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Vernon-Elliot J, Goradia S, Bellomo R, Lankadeva YR, Burrell LM, See EJ. THE EFFECT OF CATECHOLAMINE VERSUS NONCATECHOLAMINE VASOPRESSORS ON RENAL FUNCTION AND RECOVERY IN VASODILATORY SHOCK: A SYSTEMATIC REVIEW OF PRECLINICAL AND CLINICAL STUDIES. Shock 2025; 63:351-362. [PMID: 39617403 DOI: 10.1097/shk.0000000000002515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2025]
Abstract
ABSTRACT Background: Acute kidney injury (AKI) is a common complication of vasodilatory shock. AKI is associated with an increased risk of death, prolonged hospital stays, and subsequent transition to chronic kidney disease. Catecholamines have historically been used as the first-line vasopressors for vasodilatory shock; however, they may adversely affect renal function and recovery. Objectives: To compare the effects of catecholamine and noncatecholamine vasopressors on AKI risk and recovery in preclinical and clinical studies of vasodilatory shock. Methods: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were systematically searched to identify studies reporting renal outcomes associated with catecholamine (norepinephrine, epinephrine, metaraminol, phenylephrine, dopamine) and noncatecholamine vasopressors (vasopressin, angiotensin II), in preclinical models or adult cohorts of vasodilatory shock. Two independent reviewers screened studies and extracted data using a prespecified form for qualitative synthesis and risk of bias assessment. Results: Of 3,504 citations, 90 studies were eligible for inclusion: 41 preclinical studies, 17 nonrandomized clinical studies, 28 randomized clinical studies, and 4 post-hoc analyses. Risk of bias was generally low in preclinical studies and low to moderate in clinical studies. In preclinical studies, catecholamine vasopressors exacerbated medullary hypoxia and intrarenal inflammation compared to noncatecholamine vasopressors. In clinical studies, catecholamines were associated with higher serum creatinine, lower urine output, and increased requirements for renal replacement therapy compared to noncatecholamine vasopressors. In patients on high-dose catecholamines, adjunctive angiotensin II was associated with improved renal replacement therapy liberation. Conclusion: Preclinical and clinical studies suggest that noncatecholamine vasopressors may confer renal benefits compared to catecholamine vasopressors. These hypothesis-generating observations suggest the need for comparative studies focused on renal outcomes. Systematic Review Registration : PROSPERO 2024 CRD42024527773.
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Park C, Ku NS, Park DW, Park JH, Ha TS, Kim DW, Park SY, Chang Y, Jo KW, Baek MS, Seo Y, Shin TG, Yu G, Lee J, Choi YJ, Jang JY, Jung YT, Jeong I, Cho HJ, Woo A, Kim S, Bae DH, Kang SW, Park SH, Suh GY, Park S. Early management of adult sepsis and septic shock: Korean clinical practice guidelines. Acute Crit Care 2024; 39:445-472. [PMID: 39622601 PMCID: PMC11617831 DOI: 10.4266/acc.2024.00920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Revised: 09/06/2024] [Accepted: 09/09/2024] [Indexed: 12/08/2024] Open
Abstract
BACKGROUND Despite recent advances and global improvements in sepsis recognition and supportive care, mortality rates remain high, and adherence to sepsis bundle components in Korea is low. To address this, the Korean Sepsis Alliance, affiliated with the Korean Society of Critical Care Medicine, developed the first sepsis treatment guidelines for Korea based on a comprehensive systematic review and meta-analysis. METHODS A de novo method was used to develop the guidelines. Methodologies included determining key questions, conducting a literature search and selection, assessing the risk of bias, synthesizing evidence, and developing recommendations. The certainty of evidence and the strength of recommendations were determined using the Grading of Recommendations, Assessment, Development, and Evaluations approach. Draft recommendations underwent internal and external review processes and public hearings. The development of these guidelines was supported by a research grant from the Korean Disease Control and Prevention Agency. RESULTS In these guidelines, we focused on early treatments for adult patients with sepsis and septic shock. Through the guideline development process, 12 key questions and their respective recommendations were formulated. These include lactate measurement, fluid therapies, target blood pressure, antibiotic administration, use of vasopressors and dobutamine, extracorporeal membrane oxygenation, and echocardiography. CONCLUSIONS These guidelines aim to support medical professionals in making appropriate decisions about treating adult sepsis and septic shock. We hope these guidelines will increase awareness of sepsis and reduce its mortality rate.
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Affiliation(s)
- Chul Park
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ulsan University Hospital, Ulsan, Korea
| | - Nam Su Ku
- Division of Infective Diseases, Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Dae Won Park
- Division of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Joo Hyun Park
- Respiratory Medicine, Department of Internal Medicine, Seoul Metropolitan Seonam Hospital, Seoul, Korea
| | - Tae Sun Ha
- Department of Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Do Wan Kim
- Department of Thoracic and Cardiovascular Surgery, Chonnam National University Hospital and Medical School, Gwangju, Korea
| | - So Young Park
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Youjin Chang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Inje University Sanggye Paik Hospital, College of Medicine, Inje University Seoul, Korea
| | - Kwang Wook Jo
- Department of Neurosurgery, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Korea
| | - Moon Seong Baek
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea
| | - Yijun Seo
- Department of Anesthesiology and Pain Medicine, and Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Tae Gun Shin
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gina Yu
- Department of Emergency Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jongmin Lee
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yong Jun Choi
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Ji Young Jang
- Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Yun Tae Jung
- Department of Surgery, Gangneung Asan Hospital, Gangneung, Korea
| | - Inseok Jeong
- Department of Thoracic and Cardiovascular Surgery, Chonnam National University Hospital and Medical School, Gwangju, Korea
| | - Hwa Jin Cho
- Department of Pediatrics, Chonnam National University Children's Hospital, Chonnam National University Medical School, Gwangju, Korea
| | - Ala Woo
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sua Kim
- Department of Critical Care Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Dae-Hwan Bae
- Division of Cardiology, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea
- Division of Cardiology, Department of Internal Medicine, Bucheon Sejong Hospital, Bucheon, Korea
| | - Sung Wook Kang
- Department of Pulmonary and Critical Care Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Korea
| | - Sun Hyo Park
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Keimyung University Dongsan Hospital, Daegu, Korea
| | - Gee Young Suh
- Department of Critical Care Medicine, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sunghoon Park
- Department of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
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McCloskey MM, Gibson GA, Pope HE, Giacomino BD, Hampton N, Micek ST, Kollef MH, Betthauser KD. Effect of Early Administration of Vasopressin on New-Onset Arrhythmia Development in Patients With Septic Shock: A Retrospective, Observational Cohort Study. Ann Pharmacother 2024; 58:5-14. [PMID: 37056040 DOI: 10.1177/10600280221095543] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/15/2023] Open
Abstract
Background: Adjunctive vasopressin use in septic shock reduces catecholamine requirements and is associated with a lower incidence of new-onset arrhythmias (NOAs). The association of vasopressin timing on NOA development is ill-described. Objective: To determine whether early administration of vasopressin was associated with a lower incidence of NOA in septic shock patients. Methods: A retrospective analysis of intensive care unit (ICU) patients at a large, academic medical center. Septic shock patients who required vasopressin and norepinephrine were eligible for inclusion. Patients were excluded for receipt of other vasoactive agents, history of cardiac arrhythmias, or outside hospital admission. Early vasopressin was defined as receipt within 6 hours of septic shock onset. The primary outcome was incidence of NOA. Results: In total, 436 patients, 220 (50.4%) in the early and 216 (49.6%) in the late vasopressin group, were included. Early vasopressin was not associated with a lower incidence of NOA compared with late vasopressin (9% vs 7%, median absolute difference [95% confidence interval, CI]: -2.1 [-7.2, 3.0], P = 0.41). Early vasopressin patients were observed to have shorter shock duration (2 vs 4 days, median absolute difference [95% CI]: 2 [1, 2], P < 0.001), and ICU length of stay (6 vs 7 days, median absolute difference [95% CI]: 1 [0, 2], P = 0.02). Conclusions and Relevance: Early vasopressin use was not associated with a lower incidence of NOA. Additional studies are needed to elucidate the effect of vasopressin timing on NOA and other clinical outcomes.
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Affiliation(s)
| | | | - Hannah E Pope
- Department of Pharmacy, Barnes-Jewish Hospital, Saint Louis, MO, USA
| | - Bria D Giacomino
- Department of Cardiology, Washington University School of Medicine, Saint Louis, MO, USA
| | - Nicholas Hampton
- Department of Pharmacy, Barnes-Jewish Hospital, Saint Louis, MO, USA
| | - Scott T Micek
- Department of Pharmacy, Barnes-Jewish Hospital, Saint Louis, MO, USA
- Division of Specialty Care Pharmacy Practice, Saint Louis College of Pharmacy, Saint Louis, MO, USA
- Center for Health Outcomes and Education, Saint Louis College of Pharmacy, Saint Louis, MO, USA
| | - Marin H Kollef
- Department of Pulmonology, Washington University School of Medicine, Saint Louis, MO, USA
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White CM. Does Early Vasopressin in Septic Shock Improve Outcomes? An Important Piece to This Emerging Puzzle Has Arrived. Ann Pharmacother 2024; 58:86-88. [PMID: 37056042 DOI: 10.1177/10600280221096881] [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: 04/15/2023] Open
Abstract
In this month's Annals of Pharmacotherapy, the largest observational study assessing the early versus later use of vasopressin has been published. When this new study is combined with the other available observational studies, there are 2 important outcomes to focus on. When all the observational studies are pooled together, no reduction in new onset arrhythmias is seen (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.41-1.95) with early versus late vasopressin use while the reduction in renal replacement therapy just missed statistical significance (OR = 0.56, 95% CI = 0.32-1.00). Early vasopressin likely does not reduce new onset arrhythmias versus later use but might reduce the need for renal replacement therapy.
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Affiliation(s)
- C Michael White
- Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, CT, USA
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Zhou HX, Yang CF, Wang HY, Teng Y, He HY. Should we initiate vasopressors earlier in patients with septic shock: A mini systemic review. World J Crit Care Med 2023; 12:204-216. [PMID: 37745258 PMCID: PMC10515096 DOI: 10.5492/wjccm.v12.i4.204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 06/28/2023] [Accepted: 07/17/2023] [Indexed: 09/05/2023] Open
Abstract
Septic shock treatment remains a major challenge for intensive care units, despite the recent prominent advances in both management and outcomes. Vasopressors serve as a cornerstone of septic shock therapy, but there is still controversy over the timing of administration. Specifically, it remains unclear whether vasopressors should be used early in the course of treatment. Here, we provide a systematic review of the literature on the timing of vasopressor administration. Research was systematically identified through PubMed, Embase and Cochrane searching according to PRISMA guidelines. Fourteen studies met the eligibility criteria and were included in the review. The pathophysiological basis for early vasopressor use was classified, with the exploration on indications for the early administration of mono-vasopressors or their combination with vasopressin or angiotensinII. We found that mortality was 28.1%-47.7% in the early vasopressors group, and 33.6%-54.5% in the control group. We also investigated the issue of vasopressor responsiveness. Furthermore, we acknowledged the subsequent challenge of administration of high-dose norepinephrine via peripheral veins with early vasopressor use. Based on the literature review, we propose a possible protocol for the early initiation of vasopressors in septic shock resuscitation.
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Affiliation(s)
- Hang-Xiang Zhou
- Department of Critical Care Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou Province, China
- Department of Critical Care Medicine, The Sixth Hospital of Guiyang, Guiyang 550002, Guizhou Province, China
| | - Chun-Fu Yang
- Department of Critical Care Medicine, The Sixth Hospital of Guiyang, Guiyang 550002, Guizhou Province, China
- Department of Respiratory Medicine, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550002, Guizhou Province, China
| | - He-Yan Wang
- Department of Critical Care Medicine, The Sixth Hospital of Guiyang, Guiyang 550002, Guizhou Province, China
- School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550002, Guizhou Province, China
| | - Yin Teng
- Department of Thoracic Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou Province, China
| | - Hang-Yong He
- Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Beijing 100020, China
- Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Beijing 100020, China
- Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Chao-Yang Hospital, Beijing 100020, China
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Huang H, Wu C, Shen Q, Xu H, Fang Y, Mao W. The effect of early vasopressin use on patients with septic shock: A systematic review and meta-analysis. Am J Emerg Med 2021; 48:203-208. [PMID: 33975132 DOI: 10.1016/j.ajem.2021.05.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 04/07/2021] [Accepted: 05/02/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The effect of early vasopressin initiation on clinical outcomes in patients with septic shock is uncertain. A systematic review and meta-analysis was performed to evaluate the impact of early start of vasopressin support within 6 h after the diagnosis on clinical outcomes in septic shock patients. METHODS We searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of February 2021. We included studies involving adult patients (> 16 years)with septic shock. All authors reported our primary outcome of short-term mortality and in the experimental group patients in the studies receiving vasopressin infusion within 6 h after diagnosis of septic shock and in the control group patients in the studies receiving no vasopressin infusion or vasopressin infusion 6 h after diagnosis of septic shock, clearly comparing with clinically relevant secondary outcomes(use of renal replacement therapy(RRT),new onset arrhythmias, ICU length of stay and length of hospitalization). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI). RESULTS Five studies including 788 patients were included. The primary outcome of this meta-analysis showed that short-term mortality between the two groups was no difference (odds ratio [OR] = 1.09; 95% CI, 0.8 to 1.48; P = 0.6; χ2 = 0.83; I2 = 0%). Secondary outcomes demonstrated that the use of RRT was less in the experimental group than that of the control group (OR = 0.63; 95% CI, 0.44 to 0.88; P = 0.007; χ2 = 3.15; I2 = 36%).The new onset arrhythmias between the two groups was no statistically significant difference (OR = 0.59; 95% CI, 0.31 to 1.1; P = 0.10; χ2 = 4.7; I2 = 36%). There was no statistically significant difference in the ICU length of stay(mean difference = 0.16; 95% CI, - 0.91 to 1.22; P = 0.77; χ2 = 6.08; I2 = 34%) and length of hospitalization (mean difference = -2.41; 95% CI, -6.61 to 1.78; P = 0.26; χ2 = 8.57; I2 = 53%) between the two groups. CONCLUSIONS Early initiation of vasopressin in patients within 6 h of septic shock onset was not associated with decreased short-term mortality, new onset arrhythmias, shorter ICU length of stay and length of hospitalization, but can reduce the use of RRT. Further large-scale RCTs are still needed to evaluate the benefit of starting vasopressin in the early phase of septic shock.
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Affiliation(s)
- Haijun Huang
- Department of Emergency, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang 310018, Hangzhou, China
| | - Chenxia Wu
- Department of Emergency, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang 310018, Hangzhou, China
| | - Qinkang Shen
- Department of Emergency, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang 310018, Hangzhou, China
| | - Hua Xu
- Department of Emergency, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang 310018, Hangzhou, China
| | - Yixin Fang
- Department of Emergency, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang 310018, Hangzhou, China
| | - Wei Mao
- Department of Emergency, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang 310018, Hangzhou, China.
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Webb AJ, Seisa MO, Nayfeh T, Wieruszewski PM, Nei SD, Smischney NJ. Vasopressin in vasoplegic shock: A systematic review. World J Crit Care Med 2020; 9:88-98. [PMID: 33384951 PMCID: PMC7754532 DOI: 10.5492/wjccm.v9.i5.88] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 10/10/2020] [Accepted: 10/26/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Vasoplegic shock is a challenging complication of cardiac surgery and is often resistant to conventional therapies for shock. Norepinephrine and epinephrine are standards of care for vasoplegic shock, but vasopressin has increasingly been used as a primary pressor in vasoplegic shock because of its unique pharmacology and lack of inotropic activity. It remains unclear whether vasopressin has distinct benefits over standard of care for patients with vasoplegic shock. AIM To summarize the available literature evaluating vasopressin vs non-vasopressin alternatives on the clinical and patient-centered outcomes of vasoplegic shock in adult intensive care unit (ICU) patients. METHODS This was a systematic review of vasopressin in adults (≥ 18 years) with vasoplegic shock after cardiac surgery. Randomized controlled trials, prospective cohorts, and retrospective cohorts comparing vasopressin to norepinephrine, epinephrine, methylene blue, hydroxocobalamin, or other pressors were included. The primary outcomes of interest were 30-d mortality, atrial/ventricular arrhythmias, stroke, ICU length of stay, duration of vasopressor therapy, incidence of acute kidney injury stage II-III, and mechanical ventilation for greater than 48 h. RESULTS A total of 1161 studies were screened for inclusion with 3 meeting inclusion criteria with a total of 708 patients. Two studies were randomized controlled trials and one was a retrospective cohort study. Primary outcomes of 30-d mortality, stroke, ventricular arrhythmias, and duration of mechanical ventilation were similar between groups. Conflicting results were observed for acute kidney injury stage II-III, atrial arrhythmias, duration of vasopressors, and ICU length of stay with higher certainty of evidence in favor of vasopressin serving a protective role for these outcomes. CONCLUSION Vasopressin was not found to be superior to alternative pressor therapy for any of the included outcomes. Results are limited by mixed methodologies, small overall sample size, and heterogenous populations.
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Affiliation(s)
- Andrew J Webb
- Department of Pharmacy, Oregon Health and Science University, Portland, OR 97239, United States
| | - Mohamed O Seisa
- Robert D and Patricia E Kern Center For The Science of Health Care Delivery, Mayo Clinic, Rochester, MN 55905, United States
| | - Tarek Nayfeh
- Robert D and Patricia E Kern Center For The Science of Health Care Delivery, Mayo Clinic, Rochester, MN 55905, United States
| | | | - Scott D Nei
- Department of Pharmacy, Mayo Clinic, Rochester, MN 55905, United States
| | - Nathan J Smischney
- Department of Anesthesia, Mayo Clinic, Rochester, MN 55905, United States
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Li Y, Li H, Zhang D. Timing of norepinephrine initiation in patients with septic shock: a systematic review and meta-analysis. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2020; 24:488. [PMID: 32762765 PMCID: PMC7409707 DOI: 10.1186/s13054-020-03204-x] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Accepted: 07/26/2020] [Indexed: 12/13/2022]
Abstract
Background The effect of the timing of norepinephrine initiation on clinical outcomes in patients with septic shock is uncertain. A systematic review and meta-analysis was performed to evaluate the impact of early and late start of norepinephrine support on clinical outcomes in patients with septic shock. Methods We searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of March 2020. We included studies involving adult patients (> 18 years) with septic shock. All authors reported our primary outcome of short-term mortality and clearly comparing early versus late norepinephrine initiation with clinically relevant secondary outcomes (ICU length of stay, time to achieved target mean arterial pressure (≥ 65 mmHg), and volume of intravenous fluids within 6 h). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI). Results Five studies including 929 patients were included. The primary outcome of this meta-analysis showed that the short-term mortality of the early group was lower than that of the late group (odds ratio [OR] = 0.45; 95% CI, 0.34 to 0.61; P < 0.00001; χ2 = 3.74; I2 = 0%). Secondary outcomes demonstrated that the time to achieved target MAP of the early group was shorter than that of the late group (mean difference = − 1.39; 95% CI, − 1.81 to − 0.96; P < 0.00001; χ2 = 1.03; I2 = 0%). The volume of intravenous fluids within 6 h of the early group was less than that of the late group (mean difference = − 0.50; 95% CI, − 0.68 to − 0.32; P < 0.00001; χ2 = 33.76; I2 = 94%). There was no statistically significant difference in the ICU length of stay between the two groups (mean difference = − 0.11; 95% CI, − 1.27 to 1.05; P = 0.86; χ2 = 0.85; I2 = 0%). Conclusions Early initiation of norepinephrine in patients with septic shock was associated with decreased short-term mortality, shorter time to achieved target MAP, and less volume of intravenous fluids within 6 h. There was no significant difference in ICU length of stay between early and late groups. Further large-scale RCTs are still required to confirm these results.
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Affiliation(s)
- Yuting Li
- Department of Intensive Care Unit, The First Hospital of Jilin University, Changchun, 130021, Jilin, China
| | - Hongxiang Li
- Department of Intensive Care Unit, The First Hospital of Jilin University, Changchun, 130021, Jilin, China
| | - Dong Zhang
- Department of Intensive Care Unit, The First Hospital of Jilin University, Changchun, 130021, Jilin, China.
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Li Y, Li H, Zhang D. Timing of norepinephrine initiation in patients with septic shock: a systematic review and meta-analysis. CRITICAL CARE (LONDON, ENGLAND) 2020. [PMID: 32762765 DOI: 10.1186/s13054-020-03204-x.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
BACKGROUND The effect of the timing of norepinephrine initiation on clinical outcomes in patients with septic shock is uncertain. A systematic review and meta-analysis was performed to evaluate the impact of early and late start of norepinephrine support on clinical outcomes in patients with septic shock. METHODS We searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of March 2020. We included studies involving adult patients (> 18 years) with septic shock. All authors reported our primary outcome of short-term mortality and clearly comparing early versus late norepinephrine initiation with clinically relevant secondary outcomes (ICU length of stay, time to achieved target mean arterial pressure (≥ 65 mmHg), and volume of intravenous fluids within 6 h). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI). RESULTS Five studies including 929 patients were included. The primary outcome of this meta-analysis showed that the short-term mortality of the early group was lower than that of the late group (odds ratio [OR] = 0.45; 95% CI, 0.34 to 0.61; P < 0.00001; χ2 = 3.74; I2 = 0%). Secondary outcomes demonstrated that the time to achieved target MAP of the early group was shorter than that of the late group (mean difference = - 1.39; 95% CI, - 1.81 to - 0.96; P < 0.00001; χ2 = 1.03; I2 = 0%). The volume of intravenous fluids within 6 h of the early group was less than that of the late group (mean difference = - 0.50; 95% CI, - 0.68 to - 0.32; P < 0.00001; χ2 = 33.76; I2 = 94%). There was no statistically significant difference in the ICU length of stay between the two groups (mean difference = - 0.11; 95% CI, - 1.27 to 1.05; P = 0.86; χ2 = 0.85; I2 = 0%). CONCLUSIONS Early initiation of norepinephrine in patients with septic shock was associated with decreased short-term mortality, shorter time to achieved target MAP, and less volume of intravenous fluids within 6 h. There was no significant difference in ICU length of stay between early and late groups. Further large-scale RCTs are still required to confirm these results.
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Affiliation(s)
- Yuting Li
- Department of Intensive Care Unit, The First Hospital of Jilin University, Changchun, 130021, Jilin, China
| | - Hongxiang Li
- Department of Intensive Care Unit, The First Hospital of Jilin University, Changchun, 130021, Jilin, China
| | - Dong Zhang
- Department of Intensive Care Unit, The First Hospital of Jilin University, Changchun, 130021, Jilin, China.
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Haan BJ, Cadiz ML, Natavio AM. Efficacy and Safety of Vasopressin as First-Line Treatment of Distributive and Hemorrhagic Shock States. Ann Pharmacother 2019; 54:213-218. [PMID: 31625395 DOI: 10.1177/1060028019882035] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Background: Norepinephrine remains the first-line option to manage patients with circulatory shock. Limited evidence exists evaluating noncatecholamine compounds as first-line monotherapy for managing noncardiogenic shock. Objective: To compare vasopressin monotherapy with norepinephrine monotherapy for reversal of distributive and hemorrhagic shock. Methods: This was a retrospective cohort study including adult patients who were diagnosed with hypovolemic or septic shock, received fluids, and received norepinephrine or vasopressin monotherapy for at least 1 hour. Patients excluded lacked a clear diagnosis, were initiated on 2 or more vasopressors at once, or underwent cardiac surgery. The primary outcome was time to shock reversal. Secondary outcomes included mortality, lengths of stay, and safety end points. A multivariable Cox proportional hazards model was performed incorporating baseline and treatment variables. Results: A total of 85 and 160 patients were treated with vasopressin and norepinephrine, respectively. A decrease in time to shock reversal was observed in the vasopressin group (58.32 hours [95% CI, 50.88-66.00] vs 74.64 hours [95% CI, 60.96-88.32], P = 0.004). Mortality was lower in the vasopressin group (25% vs 41%, P = 0.01), and intensive care unit length of stay was longer (13 days [interquartile range, IQR = 7-19] vs 7 days [IQR = 5-9], P = 0.006). Remaining secondary outcomes were similar. The multivariable analysis revealed no difference in time to shock reversal. Conclusion and Relevance: First-line vasopressin exhibited faster time to distributive shock reversal in the unadjusted analysis but failed to maintain this difference in the multivariable analysis. These findings support safe use of vasopressin as first-line therapy or as an alternative to norepinephrine in distributive shock.
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Affiliation(s)
- Bradley J Haan
- Beaumont Hospital, Royal Oak, MI, USA.,Ascension Genesys Hospital, Grand Blanc, MI, USA
| | - Megan L Cadiz
- Beaumont Hospital, Royal Oak, MI, USA.,Wayne State University, Detroit, MI, USA
| | - Allycia M Natavio
- Beaumont Hospital, Royal Oak, MI, USA.,Wayne State University, Detroit, MI, USA
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Hammond DA, Rech MA, Daley MJ, Devlin JW, Hodge EK, Kooda KJ, Lat I, Personett HA, Roberts R, Sacha G, Stollings JL, Swanson JM, Bauer SR. Perceptions regarding vasopressin use and practices in septic shock, and cost containment strategies. JOURNAL OF THE AMERICAN COLLEGE OF CLINICAL PHARMACY 2019; 2:257-267. [PMID: 38213315 PMCID: PMC10783535 DOI: 10.1002/jac5.1079] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Accepted: 11/20/2018] [Indexed: 11/10/2022]
Abstract
Background Clinician preferences and practices regarding appropriate vasopressin use in light of its increased acquisition cost secondary to rebranding has not been evaluated or described since the most recent iteration of the Surviving Sepsis Campaign Guideline was published. Objective To assess vasopressin cost containment initiatives and pharmacists' opinions regarding appropriate vasopressin use. Methods A scenario-based survey was distributed to critical care and emergency medicine pharmacists. Responses were characterized using frequency and descriptive statistics. Categorical variables between those who implemented changes (Vasopressin Cost Consideration) and those who did not (Usual Care) were compared using chi-square or Fisher's exact tests. McNemar's test was used to compare responses in clinical scenarios between Vasopressin Cost Consideration and Usual Care groups. Results Among 1757 pharmacists surveyed, 200 (11.3%) responded. When respondents considered vasopressin cost and evidence (vs evidence alone), fewer respondents would use vasopressin adjunctively with norepinephrine (21% vs 26.6%, P = 0.031), to raise mean arterial pressure compared with epinephrine (65.2% vs 72.3%, P = 0.012), or to reduce norepinephrine infusion rates (71.4% vs 81.4%, P < 0.001), but would use with steroids (62.4% vs 28.3%, P < 0.001). Most (72%) respondents had implemented vasopressin cost containment and/or education initiatives. The Vasopressin Cost Consideration group respondents were more likely to initiate vasopressin at 0.03 units/minute without titrating (47.9% vs 33.9%, P = 0.045). Conclusion Since vasopressin was generically rebranded, most institutions have implemented at least one initiative to reduce vasopressin use and/or educate clinicians about its appropriate use. When vasopressin acquisition costs were considered, pharmacists recommended its use less frequently, particularly in clinical scenarios where its use is controversial.
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Affiliation(s)
- Drayton A. Hammond
- Department of Pharmacy, Rush University Medical Center, Chicago, Illinois
| | - Megan A. Rech
- Department of Pharmacy, Loyola University Medical Center, Maywood, Illinois
| | - Mitchell J. Daley
- Department of Pharmacy, Dell Seton Medical Center at The University of Texas, Austin, Texas
| | - John W. Devlin
- Department of Pharmacy Practice, College of Pharmacy, Northeastern University, Boston, Massachusetts
| | - Emily K. Hodge
- Department of Pharmacy, Dell Seton Medical Center at The University of Texas, Austin, Texas
| | | | - Ishaq Lat
- Department of Pharmacy, Shirley Ryan AbilityLab, Chicago, Illinois
| | | | - Russel Roberts
- Department of Pharmacy, Massachusetts General Hospital, Boston, Massachusetts
| | - Gretchen Sacha
- Department of Pharmacy, Cleveland Clinic, Cleveland, Ohio
| | - Joanna L. Stollings
- Department of Pharmaceutical Services, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Joseph M. Swanson
- Department of Pharmacy Practice, University of Tennessee College of Pharmacy, Memphis, Tennessee
| | - Seth R. Bauer
- Department of Pharmacy, Cleveland Clinic, Cleveland, Ohio
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Neuroendocrine Derangements in Early Septic Shock: Pharmacotherapy for Relative Adrenal and Vasopressin Insufficiency. Shock 2018; 48:284-293. [PMID: 28296657 DOI: 10.1097/shk.0000000000000864] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Septic shock is a leading cause of mortality in intensive care units throughout the world. While this disease state represents a highly complex pathophysiology involving numerous organ systems, the early approach to care includes adequate hemodynamic support traditionally achieved via infusions of vasoactive medications after adequate fluid resuscitation. Relative adrenal and vasopressin deficiencies are a common feature of septic shock that contribute to impaired hemodynamics. Hydrocortisone and vasopressin are endocrine system hormone analogues that target the acute neuroendocrine imbalance associated with septic shock. This clinically focused annotated review describes the pathophysiological mechanisms behind their use and explores the potential clinical roles of early administration and synergy when combined.
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Allen B, Kram B, Kram S, Schultheis J, Wolf S, Gilstrap D, Shapiro M. Predictors of Vasopressin Responsiveness in Critically Ill Adults. Ann Pharmacother 2017; 52:126-132. [PMID: 28853293 DOI: 10.1177/1060028017729480] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Vasopressin is commonly used as an adjunct vasopressor in shock. However, response to vasopressin varies among critically ill patients. OBJECTIVE To identify patient-specific factors that are associated with vasopressin responsiveness in critically ill adults. METHODS This retrospective, multicenter study included adult patients who were admitted to an intensive care unit (ICU) and received vasopressin for shock. Patients were excluded if they received vasopressin for less than 30 minutes, if vasopressin was initiated prior to ICU arrival, or if an additional vasopressor was initiated within 30 minutes of starting vasopressin. Responsiveness was defined as an increase in mean arterial pressure of ≥10 mm Hg or the ability to taper a concurrent catecholamine vasopressor. Patient-specific factors evaluated in a multivariate analysis included age, gender, ethnicity, body mass index, type of shock, serum pH, Sequential Organ Failure Assessment (SOFA) score, and use of stress-dose steroids. These variables were also evaluated in a subgroup analysis of patients with septic shock. RESULTS Of 1619 patients screened, 400 patients were included, with 231 identified as vasopressin responsive and 169 as nonresponsive. Vasopressin used as an adjunct vasopressor, as opposed to first line, during shock was the only variable associated with vasopressin responsiveness (odds ratio [OR] = 1.71; 95% CI = 1.10 to 2.65). Among the subgroup of patients with septic shock, female patients had a higher odds of responding than male patients (OR = 2.10; 95% CI = 1.12 to 3.95). CONCLUSIONS Vasopressin initiated as an adjunct vasopressor, as opposed to first-line therapy, was associated with response.
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Affiliation(s)
| | | | - Shawn Kram
- 2 Duke University Hospital, Durham, NC, USA
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Impact of Norepinephrine Weight-Based Dosing Compared With Non–Weight-Based Dosing in Achieving Time to Goal Mean Arterial Pressure in Obese Patients With Septic Shock. Ann Pharmacother 2016; 51:194-202. [DOI: 10.1177/1060028016682030] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Background: Currently, a lack of standardization exists in norepinephrine dosing units, the first-line vasopressor for septic shock. Timely achievement of goal mean arterial pressure (MAP) is dependent on optimal vasopressor dosing. Objective: To determine if weight-based dosing (WBD) of norepinephrine leads to earlier time to goal MAP compared with non-WBD in obese patients with septic shock. Methods: This was a retrospective, multicenter cohort study. Patients had a body mass index (BMI) ≥30 kg/m2 and received norepinephrine for septic shock with either a non-WBD strategy (between December 2009 and January 2013) or WBD strategy (between January 2013 and December 2015). The primary outcome was time to goal MAP. Secondary outcomes were norepinephrine duration, dose requirements, and development of treatment-related complications. Results: A total of 287 patients were included (WBD 144; non-WBD 143). There was no difference in median time to goal MAP (WBD 58 minutes, interquartile range [IQR] = 16.8-118.5, vs non-WBD 60 minutes, IQR = 17.5-193.5; P = 0.28). However, there was a difference in median cumulative norepinephrine dose (WBD 12.6 mg, IQR = 4.9-45.9, vs non-WBD 10.5 mg, IQR = 3.9-25.6; P = 0.04) and time to norepinephrine discontinuation (WBD 33 hours, IQR = 15-69, vs non-WBD 27 hours, IQR = 12-51; P = 0.03). There was no difference in rates of atrial fibrillation (WBD 15.3% vs non-WBD 23.7%; P = 0.07) or mortality (WBD 23.6% vs non-WBD 23.1%; P = 0.92). Conclusion: WBD of norepinephrine does not achieve time to goal MAP earlier in obese patients with septic shock. However, WBD may lead to higher norepinephrine cumulative dose requirements and prolonged time until norepinephrine discontinuation.
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Shi WL, Zhang T, Zhou JR, Huang YH, Jiang CL. Rapid permissive action of dexamethasone on the regulation of blood pressure in a rat model of septic shock. Biomed Pharmacother 2016; 84:1119-1125. [PMID: 27780141 DOI: 10.1016/j.biopha.2016.10.029] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2016] [Revised: 10/08/2016] [Accepted: 10/09/2016] [Indexed: 11/25/2022] Open
Abstract
Glucocorticoids (GCs) play a vital role in the regulation of blood pressure by their permissive effects in potentiating vasoactive responses to catecholamines through glucocorticoid receptors. GCs achieve this function by controlling vascular smooth muscle tone. Clinically, low to moderate doses of GCs are generally used in the treatment of septic shock in recent years. GCs are now known to have both genomic and non-genomic effects. While genomic effects of GCs were well studied, few non-genomic effects were reported, much less the non-genomic mechanisms. One of the most important characters of their non-genomic effects is short latency. The aim of this study was to determine whether GCs can rapidly regulate blood pressure by their permissive action on norepinephrine (NE). Adrenalectomized rats were subjected to cecal ligation and puncture to induce septic shock. The septic rats displayed a significant decrease in the blood pressure response to NE. Dexamethasone (DEX) rapidly restores this hyporeactivity to NE in adrenalectomized septic rats. Further studies showed that DEX potentiates the NE-induced shrinkage and actin cytoskeleton rearrangement of single cell from mesenteric arteries in a short time. These findings suggest that GCs probably exert their permissive actions on the pressure response to NE through rapid non-genomic mechanisms. In this article, we found that as an adjunctive therapy for septic shock, the use of GCs may involve a rapid permissive action, and non-genomic effects of GCs may be involved in these processes.
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Affiliation(s)
- Wen-Lei Shi
- Department of Neurology, General Army Hospital, Beijing 10070, China; Department of Neurology, Bethune International Peace Hospital, Shijiazhuang, Hebei 050082, China; Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, Shanghai 200433, China
| | - Ting Zhang
- Department of Naval Aviation Medicine, Second Military Medical University (SMMU), Shanghai 200433, China
| | - Jiang-Rui Zhou
- Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, Shanghai 200433, China
| | - Yong-Hua Huang
- Department of Neurology, General Army Hospital, Beijing 10070, China.
| | - Chun-Lei Jiang
- Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, Shanghai 200433, China.
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Sacha GL, Lam SW, Bauer SR. Did the beneficial renal outcomes with vasopressin VANISH? ANNALS OF TRANSLATIONAL MEDICINE 2016; 4:S67. [PMID: 27868035 DOI: 10.21037/atm.2016.10.59] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- Gretchen L Sacha
- Department of Pharmacy, Cleveland Clinic, Cleveland, Ohio 44195, USA
| | - Simon W Lam
- Department of Pharmacy, Cleveland Clinic, Cleveland, Ohio 44195, USA
| | - Seth R Bauer
- Department of Pharmacy, Cleveland Clinic, Cleveland, Ohio 44195, USA
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Monsieurs K, Nolan J, Bossaert L, Greif R, Maconochie I, Nikolaou N, Perkins G, Soar J, Truhlář A, Wyllie J, Zideman D. Kurzdarstellung. Notf Rett Med 2015. [DOI: 10.1007/s10049-015-0097-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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Monsieurs KG, Nolan JP, Bossaert LL, Greif R, Maconochie IK, Nikolaou NI, Perkins GD, Soar J, Truhlář A, Wyllie J, Zideman DA, Alfonzo A, Arntz HR, Askitopoulou H, Bellou A, Beygui F, Biarent D, Bingham R, Bierens JJ, Böttiger BW, Bossaert LL, Brattebø G, Brugger H, Bruinenberg J, Cariou A, Carli P, Cassan P, Castrén M, Chalkias AF, Conaghan P, Deakin CD, De Buck ED, Dunning J, De Vries W, Evans TR, Eich C, Gräsner JT, Greif R, Hafner CM, Handley AJ, Haywood KL, Hunyadi-Antičević S, Koster RW, Lippert A, Lockey DJ, Lockey AS, López-Herce J, Lott C, Maconochie IK, Mentzelopoulos SD, Meyran D, Monsieurs KG, Nikolaou NI, Nolan JP, Olasveengen T, Paal P, Pellis T, Perkins GD, Rajka T, Raffay VI, Ristagno G, Rodríguez-Núñez A, Roehr CC, Rüdiger M, Sandroni C, Schunder-Tatzber S, Singletary EM, Skrifvars MB, Smith GB, Smyth MA, Soar J, Thies KC, Trevisanuto D, Truhlář A, Vandekerckhove PG, de Voorde PV, Sunde K, Urlesberger B, Wenzel V, Wyllie J, Xanthos TT, Zideman DA. European Resuscitation Council Guidelines for Resuscitation 2015: Section 1. Executive summary. Resuscitation 2015; 95:1-80. [PMID: 26477410 DOI: 10.1016/j.resuscitation.2015.07.038] [Citation(s) in RCA: 583] [Impact Index Per Article: 58.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Koenraad G Monsieurs
- Emergency Medicine, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; Faculty of Medicine and Health Sciences, University of Ghent, Ghent, Belgium.
| | - Jerry P Nolan
- Anaesthesia and Intensive Care Medicine, Royal United Hospital, Bath, UK; School of Clinical Sciences, University of Bristol, Bristol, UK
| | | | - Robert Greif
- Department of Anaesthesiology and Pain Medicine, University Hospital Bern, Bern, Switzerland; University of Bern, Bern, Switzerland
| | - Ian K Maconochie
- Paediatric Emergency Medicine Department, Imperial College Healthcare NHS Trust and BRC Imperial NIHR, Imperial College, London, UK
| | | | - Gavin D Perkins
- Warwick Medical School, University of Warwick, Coventry, UK; Heart of England NHS Foundation Trust, Birmingham, UK
| | - Jasmeet Soar
- Anaesthesia and Intensive Care Medicine, Southmead Hospital, Bristol, UK
| | - Anatolij Truhlář
- Emergency Medical Services of the Hradec Králové Region, Hradec Králové, Czech Republic; Department of Anaesthesiology and Intensive Care Medicine, University Hospital Hradec Králové, Hradec Králové, Czech Republic
| | - Jonathan Wyllie
- Department of Neonatology, The James Cook University Hospital, Middlesbrough, UK
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Maconochie IK, Bingham R, Eich C, López-Herce J, Rodríguez-Núñez A, Rajka T, Van de Voorde P, Zideman DA, Biarent D, Monsieurs KG, Nolan JP. European Resuscitation Council Guidelines for Resuscitation 2015. Resuscitation 2015; 95:223-48. [DOI: 10.1016/j.resuscitation.2015.07.028] [Citation(s) in RCA: 217] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
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Silverstein DC, Santoro Beer KA. Controversies regarding choice of vasopressor therapy for management of septic shock in animals. J Vet Emerg Crit Care (San Antonio) 2015; 25:48-54. [DOI: 10.1111/vec.12282] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2014] [Accepted: 10/26/2014] [Indexed: 12/22/2022]
Affiliation(s)
- Deborah C. Silverstein
- From the Department of Clinical Studies; University of Pennsylvania; Philadelphia PA 19104-6010
| | - Kari A. Santoro Beer
- From the Department of Clinical Studies; University of Pennsylvania; Philadelphia PA 19104-6010
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Bai X, Yu W, Ji W, Lin Z, Tan S, Duan K, Dong Y, Xu L, Li N. Early versus delayed administration of norepinephrine in patients with septic shock. CRITICAL CARE (LONDON, ENGLAND) 2014. [PMID: 25277635 DOI: 10.1186/s13054-014-0532-y.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
INTRODUCTION This study investigated the incidence of delayed norepinephrine administration following the onset of septic shock and its effect on hospital mortality. METHODS We conducted a retrospective cohort study using data from 213 adult septic shock patients treated at two general surgical intensive care units of a tertiary care hospital over a two year period. The primary outcome was 28-day mortality. RESULTS The 28-day mortality was 37.6% overall. Among the 213 patients, a strong relationship between delayed initial norepinephrine administration and 28-day mortality was noted. The average time to initial norepinephrine administration was 3.1 ± 2.5 hours. Every 1-hour delay in norepinephrine initiation during the first 6 hours after septic shock onset was associated with a 5.3% increase in mortality. Twenty-eight day mortality rates were significantly higher when norepinephrine administration was started more than or equal to 2 hours after septic shock onset (Late-NE) compared to less than 2 hours (Early-NE). Mean arterial pressures at 1, 2, 4, and 6 hours after septic shock onset were significantly higher and serum lactate levels at 2, 4, 6, and 8 hours were significantly lower in the Early-NE than the Late-NE group. The duration of hypotension and norepinephrine administration was significantly shorter and the quantity of norepinephrine administered in a 24-hour period was significantly less for the Early-NE group compared to the Late-NE group. The time to initial antimicrobial treatment was not significantly different between the Early-NE and Late-NE groups. CONCLUSION Our results show that early administration of norepinephrine in septic shock patients is associated with an increased survival rate.
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Bai X, Yu W, Ji W, Lin Z, Tan S, Duan K, Dong Y, Xu L, Li N. Early versus delayed administration of norepinephrine in patients with septic shock. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2014; 18:532. [PMID: 25277635 PMCID: PMC4194405 DOI: 10.1186/s13054-014-0532-y] [Citation(s) in RCA: 181] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/09/2014] [Accepted: 09/04/2014] [Indexed: 12/13/2022]
Abstract
Introduction This study investigated the incidence of delayed norepinephrine administration following the onset of septic shock and its effect on hospital mortality. Methods We conducted a retrospective cohort study using data from 213 adult septic shock patients treated at two general surgical intensive care units of a tertiary care hospital over a two year period. The primary outcome was 28-day mortality. Results The 28-day mortality was 37.6% overall. Among the 213 patients, a strong relationship between delayed initial norepinephrine administration and 28-day mortality was noted. The average time to initial norepinephrine administration was 3.1 ± 2.5 hours. Every 1-hour delay in norepinephrine initiation during the first 6 hours after septic shock onset was associated with a 5.3% increase in mortality. Twenty-eight day mortality rates were significantly higher when norepinephrine administration was started more than or equal to 2 hours after septic shock onset (Late-NE) compared to less than 2 hours (Early-NE). Mean arterial pressures at 1, 2, 4, and 6 hours after septic shock onset were significantly higher and serum lactate levels at 2, 4, 6, and 8 hours were significantly lower in the Early-NE than the Late-NE group. The duration of hypotension and norepinephrine administration was significantly shorter and the quantity of norepinephrine administered in a 24-hour period was significantly less for the Early-NE group compared to the Late-NE group. The time to initial antimicrobial treatment was not significantly different between the Early-NE and Late-NE groups. Conclusion Our results show that early administration of norepinephrine in septic shock patients is associated with an increased survival rate.
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Reardon DP, DeGrado JR, Anger KE, Szumita PM. Early vasopressin reduces incidence of new onset arrhythmias. J Crit Care 2014; 29:482-5. [PMID: 24747036 DOI: 10.1016/j.jcrc.2014.03.005] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2014] [Revised: 03/05/2014] [Accepted: 03/11/2014] [Indexed: 10/25/2022]
Abstract
PURPOSE The objective of this study was to determine the effect of early vs late vasopressin therapy on catecholamine dose and duration. MATERIALS AND METHODS We conducted a single-center, retrospective chart review of adult patients admitted to the medical intensive care unit between January 2010 and December 2011 with septic shock requiring catecholamine and vasopressin therapy. Patients were included in the early group if vasopressin was initiated within 6 hours and the late group if vasopressin was initiated between 6 and 48 hours of catecholamine(s). RESULTS Duration of catecholamine and vasopressin therapy was similar between the 35 patients in the early group and the 36 in the late group. Vasopressin therapy was associated with a decrease in catecholamine requirements in both groups. Early vasopressin was associated with fewer new onset arrhythmias (37.1% vs 62.9%, P<.001). There was no difference in mortality, hospital, or intensive care unit length of stay between the early and late group vasopressin groups (88.6% vs 88.9%, P=1; 14 vs 10 days, P=.48; 9 vs 7 days, P=.71, respectively). CONCLUSIONS Early initiation of vasopressin therapy in adult critically ill patients with septic shock was associated with no difference in total catecholamine requirements but decreased incidence of new onset arrhythmias.
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Affiliation(s)
- David P Reardon
- Department of Pharmacy Services, Brigham and Women's Hospital, Boston, MA.
| | - Jeremy R DeGrado
- Department of Pharmacy Services, Brigham and Women's Hospital, Boston, MA
| | - Kevin E Anger
- Department of Pharmacy Services, Brigham and Women's Hospital, Boston, MA
| | - Paul M Szumita
- Department of Pharmacy Services, Brigham and Women's Hospital, Boston, MA
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Clinical trials comparing norepinephrine with vasopressin in patients with septic shock: a meta-analysis. Mil Med Res 2014; 1:6. [PMID: 25722864 PMCID: PMC4336114 DOI: 10.1186/2054-9369-1-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2014] [Accepted: 04/17/2014] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND The effect of norepinephrine in patients with septic shock remains controversial. We conducted a meta-analysis to compare the mortality rates and benefits of norepinephrine and vasopressin. METHODS PubMed, EMBASE, and the Cochrane Library database were searched from database inception to December 2013. We selected randomized controlled trials in adults with septic shock and compared norepinephrine with vasopressin. After assessing the heterogeneity of treatment effects across trials using the I (2) statistic, we used a fixed effects model (P ≥ 0.1) and expressed the results as risk ratios (RRs) for dichotomous outcomes or as standardized mean differences (SMDs) for continuous data with 95% confidence intervals (CIs). Meta-analysis was conducted using Review Manager 5.1 software. RESULTS Seven trials (n = 2323) met the inclusion criteria. Overall, the mortality rate in these seven trials was 36.2% (840/2323). There was no difference in mortality following the use of norepinephrine or vasopressin (RR 1.07; 95%CI 0.97-1.20; P = 0.19). Compared to norepinephrine, vasopressin had no significant effect on heart rate (HR) (SMD 0.21; 95%CI -0.08-0.50; P = 0.15), mean arterial pressure (MAP) (SMD 0.15; 95%CI -0.15-0.44; P = 0.33), cardiac index (CI) (SMD -0.10; 95%CI -0.64-0.44; P = 0.73), systemic vascular resistance index (SVRI) (SMD 0.15; 95%CI -0.39-0.70; P = 0.58), oxygen delivery (DO2) (SMD -0.06; 95%CI -0.62-0.49; P = 0.82), oxygen consumption (VO2) (SMD 0.03; 95%CI -0.52-0.59; P = 0.91) or lactic acid (SMD 0.07; 95%CI -0.23-0.36; P = 0.66). No significant heterogeneity was found in these comparisons (P ≥ 0.1). CONCLUSIONS There is not sufficient evidence to prove conclusively that norepinephrine is superior to vasopressin in terms of mortality and hemodynamics. The effects of norepinephrine and vasopressin on patients with septic shock require further study in large randomized controlled trials.
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