Methylene Blue Reduces Mortality in Critically Ill and Perioperative Patients: A Meta-Analysis of Randomized Trials.

Vasodilatory hypotension is common in critically ill and perioperative patients, and is associated with adverse outcomes. As a nitric oxide production inhibitor, methylene blue (MB) exerts its vasoconstrictor property and is an adjuvant for catecholamine-refractory vasodilatory shock. However, the effects of MB on clinically relevant outcomes remain unclear. Therefore, the authors performed a meta-analysis of randomized trials on MB in critically ill and perioperative patients. The authors searched through databases for randomized trials on MB in critically ill and perioperative patients, which yielded 11 studies consisting of 556 patients. The primary outcome was mortality at the longest follow-up. Secondary outcomes included hemodynamic parameters and organ dysfunction (PROSPERO: CRD42023409243). Nine out of the 11 included randomized trials reported mortality, which was significantly lower in the MB group (risk ratio, 0.60 [95% CI 0.43-0.84] p = 0.003), with findings confirmed in septic shock and cardiac surgery subgroups. The authors found reduced lengths of stay in the intensive care unit (mean difference [MD], -0.9 days [95% CI -1.06 to -0.77] p < 0.001) and in the hospital (MD, -2.2 days [95% CI, -2.68 to -1.70] p < 0.001) in the MB group. MB was associated with increased mean arterial pressure (MD, 8.4 mmHg [95% CI 5.01-11.75] p < 0.001) and systemic vascular resistance (MD, 94.5 dyn/s/cm5 [95% CI 17.73-171.15] p = 0.02), with no difference in cardiac output (standardized MD, 0.16 [95% CI, -0.25 to 0.57] p = 0.45). This meta-analysis showed that MB reverses vasodilation in critically ill and perioperative patients and might improve survival. Further adequately powered randomized trials are needed to confirm these findings.

Gender-gap in randomized clinical trials reporting mortality in the perioperative setting and critical care: 20 years behind the scenes.

Background: Women researchers might experience obstacles in academic environments and might be underrepresented in the authorship of articles published in peer-reviewed journals. Material and Methods: This is a cross-sectional analysis of female-led RCTs describing all interventions reducing mortality in critically ill and perioperative patients from 1981 to December 31, 2020. We searched PubMed/MEDLINE and EMBASE with the keywords RCTs and mortality. The gender of the first author was extracted and descriptive analysis was performed including the year of publication, impact factor, country of the first author, and methodological aspects. Results: We analyzed 340 RCTs, of which 42 (12%) were led by female researchers. The presence of women increased from 8% (14/172) until 2010 up to 17% (28/168) in 2010 and beyond. The United States, the United Kingdom, and Brazil were the main countries of origin of female researchers. Women authors conducted mainly single-center and single-nation studies as compared to male authors. The median impact factor of the target journal was 6 (3-27) in women vs. 7 (3-28) in men, with a p-value of 0.67; Critical Care Medicine, JAMA, and The New England Journal of Medicine were the most frequent target journals for both women and men. Conclusion: In the last 40 years, only one out of eight RCTs had a woman as the first author but the presence of women increased up to 17% by 2010 and beyond. The impact factor of publication target journals was high and not different between genders.

Refractory out-of-hospital cardiac arrest and extracorporeal cardiopulmonary resuscitation: A meta-analysis of randomized trials.

BACKGROUND: In adults with refractory out-of-hospital cardiac arrest, when conventional cardiopulmonary resuscitation (CPR) alone does not achieve return of spontaneous circulation, extracorporeal CPR is attempted to restore perfusion and improve outcomes. Considering the contrasting findings of recent studies, we conducted a meta-analysis of randomized controlled trials to ascertain the effect of extracorporeal CPR on survival and neurological outcome. METHODS: Pubmed via MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched up to February 3, 2023, for randomized controlled trials comparing extracorporeal CPR versus conventional CPR in adults with refractory out-of-hospital cardiac arrest. Survival with a favorable neurological outcome at the longest follow-up available was the primary outcome. RESULTS: Among four randomized controlled trials included, extracorporeal CPR compared with conventional CPR increased survival with favorable neurological outcome at the longest follow-up available for all rhythms (59/220 [27%] vs. 39/213 [18%]; OR = 1.72; 95% CI, 1.09-2.70; p = 0.02; I2  = 26%; number needed to treat of 9), for initial shockable rhythms only (55/164 [34%] vs. 38/165 [23%]; OR = 1.90; 95% CI, 1.16-3.13; p = 0.01; I2  = 23%; number needed to treat of 7), and at hospital discharge or 30 days (55/220 [25%] vs. 34/212 [16%]; OR = 1.82; 95% CI, 1.13-2.92; p = 0.01; I2  = 0.0%). Overall survival at the longest follow-up available was similar (61/220 [25%] vs. 34/212 [16%]; OR = 1.82; 95% CI, 1.13-2.92; p = 0.59; I2  = 58%). CONCLUSIONS: Extracorporeal CPR compared with conventional CPR increased survival with favorable neurological outcome in adults with refractory out-of-hospital cardiac arrest, especially when the initial rhythm was shockable. REVIEW REGISTRATION: PROSPERO CRD42023396482.

Inhaled Sedation for Invasively Ventilated COVID-19 Patients: A Systematic Review.

Background: Volatile anesthetics were used as sedative agents in COVID-19 (Coronavirus Disease 2019) invasively ventilated patients for their potentially beneficial pharmacological effects and due to the temporary shortages of intravenous agents during the pandemic crisis. Methods: Online databases (PubMed, EMBASE, The Cochrane Central Register of Controlled Trial) and the "clinicaltrials.gov" website were searched for studies reporting the use of isoflurane, sevoflurane or desflurane. Results: We identified three manuscripts describing the beneficial effects of isoflurane on 41 COVID-19 patients with acute respiratory distress syndrome (ARDS) in Germany (n = 2) and in the USA (n = 1), in terms of reduction in the use of opioids and other sedatives. We also found a case report of two patients with transient nephrogenic diabetes insipidus, which started after 6 and 8 days of sevoflurane sedation. We identified two randomized controlled trials (RCTs; 92 patients overall), two observational studies (238 patients) on the use of volatile anesthetics in COVID-19 patients that were completed but not yet published, and one RCT interrupted for a low recruitment ratio (19 patients) and thus not published. We also identified five ongoing RCTs on the use of inhaled sedation in ARDS, which are also likely to be recruiting COVID-19 patients and which have currently enrolled a total of >1643 patients. Conclusion: Isoflurane was the most frequently used volatile agent in COVID-19 patients and allowed a reduction in the use of other sedative and analgesic drugs. Randomized evidence is building up and will be useful to confirm or challenge these findings.

Extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A systematic review and meta-analysis of randomized and propensity score-matched studies.

BACKGROUND: In selected patients with refractory out-of-hospital cardiac arrest, extracorporeal cardiopulmonary resuscitation represents a promising approach when conventional cardiopulmonary resuscitation fails to achieve return of spontaneous circulation. This systematic review and meta-analysis aimed to compare extracorporeal cardiopulmonary resuscitation to conventional cardiopulmonary resuscitation. METHODS: We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials up to November 28, 2021, for randomized trials and observational studies reporting propensity score-matched data and comparing adults with out-of-hospital cardiac arrest treated with extracorporeal cardiopulmonary resuscitation with those treated with conventional cardiopulmonary resuscitation. The primary outcome was survival with favorable neurological outcome at the longest follow-up available. Secondary outcomes were survival at the longest follow-up available and survival at hospital discharge/30 days. RESULTS: We included six studies, two randomized and four propensity score-matched studies. Patients treated with extracorporeal cardiopulmonary resuscitation had higher rates of survival with favorable neurological outcome (81/584 [14%] vs. 46/593 [7.8%]; OR = 2.11; 95% CI, 1.41-3.15; p < 0.001, number needed to treat 16) and of survival (131/584 [22%] vs. 102/593 [17%]; OR = 1.40; 95% CI, 1.05-1.87; p = 0.02) at the longest follow-up available compared with conventional cardiopulmonary resuscitation. Survival at hospital discharge/30 days was similar between the two groups (142/584 [24%] vs. 122/593 [21%]; OR = 1.26; 95% CI, 0.95-1.66; p = 0.10). CONCLUSIONS: Evidence from randomized trials and propensity score-matched studies suggests increased survival and favorable neurological outcome in patients with refractory out-of-hospital cardiac arrest treated with extracorporeal cardiopulmonary resuscitation. Large, multicentre randomized studies are still ongoing to confirm these findings.