Daily Anesthesiology Research Analysis

BACKGROUND: Postoperative pulmonary complications (PPCs) are a leading cause of morbidity, death, and increased use of health-care resources. We aimed to determine whether a perioperative lung expansion bundle including individualised intraoperative management reduces PPC severity in patients undergoing major open abdominal surgery compared with usual care. METHODS: In this multicentre, randomised controlled phase 3 trial (PRIME-AIR), we enrolled adult patients (age ≥18 years) scheduled for an elective open abdominal surgery that would last at least 2 h, who were at intermediate or high risk for PPCs on the basis of their Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score (a score of ≥26), and who had a BMI below 35 kg/m FINDINGS: Between Jan 24, 2020, and April 5, 2023, we screened 1462 patients, of whom 794 were enrolled and randomly assigned to treatment. The mITT population included 751 participants, of whom 379 (50%) were in the intervention bundle group and 372 (50%) were in the usual care group. Mean age was 61·8 years (SD 12·8); 360 (48%) of 751 patients were female and 391 (52%) were male; 572 (76%) were White, 44 (6%) were Black, 35 (5%) were Asian, and ten (1%) were other races or more than one race. Adherence to bundle components was high (72-98%). Patients in the intervention bundle group received higher mean PEEP (7·5 cmH INTERPRETATION: In patients with a BMI of less than 35 kg/m FUNDING: US National Institutes for Health National Heart, Lung, and Blood Institute.

BACKGROUND: Perioperative lidocaine infusions show potential as a systemic analgesic and to enhance postoperative recovery. This study characterised the pharmacokinetics (PK) of lidocaine and its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), in adult surgical patients using non-linear mixed-effects modelling. METHODS: Thirty-four donor nephrectomy and 64 cholecystectomy patients received intraoperative IV lidocaine. Plasma samples were collected perioperatively and analysed in NONMEM. Covariate effects and alternative dosing regimens were investigated. RESULTS: 1,520 concentration-timepoints were analysed. Lidocaine PK was best fitted with a 3-compartment model, while MEGX and GX used a 2-compartment model. All parameters were scaled allometrically with total body mass and fat-free mass (FFM). Lidocaine had a typical clearance of 45.9 L/h, decreasing by 60% postoperatively, and a central volume of 25.2 L. Peripheral compartments 1 and 2 exhibited intercompartmental clearances of 142 L/h and 5.81 L/h, with volumes of 44.4 L and 29.3 L, respectively. Peripheral compartment 1's volume expanded with intraoperative fluid administration. Simulations suggested an FFM-based dosing regimen (bolus: 2.5 mg/kg over 30 min, single infusion: 2 mg/kg over 1 h, maintenance infusion: 1.5 mg/kg/h) quickly achieved and maintained a lidocaine target plasma concentration of 1.5 mg/L. CONCLUSIONS: The joint parent-metabolites model adequately describes the disposition of lidocaine and its metabolites, incorporating allometric scaling and key covariates. It provides a foundation for optimising lidocaine dosing and guiding investigations to establish target plasma concentrations for safe and effective use in the general surgical population. Further research is warranted to refine and evaluate the model's utility in other surgical populations.

BACKGROUND: Microtubules (MTs) have been postulated as one of the molecular targets underlying loss of consciousness induced by inhalational anesthetics. Microtubule-targeting chemotherapy drugs and opioids affect MT stability and function. However, the impact of prolonged administration of these drugs on anesthetic potency and anesthesia induction and emergence times remain unelucidated. METHODS: Epothilone D, paclitaxel, vinblastine or opioid morphine were administered alone for a prolonged period (> 2 weeks) to male CD1 mice and their sensitivity to incremental concentrations of isoflurane were examined using loss of righting reflex (LORR) response as a measure of sensivity. The induction and emergence time after administration and termination of fixed concentration of isoflurance (1.2%) were also assessed. RESULTS: Compared with saline treatment, epothilone D and vinblastine induced a leftward (more sensitive) shift of LORR response curves (95% confidence intervals for EC50: epothilone D, 0.75[0.73, 0.77] vs. saline, 0.97[0.96, 0.98]; vinblastine, 0.74[0.73, 0.75] vs. saline, 0.98[0.97, 0.99]). In contrast, morphine caused a rightward (more resistant) LORR response curve (morphine, 1.16[1.15, 1.17] vs. saline, 0.97[0.96, 0.98]), while paclitaxel produced a marginal but significant rightward shift of LORR (paclitaxel, 1.05[1.03, 1.06] vs. saline, 0.98[0.97, 0.99]). At concentration of 1.2% isoflurane, morphine treatment prolonged (275 ± 50) and vinblastine treatment reduced (96.5 ± 26) the anesthetic induction latency (in second) relative to saline treatment (211 ± 39). The latency of emergence from anesthesia was shorter in morphine (58 ± 20) and vinblastine-treated (98 ± 43) mice compared to saline (176 ± 50) treatment. The induction or emergence latencies of epothilone D or paclitaxel treatment did not differ from saline treatment between groups. CONCLUSIONS: Microtubule-modulating drugs can affect not only sensitivity but also induction and emergence times to inhalational anesthetic isoflurane in mice. This study highlights a possible role of MTDs in modulating anesthetic effects in disparate directions, which has implications for anesthetic concentrations that should be used for induction, maintenance and emergence of anesthesia. These findings in rodents may have relevance to the perioperative care of cancer patients who receive MT-targeting chemotherapy drugs or even opioids for pain for prolonged periods.