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Background Propofol is one of the most widely used hypnotic agents in the world. Nonetheless, propofol might have detrimental effects on clinically relevant outcomes, possibly due to inhibition of other interventions' organ protective properties. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate if propofol reduced survival compared to any other hypnotic agent in any clinical setting. Methods We searched eligible studies in PubMed, Google Scholar, and the Cochrane Register of Clinical Trials. The following inclusion criteria were used: random treatment allocation and comparison between propofol and any comparator in any clinical setting. The primary outcome was mortality at the longest follow-up available. We conducted a fixed-effects meta-analysis for the risk ratio (RR). Using this RR and 95% confidence interval, we estimated the probability of any harm (RR > 1) through Bayesian statistics. We registered this systematic review and meta-analysis in PROSPERO International Prospective Register of Systematic Reviews (CRD42022323143). Results We identified 252 randomized trials comprising 30,757 patients. Mortality was higher in the propofol group than in the comparator group (760/14,754 [5.2%] vs. 682/16,003 [4.3%]; RR = 1.10; 95% confidence interval, 1.01–1.20; p = 0.03; I 2  = 0%; number needed to harm = 235), corresponding to a 98.4% probability of any increase in mortality. A statistically significant mortality increase in the propofol group was confirmed in subgroups of cardiac surgery, adult patients, volatile agent as comparator, large studies, and studies with low mortality in the comparator arm. Conclusions Propofol may reduce survival in perioperative and critically ill patients. This needs careful assessment of the risk versus benefit of propofol compared to other agents while planning for large, pragmatic multicentric randomized controlled trials to provide a definitive answer. Graphical Abstract

Background Besides airway suctioning, patients undergoing invasive mechanical ventilation (iMV) benefit of different combinations of chest physiotherapy techniques, to improve mucus removal. To date, little is known about the clearance effects of oscillating devices on patients with acute respiratory failure undergoing iMV. This study aimed to assess (1) the effects of high-frequency chest wall oscillation (HFCWO) on lung aeration and ventilation distribution, as assessed by electrical impedance tomography (EIT), and (2) the effect of the association of HFCWO with recruitment manoeuvres (RM). Methods Sixty critically ill patients, 30 classified as normosecretive and 30 as hypersecretive, who received ≥ 48 h of iMV, underwent HFCWO; patients from both subgroups were randomized to receive RM or not, according to two separated randomization sequences. We therefore obtained four arms of 15 patients each. After baseline record (T0), HFCWO was applied for 10 min. At the end of the treatment (T1) or after 1 (T2) and 3 h (T3), EIT data were recorded. At the beginning of each step, closed tracheobronchial suctioning was performed. In the RM subgroup, tracheobronchial suctioning was followed by application of 30 cmH 2 O to the patient’s airway for 30 s. At each step, we assessed the change in end-expiratory lung impedance (ΔEELI) and in tidal impedance variation (ΔTIV), and the center of gravity (COG) through EIT. We also analysed arterial blood gases (ABGs). Results ΔTIV and COG did not differ between normosecretive and hypersecretive patients. Compared to T0, ΔEELI significantly increased in hypersecretive patients at T2 and T3, irrespective of the RM; on the contrary, no differences were observed in normosecretive patients. No differences of ABGs were recorded. Conclusions In hypersecretive patients, HFCWO significantly improved aeration of the dorsal lung region, without affecting ABGs. The application of RM did not provide any further improvements. Trial registration Prospectively registered at the Australian New Zealand Clinical Trial Registry ( www.anzctr.org.au ; number of registration: ACTRN12615001257550; date of registration: 17th November 2015).

Background We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the association of higher positive end-expiratory pressure (PEEP), as opposed to lower PEEP, with hospital mortality in adult intensive care unit (ICU) patients undergoing invasive mechanical ventilation for reasons other than acute respiratory distress syndrome (ARDS). Methods We performed an electronic search of MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials, CINAHL, and Web of Science from inception until June 16, 2021 with no language restrictions. In addition, a research-in-progress database and grey literature were searched. Results We identified 22 RCTs (2225 patients) comparing higher PEEP (1007 patients) with lower PEEP (991 patients). No statistically significant association between higher PEEP and hospital mortality was observed (risk ratio 1.02, 95% confidence interval 0.89–1.16; I 2  = 0%, p  = 0.62; low certainty of evidence). Among secondary outcomes, higher PEEP was associated with better oxygenation, higher respiratory system compliance, and lower risk of hypoxemia and ARDS occurrence. Furthermore, barotrauma, hypotension, duration of ventilation, lengths of stay, and ICU mortality were similar between the two groups. Conclusions In our meta-analysis of RCTs, higher PEEP, compared with lower PEEP, was not associated with mortality in patients without ARDS receiving invasive mechanical ventilation. Further large high-quality RCTs are required to confirm these findings.

Hypotensive state is frequently observed in several critical conditions. If an adequate mean arterial pressure is not promptly restored, insufficient tissue perfusion and organ dysfunction may develop. Fluids and catecholamines are the cornerstone of critical hypotensive states management. Catecholamines side effects such as increased myocardial oxygen consumption and development of arrhythmias are well known. Thus, in recent years, interest in catecholamine-sparing agents such as vasopressin, terlipressin and methylene blue has increased; however, few randomized trials, mostly with small sample sizes, have been performed. We therefore conducted a meta-analysis of randomized trials to investigate the effect of non-catecholaminergic vasopressors on mortality. PubMed, BioMed Central and Embase were searched (update December 31st, 2014) by two independent investigators. Inclusion criteria were: random allocation to treatment, at least one group receiving a non-catecholaminergic vasopressor, patients with or at risk for vasodilatory shock. Exclusion criteria were: crossover studies, pediatric population, non-human studies, studies published as abstract only, lack of data on mortality. Studied drugs were vasopressin, terlipressin and methylene blue. Primary endpoint was mortality at the longest follow-up available. A total of 1,608 patients from 20 studies were included in our analysis. The studied settings were sepsis (10/20 studies [50%]), cardiac surgery (7/20 [35%]), vasodilatory shock due to any cause (2/20 [19%]), and acute traumatic injury (1/20 [5%]). Overall, pooled estimates showed that treatment with non-catecholaminergic agents improves survival (278/810 [34.3%] versus 309/798 [38.7%], risk ratio = 0.88, 95% confidence interval = 0.79 to 0.98, p = 0.02). None of the drugs was associated with significant reduction in mortality when analyzed independently. Results were not confirmed when analyzing studies with a low risk of bias. Catecholamine-sparing agents in patients with or at risk for vasodilatory shock may improve survival. Further researches on this topic are needed to confirm the finding.

Background Acute kidney injury (AKI) is strongly associated with high morbidity and mortality of critically ill patients. In the last years several different biological markers with higher sensitivity and specificity for the occurrence of renal impairment have been developed in order to promptly recognize and treat AKI. Nonetheless, their potential role in improving patients’ outcome remains unclear since the effectiveness of an “earlier” initiation of renal replacement therapy (RRT) is still debated. Since one large, high-quality randomized clinical trial has been recently pubblished, we decided to perform a meta-analysis of all the RCTs ever performed on “earlier” initiation of RRT versus standard RRT in critically ill patients with AKI to evaluate its effect on major outcomes. Methods Pertinent studies were independently searched in BioMedCentral, PubMed, Embase, and Cochrane Central Register of clinical trials. The following inclusion criteria were used: random allocation to treatment (“earlier” initiation of RRT versus later/standard initiation); critically ill patients. Results Ten trials randomizing 2214 patients, 1073 to earlier initiation of RRT and 1141 to later initiation were included. No difference in mortality (43.3% (465 of 1073) for those receiving early RRT and 40.8% (466 of 1141) for controls, p  = 0.97) and survival without dependence on RRT (3.6% (34 of 931) for those receiving early RRT and 4.2% (40 of 939) for controls, p  = 0.51) were observed in the overall population. On the contrary, early initiation of RRT was associated with a significant reduction in hospital length of stay. No differences in occurrence of adverse events were observed. Conclusions Our study suggests that early initiation of RRT in critically ill patients with AKI does not provide a clinically relevant advantage when compared with standard/late initiation.

The effect of dexmedetomidine on length of intensive care unit (ICU) stay and time to extubation is still unclear. Pertinent studies were independently searched in BioMedCentral, PubMed, Embase, and the Cochrane Central Register of clinical trials (updated February first 2013). Randomized studies (dexmedetomidine versus any comparator) were included if including patients mechanically ventilated in an intensive care unit (ICU). Co-primary endpoints were the length of ICU stay (days) and time to extubation (hours). Secondary endpoint was mortality rate at the longest follow-up available. The 27 included manuscripts (28 trials) randomized 3,648 patients (1,870 to dexmedetomidine and 1,778 to control). Overall analysis showed that the use of dexmedetomidine was associated with a significant reduction in length of ICU stay (weighted mean difference (WMD) = -0.79 [-1.17 to -0.40] days, p for effect <0.001) and of time to extubation (WMD = -2.74 [-3.80 to -1.65] hours, p for effect <0.001). Mortality was not different between dexmedetomidine and controls (risk ratio = 1.00 [0.84 to 1.21], p for effect = 0.9). High heterogeneity between included studies was found. This meta-analysis of randomized controlled studies suggests that dexmedetomidine could help to reduce ICU stay and time to extubation, in critically ill patients even if high heterogeneity between studies might confound the interpretation of these results.

Statins are among the most prescribed drugs worldwide and their recently discovered anti-inflammatory effect seems to have an important role in inhibiting proinflammatory cytokine production, chemokines expression and counteracting the harmful effects of sepsis on the coagulation system. We decided to perform a meta-analysis of all randomized controlled trials ever published on statin therapy in septic patients to evaluate their effect on survival and length of hospital stay. Articles were assessed by four trained investigators, with divergences resolved by consensus. BioMedCentral, PubMed, Embase and the Cochrane Central Register of clinical trials were searched for pertinent studies. Inclusion criteria were random allocation to treatment and comparison of statins versus any comparator in septic patients. Data from 650 patients in 5 randomized controlled studies were analyzed. No difference in mortality between patients receiving statins versus control (44/322 [14%] in the statins group vs 50/328 [15%] in the control arm, RR = 0.90 [95% CI 0.65 to 1.26], p = 0.6) was observed. No differences in hospital stay (p = 0.7) were found. Published data show that statin therapy has no effect on mortality in the overall population of adult septic patients. Scientific evidence on statins role in septic patients is still limited and larger randomized trials should be performed on this topic.

Background Post-operative pulmonary complications (PPC) can develop in up to 13% of patients undergoing neurosurgical procedures and may adversely affect clinical outcome. The use of intraoperative lung protective ventilation (LPV) strategies, usually including the use of a low V t , low PEEP and low plateau pressure, seem to reduce the risk of PPC and are strongly recommended in almost all surgical procedures. Nonetheless, feasibility of LPV strategies in neurosurgical patients are still debated because the use of low Vt during LPV might result in hypercapnia with detrimental effects on cerebrovascular physiology. Aim of our study was to determine whether LPV strategies would be feasible compared with a control group in adult patients undergoing cranial or spinal surgery. Methods This single-centre, pilot randomized clinical trial was conducted at the University Hospital “Maggiore della Carità” (Novara, Italy). Adult patients undergoing major cerebral or spinal neurosurgical interventions with risk index for pulmonary post-operative complications > 2 and not expected to need post-operative intensive care unit (ICU) admission were considered eligible. Patients were randomly assigned to either LPV (Vt = 6 ml/kg of ideal body weight (IBW), respiratory rate initially set at 16 breaths/min, PEEP at 5 cmH2O and application of a recruitment manoeuvre (RM) immediately after intubation and at every disconnection from the ventilator) or control treatment (Vt = 10 ml/kg of IBW, respiratory rate initially set at 6–8 breaths/min, no PEEP and no RM). Primary outcomes of the study were intraoperative adverse events, the level of cerebral tension at dura opening and the intraoperative control of PaCO 2. Secondary outcomes were the rate of pulmonary and extrapulmonary complications, the number of unplanned ICU admissions, ICU and hospital lengths of stay and mortality. Results A total of 60 patients, 30 for each group, were randomized. During brain surgery, the number of episodes of intraoperative hypercapnia and grade of cerebral tension were similar between patients randomized to receive control or LPV strategies. No difference in the rate of intraoperative adverse events was found between groups. The rate of postoperative pulmonary and extrapulmonary complications and major clinical outcomes were similar between groups. Conclusions LPV strategies in patients undergoing major neurosurgical intervention are feasible. Larger clinical trials are needed to assess their role in postoperative clinical outcome improvements. Trial registration registered on the Australian New Zealand Clinical Trial Registry ( www.anzctr.org.au ), registration number ACTRN12615000707561.

Background Limited data existed on the burden of coronavirus disease 2019 (COVID-19) renal complications and the outcomes of the most critical patients who required kidney replacement therapy (KRT) during intensive care unit (ICU) stay. We aimed to describe mortality and renal function at 90 days in patients admitted for COVID-19 and KRT. Methods A retrospective cohort study of critically ill patients admitted for COVID-19 and requiring KRT from March 2020 to January 2022 was conducted in an Italian ICU from a tertiary care hospital. Primary outcome was mortality at 90 days and secondary outcome was kidney function at 90 days. Results A cohort of 45 patients was analyzed. Mortality was 60% during ICU stay and increased from 64% at the time of hospital discharge to 71% at 90 days. Among 90-day survivors, 31% required dialysis, 38% recovered incompletely, and 31% completely recovered renal function. The probability of being alive and dialysis-free at 3 months was 22%. Conclusions Critically ill patients with COVID-19 disease requiring KRT during ICU stay had elevated mortality rate at 90 days, with low probability of being alive and dialysis-free at 3 months. However, a non-negligible number of patients completely recovered renal function.

Background Septic shock, a critical condition characterized by organ failure, presents a substantial mortality risk in intensive care units (ICUs), with the 28-day mortality rate possibly reaching 40%. Conventional management of septic shock typically involves the administration of antibiotics, supportive care for organ dysfunction, and, if necessary, surgical intervention to address the source of infection. In recent decades, extracorporeal blood purification therapies (EBPT) have emerged as potential interventions aimed at modulating the inflammatory response and restoring homeostasis in patients with sepsis. Likewise, sequential extracorporeal therapy in sepsis (SETS) interventions offer comprehensive organ support in the setting of multiple organ dysfunction syndrome (MODS). The EROICASS study will assess and describe the utilization of EBPT in patients with septic shock. Additionally, we will evaluate the potential association between EBPT treatment utilization and 90-day mortality in septic shock cases in Italy. Methods The EROICASS study is a national, non-interventional, multicenter observational prospective cohort study. All consecutive patients with septic shock at participating centers will be prospectively enrolled, with data collection extending from intensive care unit (ICU) admission to hospital discharge. Variables including patient demographics, clinical parameters, EBPT/SETS utilization, and outcomes will be recorded using a web-based data capture system. Statistical analyses will encompass descriptive statistics, hypothesis testing, multivariable regression models, and survival analysis to elucidate the associations between EBPT/SETS utilization and patient outcomes. Conclusions The EROICASS study provides valuable insights into the utilization and outcomes of EBPT and SETS in septic shock management. Through analysis of usage patterns and clinical data, this study aims to guide treatment decisions and enhance patient care. The implications of these findings may impact clinical guidelines, potentially improving survival rates and patient outcomes in septic shock cases.