Effective dose of ephedrine for treatment of hypotension after induction of general anaesthesia in neonates and infants less than 6 months of age: a multicentre randomised, controlled, open label, dose escalation trial.

BACKGROUND: The recommended dose of ephedrine in adults (0.1 mg kg-1) frequently fails to treat hypotension after induction of general anaesthesia in neonates and infants less than 6 months of age. The aim of this study was to determine the optimal dose of ephedrine in this population for the treatment of hypotension after induction of general anaesthesia with sevoflurane. METHODS: We conducted a multicentre, prospective, randomised, open-label, controlled, dose-escalation trial. Subjects were randomised if presenting a >20% change from baseline in MAP. Six cohorts of 20 subjects each were enrolled. Ten subjects in the first cohort received 0.1 mg kg-1 i. v. (reference dose). For each subsequent cohort, 10 subjects were assigned to the next higher dose (consecutively 0.6, 0.8, 1, 1.2, and 1.4 mg kg-1 i. v.), and the other subjects were assigned to one or more doses already investigated in previous cohorts. The primary outcome was the return of MAP to >80% of baseline at least once within 10 min after ephedrine administration. RESULTS: A total of 119 infants (25% females), with a mean age (standard deviation) of 2.7 (1.3) months, received their allocated dose of ephedrine. The optimal dose of ephedrine was 1.2 mg kg-1, with a percentage of success of 65.5% (95% confidence interval, 35.6-86.4). The doses of ephedrine investigated did not induce adverse events. CONCLUSIONS: Doses of ephedrine much higher (∼10-fold) than those used in adults are necessary in neonates and infants for the treatment of hypotension after induction of general anaesthesia with sevoflurane. CLINICAL TRIAL REGISTRATION: NCT02384876.

Cervical epidural anesthesia is associated with increased cancer-free survival in laryngeal and hypopharyngeal cancer surgery: a retrospective propensity-matched analysis.

BACKGROUND AND OBJECTIVES: Regional anesthesia preserves perioperative immune competence and may reduce the risk of recurrence and metastasis after cancer surgery. Cervical epidural anesthesia provides adequate analgesia for head and neck cancer surgery, but its impact on cancer recurrence is unknown. METHODS: This study was a single-center retrospective cohort study of patients undergoing larynx or hypopharynx cancer surgery between January 1984 and December 2008. One hundred eleven patients had general anesthesia combined with intraoperative and postoperative cervical epidural; 160 had general anesthesia alone with postoperative morphine. From this cohort, matched pairs were selected using a propensity score to balance potential confounders of receiving epidural anesthesia. The primary end point was the length of cancer-free survival after surgery until September 2009. RESULTS: Propensity-based matching produced 65 pairs. Matching was effective in achieving balance between groups for each of the preoperative variables collected. Combined epidural and general anesthesia (68% 5-year cancer-free survival; 95% confidence interval [CI], 57%-82%) was associated with significantly increased cancer-free survival compared with general anesthesia alone (37% 5-year cancer-free survival; 95% CI, 25%-54%) with a corresponding adjusted hazard ratio of 0.49 (95% CI, 0.25-0.96; P = 0.04). Patients in the epidural group had an increased overall survival compared with the non-epidural group (P = 0.03). CONCLUSIONS: The association between cervical epidural anesthesia and increased cancer-free survival found in this retrospective study should be an important hypothesis to further investigate in head and neck cancer surgery.

Do antifibrinolytics reduce allogeneic blood transfusion in orthopedic surgery?

Studies have shown that antifibrinolytic (aprotinin, tranexamic acid, epsilon-aminocaproic acid) reduce blood loss in orthopedic surgery. However, most lacked sufficient power to evaluate the efficacy and safety on clinical outcomes. This meta-analysis aims to evaluate whether intravenous antifibrinolytics, when compared with placebo, reduce perioperative allogeneic erythrocyte transfusion requirement in adults undergoing orthopedic surgery and whether it might increase the risk of venous thromboembolism. From MEDLINE, EMBASE, and the Cochrane Controlled Trials Register, the authors identified 43 randomized controlled trials in total hip and knee arthroplasty, spine fusion, musculoskeletal sepsis, or tumor surgery performed to July 2005 (for aprotinin, 23 trials with 1,268 participants; tranexamic acid, 20 with 1,084; epsilon-aminocaproic acid, 4 with 171). Aprotinin and tranexamic acid reduced significantly the proportion of patients requiring allogeneic erythrocyte transfusion according to a transfusion protocol. The odds ratio was 0.43 (95% confidence interval, 0.28-0.64) for aprotinin and 0.17 (0.11-0.24) for tranexamic acid. Results suggest a dose-effect relation with tranexamic acid. Epsilon-aminocaproic acid was not efficacious. Unfortunately, data were too limited for any conclusions regarding safety. Although the results suggest that aprotinin and tranexamic acid significantly reduce allogeneic erythrocyte transfusion, further evaluation of safety is required before recommending the use of antifibrinolytics in orthopedic surgery.