Daily Anesthesiology Research Analysis

BACKGROUND: Patients undergoing cardiac surgery often receive red-cell transfusions, along with the associated risks and costs. Early intraoperative normovolemic hemodilution (i.e., acute normovolemic hemodilution [ANH]) is a blood-conservation technique that entails autologous blood collection before initiation of cardiopulmonary bypass and reinfusion of the collected blood after bypass weaning. More data are needed on whether ANH reduces the number of patients receiving allogeneic red-cell transfusion. METHODS: In a multinational, single-blind trial, we randomly assigned adults from 32 centers and 11 countries who were undergoing cardiac surgery with cardiopulmonary bypass to receive ANH (withdrawal of ≥650 ml of whole blood with crystalloids replacement if needed) or usual care. The primary outcome was the transfusion of at least one unit of allogeneic red cells during the hospital stay. Secondary outcomes were death from any cause within 30 days after surgery or during the hospitalization for surgery, bleeding complications, ischemic complications, and acute kidney injury. RESULTS: A total of 2010 patients underwent randomization; 1010 were assigned to ANH and 1000 to usual care. Among patients with available data, 274 of 1005 (27.3%) in the ANH group and 291 of 997 (29.2%) in the usual-care group received at least one allogeneic red-cell transfusion (relative risk, 0.93; 95% confidence interval, 0.81 to 1.07; P = 0.34). Surgery for postoperative bleeding was performed in 38 of 1004 patients (3.8%) in the ANH group and 26 of 995 patients (2.6%) in the usual-care group. Death within 30 days or during hospitalization occurred in 14 of 1008 patients (1.4%) in the ANH group and 16 of 997 patients (1.6%) in the usual-care group. Safety outcomes were similar in the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, ANH did not reduce the number of patients receiving allogeneic red-cell transfusion. (Funded by the Italian Ministry of Health; ANH ClinicalTrials.gov number, NCT03913481.).

In the intensive care unit (ICU), management of unresponsive patients with brain injury focuses on preventing secondary brain damage. Therapeutic strategies that directly promote the recovery of consciousness are urgently needed. In an investigator-initiated, randomized, placebo-controlled, double-blind, cross-over trial, we studied the effects of apomorphine and methylphenidate in ICU patients with acute disorders of consciousness (DoC). We hypothesized that these stimulants would improve consciousness biomarkers assessed by automated pupillometry (primary outcome) and clinical signs of consciousness (secondary outcome). We randomized 50 ICU patients with DoC (14 female; mean age 63 ± 10 years; 48 with non-traumatic brain injuries) to strata consisting of three consecutive treatment sessions during which apomorphine, methylphenidate or placebo were administered. In total, we administered 112 study medications, including 36 doses of apomorphine, 39 doses of methylphenidate and 37 doses of placebo. Missing administrations were due to death, ICU discharge or spontaneous consciousness recovery. Plasma concentrations of stimulants confirmed drug exposure. We found no adverse events related to the trial drugs. Pupillometry recordings of sufficient quality (n = 590) were available from 48 (96%) patients. A pupillary response to a verbal arithmetic command (i.e. ≥3 pupillary dilations on five verbal arithmetic tasks) was identified during 70 (12%) of these recordings. Seven (15%) patients without any other observable response to spoken commands also passed a stricter threshold of ≥4 pupillary dilations, suggesting cognitive motor dissociation. Apomorphine [odds ratio (OR) 1.35, 95% confidence interval (CI): 0.93 to 1.96] and methylphenidate (OR 1.29, 95% CI: 0.89 to 1.86) did not significantly increase pupillary responses. However, after study drug administration, 10 (20%) patients showed improved clinical arousal at least once. Signs of arousal were noted after one dose of placebo, four doses of apomorphine (OR 5.04, 95% CI: 0.56 to 120.7) and seven doses of methylphenidate (OR 9.96, 95% CI: 1.36 to 235.8). Changes toward higher consciousness level categories were observed once after placebo, four times after apomorphine (OR 5.67, 95% CI 0.63 to 169.46) and three times after methylphenidate (OR 3.41, 95% CI 0.34 to 88.00). In a post hoc analysis, patients with greater pupillary responsiveness showed better arousal, suggesting that this condition may predict stimulant drug effects. In conclusion, while pupillometry revealed no direct drug effects on overall pupillary responses, stimulants may have triggered clinical arousal in some patients, particularly in those with greater pupillary responsiveness. These findings require replication but should guide future pharmacological trials aimed at improving consciousness recovery after brain injury.

BACKGROUND: Remimazolam is a novel, ultra-short-acting benzodiazepine. This systematic review and meta-analysis compared the anesthetic efficacy and safety of remimazolam versus propofol for procedural sedation and general anesthesia. METHOD: A comprehensive search of PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials was conducted through 26 July 2024. Randomized controlled trials comparing remimazolam and propofol for procedural sedation or general anesthesia were included. The primary outcome was the success rate of sedation or general anesthesia. Data were analyzed using fixed and random-effects models to calculate pooled risk ratios (RRs), mean differences, 95% confidence intervals (CIs), and P values. RESULTS: Twenty-seven studies involving 7283 patients met the inclusion criteria. Sedation and general anesthesia success rates were comparable between remimazolam and propofol (RR: 0.99; 95% CI: 0.97-1.00; P = 0.10; N = 4858). While remimazolam had a longer time to awake, it was associated with significantly lower rates of hypotension and injection pain. Rates of nausea, vomiting, and discharge times were similar between the drugs. Subgroup analyses revealed that during procedural sedation, remimazolam resulted in longer awakening times and a reduced risk of hypoxemia. However, these effects were not observed in general anesthesia. CONCLUSION: Remimazolam and propofol achieved comparable success rates for sedation and general anesthesia. Remimazolam reduced hypoxemia risk but prolonged awakening times during procedural sedation. It also lowered the incidence of hypotension and injection pain across both procedural sedation and general anesthesia. Additional studies are needed to further clarify its role, particularly in general anesthesia.