Rationale: Initial reports of case fatality rates (CFRs) among adults with coronavirus disease (COVID-19) receiving invasive mechanical ventilation (IMV) are highly variable. Objectives: To examine the CFR of patients with COVID-19 receiving IMV. Methods: Two authors independently searched PubMed, Embase, medRxiv, bioRxiv, the COVID-19 living systematic review, and national registry databases. The primary outcome was the “reported CFR” for patients with confirmed COVID-19 requiring IMV. “Definitive hospital CFR” for patients with outcomes at hospital discharge was also investigated. Finally, CFR was analyzed by patient age, geographic region, and study quality on the basis of the Newcastle-Ottawa Scale. Measurements and Results: Sixty-nine studies were included, describing 57,420 adult patients with COVID-19 who received IMV. Overall reported CFR was estimated as 45% (95% confidence interval [CI], 39–52%). Fifty-four of 69 studies stated whether hospital outcomes were available but provided a definitive hospital outcome on only 13,120 (22.8%) of the total IMV patient population. Among studies in which age-stratified CFR was available, pooled CFR estimates ranged from 47.9% (95% CI, 46.4–49.4%) in younger patients (age ≤40 yr) to 84.4% (95% CI, 83.3–85.4%) in older patients (age >80 yr). CFR was also higher in early COVID-19 epicenters. Overall heterogeneity is high (I² >90%), with nonsignificant Egger’s regression test suggesting no publication bias. Conclusions: Almost half of patients with COVID-19 receiving IMV died based on the reported CFR, but variable CFR reporting methods resulted in a wide range of CFRs between studies. The reported CFR was higher in older patients and in early pandemic epicenters, which may be influenced by limited ICU resources. Reporting of definitive outcomes on all patients would facilitate comparisons between studies. Systematic review registered with PROSPERO (CRD42020186997).

It is unclear if avoiding hyperglycemia during intensive care after acute brain injury improves morbidity, mortality, and neurologic outcome. This prospective randomized trial tested whether intensive insulin therapy affected infection rates, vasospasm, mortality, or long-term neurologic outcome in subarachnoid hemorrhage patients during their intensive care unit (ICU) stay. Comparison was made against conventional insulin therapy using a randomized trial design. The primary outcome measure was infection rate until the fourteenth postoperative day in the ICU or until patient discharge. Secondary end points were the incidence of vasospasm until the fourteenth postoperative day in the ICU or until patient discharge, and neurologic outcome and mortality at 6 months follow-up. A total of 78 patients were prospectively enrolled and randomly assigned either to conventional insulin therapy or to intensive insulin therapy (38 and 40 patients, respectively). The infection rate during the study was significantly higher in patients who received conventional insulin therapy than in patients who received intensive insulin therapy (42% vs. 27%; P3 in 22/38 patients (57.8%) in the conventional therapy group vs. 21/40 patients (52.5%) in the intensive insulin therapy group; P=0.7]. Intensive insulin therapy in patients with acute subarachnoid hemorrhage admitted to a postoperative neurosurgical ICU after surgical clipping of intracranial aneurysms decreases infection rates. The benefit of strict glycemic control on postoperative vasospasm, neurologic outcome, and mortality rates does not seem to be affected by intensive insulin therapy.

Background: Intensive insulin therapy to maintain blood glucose at or below 6.11 mM reduces morbidity and mortality after cardiac surgery and morbidity in medical intensive care unit (ICU) patients. The authors investigated the clinical safety and outcome effects of intensive insulin therapy compared to conventional insulin therapy in patients receiving postoperative intensive care after neurosurgical procedures. Methods: In this prospective randomized controlled trial, 483 patients undergoing elective or emergency brain surgery were prospectively and randomly assigned either to intensive insulin therapy (241 patients), receiving insulin titrated to maintain blood glucose levels within the range of 4.44-6.11 mM, or to conventional insulin therapy (242 patients), receiving insulin to maintain blood glucose levels below 11.94 mM. Primary endpoint was incidence of hypoglycemia (defined as blood glucose < 2.78 mM). Efficacy measures included the length of ICU stay, infection rate, and 6 months follow-up Glasgow outcome scale score and overall survival. Results: Hypoglycemia episodes were more frequent in patients receiving intensive insulin therapy, median (min-max): 8 (0-23) versus 3 (0-4); P < 0.0001. The length of stay in the ICU was shorter (6 vs. 8 days; P = 0.0001), and the infection rate was lower (25.7% vs. 39.3%; P = 0.0018). Glasgow outcome scale score and overall survival at 6 months were similar in the two groups. Conclusions: Intensive insulin therapy in patients admitted to a postoperative neurosurgical ICU after brain surgery is associated with iatrogenic hypoglycemia, but it can also reduce the infection rate and shorten the ICU stay.

Perioperative cerebral damage may be associated with surgery and anaesthesia. Pharmacological perioperative neuroprotection is associated with conflicting results. In this qualitative review of randomized controlled clinical trials on perioperative pharmacological brain neuroprotection, we report the effects of tested therapies on new postoperative neurological deficit, postoperative cognitive decline (POCD), and mortality rate. Studies were identified from Cochrane Central Register and MEDLINE and by hand-searching. Of 5904 retrieved studies, 25 randomized trials met our inclusion criteria. Tested therapies were: lidocaine, thiopental, S(+)-ketamine, propofol, nimodipine, GM1 ganglioside, lexipafant, glutamate/aspartate and xenon remacemide, atorvastatin, magnesium sulphate, erythropoietin, piracetam, rivastigmine, pegorgotein, and 17β-estradiol. The use of atorvastatin and magnesium sulphate was associated with a lower incidence of new postoperative neurological deficit. The use of lidocaine, ketamine, and magnesium sulphate was associated with controversial results on POCD. The POCD did not differ between treated patients and control group for other tested drugs (thiopental, propofol, nimodipine, GM1 ganglioside, lexipafant, glutamate/aspartate, xenon, erythropoietin, remacemide, piracetam, rivastigmine, pegorgotein, and 17β-estradiol). None of the tested drugs was associated with a reduction in mortality rate. Drugs with various mechanisms of action have been tested over time; current evidence suggests that pharmacological brain neuroprotection might reduce the incidence of new postoperative neurological deficits and POCD, while no benefits on perioperative mortality are described. Of importance from this review is the need for shared methodological approach when clinical studies on pharmacological neuroprotection are designed.

Introduction: Neurocritical care (NCC) patients often require prolonged mechanical ventilation, and they are at high risk of respiratory complications. Therefore, the potential benefit role of protective lung ventilation (PLV), which demonstrated to reduce postoperative complications in patients with acute distress respiratory syndrome, has been suggested even on NCC patients. However, PLV can increase intracranial pressure as result of permissive hypercapnia and of high airway pressures during recruitment maneuvers. The aim of this review (PROSPERO registration number: CRD42015027011) is to describe the ventilatory strategies, and in particular PLV, commonly used in NCC patients. Areas covered: We selected a total of 16 clinical studies, searching on PubMed and EMBASE databases, reporting original information on the MV on patients receiving NCC after acute brain injury, published in the last 10 years, in English language. Some of the included studies report data on a limited sample size. Expert commentary: The use of PLV techniques (PEEP, recruitment maneuvers, etc) in NCC patients is controversial. There is a wide variability among different centers in the treatment strategies and respiratory management of NCC patients, and there is the need for shared diagnostics and therapeutic studies, in order to improve the patients’ outcome.