Steroids and Survival in Critically Ill Adult Patients: A Meta-analysis of 135 Randomized Trials.

OBJECTIVE: Corticosteroids have important effects on intermediate outcomes in critically ill patients, but their effect on survival is unknown. The objective of this meta-analysis was to analyze the effect on mortality of corticosteroids in critical and perioperative settings. DESIGN: A meta-analysis of randomized trials. SETTING: PubMed, Embase, BioMed Central, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched to February 1, 2018, for randomized trials comparing corticosteroids with placebo or standard care. PARTICIPANTS: Critically ill or surgical adult patients. INTERVENTIONS: Corticosteroids compared with placebo or standard care. MEASUREMENTS AND MAIN RESULTS: A total of 44,553 patients from 135 studies were included. Overall, mortality in the corticosteroid group and in the control group were similar (16% v 16%; p = 0.9). Subanalyses identified a beneficial effect of corticosteroids on survival in patients with respiratory system diseases (9% v 13%; p < 0.001) and bacterial meningitis (28% v 32%; p= 0.04), and a detrimental effect on survival in patients with traumatic brain injury (22% v 19%; p < 0.001). No differences in mortality were found in patients with cardiac diseases (7% v 6%; p = 0.7), in patients undergoing cardiac surgery (2.8% v 3.2% p = 0.14), and when treatment duration or patient age were considered. CONCLUSIONS: This meta-analysis documents the safety of corticosteroids in the overall critically ill population with the notable exception of brain injury patients, a setting where the authors confirmed their detrimental effect on survival. A possible beneficial effect of corticosteroids on survival was found among patients with respiratory diseases and in patients with bacterial meningitis.

Vasopressors During Cardiopulmonary Resuscitation. A Network Meta-Analysis of Randomized Trials.

OBJECTIVES: Several randomized controlled trials have compared adrenaline (epinephrine) with alternative therapies in patients with cardiac arrest with conflicting results. Recent observational studies suggest that adrenaline might increase return of spontaneous circulation but worsen neurologic outcome. We systematically compared all the vasopressors tested in randomized controlled trials in adult cardiac arrest patients in order to identify the treatment associated with the highest rate of return of spontaneous circulation, survival, and good neurologic outcome. DESIGN: Network meta-analysis. PATIENTS: Adult patients undergoing cardiopulmonary resuscitation. INTERVENTIONS: PubMed, Embase, BioMed Central, and the Cochrane Central register were searched (up to April 1, 2017). We included all the randomized controlled trials comparing a vasopressor with any other therapy. A network meta-analysis with a frequentist approach was performed to identify the treatment associated with the highest likelihood of survival. MEASUREMENTS AND MAIN RESULTS: Twenty-eight studies randomizing 14,848 patients in 12 treatment groups were included. Only a combined treatment with adrenaline, vasopressin, and methylprednisolone was associated with increased likelihood of return of spontaneous circulation and survival with a good neurologic outcome compared with several other comparators, including adrenaline. Adrenaline alone was not associated with any significant difference in mortality and good neurologic outcome compared with any other comparator. CONCLUSIONS: In randomized controlled trials assessing vasopressors in adults with cardiac arrest, only a combination of adrenaline, vasopressin, and methylprednisolone was associated with improved survival with a good neurologic outcome compared with any other drug or placebo, particularly in in-hospital cardiac arrest. There was no significant randomized evidence to support neither discourage the use of adrenaline during cardiac arrest.

Feasibility of Protective Ventilation During Elective Supratentorial Neurosurgery: A Randomized, Crossover, Clinical Trial.

BACKGROUND: Traditional ventilation approaches, providing high tidal volumes (Vt), produce excessive alveolar distention and lung injury. Protective ventilation, employing lower Vt and positive end-expiratory pressure (PEEP), is an attractive alternative also for neuroanesthesia, when prolonged mechanical ventilation is needed. Nevertheless, protective ventilation during intracranial surgery may exert dangerous effects on intracranial pressure (ICP). We tested the feasibility of a protective ventilation strategy in neurosurgery. MATERIALS AND METHODS: Our monocentric, double-blind, 1:1 randomized, 2×2 crossover study aimed at studying the effect size and variability of ICP in patients undergoing elective supratentorial brain tumor removal and alternatively ventilated with Vt 9 mL/kg-PEEP 0 mm Hg and Vt 7 mL/kg-PEEP 5 mm Hg. Respiratory rate was adjusted to maintain comparable end-tidal carbon dioxide between ventilation modes. ICP was measured through a subdural catheter inserted before dural opening. RESULTS: Forty patients were enrolled; 8 (15%) were excluded after enrollment. ICP did not differ between traditional and protective ventilation (11.28±5.37, 11 [7 to 14.5] vs. 11.90±5.86, 11 [8 to 15] mm Hg; P=0.541). End-tidal carbon dioxide (28.91±2.28, 29 [28 to 30] vs. 28.00±2.17, 28 [27 to 29] mm Hg; P<0.001). Peak airway pressure (17.25±1.97, 17 [16 to 18.5] vs. 15.81±2.87, 15.5 [14 to 17] mm Hg; P<0.001) and plateau airway pressure (16.06±2.30, 16 [14.5 to 17] vs. 14.19±2.82, 14 [12.5 to 16] mm Hg; P<0.001) were higher during protective ventilation. Blood pressure, heart rate, and body temperature did not differ between ventilation modes. Dural tension was "acceptable for surgery" in all cases. ICP differences between ventilation modes were not affected by ICP values under traditional ventilation (coefficient=0.067; 95% confidence interval, -0.278 to 0.144; P=0.523). CONCLUSIONS: Protective ventilation is a feasible alternative to traditional ventilation during elective neurosurgery.

Silent cerebral injury after transcatheter aortic valve implantation and the preventive role of embolic protection devices: A systematic review and meta-analysis.

BACKGROUND: The aims of this study were: 1) to evaluate silent cerebral injury detected by cerebral diffusion weighted magnetic resonance imaging (DW-MRI) after transcatheter aortic valve implantation (TAVI); and 2) to assess the efficacy of embolic protection devices (EPDs) on DW-MRI endpoints. METHODS: We included in a pooled analysis 25 prospective studies reporting post-procedural cerebral DW-MRI data after TAVI (n=1225). Among these studies, we included in a meta-analysis 6 studies investigating TAVI performed with versus without EPDs (n=384). Primary endpoints were the number of new lesions per patient and the total lesion volume, while secondary endpoints were the number of patients with new lesions and the single lesion volume. RESULTS: The main pooled DW-MRI outcomes were: patients with new ischemic lesions, 77.5% (95% confidence interval=71.7-83.3%); total lesion volume, 437.5mm(3) (286.7-588.3mm(3)); single lesion volume, 78.1mm(3) (56.7-99.5mm(3)); and number of new lesions per patient, 4.2 (3.4-5.0). The use of EPDs was associated with a significant reduction in total lesion volume (mean difference [95% confidence interval]=-111.1mm(3) [-203.6 to -18.6mm(3)]; p=0.02) and single lesion volume (-12.1mm(3) [-18.3 to -6.0mm(3)]; p=0.0001) after TAVI. CONCLUSIONS: Silent cerebral injury occurs in the majority of patients undergoing TAVI and DW-MRI allows a precise characterization of new ischemic brain lesions. EPDs reduce the total and single volume of such lesions detected after the procedure, although the number of new lesions per patient and the number of patients with new lesions are not significantly reduced by such devices.