Balanced Crystalloids versus Normal Saline in Adults with Sepsis: A Comprehensive Systematic Review and Meta-Analysis
Beran A, Altorok N, Srour O, Malhas SE, Khokher W, Mhanna M, Ayesh H, Aladamat N, Abuhelwa Z, Srour K, et al
Journal of clinical medicine. 2022;11(7)
The crystalloid fluid of choice in sepsis remains debatable. We aimed to perform a comprehensive meta-analysis to compare the effect of balanced crystalloids (BC) vs. normal saline (NS) in adults with sepsis. A systematic search of PubMed, EMBASE, and Web of Sciences databases through 22 January 2022, was performed for studies that compared BC vs. NS in adults with sepsis. Our outcomes included mortality and acute kidney injury (AKI), need for renal replacement therapy (RRT), and ICU length of stay (LOS). Pooled risk ratio (RR) and mean difference (MD) with the corresponding 95% confidence intervals (CIs) were obtained using a random-effect model. Fifteen studies involving 20,329 patients were included. Overall, BC showed a significant reduction in the overall mortality (RR 0.88, 95% CI 0.81-0.96), 28/30-day mortality (RR 0.87, 95% CI 0.79-0.95), and AKI (RR 0.85, 95% CI 0.77-0.93) but similar 90-day mortality (RR 0.96, 95% CI 0.90-1.03), need for RRT (RR 0.91, 95% CI 0.76-1.08), and ICU LOS (MD -0.25 days, 95% CI -3.44, 2.95), were observed between the two groups. However, subgroup analysis of randomized controlled trials (RCTs) showed no statistically significant differences in overall mortality (RR 0.92, 95% CI 0.82-1.02), AKI (RR 0.71, 95% CI 0.47-1.06), and need for RRT (RR 0.71, 95% CI 0.36-1.41). Our meta-analysis demonstrates that overall BC was associated with reduced mortality and AKI in sepsis compared to NS among patients with sepsis. However, subgroup analysis of RCTs showed no significant differences in both overall mortality and AKI between the groups. There was no significant difference in the need for RRT or ICU LOS between BC and NS. Pending further data, our study supports using BC over NS for fluid resuscitation in adults with sepsis. Further large-scale RCTs are necessary to validate our findings.
Mortality Benefit From the Passive Leg Raise Maneuver in Guiding Resuscitation of Septic Shock Patients: A Systematic Review and Meta-Analysis of Randomized Trials
Azadian M, Win S, Abdipour A, Kim CK, Nguyen HB
Journal of intensive care medicine. 2021;:8850666211019713
BACKGROUND Fluid therapy plays a major role in the management of critically ill patients. Yet assessment of intravascular volume in these patients is challenging. Different invasive and non-invasive methods have been used with variable results. The passive leg raise (PLR) maneuver has been recommended by international guidelines as a means to determine appropriate fluid resuscitation. We performed this systematic review and meta-analysis to determine if using this method of volume assessment has an impact on mortality outcome in patients with septic shock. METHODS This study is a systematic review and meta-analysis. We searched available data in the MEDLINE, CINAHL, EMBASE, and CENTRAL databases from inception until October 2020 for prospective, randomized, controlled trials that compared PLR-guided fluid resuscitation to standard care in adult patients with septic shock. Our primary outcome was mortality at the longest duration of follow-up. RESULTS We screened 1,425 article titles and abstracts. Of the 23 full-text articles reviewed, 5 studies with 462 patients met our eligibility criteria. Odds ratios (ORs) and associated 95% confidence intervals (CIs) for mortality at the longest reported time interval were calculated for each study. Using random effects modeling, the pooled OR (95% CI) for mortality with a PLR-guided resuscitation strategy was 0.82 (0.52 -1.30). The included studies were not blinded and they ranged from having low to high risk of bias using the Cochrane Risk of Bias Tool. CONCLUSION Our analysis showed there was no statistically significant difference in mortality among septic shock patients treated with PLR-guided resuscitation vs. those with standard care.
Is restrictive fluid resuscitation beneficial not only for hemorrhagic shock but also for septic shock?: A meta-analysis
Jiang S, Wu M, Lu X, Zhong Y, Kang X, Song Y, Fan Z
BACKGROUND Whether to use limited fluid resuscitation (LFR) in patients with hemorrhagic shock or septic shock remains controversial. This research was aimed to assess the pros and cons of utilizing LFR in hemorrhagic shock or septic shock patients. METHODS PubMed, Cochrane Library, Embase, Web of science, CNKI, VIP, and Wan Fang database searches included for articles published before December 15, 2020. Randomized controlled trials of LFR or adequate fluid resuscitation in hemorrhagic shock or septic shock patients were selected. RESULT This meta-analysis including 28 randomized controlled trials (RCTs) and registered 3288 patients. The 7 of 27 RCTs were the patients with septic shock. Others were traumatic hemorrhagic shock patients. Comparing LFR or adequate fluid resuscitation in hemorrhagic shock or septic shock patients, the summary odds ratio (OR) was 0.50 (95% confidence interval [CI] 0.42-0.60, P < .00001) for mortality, 0.46 (95% CI 0.31-0.70, P = .0002) for multiple organ dysfunction syndrome (MODS), 0.35 (95% CI 0.25-0.47) for acute respiratory distress syndrome (ARDS), and 0.33 (95% CI 0.20-0.56) for disseminated intravascular coagulation (DIC). CONCLUSION Limited fluid resuscitation is the benefit of both traumatic hemorrhagic shock patients and septic shock patients.
Mortality benefit of crystalloids administered in 1-6 hours in septic adults in the ED systematic review with narrative synthesis
Xantus GZ, Allen P, Norman S, Kanizsai PL
Emergency medicine journal : EMJ. 2021
BACKGROUND Based on the 2018 update of the Surviving Sepsis Campaign, the Committee for Quality Improvement of the NHSs of England recommended the instigation of the elements of the 'Sepsis-6 bundle' within 1 hour to adult patients screened positive for sepsis. This bundle includes a bolus infusion of 30 mL/kg crystalloids in the ED. Besides the UK, both in the USA and Australia, compliance with similar 1-hour targets became an important quality indicator. However, the supporting evidence may neither be contemporaneous nor necessarily valid for emergency medicine settings. METHOD A systematic review was designed and registered at PROSPERO to assess available emergency medicine/prehospital evidence published between 2012 and 2020, investigating the clinical benefits associated with a bolus infusion of a minimum 30 mL/kg crystalloids within 1 hour to adult patients screened positive for sepsis. Due to the small number of papers that addressed this volume of fluids in 1 hour, we expanded the search to include studies looking at 1-6 hours. RESULTS Seven full-text articles were identified, which investigated various aspects of the fluid resuscitation in adult sepsis. However, none answered completely to the original research question aimed to determine either the effect of time-to-crystalloids or the optimal fluid volume of resuscitation. Our findings demonstrated that in the USA/UK/Australia/Canada, adult ED septic patients receive 23-43 mL/kg of crystalloids during the first 6 hours of resuscitation without significant differences either in mortality or in adverse effects. CONCLUSION This systematic review did not find high-quality evidence supporting the administration of 30 mL/kg crystalloid bolus to adult septic patients within 1 hour of presentation in the ED. Future research must investigate both the benefits and the potential harms of the recommended intervention.
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
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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.
Use of hydroxyethyl starch in sepsis research: A systematic review with meta-analysis
Johansen JR, Perner A, Brodtkorb JH, Møller MH
Acta anaesthesiologica Scandinavica. 2021
BACKGROUND After being used for more than a decade the use of hydroxyethyl starch (HES) 130/0.38-0.45 in clinical practice was discouraged because of serious adverse events including bleeding, acute kidney injury and death. But could these adverse effects have been discovered sooner? By comparing the summary effect estimates of the adverse effects of HES 130/0.38-0.45 in different study designs we aimed to disclose any signal of this. METHODS We systematically searched MEDLINE, EMBASE and Cochrane Library and hand-searched the reference lists of relevant studies to identify studies for inclusion. Eligible trials were randomised clinical trials (RCTs) and observational studies in patients with sepsis and randomised trials in animals with induced sepsis comparing HES 130/0.38-0.45 to any type of crystalloid. Relevant outcomes were all-cause mortality at longest follow-up, renal replacement therapy (RRT), acute kidney injury (AKI) and bleeding. We extracted data, conducted conventional meta-analyses and assessed risk of bias and the quality of evidence. RESULTS We included 8 RCTs including 3,273 patients, 1 observational study including 379 patients and 5 randomised animal trials including 94 test animals. There was no suggestion of interaction in subgroup analyses comparing the different study designs for any outcomes (all-cause mortality at longest follow-up P=0.33; RRT P=0.70; AKI P=0.63; bleeding P=0.20). CONCLUSIONS We observed no interaction between the summary effect estimates of RCTs, observational studies in patients and randomised animal trials for any of the outcomes. Accordingly, we found no evidence indicating that the adverse effects of HES 130/0.38-0.45 could have been discovered sooner.
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
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.
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
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.
Effect of Extracorporeal Blood Purification on Mortality in Sepsis: A Meta-Analysis and Trial Sequential Analysis
Snow TAC, Littlewood S, Corredor C, Singer M, Arulkumaran N
Blood purification. 2020;:1-11
OBJECTIVE The objective of this study was to conduct a meta-analysis and trial sequential analysis (TSA) of published randomized controlled trials (RCTs) to determine whether mortality benefit exists for extracorporeal blood purification techniques in sepsis. DATA SOURCES A systematic search on MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for RCTs was performed. STUDY SELECTION RCTs investigating the effect of extracorporeal blood purification device use on mortality among critically ill septic patients were selected. DATA EXTRACTION Mortality was assessed using Mantel-Haenszel models, and I2 was used for heterogeneity. Data are presented as odds ratios (OR); 95% confidence intervals (CIs); p values; I2. Using the control event mortality proportion, we performed a TSA and calculated the required information size using an anticipated intervention effect of a 14% relative reduction in mortality. DATA SYNTHESIS Thirty-nine RCTs were identified, with 2,729 patients. Fourteen studies used hemofiltration (n = 789), 17 used endotoxin adsorption devices (n = 1,363), 3 used nonspecific adsorption (n = 110), 2 were cytokine removal devices (n = 117), 2 used coupled plasma filtration adsorption (CPFA) (n = 207), 2 combined hemofiltration and perfusion (n = 40), and 1 used plasma exchange (n = 106). On conventional meta-analysis, hemofiltration (OR 0.56 [0.40-0.79]; p < 0.001; I2 = 0%), endotoxin removal devices (OR 0.40 [0.23-0.67], p < 0.001; I2 = 71%), and nonspecific adsorption devices (OR 0.32 [0.13-0.82]; p = 0.02; I2 = 23%) were associated with mortality benefit, but not cytokine removal (OR 0.99 [0.07-13.42], p = 0.99; I2 = 64%), CPFA (OR 0.50 [0.10-2.47]; p = 0.40; I2 = 64%), or combined hemofiltration and adsorption (OR 0.71 [0.13-3.79]; p = 0.69; I2 = 0%). TSA however revealed that based on the number of existing patients recruited for RCTs, neither hemofiltration (TSA-adjusted CI 0.29-1.10), endotoxin removal devices (CI 0.05-3.40), nor nonspecific adsorption devices (CI 0.01-14.31) were associated with mortality benefit. CONCLUSION There are inadequate data at present to conclude that the use of extracorporeal blood purification techniques in sepsis is beneficial. Further adequately powered RCTs are required to confirm any potential mortality benefit, which may be most evident in patients at greatest risk of death.
[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
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.