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1.
The effect of early vasopressin use on patients with septic shock: A systematic review and meta-analysis
Huang H, Wu C, Shen Q, Xu H, Fang Y, Mao W
The American journal of emergency medicine. 2021;48:203-208
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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2.
[Effect of terlipressin on prognosis of adult septic shock patients: a Meta-analysis]
Li W, Pan P, Wang Y, Du X, Yu X
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2020;32(2):134-139
Abstract
OBJECTIVE To investigate the effect of terlipressin on prognosis of adult septic shock patients. METHODS All randomized controlled clinical trials (RCT) of terlipressin in the treatment of adult septic shock patients from January 1980 to December 2019 were retrieved from CNKI, Wanfang, SinoMed, PubMed, Embase, Springer Link, Cochrane Library, Google Scholar, and etc. Patients in the treatment group received terlipressin while patients in the control group received norepinephrine or other vasopressors. Main outcome indicator was mortality. Secondary outcome indicators included the incidence of severe adverse events, limb peripheral ischemic events and renal complications. Literature screening, data extraction and quality evaluation were conducted by two researchers respectively. Meta-analysis was performed with RevMan 5.3 software. Funnel plot was used to analyze the publication bias. RESULTS A total of 507 related literatures were retrieved. According to the inclusion and exclusion criteria, 8 RCT studies were finally included, with a total of 811 patients. One study was considered to have a lower risk of bias, 6 studies had uncertain risk of bias, and 1 study had a higher risk of bias. The Meta-analysis showed that terlipressin did not significantly improve the mortality of septic shock patients compared with the control group [odds ratio (OR) = 0.89, 95% confidence interval (95%CI) was 0.67-1.19, P = 0.45]; increased the incidence of severe adverse events (OR = 2.98, 95%CI was 1.99-4.45, P < 0.000 01); there was a tendency to increase the incidence of limb peripheral ischemic events, but without statistical difference (OR = 10.81, 95%CI was 0.88-133.19, P = 0.06); and reduced the incidence of renal complications (OR = 0.30, 95%CI was 0.09-0.96, P = 0.04). Funnel plot analysis indicated that there might be publication bias in a study on case fatality and incidence of serious adverse events in the included literature. No significant publication bias was found in studies on the incidence of limb peripheral ischemic events and the incidence of kidney-related complications. CONCLUSIONS The available evidence suggests that terlipressin could not significantly improve mortality in adult's septic shock patients, but it may reduce the incidence of renal complications. A tendency to increase the incidence of limb peripheral ischemic events in the terlipressin-treated group needs to be emphasized.
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3.
Clinical Efficiency of Vasopressin or Its Analogs in Comparison With Catecholamines Alone on Patients With Septic Shock: A Systematic Review and Meta-Analysis
Yao RQ, Xia DM, Wang LX, Wu GS, Zhu YB, Zhao HQ, Liu Q, Xia ZF, Ren C, Yao YM
Front Pharmacol. 2020;11:563
Abstract
Background: Vasopressin is an efficient remedy for septic shock patients as its great capacity in promoting hemodynamic stabilization. The aim of current systematic review and meta-analysis is to compare the clinical efficiency of vasopressin or its analogs with sole catecholamines on patients with septic shock. Methods: A systematic search of Cochrane Library, EMBASE, and PubMed online databases was performed up to 30 Oct 2019 to identify randomized controlled trials comparing use of vasopressin or its analogs (e.g., terlipressin, selepressin) with administration of catecholamines alone. Results: We included 23 RCTs with 4,225 patients in the current study. Compared with solely use of catecholamines, administration of vasopressin or its analogs was not associated with reduced 28-day or 30-day mortality among patients with septic shock [RR=0.94 (95% CI, 0.87-1.01), P=0.08, I(2) = 0%]. The result of primary endpoint remained unchanged after conducting sensitivity analysis. Despite a significantly higher risk of digital ischemia in patients receiving vasopressin or its analogs [RR=2.65 (95% CI, 1.26-5.56), P < 0.01, I(2) = 48%], there was no statistical significance in the pooled estimate for other secondary outcomes, including total adverse events, arrhythmia, acute myocardial infarction (AMI) and cardiac arrest, acute mesenteric ischemia, ICU/hospital length of stay, and mechanical ventilation (MV) duration. Conclusions: The administration of vasopressin or its analogs was not associated with reduced 28-day or 30-day mortality among patients with septic shock, while an increased incidence of digital ischemia should be noted in patients receiving agonists for vasopressin receptors.
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4.
Terlipressin for the treatment of septic shock in adults: a systematic review and meta-analysis
Huang L, Zhang S, Chang W, Xia F, Liu S, Yang Y, Qiu H
BMC anesthesiology. 2020;20(1):58
Abstract
BACKGROUND Catecholamines are the first-line vasopressors used in patients with septic shock. However, the search for novel drug candidates is still of great importance due to the development of adrenergic hyposensitivity accompanied by a decrease in catecholamine activity. Terlipressin (TP) is a synthetic vasopressin analogue used in the management of patients with septic shock. In the current study, we aimed to compare the effects of TP and catecholamine infusion in treating septic shock patients. METHODS A systematic review and meta-analysis was conducted by searching articles published in PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials between inception and July 2018. We only selected randomized controlled trials evaluating the use of TP and catecholamine in adult patients with septic shock. The primary outcome was overall mortality. The secondary outcomes were the ICU length of stay, haemodynamic changes, tissue perfusion, renal function, and adverse events. RESULTS A total of 9 studies with 850 participants were included in the analysis. Overall, no significant difference in mortality was observed between the TP and catecholamine groups (risk ratio(RR), 0.85 (0.70 to 1.03); P = 0.09). In patients < 60 years old, the mortality rate was lower in the TP group than in the catecholamine group (RR, 0.66 (0.50 to 0.86); P = 0.002). There was no significant difference in the ICU length of stay (mean difference, MD), - 0.28 days; 95% confidence interval (CI), - 1.25 to 0.69; P = 0.58). Additionally, TP improved renal function. The creatinine level was decreased in patients who received TP therapy compared to catecholamine-treated participants (standard mean difference, SMD), - 0.65; 95% CI, - 1.09 to - 0.22; P = 0.003). No significant difference was found regarding the total adverse events (Odds Ratio(OR), 1.48(0.51 to 4.24); P = 0.47), whereas peripheral ischaemia was more common in the TP group (OR, 8.65(1.48 to 50.59); P = 0.02). CONCLUSION The use of TP was associated with reduced mortality in septic shock patients less than 60 years old. TP may also improve renal function and cause more peripheral ischaemia. PROSPERO registry: CRD42016035872.
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5.
Effects of the discontinuation sequence of norepinephrine and vasopressin on hypotension incidence in patients with septic shock: A meta-analysis
Duclos G, Baumstarck K, Dunser M, Zieleskiewicz L, Leone M
Heart & lung : the journal of critical care. 2019
Abstract
BACKGROUND Although the order of vasopressor initiation in patients with septic shock is established, limited information is available on the order of vasopressor discontinuation. METHODS We performed a meta-analysis of nine studies involving 1245 patients in whom norepinephrine (n=787) or vasopressin (n=458) was withdrawn first to compare the risk of hypotension. RESULTS The risk of hypotension increased in patients whom vasopressin was withdrawn first (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.3-8.9; p=0.01). A sensitivity analysis indicated that this effect was observed in four studies with a high risk of bias (OR, 5.4; 95%CI, 1.3-23.5; p=0.02) and was not observed in five studies with a low risk of bias (OR, 2.4; 95%CI, 0.6-8.4; p=0.18). CONCLUSION Our results suggest that the risk of hypotension is higher in patients with septic shock in whom vasopressin is withdrawn before norepinephrine.
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6.
Effects of norepinephrine and vasopressin discontinuation order in the recovery phase of septic shock: a systematic review and individual patient data meta-analysis
Hammond DA, Sacha GL, Bissell BD, Musallam N, Altshuler D, Flannery AH, Lam SW, Bauer SR
Pharmacotherapy. 2019
Abstract
OBJECTIVE The impact of vasopressin and norepinephrine discontinuation order in the recovery phase of septic shock remains controversial. This systematic review and patient-level meta-analysis was performed to determine the impact of vasopressin and norepinephrine discontinuation order on clinically significant outcomes in the recovery phase of septic shock. METHODS Cumulative Index to Nursing and Allied Health Literature, Embase, PubMed, and Clinicaltrials. gov were searched from inception through November 2018 for studies comparing outcomes after the discontinuation of vasopressin or norepinephrine in septic shock. Individual patient-level data were obtained from included studies and combined using a 2-stage meta-analysis. RESULTS Six studies of low or moderate risk of bias with 957 patients were included. Clinically significant hypotension occurred more frequently when vasopressin was discontinued first compared to norepinephrine (60.7% vs. 43.3%, respectively). First discontinuation of norepinephrine compared to vasopressin had lower pooled odds of developing clinically significant hypotension (odds ratio (OR) 0.22, 95% confidence interval (CI) 0.07-0.68, I(2) 87%). No differences were detected in short-term mortality (OR 1.12, 95% CI 0.67-1.86, I(2) 45%), intensive care unit length of stay (mean difference 0.15 day, 95% CI -1.58 to 1.88, I(2) 21%), or hospital length of stay (mean difference 1.65 days, 95% CI -0.47 to 3.76, I(2) 0%). CONCLUSIONS Discontinuation of norepinephrine prior to vasopressin during the recovery phase of septic shock resulted in less clinically significant hypotension but no difference in mortality or lengths of stay. Larger, prospective studies evaluating the impact of relative vasopressin deficiency and norepinephrine and vasopressin discontinuation order and timing on patient-centered outcomes are needed. This article is protected by copyright. All rights reserved.
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7.
Vasopressin in septic shock: an individual patient data meta-analysis of randomised controlled trials
Nagendran M, Russell JA, Walley KR, Brett SJ, Perkins GD, Hajjar L, Mason AJ, Ashby D, Gordon AC
Intensive care medicine. 2019
Abstract
PURPOSE We performed an individual patient data meta-analysis to investigate the possible benefits and harms of vasopressin therapy in adults with septic shock both overall and in pre-defined subgroups. METHODS Our pre-specified study protocol is published on PROSPERO, CRD42017071698. We identified randomised clinical trials up to January 2019 investigating vasopressin therapy versus any other vasoactive comparator in adults with septic shock. Individual patient data from each trial were compiled. Conventional two-stage meta-analyses were performed as well as one-stage regression models with single treatment covariate interactions for subgroup analyses. RESULTS Four trials were included with a total of 1453 patients. For the primary outcomes, there was no effect of vasopressin on 28-day mortality [relative risk (RR) 0.98, 95% CI 0.86-1.12] or serious adverse events (RR 1.02, 95% CI 0.82-1.26). Vasopressin led to more digital ischaemia [absolute risk difference (ARD) 1.7%, 95% CI 0.3%-3.2%] but fewer arrhythmias (ARD - 2.8%, 95% CI - 0.2% to - 5.3%). Mesenteric ischaemia and acute coronary syndrome events were similar between groups. Vasopressin reduced the requirement for renal replacement therapy (RRT) (RR 0.86, 95% CI 0.74-0.99), but this finding was not robust to sensitivity analyses. There were no statistically significant interactions in the pre-defined subgroups (baseline kidney injury severity, baseline lactate, baseline norepinephrine requirement and time to study inclusion). CONCLUSIONS Vasopressin therapy in septic shock had no effect on 28-day mortality although the confidence intervals are wide. It appears safe but with a different side effect profile from norepinephrine. The finding on reduced RRT should be interpreted cautiously. Future trials should focus on long-term outcomes in select patient groups as well as incorporating cost effectiveness analyses regarding possible reduced RRT use.
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8.
The effects and safety of vasopressin receptor agonists in patients with septic shock: a meta-analysis and trial sequential analysis
Jiang L, Sheng Y, Feng X, Wu J
Critical care (London, England). 2019;23(1):91
Abstract
BACKGROUND The aim of this study was to evaluate the effects and safety of vasopressin receptor agonists in patients with septic shock. METHODS PubMed, EMBASE, and Cochrane library were searched for randomized controlled trials evaluating the effects of vasopressin receptor agonists in septic shock patients. Two reviewers performed literature selection, data extraction, and quality evaluation independently. The primary outcome was mortality. And secondary outcomes included intensive care unit (ICU) length of stay, duration of mechanical ventilation, and incidence of adverse events. In addition, a trial sequential analysis (TSA) was performed. RESULTS Twenty studies were eligible for meta-analysis. The results showed vasopressin receptor agonists use was associated with reduced mortality (relative risk (RR) 0.92; 95% confidence interval (CI) 0.84 to 0.99; I(2) = 0%). Nevertheless, they had no significant effects on ICU length of stay (mean deviation (MD) - 0.08, 95% CI, - 0.68 to 0.52, I(2) = 0%) and duration of mechanical ventilation (MD - 0.58, 95% CI - 1.47 to 0.31, I(2) = 57%). Additionally, there was no significant difference in total adverse events between two groups (RR 1.28, 95% CI 0.87 to 1.90, I(2) = 57%), but vasopressin receptor agonists administration could significantly increase the risk of digital ischemia (RR 4.85, 95% CI 2.81 to 8.39, I(2) = 26%). Finally, there was no statistical difference of cardiovascular events (RR 0.91, 95% CI 0.53 to 1.57, I(2) = 1%), arrhythmia (0.77, 95% CI 0.48 to 1.23, I(2) = 23%), mesenteric ischemia (0.83, 95% CI 0.44 to 1.55, I(2) = 0%), diarrhea (2.47, 95% CI 0.77 to 7.96, I(2) = 49%), cerebrovascular events (1.36, 95% CI 0.18 to 10.54, I(2) = 0%), and hyponatremia (1.47, 95% CI 0.84 to 2.55, I(2) = 0%) between two groups. Egger's test showed there was no significant publication bias among studies (P = 0.36). CONCLUSIONS The use of vasopressin might result in reduced mortality in patients with septic shock. An increased risk of digital ischemia must be taken into account.
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9.
Norepinephrine vs vasopressin: which vasopressor should be discontinued first in septic shock? a meta-analysis
Wu Z, Zhang S, Xu J, Xie J, Huang L, Huang Y, Yang Y, Qiu H
Shock (Augusta, Ga.). 2019
Abstract
BACKGROUND Patients with septic shock in whom Norepinephrine (NE) infusion alone is insufficient to raise blood pressure require the concomitant administration of Vasopressin (VP). However, current guidelines do not advise clinicians as to which vasoactive agent to discontinue first once the patient's septic shock begins to resolve. Moreover, there is controversial data guiding clinicians on how to discontinue vasopressors for septic shock patients who are receiving a combination therapy of NE and VP. METHODS The PubMed, Embase and Cochrane Central Register databases were searched from the database inception until October 18, 2018. Studies were limited to adult patients with septic shock who received concomitant NE and VP treatment, that included different orders of vasopressor discontinuation. The primary outcome was the incidence of hypotension. Overall mortality, ICU mortality and length of stay in the ICU (LOS) were secondary outcomes. Sensitivity and subgroup analyses, as well as trial sequential analysis (TSA), were performed. RESULTS One prospective randomized controlled trial and seven retrospective cohort studies were included in present meta-analysis. Compared with discontinuing VP first, the incidence of hypotension was significantly lower when NE was discontinued first (OR 0.3, 95% CI 0.10 to 0.86, P = 0.02; I = 91%). No significant difference was detected in either overall mortality (OR 1.28, 95% CI 0.77 to 2.10, P = 0.34) or ICU mortality (OR 0.99, 95% CI 0.74 to 1.34, P = 0.96) between these two groups. Furthermore, ICU length of stay (LOS) was also evaluated in five studies, and no statistical significance was observed between the two groups with different orders in weaning vasopressors (mean difference, 1.35, 95% CI -2.05 to 4.74, P = 0.44). The subgroup analyses suggested a significant association between hypotension and the practice of discontinuing VP first specifically in patients with a low usage rate of corticosteroids (OR 0.18, 95% CI 0.04 to 0.78, P = 0.02). The TSA indicated a lack of sufficient evidence to draw conclusions from the current results (RIS = 11,821). CONCLUSIONS In adults with septic shock treated with concomitant VP and NE therapy, discontinuing VP first may lead to a higher incidence of hypotension but is not associated with mortality or ICU LOS. Further prospective studies with larger sample sizes are warranted.
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10.
Terlipressin for septic shock patients: a meta-analysis of randomized controlled study
Zhu Y, Huang H, Xi X, Du B
Journal of intensive care. 2019;7:16
Abstract
Background: Catecholamines are commonly used in septic shock but face limitations of their hypo-responsiveness and adverse events due to high dose. Terlipressin is a synthetic vasopressin analog with greater selectivity for the V1-receptor. A meta-analysis was conducted to evaluate the efficacy and safety of terlipressin in septic shock. Methods: We searched for relevant studies in PubMed, Embase, and the Cochrane database from inception up to July 15, 2018. Randomized controlled trials (RCTs) were included if they reported data on any of the predefined outcomes in patients with septic shock and managed with terlipressin or any catecholamines. Results were expressed as risk ratio (RR) or mean difference (MD) with accompanying 95% confidence interval (CI). Heterogeneity, subgroup analysis, sensitivity analysis, and publication bias were explored. Results: Ten studies with 928 patients were included. Despite the shorter duration of mechanical ventilation, use of terlipressin did not reduce the risk of mortality (RR = 0.94; 95% CI, 0.85 to 1.05; I (2) = 0%; P = 0.28) when compared with control. This finding was confirmed by further subgroup and sensitivity analyses. In addition, lactate clearance, length of stay in ICU or hospital, total adverse events, digital ischemia, and arrhythmia were also similar between groups, while terlipressin was associated with shorter duration of mechanical ventilation and less norepinephrine requirements. Conclusions: Current results suggest terlipressin did not show added survival benefit in septic shock therapy when compared with catecholamines.