculty of Engineering, University of Manitoba, Winnipeg, MB, Canada
| | - Dustin Erickson
- Section of Critical Care Medicine, Department of Medicine, University of Manitoba, Winnipeg, MB, Canada
| | - Soumya Alias
- Section of Critical Care Medicine, Department of Medicine, University of Manitoba, Winnipeg, MB, Canada
| | - Logan Froese
- Department of Biomedical Engineering, Faculty of Engineering, University of Manitoba, Winnipeg, MB, Canada
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Amanjyot Singh Sainbhi
- Department of Biomedical Engineering, Faculty of Engineering, University of Manitoba, Winnipeg, MB, Canada
| | - Alwyn Gomez
- Division of Neurosurgery, Department of Surgery, University of Manitoba, Winnipeg, MB, Canada
- Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada
| | - Raju Majumdar
- Section of Critical Care Medicine, Department of Medicine, University of Manitoba, Winnipeg, MB, Canada
| | - Isuru Herath
- Department of Biomedical Engineering, Faculty of Engineering, University of Manitoba, Winnipeg, MB, Canada
| | - Maggie Wilson
- Section of Critical Care Medicine, Department of Medicine, University of Manitoba, Winnipeg, MB, Canada
| | - Ryan Zarychanski
- Section of Critical Care Medicine, Department of Medicine, University of Manitoba, Winnipeg, MB, Canada
- Department of Medical Oncology and Hematology, University of Manitoba/CancerCare Manitoba, Winnipeg, MB, Canada
| | - Frederick A. Zeiler
- Department of Biomedical Engineering, Faculty of Engineering, University of Manitoba, Winnipeg, MB, Canada
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
- Division of Neurosurgery, Department of Surgery, University of Manitoba, Winnipeg, MB, Canada
- Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada
- Pan Am Clinic Foundation, Winnipeg, MB, Canada
| | - Asher A. Mendelson
- Department of Biomedical Engineering, Faculty of Engineering, University of Manitoba, Winnipeg, MB, Canada
- Section of Critical Care Medicine, Department of Medicine, University of Manitoba, Winnipeg, MB, Canada
- Department of Physiology, University of Manitoba, Winnipeg, MB, Canada
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6
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Abel B, Gerling KA, Mares JA, Hutzler J, Pierskalla I, Hays J, Propper B, White JM, Burmeister DM. Real-Time Measurements of Oral Mucosal Carbon Dioxide (POMCO2) Reveals an Inverse Correlation With Blood Pressure in a Porcine Model of Coagulopathic Junctional Hemorrhage. Mil Med 2024; 189:e612-e619. [PMID: 37632757 DOI: 10.1093/milmed/usad336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 06/28/2023] [Accepted: 08/11/2023] [Indexed: 08/28/2023] Open
Abstract
INTRODUCTION Shock states that occur during, for example, profound hemorrhage can cause global tissue hypoperfusion leading to organ failure. There is an unmet need for a reliable marker of tissue perfusion during hemorrhage that can be followed longitudinally. Herein, we investigated whether longitudinal POMCO2 tracks changes in hemodynamics in a swine model of coagulopathic uncontrolled junctional hemorrhage. MATERIALS AND METHODS Female Yorkshire-crossbreed swine (n = 7, 68.1 ± 0.7 kg) were anesthetized and instrumented for continuous measurement of mean arterial pressure (MAP). Coagulopathy was induced by the exchange of 50 to 60% of blood volume with 6% Hetastarch over 30 minutes to target a hematocrit of <15%. A 4.5-mm arteriotomy was made in the right common femoral artery with 30 seconds of free bleeding. POMCO2 was continuously measured from baseline through hemodilution, hemorrhage, and a subsequent 3-h intensive care unit period. Rotational thromboelastometry and blood gases were measured. RESULTS POMCO2 and MAP showed no significant changes during the hemodilution phase of the experiment, which produced coagulopathy evidenced by prolonged clot formation times. However, POMCO2 increased because of the uncontrolled hemorrhage by 11.3 ± 3.1 mmHg and was inversely correlated with the drop (17.9 ± 5.9 mmHg) in MAP (Y = -0.4122*X + 2.649, P = .02, r2 = 0.686). In contrast, lactate did not significantly correlate with the changes in MAP (P = .35) or POMCO2 (P = .37). CONCLUSIONS Despite the logical appeal of measuring noninvasive tissue CO2 measurement as a surrogate for gastrointestinal perfusion, prior studies have only reported snapshots of this readout. The present investigation shows real-time longitudinal measurement of POMCO2 to confirm that MAP inversely correlates to POMCO2 in the face of coagulopathy. The simplicity of measuring POMCO2 in real time can provide an additional practical option for military or civilian medics to monitor trends in hypoperfusion during hemorrhagic shock.
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Affiliation(s)
- Biebele Abel
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA
- Department of Surgery, Uniformed Services University of the Health Science, Bethesda, MD 20814, USA
| | | | - John A Mares
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA
- Department of Surgery, Uniformed Services University of the Health Science, Bethesda, MD 20814, USA
| | - Justin Hutzler
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA
- Department of Surgery, Uniformed Services University of the Health Science, Bethesda, MD 20814, USA
| | | | - Jim Hays
- ExoStat Medical, Inc., Prior Lake, MN 55372, USA
| | - Brandon Propper
- Department of Surgery, Uniformed Services University of the Health Science, Bethesda, MD 20814, USA
- Walter Reed National Military Medical Center, Bethesda, MD 20814, USA
| | - Joseph M White
- Division of Vascular Surgery and Endovascular Therapy, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA
| | - David M Burmeister
- Department of Surgery, Uniformed Services University of the Health Science, Bethesda, MD 20814, USA
- Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
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Belousoviene E, Pranskuniene Z, Vaitkaitiene E, Pilvinis V, Pranskunas A. Effect of high-dose intravenous ascorbic acid on microcirculation and endothelial glycocalyx during sepsis and septic shock: a double-blind, randomized, placebo-controlled study. BMC Anesthesiol 2023; 23:309. [PMID: 37700249 PMCID: PMC10496271 DOI: 10.1186/s12871-023-02265-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Accepted: 08/30/2023] [Indexed: 09/14/2023] Open
Abstract
Previous studies indicate supplemental vitamin C improves microcirculation and reduces glycocalyx shedding in septic animals. Our randomized, double-blind, placebo-controlled trial aimed to investigate whether a high dose of intravenous ascorbic acid (AA) might improve microcirculation and affect glycocalyx in septic patients. In our study, 23 septic patients were supplemented with a high dose (50 mg/kg every 6 h) of intravenous AA or placebo for 96 h. Sublingual microcirculation was examined using a handheld Cytocam-incident dark field (IDF) video microscope. A sidestream dark field video microscope (SDF), connected to the GlycoCheck software (GlycoCheck ICU®; Maastricht University Medical Center, Maastricht, the Netherlands), was employed to observe glycocalyx. We found a significantly higher proportion of perfused small vessels (PPV) 6 h after the beginning of the trial in the experimental group compared with placebo. As an indicator of glycocalyx thickness, the perfused boundary region was lower in capillaries of the 5-9 μm diameter in the AA group than placebo after the first dose of AA. Our data suggest that high-dose parenteral AA tends to improve microcirculation and glycocalyx in the early period of septic shock. The study was retrospectively registered in the clinicaltrials.gov database on 26/02/2021 (registration number NCT04773717).
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Affiliation(s)
- Egle Belousoviene
- Department of Intensive Care Medicine, Lithuanian University of Health Sciences, Eiveniu g. 2, Kaunas, LT-50161, Lithuania
| | - Zivile Pranskuniene
- Department of Drug Technology and Social Pharmacy, Lithuanian University of Health Sciences, Sukileliu pr.13, Kaunas, LT-50162, Lithuania
- Institute of Pharmaceutical Technologies, Lithuanian University of Health Sciences, Sukileliu pr.13, Kaunas, LT-50162, Lithuania
| | - Egle Vaitkaitiene
- Department of Disaster Medicine and Health Research Institute, Lithuanian University of Health Sciences, Eiveniu g. 4, Kaunas, LT-50161, Lithuania
| | - Vidas Pilvinis
- Department of Intensive Care Medicine, Lithuanian University of Health Sciences, Eiveniu g. 2, Kaunas, LT-50161, Lithuania
| | - Andrius Pranskunas
- Department of Intensive Care Medicine, Lithuanian University of Health Sciences, Eiveniu g. 2, Kaunas, LT-50161, Lithuania.
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Dubin A, Pozo MO. Venous Minus Arterial Carbon Dioxide Gradients in the Monitoring of Tissue Perfusion and Oxygenation: A Narrative Review. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1262. [PMID: 37512072 PMCID: PMC10384777 DOI: 10.3390/medicina59071262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/18/2023] [Accepted: 07/04/2023] [Indexed: 07/30/2023]
Abstract
According to Fick's principle, the total uptake of (or release of) a substance by tissues is the product of blood flow and the difference between the arterial and the venous concentration of the substance. Therefore, the mixed or central venous minus arterial CO2 content difference depends on cardiac output (CO). Assuming a linear relationship between CO2 content and partial pressure, central or mixed venous minus arterial PCO2 differences (Pcv-aCO2 and Pmv-aCO2) are directly related to CO. Nevertheless, this relationship is affected by alterations in the CO2Hb dissociation curve induced by metabolic acidosis, hemodilution, the Haldane effect, and changes in CO2 production (VCO2). In addition, Pcv-aCO2 and Pmv-aCO2 are not interchangeable. Despite these confounders, CO is a main determinant of Pcv-aCO2. Since in a study performed in septic shock patients, Pmv-aCO2 was correlated with changes in sublingual microcirculation but not with those in CO, it has been proposed as a monitor for microcirculation. The respiratory quotient (RQ)-RQ = VCO2/O2 consumption-sharply increases in anaerobic situations induced by exercise or critical reductions in O2 transport. This results from anaerobic VCO2 secondary to bicarbonate buffering of anaerobically generated protons. The measurement of RQ requires expired gas analysis by a metabolic cart, which is not usually available. Thus, some studies have suggested that the ratio of Pcv-aCO2 to arterial minus central venous O2 content (Pcv-aCO2/Ca-cvO2) might be a surrogate for RQ and tissue oxygenation. In this review, we analyze the physiologic determinants of Pcv-aCO2 and Pcv-aCO2/Ca-cvO2 and their potential usefulness and limitations for the monitoring of critically ill patients. We discuss compelling evidence showing that they are misleading surrogates for tissue perfusion and oxygenation, mainly because they are systemic variables that fail to track regional changes. In addition, they are strongly dependent on changes in the CO2Hb dissociation curve, regardless of changes in systemic and microvascular perfusion and oxygenation.
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Affiliation(s)
- Arnaldo Dubin
- Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Cátedras de Terapia Intensiva y Farmacología Aplicada, 60 y 120, La Plata B1902AGW, Argentina
- Servicio de Terapia Intensiva, Sanatorio Otamendi, Azcuénaga 870, Ciudad Autónoma de Buenos Aires C1115AAB, Argentina
| | - Mario O Pozo
- Servicio de Terapia Intensiva, Hospital Británico, Perdriel 74, Ciudad Autónoma de Buenos Aires 1280AEB, Argentina
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Damiani E, Carsetti A, Casarotta E, Domizi R, Scorcella C, Donati A, Adrario E. Microcirculation-guided resuscitation in sepsis: the next frontier? Front Med (Lausanne) 2023; 10:1212321. [PMID: 37476612 PMCID: PMC10354242 DOI: 10.3389/fmed.2023.1212321] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 06/20/2023] [Indexed: 07/22/2023] Open
Abstract
Microcirculatory dysfunction plays a key role in the pathogenesis of tissue dysoxia and organ failure in sepsis. Sublingual videomicroscopy techniques enable the real-time non-invasive assessment of microvascular blood flow. Alterations in sublingual microvascular perfusion were detected during sepsis and are associated with poor outcome. More importantly, sublingual videomicroscopy allowed to explore the effects of commonly applied resuscitative treatments in septic shock, such as fluids, vasopressors and inotropes, and showed that the optimization of macro-hemodynamic parameters may not be accompanied by an improvement in microvascular perfusion. This loss of "hemodynamic coherence," i.e., the concordance between the response of the macrocirculation and the microcirculation, advocates for the integration of microvascular monitoring in the management of septic patients. Nonetheless, important barriers remain for a widespread use of sublingual videomicroscopy in the clinical practice. In this review, we discuss the actual limitations of this technique and future developments that may allow an easier and faster evaluation of the microcirculation at the bedside, and propose a role for sublingual microvascular monitoring in guiding and titrating resuscitative therapies in sepsis.
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Affiliation(s)
- Elisa Damiani
- Anesthesia and Intensive Care Unit, Azienda Ospedaliero Universitaria delle Marche, Ancona, Italy
- Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, Italy
| | - Andrea Carsetti
- Anesthesia and Intensive Care Unit, Azienda Ospedaliero Universitaria delle Marche, Ancona, Italy
- Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, Italy
| | - Erika Casarotta
- Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, Italy
| | - Roberta Domizi
- Anesthesia and Intensive Care Unit, Azienda Ospedaliero Universitaria delle Marche, Ancona, Italy
| | - Claudia Scorcella
- Anesthesia and Intensive Care Unit, Azienda Ospedaliero Universitaria delle Marche, Ancona, Italy
| | - Abele Donati
- Anesthesia and Intensive Care Unit, Azienda Ospedaliero Universitaria delle Marche, Ancona, Italy
- Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, Italy
| | - Erica Adrario
- Anesthesia and Intensive Care Unit, Azienda Ospedaliero Universitaria delle Marche, Ancona, Italy
- Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, Italy
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10
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Chen Y, Peng JM, Hu XY, Li S, Wan XX, Liu RT, Wang CY, Jiang W, Dong R, Su LX, He HW, Long Y, Weng L, Du B. Tissue oxygen saturation is predictive of lactate clearance in patients with circulatory shock. BMC Anesthesiol 2023; 23:179. [PMID: 37231341 DOI: 10.1186/s12871-023-02139-4] [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: 03/30/2023] [Accepted: 05/14/2023] [Indexed: 05/27/2023] Open
Abstract
BACKGROUND Tissue oxygen saturation (StO2) decrease could appear earlier than lactate alteration. However, the correlation between StO2 and lactate clearance was unknown. METHODS This was a prospective observational study. All consecutive patients with circulatory shock and lactate over 3 mmol/L were included. Based on the rule of nines, a BSA (body surface area) weighted StO2 was calculated from four sites of StO2 (masseter, deltoid, thenar and knee). The formulation was as follows: masseter StO2 × 9% + (deltoid StO2 + thenar StO2) × (18% + 27%)/ 2 + knee StO2 × 46%. Vital signs, blood lactate, arterial and central venous blood gas were measured simultaneously within 48 h of ICU admission. The predictive value of BSA-weighted StO2 on 6-hour lactate clearance > 10% since StO2 initially monitored was assessed. RESULTS A total of 34 patients were included, of whom 19 (55.9%) had a lactate clearance higher than 10%. The mean SOFA score was lower in cLac ≥ 10% group compared with cLac < 10% group (11 ± 3 vs. 15 ± 4, p = 0.007). Other baseline characteristics were comparable between groups. Compared to non-clearance group, StO2 in deltoid, thenar and knee were significantly higher in clearance group. The area under the receiver operating curves (AUROC) of BSA-weighted StO2 for prediction of lactate clearance (0.92, 95% CI [Confidence Interval] 0.82-1.00) was significantly higher than StO2 of masseter (0.65, 95% CI 0.45-0.84; p < 0.01), deltoid (0.77, 95% CI 0.60-0.94; p = 0.04), thenar (0.72, 95% CI 0.55-0.90; p = 0.01), and similar to knee (0.87, 0.73-1.00; p = 0.40), mean StO2 (0.85, 0.73-0.98; p = 0.09). Additionally, BSA-weighted StO2 model had continuous net reclassification improvement (NRI) over the knee StO2 and mean StO2 model (continuous NRI 48.1% and 90.2%, respectively). The AUROC of BSA-weighted StO2 was 0.91(95% CI 0.75-1.0) adjusted by mean arterial pressure and norepinephrine dose. CONCLUSIONS Our results suggested that BSA-weighted StO2 was a strong predictor of 6-hour lactate clearance in patients with shock.
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Affiliation(s)
- Yan Chen
- Medical Intensive Care Unit, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Jin-Min Peng
- Medical Intensive Care Unit, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Xiao-Yun Hu
- Medical Intensive Care Unit, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Shan Li
- Medical Intensive Care Unit, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Xi-Xi Wan
- Medical Intensive Care Unit, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Rui-Ting Liu
- Medical Intensive Care Unit, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Chun-Yao Wang
- Medical Intensive Care Unit, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Wei Jiang
- Medical Intensive Care Unit, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Run Dong
- Medical Intensive Care Unit, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Long-Xiang Su
- Department of Critical Care Medicine, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Huai-Wu He
- Department of Critical Care Medicine, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Yun Long
- Department of Critical Care Medicine, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Li Weng
- Medical Intensive Care Unit, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
| | - Bin Du
- Medical Intensive Care Unit, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
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11
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Duranteau J, De Backer D, Donadello K, Shapiro NI, Hutchings SD, Rovas A, Legrand M, Harrois A, Ince C. The future of intensive care: the study of the microcirculation will help to guide our therapies. Crit Care 2023; 27:190. [PMID: 37193993 PMCID: PMC10186296 DOI: 10.1186/s13054-023-04474-x] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 05/03/2023] [Indexed: 05/18/2023] Open
Abstract
The goal of hemodynamic resuscitation is to optimize the microcirculation of organs to meet their oxygen and metabolic needs. Clinicians are currently blind to what is happening in the microcirculation of organs, which prevents them from achieving an additional degree of individualization of the hemodynamic resuscitation at tissue level. Indeed, clinicians never know whether optimization of the microcirculation and tissue oxygenation is actually achieved after macrovascular hemodynamic optimization. The challenge for the future is to have noninvasive, easy-to-use equipment that allows reliable assessment and immediate quantitative analysis of the microcirculation at the bedside. There are different methods for assessing the microcirculation at the bedside; all have strengths and challenges. The use of automated analysis and the future possibility of introducing artificial intelligence into analysis software could eliminate observer bias and provide guidance on microvascular-targeted treatment options. In addition, to gain caregiver confidence and support for the need to monitor the microcirculation, it is necessary to demonstrate that incorporating microcirculation analysis into the reasoning guiding hemodynamic resuscitation prevents organ dysfunction and improves the outcome of critically ill patients.
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Affiliation(s)
- J Duranteau
- Department of Anesthesiology and Intensive Care, Bicêtre Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), INSERM UMR-S 999, Paris-Saclay University, Le Kremlin-Bicêtre, France.
| | - D De Backer
- Department of Intensive Care, CHIREC Hospitals, Université Libre de Bruxelles, Boulevard du Triomphe 201, 1160, Brussels, Belgium
| | - K Donadello
- Anaesthesia and Intensive Care Unit B, Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, University Hospital Integrated Trust of Verona, Verona, Italy
| | - N I Shapiro
- Department of Emergency Medicine, Beth Israel Deaconess Medical Center-Harvard Medical School, Boston, MA, USA
| | - S D Hutchings
- King's College Hospital NHS Foundation Trust, London, UK
- Academic Department of Military Anaesthesia and Critical Care, Royal Centre for Defence Medicine, Birmingham, UK
| | - A Rovas
- Division of General Internal and Emergency Medicine, Nephrology, and Rheumatology, Department of Medicine D, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany
| | - M Legrand
- Division of Critical Care Medicine, Department of Anesthesia and Perioperative Care, UCSF, San Francisco, USA
| | - A Harrois
- Department of Anesthesiology and Intensive Care, Bicêtre Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), INSERM UMR-S 999, Paris-Saclay University, Le Kremlin-Bicêtre, France
| | - C Ince
- Department of Intensive Care, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
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12
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Garduno A, Cusack R, Leone M, Einav S, Martin-Loeches I. Multi-Omics Endotypes in ICU Sepsis-Induced Immunosuppression. Microorganisms 2023; 11:1119. [PMID: 37317092 DOI: 10.3390/microorganisms11051119] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 04/03/2023] [Accepted: 04/21/2023] [Indexed: 06/16/2023] Open
Abstract
It is evident that the admission of some patients with sepsis and septic shock to hospitals is occurring late in their illness, which has contributed to the increase in poor outcomes and high fatalities worldwide across age groups. The current diagnostic and monitoring procedure relies on an inaccurate and often delayed identification by the clinician, who then decides the treatment upon interaction with the patient. Initiation of sepsis is accompanied by immune system paralysis following "cytokine storm". The unique immunological response of each patient is important to define in terms of subtyping for therapy. The immune system becomes activated in sepsis to produce interleukins, and endothelial cells express higher levels of adhesion molecules. The proportions of circulating immune cells change, reducing regulatory cells and increasing memory cells and killer cells, having long-term effects on the phenotype of CD8 T cells, HLA-DR, and dysregulation of microRNA. The current narrative review seeks to highlight the potential application of multi-omics data integration and immunological profiling at the single-cell level to define endotypes in sepsis and septic shock. The review will consider the parallels and immunoregulatory axis between cancer and immunosuppression, sepsis-induced cardiomyopathy, and endothelial damage. Second, the added value of transcriptomic-driven endotypes will be assessed through inferring regulatory interactions in recent clinical trials and studies reporting gene modular features that inform continuous metrics measuring clinical response in ICU, which can support the use of immunomodulating agents.
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Affiliation(s)
- Alexis Garduno
- Department of Clinical Medicine, Trinity College, University of Dublin, D02 PN40 Dublin, Ireland
| | - Rachael Cusack
- Department of Intensive Care Medicine, St. James's Hospital, James's Street, D08 NHY1 Dublin, Ireland
| | - Marc Leone
- Department of Anesthesia, Intensive Care and Trauma Center, Nord University Hospital, Aix Marseille University, APHM, 13015 Marseille, France
| | - Sharon Einav
- General Intensive Care Unit, Shaare Zedek Medical Center, Jerusalem 23456, Israel
- Faculty of Medicine, Hebrew University, Jerusalem 23456, Israel
| | - Ignacio Martin-Loeches
- Department of Clinical Medicine, Trinity College, University of Dublin, D02 PN40 Dublin, Ireland
- Department of Intensive Care Medicine, St. James's Hospital, James's Street, D08 NHY1 Dublin, Ireland
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13
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Uz Z, Dilken O, Milstein DMJ, Hilty MP, de Haan D, Ince Y, Shen L, Houtzager J, Franken LC, van Gulik TM, Ince C. Identifying a sublingual triangle as the ideal site for assessment of sublingual microcirculation. J Clin Monit Comput 2023; 37:639-649. [PMID: 36355276 PMCID: PMC10068634 DOI: 10.1007/s10877-022-00936-9] [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: 12/13/2020] [Accepted: 10/15/2022] [Indexed: 11/11/2022]
Abstract
The sublingual mucosa is a commonly used intraoral location for identifying microcirculatory alterations using handheld vital microscopes (HVMs). The anatomic description of the sublingual cave and its related training have not been adequately introduced. The aim of this study was to introduce anatomy guided sublingual microcirculatory assessment. Measurements were acquired from the floor of the mouth using incident dark-field (IDF) imaging before (T0) and after (T1) sublingual cave anatomy instructed training. Instructions consists of examining a specific region of interested identified through observable anatomical structures adjacent and bilaterally to the lingual frenulum which is next to the sublingual papilla. The anatomical location called the sublingual triangle, was identified as stationed between the lingual frenulum, the sublingual fold and ventrally to the tongue. Small, large, and total vessel density datasets (SVD, LVD and TVD respectively) obtained by non-instructed and instructed measurements (NIN (T0) and IM (T1) respectively) were compared. Microvascular structures were analyzed, and the presence of salivary duct-related microcirculation was identified. A total of 72 video clips were used for analysis in which TVD, but not LVD and SVD, was higher in IM compared to NIM (NIM vs. IM, 25 ± 2 vs. 27 ± 3 mm/mm2 (p = 0.044), LVD NIM vs. IM: 7 ± 1 vs. 8 ± 1mm/mm2 (p = 0.092), SVD NIM vs. IM: 18 ± 2 vs. 20 ± 3 mm/mm2 (p = 0.103)). IM resulted in microcirculatory assessments which included morphological properties such as capillaries, venules and arterioles, without salivary duct-associated microcirculation. The sublingual triangle identified in this study showed consistent network-based microcirculation, without interference from microcirculation associated with specialized anatomic structures. These findings suggest that the sublingual triangle, an anatomy guided location, yielded sublingual based measurements that conforms with international guidelines. IM showed higher TVD values, and future studies are needed with larger sample sizes to prove differences in microcirculatory parameters.
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Affiliation(s)
- Zühre Uz
- Department of Translational Physiology, Location: AMC, Amsterdam University Medical Centre (UMC), University of Amsterdam, Amsterdam, The Netherlands.
- Department of Surgery, Location: AMC, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
- Department of Intensive Care, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands.
| | - Olcay Dilken
- Department of Translational Physiology, Location: AMC, Amsterdam University Medical Centre (UMC), University of Amsterdam, Amsterdam, The Netherlands
| | - Dan M J Milstein
- Department of Oral & Maxillofacial Surgery, Location: AMC, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Oral Medicine, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands
| | - Matthias Peter Hilty
- Department of Translational Physiology, Location: AMC, Amsterdam University Medical Centre (UMC), University of Amsterdam, Amsterdam, The Netherlands
| | - David de Haan
- Department of Translational Physiology, Location: AMC, Amsterdam University Medical Centre (UMC), University of Amsterdam, Amsterdam, The Netherlands
| | - Yasin Ince
- Department of Translational Physiology, Location: AMC, Amsterdam University Medical Centre (UMC), University of Amsterdam, Amsterdam, The Netherlands
| | - Lucinda Shen
- Department of Translational Physiology, Location: AMC, Amsterdam University Medical Centre (UMC), University of Amsterdam, Amsterdam, The Netherlands
| | - Julia Houtzager
- Department of Surgery, Location: AMC, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Lotte C Franken
- Department of Surgery, Location: AMC, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Thomas M van Gulik
- Department of Surgery, Location: AMC, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Can Ince
- Department of Translational Physiology, Location: AMC, Amsterdam University Medical Centre (UMC), University of Amsterdam, Amsterdam, The Netherlands
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14
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Fu SJ, Xu MT, Wang B, Li BW, Ling H, Li Y, Wang Q, Liu XT, Zhang XY, Li AL, Liu MM. Global trend and future landscape of intestinal microcirculation research from 2000 to 2021: A scientometric study. World J Gastroenterol 2023; 29:1523-1535. [PMID: 36998427 PMCID: PMC10044859 DOI: 10.3748/wjg.v29.i9.1523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 02/01/2023] [Accepted: 02/24/2023] [Indexed: 03/07/2023] Open
Abstract
BACKGROUND The intestinal microcirculation functions in food absorption and metabolic substance exchanges. Accumulating evidence indicates that intestinal microcirculatory dysfunction is a significant source of multiple gastrointestinal diseases. To date, there has not been a scientometric analysis of intestinal microcirculatory research.
AIM To investigate the current status, development trends, and frontiers of intestinal microcirculatory research based on bibliometric analysis.
METHODS VOSviewer and CiteSpace 6.1.R2 were used to identify the overall characteristics and knowledge map of intestinal microcirculatory research based on the core literature published from 2000 to 2021 in the Web of Science database. The characteristics of each article, country of origin, institution, journal, cocitations, and other information were analyzed and visualized.
RESULTS There were 1364 publications enrolled in the bibliometric analysis, exhibiting an upward trend from 2000 to 2021 with increased participation worldwide. The United States and Dalhousie University took the lead among countries and institutions, respectively. Shock was the most prolific journal, and Nature Reviews Microbiology Clinical had the most citations. The topical hotspots and frontiers in intestinal microcirculatory research were centered on the pathological processes of functional impairment of intestinal microvessels, diverse intestinal illnesses, and clinical treatment.
CONCLUSION Our study highlights insights into trends of the published research on the intestinal microcirculation and offers serviceable guidance to researchers by summarizing the prolific areas in intestinal disease research to date.
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Affiliation(s)
- Sun-Jing Fu
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
| | - Meng-Ting Xu
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
| | - Bing Wang
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
| | - Bing-Wei Li
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
| | - Hao Ling
- Department of Radiology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410004, Hunan Province, China
| | - Yuan Li
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
| | - Qin Wang
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
| | - Xue-Ting Liu
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
| | - Xiao-Yan Zhang
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
| | - Ai-Ling Li
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
| | - Ming-Ming Liu
- Institute of Microcirculation, Key Laboratory of Microcirculation, Ministry of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
- Diabetes Research Center, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
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15
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Bogatu L, Turco S, Mischi M, Schmitt L, Woerlee P, Bezemer R, Bouwman AR, Korsten EHHM, Muehlsteff J. New Hemodynamic Parameters in Peri-Operative and Critical Care-Challenges in Translation. SENSORS (BASEL, SWITZERLAND) 2023; 23:2226. [PMID: 36850819 PMCID: PMC9961222 DOI: 10.3390/s23042226] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 02/03/2023] [Accepted: 02/06/2023] [Indexed: 06/18/2023]
Abstract
Hemodynamic monitoring technologies are evolving continuously-a large number of bedside monitoring options are becoming available in the clinic. Methods such as echocardiography, electrical bioimpedance, and calibrated/uncalibrated analysis of pulse contours are becoming increasingly common. This is leading to a decline in the use of highly invasive monitoring and allowing for safer, more accurate, and continuous measurements. The new devices mainly aim to monitor the well-known hemodynamic variables (e.g., novel pulse contour, bioreactance methods are aimed at measuring widely-used variables such as blood pressure, cardiac output). Even though hemodynamic monitoring is now safer and more accurate, a number of issues remain due to the limited amount of information available for diagnosis and treatment. Extensive work is being carried out in order to allow for more hemodynamic parameters to be measured in the clinic. In this review, we identify and discuss the main sensing strategies aimed at obtaining a more complete picture of the hemodynamic status of a patient, namely: (i) measurement of the circulatory system response to a defined stimulus; (ii) measurement of the microcirculation; (iii) technologies for assessing dynamic vascular mechanisms; and (iv) machine learning methods. By analyzing these four main research strategies, we aim to convey the key aspects, challenges, and clinical value of measuring novel hemodynamic parameters in critical care.
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Affiliation(s)
- Laura Bogatu
- Biomedical Diagnostics Lab (BM/d), Eindhoven University of Technology, 5612 AZ Eindhoven, The Netherlands
- Patient Care and Measurements, Philips Research, 5656 AE Eindhoven, The Netherlands
| | - Simona Turco
- Biomedical Diagnostics Lab (BM/d), Eindhoven University of Technology, 5612 AZ Eindhoven, The Netherlands
| | - Massimo Mischi
- Biomedical Diagnostics Lab (BM/d), Eindhoven University of Technology, 5612 AZ Eindhoven, The Netherlands
| | - Lars Schmitt
- Patient Care and Measurements, Philips Research, 5656 AE Eindhoven, The Netherlands
| | - Pierre Woerlee
- Biomedical Diagnostics Lab (BM/d), Eindhoven University of Technology, 5612 AZ Eindhoven, The Netherlands
| | - Rick Bezemer
- Patient Care and Measurements, Philips Research, 5656 AE Eindhoven, The Netherlands
| | - Arthur R. Bouwman
- Department of Anesthesiology, Intensive Care and Pain Medicine, Catharina Ziekenhuis, 5623 EJ Eindhoven, The Netherlands
| | - Erik H. H. M. Korsten
- Department of Anesthesiology, Intensive Care and Pain Medicine, Catharina Ziekenhuis, 5623 EJ Eindhoven, The Netherlands
| | - Jens Muehlsteff
- Patient Care and Measurements, Philips Research, 5656 AE Eindhoven, The Netherlands
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16
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Effects of Fluids on the Sublingual Microcirculation in Sepsis. J Clin Med 2022; 11:jcm11247277. [PMID: 36555895 PMCID: PMC9786137 DOI: 10.3390/jcm11247277] [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: 11/15/2022] [Revised: 12/02/2022] [Accepted: 12/06/2022] [Indexed: 12/13/2022] Open
Abstract
Sepsis is one of the most common and deadly syndromes faced in Intensive Care settings globally. Recent advances in bedside imaging have defined the changes in the microcirculation in sepsis. One of the most advocated interventions for sepsis is fluid therapy. Whether or not fluid bolus affects the microcirculation in sepsis has not been fully addressed in the literature. This systematic review of the evidence aims to collate studies examining the microcirculatory outcomes after a fluid bolus in patients with sepsis. We will assimilate the evidence for using handheld intra vital microscopes to guide fluid resuscitation and the effect of fluid bolus on the sublingual microcirculation in patients with sepsis and septic shock. We conducted a systematic search of Embase, CENTRAL and Medline (PubMed) using combinations of the terms "microcirculation" AND "fluid" OR "fluid resuscitation" OR "fluid bolus" AND "sepsis" OR "septic shock". We found 3376 potentially relevant studies. Fifteen studies published between 2007 and 2021 fulfilled eligibility criteria to be included in analysis. The total number of participants was 813; we included six randomized controlled trials and nine non-randomized, prospective observational studies. Ninety percent used Sidestream Dark Field microscopy to examine the microcirculation and 50% used Hydroxyethyl Starch as their resuscitation fluid. There were no clear effects of fluid on the microcirculation parameters. There was too much heterogeneity between studies and methodology to perform meta-analysis. Studies identified heterogeneity of affect in the sepsis population, which could mean that current clinical classifications were not able to identify different microcirculation characteristics. Use of microcirculation as a clinical endpoint in sepsis could help to define sepsis phenotypes. More research into the effects of different resuscitation fluids on the microcirculation is needed.
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17
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Cusack R, Leone M, Rodriguez AH, Martin-Loeches I. Endothelial Damage and the Microcirculation in Critical Illness. Biomedicines 2022; 10:biomedicines10123150. [PMID: 36551905 PMCID: PMC9776078 DOI: 10.3390/biomedicines10123150] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 11/22/2022] [Accepted: 11/28/2022] [Indexed: 12/12/2022] Open
Abstract
Endothelial integrity maintains microcirculatory flow and tissue oxygen delivery. The endothelial glycocalyx is involved in cell signalling, coagulation and inflammation. Our ability to treat critically ill and septic patients effectively is determined by understanding the underpinning biological mechanisms. Many mechanisms govern the development of sepsis and many large trials for new treatments have failed to show a benefit. Endothelial dysfunction is possibly one of these biological mechanisms. Glycocalyx damage is measured biochemically. Novel microscopy techniques now mean the glycocalyx can be indirectly visualised, using sidestream dark field imaging. How the clinical visualisation of microcirculation changes relate to biochemical laboratory measurements of glycocalyx damage is not clear. This article reviews the evidence for a relationship between clinically evaluable microcirculation and biological signal of glycocalyx disruption in various diseases in ICU. Microcirculation changes relate to biochemical evidence of glycocalyx damage in some disease states, but results are highly variable. Better understanding and larger studies of this relationship could improve phenotyping and personalised medicine in the future. Damage to the glycocalyx could underpin many critical illness pathologies and having real-time information on the glycocalyx and microcirculation in the future could improve patient stratification, diagnosis and treatment.
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Affiliation(s)
- Rachael Cusack
- Department of Intensive Care Medicine, St. James’s Hospital, James’s Street, D08 NHY1 Dublin, Ireland
- School of Medicine, Trinity College Dublin, College Green, D02 R590 Dublin, Ireland
| | - Marc Leone
- Department of Anaesthesiology and Intensive Care Unit, Hospital Nord, Assistance Publique Hôpitaux de Marseille, Aix Marseille University, 13015 Marseille, France
| | - Alejandro H. Rodriguez
- Intensive Care Unit, Hospital Universitario Joan XXIII, 43005 Tarragona, Spain
- Institut d’Investigació Sanitària Pere Virgil, 43007 Tarragona, Spain
- Departament Medicina I Cirurgia, Universitat Rovira i Virgili, 43003 Tarragona, Spain
- Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Ignacio Martin-Loeches
- Department of Intensive Care Medicine, St. James’s Hospital, James’s Street, D08 NHY1 Dublin, Ireland
- School of Medicine, Trinity College Dublin, College Green, D02 R590 Dublin, Ireland
- Correspondence:
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18
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Magnin M, Oriel J, Combet-curt J, Salama J, Allaouchiche B, Bonnet-Garin JM, Junot S, Pouzot-Nevoret C. Evaluation of the impact of blood donation on tissue perfusion and sublingual microcirculation in dogs: A pilot study. Res Vet Sci 2022; 152:707-716. [DOI: 10.1016/j.rvsc.2022.09.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/13/2022] [Accepted: 09/26/2022] [Indexed: 11/25/2022]
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Praxenthaler J, Kirchner C, Schwier E, Altmann S, Wittmer A, Henzler D, Köhler T. Case report: Early detection of mesenteric ischemia by intravital microscopy in a patient with septic shock. Front Med (Lausanne) 2022; 9:985977. [PMID: 36091703 PMCID: PMC9458872 DOI: 10.3389/fmed.2022.985977] [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: 07/04/2022] [Accepted: 08/04/2022] [Indexed: 11/17/2022] Open
Abstract
Gut ischemia is a frequent but underdiagnosed complication, especially in critically ill intensive care patients, and represents a special diagnostic challenge that can only be solved in an interdisciplinary manner. We report a case of a 54-year-old woman with acute mesenteric ischemia (AMI) as a cause of septic shock diagnosed by intravital microscopy (IVM) 2 days before visible necrotic changes in a multimodality approach. We show that intravital microscopy can be a serious alternative for the early diagnosis of mesenteric ischemia in the hands of the skilled. We use this case to discuss the value and clinical perspective of IVM in the intensive care setting.
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Affiliation(s)
- Janina Praxenthaler
- Department of Anesthesiology, Surgical Intensive Care, Emergency and Pain Medicine, Klinikum Herford, Ruhr University Bochum, Herford, Germany
- Department of Anesthesiology, Intensive Care and Pain Medicine, Kliniken Südostbayern, Klinikum Traunstein, Traunstein, Germany
| | - Carmen Kirchner
- Department of General and Visceral Surgery, Thoracic Surgery and Proctology, Klinikum Herford, Ruhr University Bochum, Herford, Germany
| | - Elke Schwier
- Department of Anesthesiology, Surgical Intensive Care, Emergency and Pain Medicine, Klinikum Herford, Ruhr University Bochum, Herford, Germany
| | - Simon Altmann
- Department of Anesthesiology, Surgical Intensive Care, Emergency and Pain Medicine, Klinikum Herford, Ruhr University Bochum, Herford, Germany
- Department of Anesthesiology, Intensive Care and Pain Medicine, Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Bochum, Germany
| | - Axel Wittmer
- Institute of Pathology, Klinikum Herford, Herford, Germany
| | - Dietrich Henzler
- Department of Anesthesiology, Surgical Intensive Care, Emergency and Pain Medicine, Klinikum Herford, Ruhr University Bochum, Herford, Germany
| | - Thomas Köhler
- Department of Anesthesiology, Surgical Intensive Care, Emergency and Pain Medicine, Klinikum Herford, Ruhr University Bochum, Herford, Germany
- Department of Anesthesiology and Intensive Care Medicine, AMEOS-Klinikum Halberstadt, Halberstadt, Germany
- *Correspondence: Thomas Köhler,
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Chalkias A, Xenos M. Relationship of Effective Circulating Volume with Sublingual Red Blood Cell Velocity and Microvessel Pressure Difference: A Clinical Investigation and Computational Fluid Dynamics Modeling. J Clin Med 2022; 11:jcm11164885. [PMID: 36013124 PMCID: PMC9410298 DOI: 10.3390/jcm11164885] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 08/12/2022] [Accepted: 08/18/2022] [Indexed: 11/18/2022] Open
Abstract
The characteristics of physiologic hemodynamic coherence are not well-investigated. We examined the physiological relationship between circulating blood volume, sublingual microcirculatory perfusion, and tissue oxygenation in anesthetized individuals with steady-state physiology. We assessed the correlation of mean circulatory filling pressure analogue (Pmca) with sublingual microcirculatory perfusion and red blood cell (RBC) velocity using SDF+ imaging and a modified optical flow-based algorithm. We also reconstructed the 2D microvessels and applied computational fluid dynamics (CFD) to evaluate the correlation of Pmca and RBC velocity with the obtained pressure and velocity fields in microvessels from CFD (pressure difference, (Δp)). Twenty adults with a median age of 39.5 years (IQR 35.5−44.5) were included in the study. Sublingual velocity distributions were similar and followed a log-normal distribution. A constant Pmca value of 14 mmHg was observed in all individuals with sublingual RBC velocity 6−24 μm s−1, while a Pmca < 14 mmHg was observed in those with RBC velocity > 24 μm s−1. When Pmca ranged between 11 mmHg and 15 mmHg, Δp fluctuated between 0.02 Pa and 0.1 Pa. In conclusion, the intact regulatory mechanisms maintain a physiological coupling between systemic hemodynamics, sublingual microcirculatory perfusion, and tissue oxygenation when Pmca is 14 mmHg.
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Affiliation(s)
- Athanasios Chalkias
- Department of Anesthesiology, Faculty of Medicine, University of Thessaly, 41500 Larisa, Greece
- Outcomes Research Consortium, Cleveland, OH 44195, USA
- Committee on Shock, Hellenic Society of Cardiopulmonary Resuscitation, 10434 Athens, Greece
- Correspondence:
| | - Michalis Xenos
- Section of Applied and Computational Mathematics, Department of Mathematics, University of Ioannina, 45110 Ioannina, Greece
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Chiscano-Camón L, Plata-Menchaca E, Ruiz-Rodríguez JC, Ferrer R. Fisiopatología del shock séptico. Med Intensiva 2022. [DOI: 10.1016/j.medin.2022.03.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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22
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Chiscano-Camón L, Plata-Menchaca E, Ruiz-Rodríguez JC, Ferrer R. [Pathophysiology of septic shock]. Med Intensiva 2022; 46 Suppl 1:1-13. [PMID: 38341256 DOI: 10.1016/j.medine.2022.03.010] [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: 02/01/2022] [Accepted: 03/20/2022] [Indexed: 02/12/2024]
Abstract
Sepsis and septic shock result from an inadequate host response to an infection, which causes organ dysfunction. The progression of this condition is manifested by the occurrence of successive clinical stages, resulting from the systemic inflammatory response secondary to the activation of different inflammatory mediators, leading to organ dysfunction. There is a high burden of evidence on the role of endotoxin in the pathogenesis of sepsis and its crucial role in triggering the inflammatory response in sepsis caused by gram-negative bacteria. The coagulation cascade activation in sepsis patients is part of the host's adaptive immune response to infection. The endothelium is the main target in sepsis, which is metabolically active and can.
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Affiliation(s)
- Luis Chiscano-Camón
- Servicio de Medicina Intensiva, Hospital Universitario Vall d'Hebron, Barcelona, España; Grupo de Investigación Sepsis Organ Dysfunction and Resuscitation (SODIR), Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, España; Departament de Medicina. Universitat Autònoma de Barcelona. Barcelona. España
| | - Erika Plata-Menchaca
- Servicio de Medicina Intensiva, Hospital Universitario Vall d'Hebron, Barcelona, España; Grupo de Investigación Sepsis Organ Dysfunction and Resuscitation (SODIR), Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, España
| | - Juan Carlos Ruiz-Rodríguez
- Servicio de Medicina Intensiva, Hospital Universitario Vall d'Hebron, Barcelona, España; Grupo de Investigación Sepsis Organ Dysfunction and Resuscitation (SODIR), Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, España; Departament de Medicina. Universitat Autònoma de Barcelona. Barcelona. España
| | - Ricard Ferrer
- Servicio de Medicina Intensiva, Hospital Universitario Vall d'Hebron, Barcelona, España; Grupo de Investigación Sepsis Organ Dysfunction and Resuscitation (SODIR), Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, España; Departament de Medicina. Universitat Autònoma de Barcelona. Barcelona. España.
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23
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Mansour C, Chaaya R, Sredensek J, Mocci R, Santangelo B, Allaouchiche B, Bonnet-Garin JMM, Boselli E, Junot SA. Evaluation of the sublingual microcirculation with sidestream dark field video microscopy in horses anesthetized for an elective procedure or intestinal surgery. Am J Vet Res 2021; 82:574-581. [PMID: 34166089 DOI: 10.2460/ajvr.82.7.574] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To compare the sublingual microcirculation between healthy horses anesthetized for elective procedures and horses with colic anesthetized for abdominal surgery and to determine the effect of mean arterial blood pressure (MAP) on the microcirculation. ANIMALS 9 horses in the elective group and 8 horses in the colic group. PROCEDURES Sublingual microcirculation was assessed with sidestream dark field video microscopy. Videos were captured at 3 time points during anesthesia. Recorded microvasculature parameters were De Backer score (DBS), total density of perfused vessels (PVD) and small vessels (PVD-S), total proportion of perfused vessels (PPV) and small vessels (PPV-S), vascular flow index (MFI), and heterogeneity index (HI). Blood pressure during hypotensive (MAP < 60 mm Hg) and normotensive (MAP ≥ 60 mm Hg) episodes was also recorded. RESULTS During normotensive episodes, the elective group had significantly better PPV and PPV-S versus the colic group (median PPV, 76% vs 50%; median PPV-S, 73% vs 51%). In both groups, PPV decreased during anesthesia (elective group, -29%; colic group, -16%) but significantly improved in the elective group 15 minutes before the end of anesthesia (59%). During hypotensive episodes, PVD-S was better preserved in the colic group (11.1 vs 3.8 mm/mm2). No differences were identified for the microcirculatory parameters between normo- and hypotensive episodes in the colic group. CONCLUSIONS AND CLINICAL RELEVANCE Sublingual microcirculation was better preserved in healthy horses anesthetized for elective procedures than in horses with colic anesthetized for abdominal surgery despite resuscitation maneuvers. Results indicated that the macrocirculation and microcirculation in critically ill horses may be independent.
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Affiliation(s)
- Christelle Mansour
- From the APCSe Unit UPSP 2016.A101, VetAgro Sup, University of Lyon, 69280 Marcy-l'Étoile, France
| | - Rana Chaaya
- From the Department of Pharmacology, Faculty of Agronomy and Veterinary Medicine, Lebanese University, Beirut, Lebanon
| | - Jerneja Sredensek
- From the Anesthesia Service at the Veterinary Campus of Lyon, VetAgro Sup, University of Lyon, 69280 Marcy-l'Étoile, France
| | - Rita Mocci
- From the Anesthesia Service at the Veterinary Campus of Lyon, VetAgro Sup, University of Lyon, 69280 Marcy-l'Étoile, France
| | - Bruna Santangelo
- From the Anesthesia Service at the Veterinary Campus of Lyon, VetAgro Sup, University of Lyon, 69280 Marcy-l'Étoile, France
| | - Bernard Allaouchiche
- From the APCSe Unit UPSP 2016.A101, VetAgro Sup, University of Lyon, 69280 Marcy-l'Étoile, France
- From the Lyon University Hospital Center, ICU, 69310 Pierre-Bénite, France
| | | | - Emmanuel Boselli
- From the APCSe Unit UPSP 2016.A101, VetAgro Sup, University of Lyon, 69280 Marcy-l'Étoile, France
- From the Department of Anesthesia, Hospital Center Pierre Oudot, 38300 Bourgoin-Jallieu, France
| | - Stéphane A Junot
- From the APCSe Unit UPSP 2016.A101, VetAgro Sup, University of Lyon, 69280 Marcy-l'Étoile, France
- From the Anesthesia Service at the Veterinary Campus of Lyon, VetAgro Sup, University of Lyon, 69280 Marcy-l'Étoile, France
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Unfractionated Heparin Improves the Intestinal Microcirculation in a Canine Septic Shock Model. Mediators Inflamm 2021; 2021:9985397. [PMID: 34257522 PMCID: PMC8245220 DOI: 10.1155/2021/9985397] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Accepted: 05/21/2021] [Indexed: 12/29/2022] Open
Abstract
Background Alterations of microcirculation are associated with organ hypoperfusion and high mortality in septic shock. This study is aimed at investigating the effects of unfractionated heparin (UFH) on intestinal microcirculatory perfusion and systemic circulation in a septic shock model. Methods Twenty-four beagle dogs were randomly allocated into four groups: (a) sham group: healthy controls, (b) shock group: septic shock induced by Escherichia coli, (c) basic therapy group: septic shock animals treated with antibiotics and 10 ml/kg/h saline, and (d) heparin group: septic shock animals treated with basic therapy plus UFH. Hemodynamic variables were measured within 24 h after E. coli administration. The intestinal microcirculation was simultaneously investigated with a sidestream dark-field imaging technique. Additionally, the function of vital organs was evaluated at 12 h postadministration (T12). Results E. coli induced a progressive septic shock in which the mean arterial pressure (MAP) decreased and lactate levels sharply increased, accompanied by deteriorated microvessel perfusion. While basic therapy partially improved the microvascular flow index and the perfused microvessel density in the jejunal villi, UFH significantly restored major microcirculation variables at T12. Physiological variables, including MAP, urine output, and lactate levels, were improved by UFH, whereas some hemodynamic indices were not affected by UFH. With respect to organ function, UFH increased the platelet count and decreased the creatinine level. Conclusions UFH improves microcirculatory perfusion of the small intestine independently of the changes in systemic hemodynamic variables in a canine model of septic shock, thereby improving coagulation and renal function.
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Effect of mean arterial pressure change by norepinephrine on peripheral perfusion index in septic shock patients after early resuscitation. Chin Med J (Engl) 2021; 133:2146-2152. [PMID: 32842018 PMCID: PMC7508439 DOI: 10.1097/cm9.0000000000001017] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background The peripheral perfusion index (PI), as a real-time bedside indicator of peripheral tissue perfusion, may be useful for determining mean arterial pressure (MAP) after early resuscitation of septic shock patients. The aim of this study was to explore the response of PI to norepinephrine (NE)-induced changes in MAP. Methods Twenty septic shock patients with pulse-induced contour cardiac output catheter, who had usual MAP under NE infusion after early resuscitation, were enrolled in this prospective, open-label study. Three MAP levels (usual MAP −10 mmHg, usual MAP, and usual MAP +10 mmHg) were obtained by NE titration, and the corresponding global hemodynamic parameters and PI were recorded. The general linear model with repeated measures was used for analysis of variance of related parameters at three MAP levels. Results With increasing NE infusion, significant changes were found in MAP (F = 502.46, P < 0.001) and central venous pressure (F = 27.45, P < 0.001) during NE titration. However, there was not a significant and consistent change in continuous cardiac output (CO) (F = 0.41, P = 0.720) and PI (F = 0.73, P = 0.482) at different MAP levels. Of the 20 patients enrolled, seven reached the maximum PI value at usual MAP −10 mmHg, three reached the maximum PI value at usual MAP, and ten reached the maximum PI value at usual MAP +10 mmHg. The change in PI was not significantly correlated with the change in CO (r = 0.260, P = 0.269) from usual MAP −10 mmHg to usual MAP. There was also no significant correlation between the change in PI and change in CO (r = 0.084, P = 0.726) from usual MAP to usual MAP +10 mmHg. Conclusions Differing MAP levels by NE infusion induced diverse PI responses in septic shock patients, and these PI responses may be independent of the change in CO. PI may have potential applications for MAP optimization based on changes in peripheral tissue perfusion.
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Cooper ES, Silverstein DC. Fluid Therapy and the Microcirculation in Health and Critical Illness. Front Vet Sci 2021; 8:625708. [PMID: 34055944 PMCID: PMC8155248 DOI: 10.3389/fvets.2021.625708] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Accepted: 04/06/2021] [Indexed: 12/15/2022] Open
Abstract
Fluid selection and administration during shock is typically guided by consideration of macrovascular abnormalities and resuscitative targets (perfusion parameters, heart rate, blood pressure, cardiac output). However, the microcirculatory unit (comprised of arterioles, true capillaries, and venules) is vital for the effective delivery of oxygen and nutrients to cells and removal of waste products from the tissue beds. Given that the microcirculation is subject to both systemic and local control, there is potential for functional changes and impacts on tissue perfusion that are not reflected by macrocirculatory parameters. This chapter will present an overview of the structure, function and regulation of the microcirculation and endothelial surface layer in health and shock states such as trauma, hemorrhage and sepsis. This will set the stage for consideration of how these microcirculatory characteristics, and the potential disconnect between micro- and macrovascular perfusion, may affect decisions related to acute fluid therapy (fluid type, amount, and rate) and monitoring of resuscitative efforts. Available evidence for the impact of various fluids and resuscitative strategies on the microcirculation will also be reviewed.
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Affiliation(s)
- Edward S Cooper
- Department of Veterinary Clinical Sciences, Ohio State University College of Veterinary Medicine, Columbus, OH, United States
| | - Deborah C Silverstein
- Department of Clinical Studies and Advanced Medicine, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, United States
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27
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Behem CR, Graessler MF, Friedheim T, Kluttig R, Pinnschmidt HO, Duprée A, Debus ES, Reuter DA, Wipper SH, Trepte CJC. The use of pulse pressure variation for predicting impairment of microcirculatory blood flow. Sci Rep 2021; 11:9215. [PMID: 33911116 PMCID: PMC8080713 DOI: 10.1038/s41598-021-88458-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 04/12/2021] [Indexed: 02/07/2023] Open
Abstract
Dynamic parameters of preload have been widely recommended to guide fluid therapy based on the principle of fluid responsiveness and with regard to cardiac output. An equally important aspect is however to also avoid volume-overload. This accounts particularly when capillary leakage is present and volume-overload will promote impairment of microcirculatory blood flow. The aim of this study was to evaluate, whether an impairment of intestinal microcirculation caused by volume-load potentially can be predicted using pulse pressure variation in an experimental model of ischemia/reperfusion injury. The study was designed as a prospective explorative large animal pilot study. The study was performed in 8 anesthetized domestic pigs (German landrace). Ischemia/reperfusion was induced during aortic surgery. 6 h after ischemia/reperfusion-injury measurements were performed during 4 consecutive volume-loading-steps, each consisting of 6 ml kg−1 bodyweight−1. Mean microcirculatory blood flow (mean Flux) of the ileum was measured using direct laser-speckle-contrast-imaging. Receiver operating characteristic analysis was performed to determine the ability of pulse pressure variation to predict a decrease in microcirculation. A reduction of ≥ 10% mean Flux was considered a relevant decrease. After ischemia–reperfusion, volume-loading-steps led to a significant increase of cardiac output as well as mean arterial pressure, while pulse pressure variation and mean Flux were significantly reduced (Pairwise comparison ischemia/reperfusion-injury vs. volume loading step no. 4): cardiac output (l min−1) 1.68 (1.02–2.35) versus 2.84 (2.15–3.53), p = 0.002, mean arterial pressure (mmHg) 29.89 (21.65–38.12) versus 52.34 (43.55–61.14), p < 0.001, pulse pressure variation (%) 24.84 (17.45–32.22) versus 9.59 (1.68–17.49), p = 0.004, mean Flux (p.u.) 414.95 (295.18–534.72) versus 327.21 (206.95–447.48), p = 0.006. Receiver operating characteristic analysis revealed an area under the curve of 0.88 (CI 95% 0.73–1.00; p value < 0.001) for pulse pressure variation for predicting a decrease of microcirculatory blood flow. The results of our study show that pulse pressure variation does have the potential to predict decreases of intestinal microcirculatory blood flow due to volume-load after ischemia/reperfusion-injury. This should encourage further translational research and might help to prevent microcirculatory impairment due to excessive fluid resuscitation and to guide fluid therapy in the future.
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Affiliation(s)
- Christoph R Behem
- Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
| | - Michael F Graessler
- Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
| | - Till Friedheim
- Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
| | - Rahel Kluttig
- Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
| | - Hans O Pinnschmidt
- Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Anna Duprée
- Department of Visceral- and Thoracic Surgery, Center of Operative Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - E Sebastian Debus
- Department of Vascular Medicine, University Heart and Vascular Center Hamburg GmbH (UHZ), Hamburg, Germany
| | - Daniel A Reuter
- Department of Anesthesiology and Intensive Care Medicine, Rostock University Medical Center, Rostock, Germany
| | - Sabine H Wipper
- University Department for Vascular Surgery, Department of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Constantin J C Trepte
- Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
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Tavy ALM, de Bruin AFJ, Boerma EC, Ince C, Hilty MP, Noordzij PG, Boerma D, van Iterson M. Association between serosal intestinal microcirculation and blood pressure during major abdominal surgery. JOURNAL OF INTENSIVE MEDICINE 2021; 1:59-64. [PMID: 36789277 PMCID: PMC9923946 DOI: 10.1016/j.jointm.2021.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 02/16/2021] [Accepted: 03/13/2021] [Indexed: 10/21/2022]
Abstract
Background In clinical practice, blood pressure is used as a resuscitation goal on a daily basis, with the aim of maintaining adequate perfusion and oxygen delivery to target organs. Compromised perfusion is often indicated as a key factor in the pathophysiology of anastomotic leakage. This study was aimed at assessing the extent to which the microcirculation of the bowel coheres with blood pressure during abdominal surgery. Methods We performed a prospective and observational cohort study. In patients undergoing abdominal surgery, the serosal microcirculation of either the small intestine or the colon was visualized using handheld vital microscopy (HVM). From the acquired HVM image sequences, red blood cell velocity (RBCv) and total vessel density (TVD) were calculated using MicroTools and AVA software, respectively. The association between microcirculatory parameters and blood pressure was assessed using Pearson's correlation analysis. We considered a two-sided P-value of <0.050 to be significant. Results In 28 patients undergoing abdominal surgery, a total of 76 HVM images were analyzed. The RBCv was 335 ± 96 µm/s and the TVD was 13.7 ± 3.4 mm/mm2. Mean arterial pressure (MAP) was 71 ± 12 mm Hg during microcirculatory imaging. MAP was not correlated with RBCv (Pearson's r = -0.049, P = 0.800) or TVD (Pearson's r = 0.310, P = 0.110). Conclusion In 28 patients undergoing abdominal surgery, we found no association between serosal intestinal microcirculatory parameters and blood pressure.
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Affiliation(s)
- Arthur LM Tavy
- Department of Anesthesiology, Intensive Care and Pain Medicine, St. Antonius Hospital, Nieuwegein 3435 CM, the Netherlands,Corresponding author: Arthur LM Tavy, Department of Anesthesiology, Intensive Care and Pain Medicine, St. Antonius Hospital, Postbus 2500, Nieuwegein 3430 EM, Netherlands.
| | - Anton FJ de Bruin
- Department of Anesthesiology, Intensive Care and Pain Medicine, St. Antonius Hospital, Nieuwegein 3435 CM, the Netherlands
| | - E Christiaan Boerma
- Department of Intensive Care, Medical Center Leeuwarden, Leeuwarden 8934 AD, the Netherlands
| | - Can Ince
- Department of Intensive Care Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3015 GD, the Netherlands
| | - Matthias P Hilty
- Institute of Intensive Care Medicine, University Hospital of Zurich, Zürich 8006, Switzerland
| | - Peter G Noordzij
- Department of Anesthesiology, Intensive Care and Pain Medicine, St. Antonius Hospital, Nieuwegein 3435 CM, the Netherlands
| | - Djamila Boerma
- Department of Surgery, St. Antonius Hospital, Nieuwegein 3435 CM, the Netherlands
| | - Mat van Iterson
- Department of Anesthesiology, Intensive Care and Pain Medicine, St. Antonius Hospital, Nieuwegein 3435 CM, the Netherlands
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Abstract
PURPOSE OF REVIEW The aim of this study was to discuss the implication of microvascular dysfunction in septic shock. RECENT FINDINGS Resuscitation of sepsis has focused on systemic haemodynamics and, more recently, on peripheral perfusion indices. However, central microvascular perfusion is altered in sepsis and these alterations often persist despite normalization of various macro haemodynamic resuscitative goals. Endothelial dysfunction is a key element in sepsis pathophysiology. It is responsible for the sepsis-induced hypotension. In addition, endothelial dysfunction is also implicated involved in the activation of inflammation and coagulation processes leading to amplification of the septic response and development of organ dysfunction. It also promotes an increase in permeability, mostly at venular side, and impairs microvascular perfusion and hence tissue oxygenation.Microvascular alterations are characterized by heterogeneity in blood flow distribution, with adequately perfused areas in close vicinity to not perfused areas, thus characterizing the distributive nature of septic shock. Such microvascular alterations have profound implications, as these are associated with organ dysfunction and unfavourable outcomes. Also, the response to therapy is highly variable and cannot be predicted by systemic hemodynamic assessment and hence cannot be detected by classical haemodynamic tools. SUMMARY Microcirculation is a key element in the pathophysiology of sepsis. Even if microcirculation-targeted therapy is not yet ready for the prime time, understanding the processes implicated in microvascular dysfunction is important to prevent chasing systemic hemodynamic variables when this does not contribute to improve tissue perfusion.
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Khanna AK, Karamchandani K. Macrocirculation and Microcirculation: The "Batman and Superman" Story of Critical Care Resuscitation. Anesth Analg 2021; 132:280-283. [PMID: 33177325 DOI: 10.1213/ane.0000000000005272] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Ashish K Khanna
- From the Department of Anesthesiology, Section on Critical Care Medicine, Wake Forest School of Medicine, Wake Forest Baptist Health Network, Winston-Salem, North Carolina.,Outcomes Research Consortium, Cleveland, Ohio
| | - Kunal Karamchandani
- Department of Anesthesiology & Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania
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Dubin A, Kanoore Edul VS, Caminos Eguillor JF, Ferrara G. Monitoring Microcirculation: Utility and Barriers - A Point-of-View Review. Vasc Health Risk Manag 2020; 16:577-589. [PMID: 33408477 PMCID: PMC7780856 DOI: 10.2147/vhrm.s242635] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 11/27/2020] [Indexed: 12/22/2022] Open
Abstract
Microcirculation is a particular organ of the cardiovascular system. The goal of this narrative review is a critical reappraisal of the present knowledge of microcirculation monitoring, mainly focused on the videomicroscopic evaluation of sublingual microcirculation in critically ill patients. We discuss the technological developments in handheld videomicroscopy, which have resulted in adequate tools for the bedside monitoring of microcirculation. By means of these techniques, a large body of evidence has been acquired about the role of microcirculation in the pathophysiological mechanisms of shock, especially septic shock. We review the characteristics of sublingual microcirculation in septic shock, which mainly consist in a decrease in the perfused vascular density secondary to a reduction in the proportion of perfused vessels along with a high heterogeneity in perfusion. Even in patients with high cardiac output, red blood cell velocity is decreased. Thus, hyperdynamic flow is absent in the septic microcirculation. We also discuss the dissociation between microcirculation and systemic hemodynamics, particularly after shock resuscitation, and the different behavior among microvascular beds. In addition, we briefly comment the effects of some treatments on microcirculation. Despite the fact that sublingual microcirculation arises as a valuable goal for the resuscitation in critically ill patients, significant barriers remain present for its clinical application. Most of them are related to difficulties in video acquisition and analysis. We comprehensively analyzed these shortcomings. Unfortunately, a simpler approach, such as the central venous minus arterial PCO2 difference, is a misleading surrogate for sublingual microcirculation. As conclusion, the monitoring of sublingual microcirculation is an appealing method for monitoring critically ill patients. Nevertheless, the lack of controlled studies showing benefits in terms of outcome, as well as technical limitations for its clinical implementation, render this technique mainly as a research tool.
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Affiliation(s)
- Arnaldo Dubin
- Cátedra de Farmacología Aplicada, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina
| | | | | | - Gonzalo Ferrara
- Cátedra de Farmacología Aplicada, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina
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Exposure to acute normobaric hypoxia results in adaptions of both the macro- and microcirculatory system. Sci Rep 2020; 10:20938. [PMID: 33262355 PMCID: PMC7708486 DOI: 10.1038/s41598-020-77724-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 10/14/2020] [Indexed: 12/19/2022] Open
Abstract
Although acute hypoxia is of utmost pathophysiologic relevance in health and disease, studies on its effects on both the macro- and microcirculation are scarce. Herein, we provide a comprehensive analysis of the effects of acute normobaric hypoxia on human macro- and microcirculation. 20 healthy participants were enrolled in this study. Hypoxia was induced in a normobaric hypoxia chamber by decreasing the partial pressure of oxygen in inhaled air stepwisely (pO2; 21.25 kPa (0 k), 16.42 kPa (2 k), 12.63 kPa (4 k) and 9.64 kPa (6 k)). Macrocirculatory effects were assessed by cardiac output measurements, microcirculatory changes were investigated by sidestream dark-field imaging in the sublingual capillary bed and videocapillaroscopy at the nailfold. Exposure to hypoxia resulted in a decrease of systemic vascular resistance (p < 0.0001) and diastolic blood pressure (p = 0.014). Concomitantly, we observed an increase in heart rate (p < 0.0001) and an increase of cardiac output (p < 0.0001). In the sublingual microcirculation, exposure to hypoxia resulted in an increase of total vessel density, proportion of perfused vessels and perfused vessel density. Furthermore, we observed an increase in peripheral capillary density. Exposure to acute hypoxia results in vasodilatation of resistance arteries, as well as recruitment of microvessels of the central and peripheral microcirculation. The observed macro- and microcirculatory effects are most likely a result from compensatory mechanisms to ensure adequate tissue oxygenation.
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Abstract
PURPOSE OF REVIEW Currently, the treatment of patients with shock is focused on the clinical symptoms of shock. In the early phase, this is usually limited to heart rate, blood pressure, lactate levels and urine output. However, as the ultimate goal of resuscitation is the improvement in microcirculatory perfusion the question is whether these currently used signs of shock and the improvement in these signs actually correspond to the changes in the microcirculation. RECENT FINDINGS Recent studies have shown that during the development of shock the deterioration in the macrocirculatory parameters are followed by the deterioration of microcirculatory perfusion. However, in many cases the restoration of adequate macrocirculatory parameters is frequently not associated with improvement in microcirculatory perfusion. This relates not only to the cause of shock, where there are some differences between different forms of shock, but also to the type of treatment. SUMMARY The improvement in macrohemodynamics during the resuscitation is not consistently followed by subsequent changes in the microcirculation. This may result in both over-resuscitation and under-resuscitation leading to increased morbidity and mortality. In this article the principles of coherence and the monitoring of the microcirculation are reviewed.
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Dickson K, Malitan H, Lehmann C. Imaging of the Intestinal Microcirculation during Acute and Chronic Inflammation. BIOLOGY 2020; 9:E418. [PMID: 33255906 PMCID: PMC7760140 DOI: 10.3390/biology9120418] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 11/18/2020] [Indexed: 12/12/2022]
Abstract
Because of its unique microvascular anatomy, the intestine is particularly vulnerable to microcirculatory disturbances. During inflammation, pathological changes in blood flow, vessel integrity and capillary density result in impaired tissue oxygenation. In severe cases, these changes can progress to multiorgan failure and possibly death. Microcirculation may be evaluated in superficial tissues in patients using video microscopy devices, but these techniques do not allow the assessment of intestinal microcirculation. The gold standard for the experimental evaluation of intestinal microcirculation is intravital microscopy, a technique that allows for the in vivo examination of many pathophysiological processes including leukocyte-endothelial interactions and capillary blood flow. This review provides an overview of changes in the intestinal microcirculation in various acute and chronic inflammatory conditions. Acute conditions discussed include local infections, severe acute pancreatitis, necrotizing enterocolitis and sepsis. Inflammatory bowel disease and irritable bowel syndrome are included as examples of chronic conditions of the intestine.
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Affiliation(s)
- Kayle Dickson
- Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada;
| | - Hajer Malitan
- Department of Anesthesia, Pain and Perioperative Management, Dalhousie University, Halifax, NS B3H 4R2, Canada;
| | - Christian Lehmann
- Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada;
- Department of Anesthesia, Pain and Perioperative Management, Dalhousie University, Halifax, NS B3H 4R2, Canada;
- Department of Physiology and Biophysics, Dalhousie University, Halifax, NS B3H 4R2, Canada
- Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada
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Bársony A, Vida N, Gajda Á, Rutai A, Mohácsi Á, Szabó A, Boros M, Varga G, Érces D. Methane Exhalation Can Monitor the Microcirculatory Changes of the Intestinal Mucosa in a Large Animal Model of Hemorrhage and Fluid Resuscitation. Front Med (Lausanne) 2020; 7:567260. [PMID: 33195312 PMCID: PMC7642453 DOI: 10.3389/fmed.2020.567260] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 09/11/2020] [Indexed: 12/02/2022] Open
Abstract
Background: Internal hemorrhage is a medical emergency, which requires immediate causal therapy, but the recognition may be difficult. The reactive changes of the mesenteric circulation may be part of the earliest hemodynamic responses to bleeding. Methane is present in the luminal atmosphere; thus, we hypothesized that it can track the intestinal circulatory changes, induced by hemorrhage, non-invasively. Our goal was to validate and compare the sensitivity of this method with an established technique using sublingual microcirculatory monitoring in a large animal model of controlled, graded hemorrhage and the early phase of following fluid resuscitation. Materials and Methods: The experiments were performed on anesthetized, ventilated Vietnamese minipigs (approval number: V/148/2013; n = 6). The animals were gradually bled seven times consecutively of 5% of their estimated blood volume (BV) each, followed by gradual fluid resuscitation with colloid (hydroxyethyl starch; 5% of the estimated BV/dose) until 80 mmHg mean arterial pressure was achieved. After each step, macrohemodynamic parameters were recorded, and exhaled methane level was monitored continuously with a custom-built photoacoustic laser-spectroscopy unit. The microcirculation of the sublingual area, ileal serosa, and mucosa was examined by intravital videomicroscopy (Cytocam-IDF, Braedius). Results: Mesenteric perfusion was significantly reduced by a 5% blood loss, whereas microperfusion in the oral cavity deteriorated after a 25% loss. A statistically significant correlation was found between exhaled methane levels, superior mesenteric artery flow (r = 0.93), or microcirculatory changes in the ileal serosa (ρ = 0.78) and mucosa (r = 0.77). After resuscitation, the ileal mucosal microcirculation increased rapidly [De Backer score (DBS): 2.36 ± 0.42 vs. 8.6 ± 2.1 mm−1], whereas serosal perfusion changed gradually and with a lower amplitude (DBS: 2.51 ± 0.48 vs. 5.73 ± 0.75). Sublingual perfusion correlated with mucosal (r = 0.74) and serosal (r = 0.66) mesenteric microperfusion during the hemorrhage phase but not during the resuscitation phase. Conclusion: Detection of exhaled methane levels is of diagnostic significance during experimental hemorrhage as it indicates blood loss earlier than sublingual microcirculatory changes and in the early phase of fluid resuscitation, the exhaled methane values change in association with the mesenteric perfusion and the microcirculation of the ileum.
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Affiliation(s)
- Anett Bársony
- Department of Surgery, University of Szeged, Szeged, Hungary
| | - Noémi Vida
- Institute of Surgical Research, University of Szeged, Szeged, Hungary
| | - Ámos Gajda
- Institute of Surgical Research, University of Szeged, Szeged, Hungary
| | - Attila Rutai
- Institute of Surgical Research, University of Szeged, Szeged, Hungary
| | - Árpád Mohácsi
- MTA-SZTE Research Group on Photoacoustic Spectroscopy, Szeged, Hungary
| | - Anna Szabó
- Department of Optics and Quantum Electronics, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary
| | - Mihály Boros
- Institute of Surgical Research, University of Szeged, Szeged, Hungary
| | - Gabriella Varga
- Institute of Surgical Research, University of Szeged, Szeged, Hungary
| | - Dániel Érces
- Institute of Surgical Research, University of Szeged, Szeged, Hungary
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Jiang Z, Ren J, Hong Z, Ren H, Wang G, Gu G, Liu Y. Deresuscitation in Patients with Abdominal Sepsis Carries a Lower Mortality Rate and Less Organ Dysfunction than Conservative Fluid Management. Surg Infect (Larchmt) 2020; 22:340-346. [PMID: 32746772 DOI: 10.1089/sur.2019.370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Background: The relation between deresuscitative fluid management after the resuscitation phase and clinical outcome in patients with abdominal sepsis is not completely clear. The aim of this study was to assess the contribution of deresuscitative management to death and organ dysfunction in abdominal sepsis. Methods: Consecutive patients with abdominal sepsis requiring fluid resuscitation were included in this study. According to the fluid management given in the later stage of resuscitation, a conservative group and a deresuscitative fluid management group were compared. The primary outcome was in-hospital death, whereas secondary outcomes were categorized as organ dysfunction and other adverse events. Results: A total of 138 patients were enrolled in this study. Conservative fluid management was given to 47.8% of patients, whereas deresuscitative fluid management occurred in 52.2%. The deresuscitative strategy was associated with a markedly lower prevalence of new-onset acute kidney injury and a decrease in the duration of continuous renal replacement therapy (CRRT). There was a greater risk of needing new-onset intubation and the mechanical ventilation duration in the conservative group than in the deresuscitative group. However, the deresuscitative group did not differ from the conservative group with respect to open abdomen and intra-abdominal hypertension or new-onset abdominal compartment syndrome. The conservative treatment was associated with prolonged stays as well as a higher in-hospital mortality rate. A multivariable logistic regression model showed that deresuscitative fluid management imparts a protective effect against in-hospital death (odds ratio 4.343; 95% confidence interva1 1.466-12.866; p = 0.008), whereas septic shock, source control failure, and CRRT duration were associated with a higher mortality rate. Conclusions: Fluid balance achieved using deresuscitative treatment is correlated with better outcomes in patients with abdominal sepsis, indicating that this treatment may be useful as a therapeutic strategy.
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Affiliation(s)
- Zhizhao Jiang
- Department of General Surgery, Jinling Hospital, Nanjing Medical University, Nanjing, People's Republic of China.,Department of Intensive Care Unit, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, People's Republic of China
| | - Jianan Ren
- Department of General Surgery, Jinling Hospital, Nanjing Medical University, Nanjing, People's Republic of China.,Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Zhiwu Hong
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Huajian Ren
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Gefei Wang
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Guosheng Gu
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, People's Republic of China
| | - Yuqi Liu
- Department of Intensive Care Unit, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, People's Republic of China
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Abstract
PURPOSE OF REVIEW The present review discusses the current role of microcirculatory assessment in the hemodynamic monitoring of critically ill patients. RECENT FINDINGS Videomicroscopic techniques have demonstrated that microvascular perfusion is altered in critically ill patients, and especially in sepsis. These alterations are associated with organ dysfunction and poor outcome. Handheld microscopes can easily be applied on the sublingual area of critically ill patients. Among the specific limitations of these techniques, the most important is that these can mostly investigate the sublingual microcirculation. The representativity of the sublingual area may be questioned, especially as some areas may sometimes be more affected than the sublingual area. Also, evaluation of the sublingual area may be difficult in nonintubated hypoxemic patients. Alternative techniques include vasoreactivity tests using either transient occlusion or performing a thermal challenge. These techniques evaluate the maximal dilatory properties of the microcirculation but do not really evaluate the actual microvascular perfusion. Focusing on the glycocalyx may be another option, especially with biomarkers of glycocalyx degradation and shedding. Evaluation of the glycocalyx is still largely experimental, with different tools still in investigation and lack of therapeutic target. Venoarterial differences in PCO2 are inversely related with microvascular perfusion, and can thus be used as surrogate for microcirculation assessment. Several limitations prevent the regular use in clinical practice. The first is the difficult use of some of these techniques outside research teams, whereas nurse-driven measurements are probably desired. The second important limitation for daily practice use is the lack of uniformly defined endpoint. The final limitation is that therapeutic interventions affecting the microcirculation are not straightforward. SUMMARY Clinical and biological surrogates of microcirculatory assessment can be used at bedside. The role of microvideoscopic techniques is still hampered by the lack of clearly defined targets as well as interventions specifically targeting the microcirculation.
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Gazmuri RJ, de Gomez CA. From a pressure-guided to a perfusion-centered resuscitation strategy in septic shock: Critical literature review and illustrative case. J Crit Care 2020; 56:294-304. [PMID: 31926637 DOI: 10.1016/j.jcrc.2019.11.008] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Revised: 07/28/2019] [Accepted: 11/13/2019] [Indexed: 01/15/2023]
Abstract
PURPOSE To support a paradigm shift in the management of septic shock from pressure-guided to perfusion-centered, expected to improve outcome while reducing adverse effects from vasopressor therapy and aggressive fluid resuscitation. MATERIAL AND METHODS Critical review of the literature cited in support of vasopressor use to achieve a predefined mean arterial pressure (MAP) of 65 mmHg and review of pertinent clinical trials and studies enabling deeper understanding of the hemodynamic pathophysiology supportive of a perfusion-centered approach, accompanied by an illustrative case. RESULTS Review of the literature cited by the Surviving Sepsis Campaign revealed lack of controlled clinical trials supporting outcome benefits from vasopressors. Additional literature review revealed adverse effects associated with vasopressors and worsened outcome in some studies. Vasopressors increase MAP primarily by peripheral vasoconstriction and in occasions by a modest increase in cardiac output when using norepinephrine. Thus, achieving the recommended MAP of 65 mmHg using vasopressors should not be presumed indicative that organ perfusion has been restored. It may instead create a false sense of hemodynamic stability hampering shock resolution. CONCLUSIONS We propose focusing the hemodynamic management of septic shock on reversing organ hypoperfusion instead of attaining a predefined MAP target as the key strategy for improving outcome.
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Affiliation(s)
- Raúl J Gazmuri
- Medicine, Physiology & Biophysics, Resuscitation Institute at Rosalind Franklin University of Medicine and Science, Critical Care Medicine and ICU, Captain James A. Lovell Federal Health Care Center, USA.
| | - Cristina Añez de Gomez
- Internal Medicine Physician, Northwestern Medical Group, Northwestern Medicine Lake Forrest Hospital, USA
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Monitoring tissue perfusion: a pilot clinical feasibility and safety study of a urethral photoplethysmography-derived perfusion device in high-risk patients. J Clin Monit Comput 2019; 34:961-969. [DOI: 10.1007/s10877-019-00414-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 10/25/2019] [Indexed: 10/25/2022]
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Untreated Relative Hypotension Measured as Perfusion Pressure Deficit During Management of Shock and New-Onset Acute Kidney Injury-A Literature Review. Shock 2019; 49:497-507. [PMID: 29040214 DOI: 10.1097/shk.0000000000001033] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Maintaining an optimal blood pressure (BP) during shock is a fundamental tenet of critical care. Optimal BP targets may be different for different patients. In current practice, too often, uniform BP targets are pursued which may result in inadvertently accepting a degree of untreated relative hypotension, i.e., the deficit between patients' usual premorbid basal BP and the achieved BP, during vasopressor support. Relative hypotension is a common but an under-recognized and an under-treated sign among patients with potential shock state. From a physiological perspective, any relative reduction in the net perfusion pressure across an organ (e.g., renal) vasculature has a potential to overwhelm autoregulatory mechanisms, which are already under stress during shock. Such perfusion pressure deficit may consequently impact organs' ability to function or recover from an injured state. This review discusses such pathophysiologic mechanisms in detail with a particular focus on the risk of new-onset acute kidney injury (AKI). To review current literature, databases of Medline, Embase, and Google scholar were searched to retrieve articles that either adjusted BP targets based on patients' premorbid BP levels or considered relative hypotension as an exposure endpoint and assessed its association with clinical outcomes among acutely ill patients. There were no randomized controlled trials. Only seven studies could be identified and these were reviewed in detail. These studies indicated a significant association between the degree of relative hypotension that was inadvertently accepted in real-world practice and new-onset organ dysfunction or subsequent AKI. However, this is not a high-quality evidence. Therefore, well-designed randomized controlled trials are needed to evaluate whether adoption of individualized BP targets, which are initially guided by patient's premorbid basal BP and then tailored according to clinical response, is superior to conventional BP targets for vasopressor therapy, particularly among patients with vasodilatory shock states.
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Collet M, Huot B, Barthélémy R, Damoisel C, Payen D, Mebazaa A, Chousterman BG. Influence of systemic hemodynamics on microcirculation during sepsis. J Crit Care 2019; 52:213-218. [PMID: 31102939 DOI: 10.1016/j.jcrc.2019.05.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Revised: 04/07/2019] [Accepted: 05/01/2019] [Indexed: 01/01/2023]
Abstract
PURPOSE During sepsis, improvement of hemodynamic may not be related to improvement of microcirculation. The aim of this study was to investigate influence of systemic circulation on microcirculation in septic ICU patients. METHODS This is a prospective cohort study of septic ICU patients. Microcirculation was investigated with Near infrared spectrometry (NIRS) measuring tissue oxygen saturation (StO2). StO2 desaturation (desStO2) and resaturation (resStO2) slopes were determined. Analyses were made at baseline and after fluid challenges. RESULTS Seventy-two patients were included. One hundred and sixty measures were performed at baseline. StO2 was 77.8% [72.4-85.0] and resStO2 was 87.3%/min [57.8-141.7]. Univariate analysis showed an association between resStO2 and diastolic arterial pressure (DAP) (p = .001), and norepinephrine dose (p = .033). In multivariate linear regression, there was an association between resStO2 and DAP (β = 1.85 (0.64 to 3.08), p = .004). Fluid challenges (n = 60) increased CO, and resStO2 (all p < .001). In multivariate analysis, variation of stroke volume was associated with variation of resStO2 (p = .004) after fluid challenge. There was no association between CVP and resStO2. CONCLUSIONS DAP was the only independent determinant of resStO2 in septic patients. Fluid challenges may improve microcirculation. CVP did not influence resStO2.
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Affiliation(s)
- Magalie Collet
- Department of Anesthesia, Burn and Critical Care, Saint-Louis-Lariboisière University Hospital, Assistance-Publique Hôpitaux de Paris, Paris, France; Paris Diderot University, Sorbonne Paris Cité, Paris, France
| | - Benjamin Huot
- Department of Anesthesia, Burn and Critical Care, Saint-Louis-Lariboisière University Hospital, Assistance-Publique Hôpitaux de Paris, Paris, France
| | - Romain Barthélémy
- Department of Anesthesia, Burn and Critical Care, Saint-Louis-Lariboisière University Hospital, Assistance-Publique Hôpitaux de Paris, Paris, France
| | - Charles Damoisel
- Department of Anesthesia, Burn and Critical Care, Saint-Louis-Lariboisière University Hospital, Assistance-Publique Hôpitaux de Paris, Paris, France
| | - Didier Payen
- Department of Anesthesia, Burn and Critical Care, Saint-Louis-Lariboisière University Hospital, Assistance-Publique Hôpitaux de Paris, Paris, France; INSERM U1160, Paris, France; Paris Diderot University, Sorbonne Paris Cité, Paris, France
| | - Alexandre Mebazaa
- Department of Anesthesia, Burn and Critical Care, Saint-Louis-Lariboisière University Hospital, Assistance-Publique Hôpitaux de Paris, Paris, France; INSERM U942, Paris, France; Paris Diderot University, Sorbonne Paris Cité, Paris, France
| | - Benjamin G Chousterman
- Department of Anesthesia, Burn and Critical Care, Saint-Louis-Lariboisière University Hospital, Assistance-Publique Hôpitaux de Paris, Paris, France; INSERM U1160, Paris, France; Paris Diderot University, Sorbonne Paris Cité, Paris, France.
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Abstract
PURPOSE OF REVIEW Microcirculatory alterations play a major role in the pathogenesis of shock. Monitoring tissue perfusion might be a relevant goal for shock resuscitation. The goal of this review was to revise the evidence supporting the monitoring of peripheral perfusion and microcirculation as goals of resuscitation. For this purpose, we mainly focused on skin perfusion and sublingual microcirculation. RECENT FINDINGS Although there are controversies about the reproducibility of capillary refill time in monitoring peripheral perfusion, it is a sound physiological variable and suitable for the ICU settings. In addition, observational studies showed its strong ability to predict outcome. Moreover, a preliminary study suggested that it might be a valuable goal for resuscitation. These results should be confirmed by the ongoing ANDROMEDA-SHOCK randomized controlled trial. On the other hand, the monitoring of sublingual microcirculation might also provide relevant physiological and prognostic information. On the contrary, methodological drawbacks mainly related to video assessment hamper its clinical implementation at the present time. SUMMARY Measurements of peripheral perfusion might be useful as goal of resuscitation. The results of the ANDROMEDA-SHOCK will clarify the role of skin perfusion as a guide for the treatment of shock. In contrast, the assessment of sublingual microcirculation mainly remains as a research tool.
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Loggi S, Mininno N, Damiani E, Marini B, Adrario E, Scorcella C, Domizi R, Carsetti A, Pantanetti S, Pagliariccio G, Carbonari L, Donati A. Changes in the sublingual microcirculation following aortic surgery under balanced or total intravenous anaesthesia: a prospective observational study. BMC Anesthesiol 2019; 19:1. [PMID: 30611197 PMCID: PMC6320625 DOI: 10.1186/s12871-018-0673-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Accepted: 12/26/2018] [Indexed: 12/19/2022] Open
Abstract
Background In vascular surgery with aortic cross-clamping, ischemia/reperfusion injury induces systemic haemodynamic and microcirculatory disturbances. Different anaesthetic regimens may have a varying impact on tissue perfusion. The aim of this study was to explore changes in microvascular perfusion in patients undergoing elective open abdominal aortic aneurysm repair under balanced or total intravenous anaesthesia. Methods Prospective observational study. Patients undergoing elective open infrarenal abdominal aortic aneurysm repair received balanced (desflurane + remifentanil, n = 20) or total intravenous anaesthesia (TIVA, propofol + remifentanil using target-controlled infusion, n = 20) according to the clinician’s decision. A goal-directed haemodynamic management was applied in all patients. Measurements were obtained before anaesthesia induction (baseline) and at end-surgery and included haemodynamics, arterial/venous blood gases, sublingual microvascular flow and density (incident dark field illumination imaging), peripheral muscle tissue oxygenation and microcirculatory reactivity (thenar near infrared spectroscopy with a vascular occlusion test). Results The two groups did not differ for baseline characteristics, mean aortic-clamping time and requirement of vasoactive agents during surgery. Changes in mean arterial pressure, systemic vascular resistance index, haemoglobin and blood lactate levels were similar between the two groups, while the cardiac index increased at end-surgery in patients undergoing balanced anaesthesia. The sublingual microcirculation was globally unaltered in the TIVA group at end-surgery, while patients undergoing balanced anaesthesia showed an increase in the total and perfused small vessel densities (from 16.6 ± 4.2 to 19.1 ± 5.4 mm/mm2, p < 0.05). Changes in microvascular density were negatively correlated with changes in the systemic vascular resistance index. The area of reactive hyperaemia during the VOT increased in the balanced anaesthesia group (from 14.8 ± 8.1 to 25.6 ± 14.8%*min, p < 0.05). At end-surgery, the tissue haemoglobin index in the TIVA group was lower than that in the balanced anaesthesia group. Conclusions In patients undergoing elective open abdominal aortic aneurysm repair with a goal-directed hemodynamic management, indices of sublingual or peripheral microvascular perfusion/oxygenation were globally preserved with both balanced anaesthesia and TIVA. Patients undergoing balanced anaesthesia showed microvascular recruitment at end-surgery. Trial registration NCT03510793, https://www.clinicaltrials.gov, date of registration April 27th 2018, retrospectively registered.
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Affiliation(s)
- Silvia Loggi
- Anaesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, via Tronto 10/a, 60126, Torrette di Ancona, Italy
| | - Nicoletta Mininno
- Anaesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, via Tronto 10/a, 60126, Torrette di Ancona, Italy
| | - Elisa Damiani
- Anaesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, via Tronto 10/a, 60126, Torrette di Ancona, Italy
| | - Benedetto Marini
- Anaesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, via Tronto 10/a, 60126, Torrette di Ancona, Italy
| | - Erica Adrario
- Anaesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, via Tronto 10/a, 60126, Torrette di Ancona, Italy
| | - Claudia Scorcella
- Anaesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, via Tronto 10/a, 60126, Torrette di Ancona, Italy
| | - Roberta Domizi
- Anaesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, via Tronto 10/a, 60126, Torrette di Ancona, Italy
| | - Andrea Carsetti
- Anaesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, via Tronto 10/a, 60126, Torrette di Ancona, Italy
| | - Simona Pantanetti
- Anaesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, via Tronto 10/a, 60126, Torrette di Ancona, Italy
| | - Gabriele Pagliariccio
- Unit of Vascular Surgery, Azienda Ospedaliera Universitaria "Ospedali Riuniti Umberto I - Lancisi - Salesi" of Ancona, Ancona, Italy
| | - Luciano Carbonari
- Unit of Vascular Surgery, Azienda Ospedaliera Universitaria "Ospedali Riuniti Umberto I - Lancisi - Salesi" of Ancona, Ancona, Italy
| | - Abele Donati
- Anaesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, via Tronto 10/a, 60126, Torrette di Ancona, Italy.
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Erdem Ö, Ince C, Tibboel D, Kuiper JW. Assessing the Microcirculation With Handheld Vital Microscopy in Critically Ill Neonates and Children: Evolution of the Technique and Its Potential for Critical Care. Front Pediatr 2019; 7:273. [PMID: 31338353 PMCID: PMC6629784 DOI: 10.3389/fped.2019.00273] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Accepted: 06/17/2019] [Indexed: 12/17/2022] Open
Abstract
Assuring adequate tissue oxygenation in the critically ill, but still developing child is challenging. Conventional hemodynamic monitoring techniques fall short in assessing tissue oxygenation as these are directed at the macrocirculation and indirect surrogates of tissue oxygenation. The introduction of handheld vital microscopy (HVM) has allowed for the direct visualization of the microcirculation and with this has offered insight into tissue oxygenation on a microcirculatory level. Since its introduction, technical improvements have been made to HVM, to both hardware and software, and guidelines have been developed through expert consensus on image assessment and analysis. Using HVM, the microcirculation of the skin, the buccal mucosa, and the sublingual mucosa of healthy and (critically) ill neonates and children have been visualized and investigated. Yet, integration of HVM in hemodynamic monitoring has been limited due to technical shortcomings. Only superficial microcirculatory beds can be visualized, inter-observer and intra-observer variabilities are not accounted for and image analysis happens offline and is semi-automated and time-consuming. More importantly, patients need to be cooperative or fully sedated to prevent pressure and movement artifacts, which is often not the case in children. Despite these shortcomings, observational research with HVM in neonates and children has revealed the following: (1) age-related developmental changes in the microcirculation, (2) loss of hemodynamic coherence, i.e., microcirculatory disturbances in the presence of a normal macrocirculation and, (3) microcirculatory disturbances which were independently associated with increased mortality risk. Although these observations underline the importance of microcirculatory monitoring, several steps have to be taken before integration in the decision process during critical care can happen. These steps include technological innovations to ease the use of HVM in the pediatric age group, measuring additional functional parameters of microvascular blood flow and integrated automated analysis software. As a next step, reference values for microcirculatory parameters need to be established, while also accounting for developmental changes. Finally, studies on microcirculatory guided therapies are necessary to assess whether the integration of microcirculatory monitoring will actually improve patient outcome. Nevertheless, HVM remains a promising, non-invasive tool to help physicians assure tissue oxygenation in the critically ill child.
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Affiliation(s)
- Özge Erdem
- Intensive Care and Department of Pediatric Surgery, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, Netherlands
| | - Can Ince
- Department of Intensive Care, Erasmus University Medical Center, Rotterdam, Netherlands.,Department of Translational Physiology, Amsterdam University Medical Center, Amsterdam, Netherlands
| | - Dick Tibboel
- Intensive Care and Department of Pediatric Surgery, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, Netherlands
| | - Jan Willem Kuiper
- Intensive Care and Department of Pediatric Surgery, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, Netherlands
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45
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Marchesi S, Ortiz Nieto F, Ahlgren KM, Roneus A, Feinstein R, Lipcsey M, Larsson A, Ahlström H, Hedenstierna G. Abdominal organ perfusion and inflammation in experimental sepsis: a magnetic resonance imaging study. Am J Physiol Gastrointest Liver Physiol 2019; 316:G187-G196. [PMID: 30335473 DOI: 10.1152/ajpgi.00151.2018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Diffusion-weighted magnetic resonance imaging (DW-MRI) uses water as contrast and enables the study of perfusion in many organs simultaneously in situ. We used DW-MRI in a hypodynamic sepsis model, comparing abdominal organ perfusion with global hemodynamic measurements and inflammation. Sixteen anesthetized piglets were randomized into 3 groups: 2 intervention (sepsis) groups: HighMAP (mean arterial pressure, MAP > 65 mmHg) and LowMAP (MAP between 50 and 60 mmHg), and a Healthy Control group (HC). Sepsis was obtained with endotoxin and the desired MAP maintained with norepinephrine. After 6 h, DW-MRI was performed. Acute inflammation was assessed with IL-6 and TNFα in abdominal organs, ascites, and blood and by histology of intestine (duodenum). Perfusion of abdominal organs was reduced in the LowMAP group compared with the HighMAP group and HC. Liver perfusion was still reduced by 25% in the HighMAP group compared with HC. Intestinal perfusion did not differ significantly between the intervention groups. Cytokine concentrations were generally higher in the LowMAP group but did not correlate with global hemodynamics. However, cytokines correlated with regional perfusion and, for liver and intestine, also with intra-abdominal pressure. Histopathology of intestine worsened with decreasing perfusion. In conclusion, although a low MAP (≤60 mmHg) indicated impeded abdominal perfusion in experimental sepsis, it did not predict inflammation, nor did other global measures of circulation. Decreased abdominal perfusion partially predicted inflammation but intestine, occupying most of the abdomen, and liver were also affected by intra-abdominal pressure. NEW & NOTEWORTHY The study increases the knowledge of abdominal perfusion during sepsis. We used diffusion weighted imaging to assess perfusion simultaneously and noninvasively in different abdominal organs. The technique has not been used in a sepsis model before. Cytokine concentrations were measured in different abdominal organs and vascular beds and related to regional perfusion. Decreased abdominal perfusion, but not global measures of circulation, predicted inflammation. Intestine, occupying most of the abdomen, and liver were also affected by intra-abdominal pressure.
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Affiliation(s)
- Silvia Marchesi
- Hedenstierna Laboratoriet, Department of Surgical Science, Uppsala University , Uppsala , Sweden
| | | | - Kerstin M Ahlgren
- Hedenstierna Laboratoriet, Department of Surgical Science, Uppsala University , Uppsala , Sweden
| | - Agneta Roneus
- Hedenstierna Laboratoriet, Department of Surgical Science, Uppsala University , Uppsala , Sweden
| | | | - Miklos Lipcsey
- Hedenstierna Laboratoriet, Department of Surgical Science, Uppsala University , Uppsala , Sweden
| | - Anders Larsson
- Hedenstierna Laboratoriet, Department of Surgical Science, Uppsala University , Uppsala , Sweden
| | - Håkan Ahlström
- Section of Radiology, Department of Surgical Science, Uppsala University , Sweden
| | - Göran Hedenstierna
- Hedenstierna Laboratoriet, Department of Surgical Science, Uppsala University , Uppsala , Sweden
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Sekino M, Funaoka H, Sato S, Okada K, Inoue H, Yano R, Matsumoto S, Ichinomiya T, Higashijima U, Matsumoto S, Hara T. Association Between Macroscopic Tongue Ischemia and Enterocyte Injury and Poor Outcome in Patients With Septic Shock: A Preliminary Observational Study. Shock 2018; 50:530-537. [PMID: 29432382 DOI: 10.1097/shk.0000000000001122] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
A correlation between sublingual and intestinal mucosa microcirculation, and ischemic necrosis of the tongue as a sign of poor prognosis has been reported. However, an association between tongue ischemia and intestinal health and subsequent outcome has never been studied. This preliminary prospective observational study evaluated the association between macroscopic tongue ischemia and enterocyte injury and poor outcome in patients with septic shock. In this study, 57 adults with septic shock on mechanical ventilators were enrolled. Macroscopic tongue ischemia upon intensive care unit (ICU) admission was assessed by two independent intensivists. We used intestinal fatty-acid binding protein (I-FABP) as a biomarker of enterocyte injury and evaluated the association with tongue ischemia. Demographic variables, risk factor data, and 28-day mortality information were also collected. Compared with patients with normal tongues (n = 45), those with ischemic tongues (n = 12) had a significantly higher Acute Physiology and Chronic Health Evaluation II score (29.0 [25.0-34.0] vs. 36.5 [30.5-44.5], P = 0.017), lactate level (2.8 [2.0-5.0] vs. 9.3 [4.5-10.6], P = 0.002), and I-FABP level (1.9 [0.8-4.0] vs. 54.4 [19.5-159.3], P < 0.001) and the all-cause 28-day mortality was significantly higher (7% vs. 83%, P < 0.001). In conclusion, macroscopic tongue ischemia at ICU admission was associated with enterocyte injury and poor outcome in patients with septic shock. Although there is a disadvantage in that assessment of the tongue was subjective, tongue ischemia could be used to gauge the severity of intestinal injury and to estimate poor outcome in the clinical setting.
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Affiliation(s)
- Motohiro Sekino
- Division of Intensive Care, Nagasaki University Hospital, Sakamoto, Nagasaki, Japan
| | | | - Shuntaro Sato
- Clinical Research Center, Nagasaki University Hospital, Sakamoto, Nagasaki, Japan
| | - Kyoko Okada
- Department of Anesthesiology, Nagasaki University Hospital, Sakamoto, Nagasaki, Japan
| | - Haruka Inoue
- Division of Intensive Care, Nagasaki University Hospital, Sakamoto, Nagasaki, Japan
| | - Rintaro Yano
- Division of Intensive Care, Nagasaki University Hospital, Sakamoto, Nagasaki, Japan
| | - Sojiro Matsumoto
- Division of Intensive Care, Nagasaki University Hospital, Sakamoto, Nagasaki, Japan
| | - Taiga Ichinomiya
- Department of Anesthesiology, Nagasaki University Graduate School of Biomedical Science, Sakamoto, Nagasaki, Japan
| | - Ushio Higashijima
- Division of Intensive Care, Nagasaki University Hospital, Sakamoto, Nagasaki, Japan
| | - Shuhei Matsumoto
- Division of Intensive Care, Nagasaki University Hospital, Sakamoto, Nagasaki, Japan
| | - Tetsuya Hara
- Department of Anesthesiology, Nagasaki University Graduate School of Biomedical Science, Sakamoto, Nagasaki, Japan
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Harki J, Suker M, Tovar-Doncel MS, van Dijk LJ, van Noord D, van Eijck CH, Bruno MJ, Kuipers EJ, Ince C. Patients with chronic mesenteric ischemia have an altered sublingual microcirculation. Clin Exp Gastroenterol 2018; 11:405-414. [PMID: 30425547 PMCID: PMC6200368 DOI: 10.2147/ceg.s159160] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
Background Little is known about the microcirculatory alterations in patients with chronic mesenteric ischemia (CMI). We hypothesized that patients with CMI have an impaired microcirculatory function and show an oral microcirculatory response after caloric challenge compared to healthy controls. Methods All patients and controls received the standard workup for CMI. Sublingual micro-circulation was evaluated before (T0) and 20 minutes after (T1) feeding. The total vessel density (TVD; mm/mm2), perfused vessel density (PVD; mm/mm2), proportion of perfused vessels (PPV; %) and microvascular flow index (MFI; AU) were assessed. Results We included 12 patients (63.2 years [IQR 48.8–70.4 years], 67% males) and 12 controls (32.7 years [IQR 27.7–38.1 years], 42% males). At baseline, patients with CMI had a decreased PPV of the sublingual small vessels (median 84.8% vs 95.7%, P=0.006), PPV of all vessels (PPV median 85.4% vs 95.3%, P=0.007) and microvascular flow index of all vessels (MFIa; median 3.00 vs 2.80, P=0.039) compared to healthy controls. After caloric challenge, PVD increased significantly in both small vessels (perfused vessel density of the small vessels [PVDs]) and all vessels (perfused vessel density of all vessels [PVDa]; PVDs [T0]) median 16.3 [IQR 13.3–22.1] vs [T1] median 19.9 [IQR 14.2–26.2], P=0.008; PVDa [T0] median 19.1 [IQR 16.2–23.6] vs [T1] median 22.2 [IQR 16.5–28.9], P=0.02; proportion of perfused vessels of the small vessels (PPVs; [T0] median 84.8% [IQR 75.3–90.4] vs [T1] median 91.0% [IQR 80.1–93.8], P=0.010). In contrast, no significant changes in microcirculatory parameters were observed after caloric challenge in healthy controls. Conclusion Patients with CMI have an impaired sublingual microcirculation at baseline and show a significant response in the sublingual microcirculation after caloric challenge, whereas healthy controls have a normal microcirculation at baseline and show no reactive response upon a caloric challenge as seen in CMI patients. Sublingual microcirculation visualization may offer a rapid noninvasive method to identify patients at risk for having CMI.
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Affiliation(s)
- Jihan Harki
- Department of Gastroenterology and Hepatology,
| | - Mustafa Suker
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | | | | | | | - Casper Hj van Eijck
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | | | - Ernst J Kuipers
- Department of Gastroenterology and Hepatology, .,Department of Internal Medicine
| | - Can Ince
- Department of Intensive Care, Erasmus MC University Medical Center, Rotterdam, the Netherlands
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Volume Based Resuscitation and Intestinal Microcirculation after Ischaemia/Reperfusion Injury: Results of an Exploratory Aortic Clamping Study in Pigs. Eur J Vasc Endovasc Surg 2018; 57:284-291. [PMID: 30309783 DOI: 10.1016/j.ejvs.2018.08.055] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Accepted: 08/27/2018] [Indexed: 11/23/2022]
Abstract
OBJECTIVES In the presence of ischaemia/reperfusion (I/R) induced endothelial injury, volume administration may not correlate with increased microcirculation. The aim of this study was to evaluate intestinal microcirculation after standardised sequential volume loading in an animal model of I/R injury following supracoeliac aortic clamping. METHODS This was a prospective exploratory pilot animal study. Intestinal I/R injury was induced in eight pigs during experimental thoraco-abdominal aortic repair. After 6 h of I/R, microcirculatory blood flow (mFlux, measured in the ileum using direct laser speckle contrast imaging) and macrohaemodynamic parameters (using trans-cardiopulmonary thermodilution) were measured and measurements were repeated after each of four sequential volume loading steps (VLS1 - 4). Each load was administered over 5 min followed by another 5 min for equilibration. RESULTS All animals survived until after VLS4. After 6 h of I/R cardiac output (CO) (p < .001) and mFlux (p < .001) had both decreased. CO increased again after VLS1 (p < .001) and VLS2 (p = .036), whereas mFlux did not change. In contrast, mFlux further decreased after VLS3 (p < .01) and VLS4 (p < .001), whereas CO did not change anymore. Extravascular lung water continued to increase after VLS2 (p = .046) and VLS4 (p = .049). CONCLUSIONS I/R leads to impaired intestinal microcirculation, which was not restored by volume administration in spite of improved CO. In contrast, further volume administration exceeding preload reserves was associated with additional decreases in the intestinal microcirculation. The potentially negative effect of excessive volume resuscitation after I/R injury should encourage further translational research.
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Holmgaard F, Vedel AG, Ravn HB, Nilsson JC, Rasmussen LS. Impact of mean arterial pressure on sublingual microcirculation during cardiopulmonary bypass-Secondary outcome from a randomized clinical trial. Microcirculation 2018; 25:e12459. [DOI: 10.1111/micc.12459] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Accepted: 05/03/2018] [Indexed: 11/30/2022]
Affiliation(s)
- Frederik Holmgaard
- Department of Cardiothoracic Anesthesia; Heart Centre; Rigshospitalet; University of Copenhagen; Copenhagen Denmark
| | - Anne G. Vedel
- Department of Cardiothoracic Anesthesia; Heart Centre; Rigshospitalet; University of Copenhagen; Copenhagen Denmark
| | - Hanne Berg Ravn
- Department of Cardiothoracic Anesthesia; Heart Centre; Rigshospitalet; University of Copenhagen; Copenhagen Denmark
| | - Jens C. Nilsson
- Department of Cardiothoracic Anesthesia; Heart Centre; Rigshospitalet; University of Copenhagen; Copenhagen Denmark
| | - Lars S. Rasmussen
- Department of Anesthesia; Centre of Head and Orthopedics; Rigshospitalet; University of Copenhagen; Copenhagen Denmark
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50
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Uz Z, Kastelein AW, Milstein DM, Liu D, Rassam F, Veelo DP, Roovers JPW, Ince C, van Gulik TM. Intraoperative Incident Dark Field Imaging of the Human Peritoneal Microcirculation. J Vasc Res 2018; 55:136-143. [PMID: 29779022 PMCID: PMC6106141 DOI: 10.1159/000488392] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Accepted: 03/08/2018] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND/AIMS This study describes the peritoneal microcirculation, compares quantitative parameters and angioarchitecture to the standard of sublingual microcirculatory assessment, and determines the practical feasibility of this method. METHODS Incident dark field imaging was performed of the peritoneum and sublingually to determine angioarchitecture, total and perfused vessel density (TVD and PVD), the proportion of perfused vessels (PPV), the microvascular flow index (MFI) and image acquisition time. RESULTS Peritoneal angioarchitecture was characterized by a quadrangular network of longitudinally oriented capillaries, often flanked by fat cells. Differences between peritoneal and sublingual microcirculation were observed with regard to TVD (peritoneum 12 mm/mm2 [95% CI 10-14] vs. sublingual 23 mm/mm2 [95% CI 21-25]; p < 0.0001), PVD (peritoneum 11 mm/mm2 [95% CI 9-13] vs. sublingual 23 mm/mm2 [95% CI 21-25]; p < 0.0001), PPV (peritoneum 88% [95% CI 79-97] vs. sublingual 99% [95% CI 99-100]; p = 0.014), and MFI (peritoneum 3 [IQR 2.3-3.0] vs. sublingual 3 [IQR 3.0-3.0]; p = 0.012). There was no difference in image acquisition time (peritoneum 2: 34 min [95% CI 1: 49-3: 19] vs. sublingual 2: 38 [95% CI 1: 37-3: 32]; p = 0.916). CONCLUSION The peritoneal microcirculation was characterized by a low capillary density and a distinctive angioarchitecture. The possibility of peri-toneal microcirculatory assessment offers promise for the study of peritoneal (patho-)physiology and (monitoring or detection of) associated diseases.
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Affiliation(s)
- Zühre Uz
- Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands
- Department of Translational Physiology, Academic Medical Center, Amsterdam, the Netherlands
| | - Arnoud W. Kastelein
- Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, the Netherlands
| | - Dan M.J. Milstein
- Department of Oral and Maxillofacial Surgery, Academic Medical Center, Amsterdam, the Netherlands
| | - Dan Liu
- Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands
| | - Fadi Rassam
- Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands
| | - Denise P. Veelo
- Department of Anesthesiology, Academic Medical Center, Amsterdam, the Netherlands
| | - Jan-Paul W.R. Roovers
- Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, the Netherlands
| | - Can Ince
- Department of Translational Physiology, Academic Medical Center, Amsterdam, the Netherlands
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