Comparative effect of intraoperative propacetamol versus placebo on morphine consumption after elective reduction mammoplasty under remifentanil-based anesthesia: a randomized control trial [ISRCTN71723173]

BACKGROUND: Postoperative administration of paracetamol or its prodrug propacetamol has been shown to decrease pain with a morphine sparing effect. However, the effect of propacetamol administered intra-operatively on post-operative pain and early postoperative morphine consumption has not been clearly evaluated. In order to evaluate the effectiveness of analgesic protocols in the management of post-operative pain, a standardized anesthesia protocol without long-acting opioids is crucial. Thus, for ethical reasons, the surgical procedure under general anesthesia with remifentanil as the only intraoperative analgesic must be associated with a moderate predictable postoperative pain. METHODS: We were interested in determining the postoperative effect of propacetamol administered intraoperatively after intraoperative remifentanil. Thirty-six adult women undergoing mammoplasty with remifentanil-based anesthesia were randomly assigned to receive propacetamol 2 g or placebo one hour before the end of surgery. After remifentanil interruption and tracheal extubation in recovery room, pain was assessed and intravenous titrated morphine was given. The primary end-point was the cumulative dose of morphine administered in the recovery room. The secondary end-points were the pain score after tracheal extubation and one hour after, the delay for obtaining a Simplified Numerical Pain Scale (SNPS) less than 4, and the incidence of morphine side effects in the recovery room. For intergroup comparisons, categorical variables were compared using the chi-squared test and continuous variables were compared using the Student t test or Mann-Whitney U test, as appropriate. A p value less than 0.05 was considered as significant. RESULTS: In recovery room, morphine consumption was lower in the propacetamol group than in the placebo group (p = 0.01). Pain scores were similar in both groups after tracheal extubation and lower in the propacetamol group (p = 0.003) one hour after tracheal extubation. The time to reach a SNPS < 4 was significantly shorter in the propacetamol group (p = 0.02). The incidence of morphine related side effects did not differ between the two groups. CONCLUSIONS: Intraoperative propacetamol administration with remifentanil based-anesthesia improved significantly early postoperative pain by sparing morphine and shortening the delay to achieve pain relief

Oxygenation versus driving pressure for determining the best positive end-expiratory pressure in acute respiratory distress syndrome

Abstract Objective The aim of this prospective longitudinal study was to compare driving pressure and absolute PaO2/FiO2 ratio in determining the best positive end-expiratory pressure (PEEP) level. Patients and methods In 122 patients with acute respiratory distress syndrome, PEEP was increased until plateau pressure reached 30 cmH2O at constant tidal volume, then decreased at 15-min intervals, to 15, 10, and 5 cmH2O. The best PEEP by PaO2/FiO2 ratio (PEEPO2) was defined as the highest PaO2/FiO2 ratio obtained, and the best PEEP by driving pressure (PEEPDP) as the lowest driving pressure. The difference between the best PEEP levels was compared to a non-inferiority margin of 1.5 cmH2O. Main results The best mean PEEPO2 value was 11.9 ± 4.7 cmH2O compared to 10.6 ± 4.1 cmH2O for the best PEEPDP: mean difference = 1.3 cmH2O (95% confidence interval [95% CI], 0.4–2.3; one-tailed P value, 0.36). Only 46 PEEP levels were the same with the two methods (37.7%; 95% CI 29.6–46.5). PEEP level was ≥ 15 cmH2O in 61 (50%) patients with PEEPO2 and 39 (32%) patients with PEEPDP (P = 0.001). Conclusion Depending on the method chosen, the best PEEP level varies. The best PEEPDP level is lower than the best PEEPO2 level. Computing driving pressure is simple, faster and less invasive than measuring PaO2. However, our results do not demonstrate that one method deserves preference over the other in terms of patient outcome. Clinical trial number: #ACTRN12618000554268 . Registered 13 April 2018

Acute bacterial pneumonia in rats increases alveolar epithelial fluid clearance by a tumor necrosis factor-alpha-dependent mechanism

To study the rate and regulation of alveolar fluid clearance in acute pneumonia, we created a model of Pseudomonas aeruginosa pneumonia in rats. To measure alveolar liquid and protein clearance, we instilled into the airspaces a 5% bovine albumin solution with 1.5 �Ci of 125 I-human albumin, 24 h after intratracheal instillation of bacteria. The concentration of unlabeled and labeled protein in the distal airspaces over 1 h was used as an index of net alveolar fluid clearance. Since there was histologic evidence of alveolar epithelial injury, several methods were used to measure alveolar fluid clearance, including the use of experiments in rats with blood flow and the use of experiments in rats without blood flow, so that movement across the epithelial barrier would be minimized in the latter group. The result