Background Intravenous fluids are used commonly for almost all intensive care unit (ICU) patients, especially for patients in need of resuscitation. The selection and use of resuscitation fluids may affect the outcomes of patients; however, the optimal resuscitative fluid remains controversial. Methods We systematically searched PubMed, Embase, and CENTRAL. Studies comparing balanced crystalloids and normal saline in ICU patients were selected. We used the Cochrane Collaboration tool to assess the risk of bias in studies. The primary outcome was mortality at the longest follow-up. Secondary outcomes included the incidence of acute kidney injury (AKI) and new renal replacement therapy (RRT). Results A total of 35,456 patients from eight studies were included. There was no significant difference between balanced crystalloid solutions and saline in mortality (risk ratio [RR]: 0.96; 95% confidence interval [CI]:0.92–1.01). The subgroup analysis with traumatic brain injury (TBI) showed lower mortality in patients receiving normal saline (RR:1.25; 95% CI 1.02–1.54). However, in patients with non-TBI, balanced crystalloid solutions achieved lower mortality than normal saline (RR: 0.94; 95% CI 0.90–0.99). There was no significant difference in moderate to severe AKI (RR: 0.96; 95% CI 0.90–1.01) or new RRT (RR: 0.94; 95% CI 0.84–1.04). Conclusions Compared with normal saline, balanced crystalloids may not improve the outcomes of mortality, the incidence of AKI, and the use of RRT for critically ill patients. However, balanced crystalloids reduce the risk of death in patients with non-TBI but increase the risk of death in those with TBI. Large-scale rigorous randomized trials with better designs are needed, especially for specific patient populations.

Background: Up to 80% of patients in the intensive care unit (ICU) suffer from delirium. Studies on the preventative use of melatonin in the ICU have produced mixed results. We performed a systematic review and meta-analysis to evaluate whether early administration of melatonin reduces the prevalence of delirium in critically ill patients.Methods: We searched Medline, Embase, and the Cochrane Library for randomized controlled trials comparing melatonin or melatonin agonists to placebo in ICU setting. The population included adult patients in the ICU. The primary outcome was the prevalence of delirium. Secondary outcomes included duration of delirium, delirium-free day, serum melatonin concentration, need for sedation, duration of mechanical ventilation, hospital and ICU length of stay (LOS), all-cause mortality, sleep quality, and adverse events. Trial sequential analysis (TSA) was performed on the primary outcome to prevent the risk of random error and multiplicity phenomenon as a result of repeated significance testing across all the included trials.Results: Twelve trials with a total of 2538 patients were analyzed. When all trials were pooled, the incidence of delirium in ICU patients who received melatonin was significantly lower than in those who received placebo (risk ratio, 0.77; 95% confidence interval: 0.61-0.96; I 2 = 56%). There were no significant differences in secondary outcomes including duration of delirium, duration of mechanical ventilation, ICU LOS, hospital LOS, and mortality. TSA indicated that Z-curve crossed the traditional boundary, but did not cross the monitoring boundary for benefit, which indicated that it is still inconclusive that melatonin affects the incidence of delirium.Conclusions: This meta-analysis found that early administration of melatonin may result in a decreased delirium prevalence in critically ill patients. However, the sensitivity analysis of high-quality studies did not support this finding. In addition, TSA demonstrated that the result may have false-positive error. Therefore, this finding should be interpreted with caution. Further studies are needed to examine the effectiveness of prophylactic melatonin on the prevalence and duration of ICU delirium in the future.

ObjectiveTo demonstrate the therapeutic effect of vasopressin as an alternative treatment for cardiac arrest.DesignSystematic review and meta-analysis.MethodsPubMed, EMBASE, the Cochrane Library and Web of Science were searched for randomised controlled trials. The intervention included administration of vasopressin alone or vasopressin combined with epinephrine or vasopressin, steroids and epinephrine (VSE) versus epinephrine combined with placebo as control group. The primary outcome was the return of spontaneous circulation (ROSC). The secondary outcomes included mid-term survival and mid-term good neurological outcome. We conducted subgroup analyses of the primary outcome based on different settings, different study drug strategies and different types of initial rhythm.ResultsTwelve studies (n=6718) were included, of which eight trials (n=5638) reported the data on patients with out-of-hospital cardiac arrest and four trials (n=1080) on patients with in-hospital cardiac arrest (IHCA). There were no significant differences between intravenous vasopressin and placebo in the outcomes of ROSC (relative risk (RR): 1.11; 95% CI: 0.99 to 1.26), mid-term survival (RR: 1.23; 95% CI: 0.90 to 1.66) and mid-term good neurological outcome (RR: 1.20; 95% CI: 0.77 to 1.87). However, in the subgroup analysis, intravenous vasopressin as part of VSE can significantly improve the rate of ROSC (RR: 1.32; 95% CI: 1.18 to 1.47) but not the rate of mid-term survival (RR: 2.15; 95% CI: 0.75 to 6.16) and mid-term good neurological outcome (RR: 1.80; 95% CI: 0.81 to 4.01) for patients with IHCA.ConclusionsOur study failed to demonstrate increased benefit from vasopressin with or without epinephrine compared with the standard of care. However, vasopressin as a part of VSE is associated with the improvement of ROSC in patients with IHCA, and the benefit on mid‐term survival or mid-term good neurological outcome is uncertain. Larger trials should be conducted in the future to address the effect of vasopressin only, vasopressin plus epinephrine or VSE on cardiac arrest.PROSPERO registration numberCRD42021293347.