Anesthesiology最新文献

Background: Few studies have assessed the dose ratio of calcium gluconate to calcium chloride or defined the time course of change in serum ionized calcium concentration after intravenous injection.

Methods: In a bioequivalence (dose ratio) trial, parturients undergoing cesarean delivery were randomly assigned to receive calcium chloride (0.5 g) or calcium gluconate (1.5 or 2 g) by 10-min intravenous infusion. Venous serum ionized calcium concentration was measured before calcium infusion and approximately 5, 10, 15, 30, and 60 min after infusion start. These data were combined with serum ionized calcium concentration measurements in parturients who received 1 g calcium chloride or saline placebo in two recent clinical trials to define the pharmacokinetics of intravenous calcium over the first hour during and after drug administration.

Results: The bioequivalence study enrolled 34 participants, from whom were collected 181 serum ionized calcium concentration measurements. The dose ratio of calcium gluconate to calcium chloride was 3.11 (95% CI, 2.77 to 3.48). Population pharmacokinetics of calcium were determined using 311 serum ionized calcium concentration measurements from 70 parturients. The pharmacokinetics of intravenous calcium were described by a two-compartment model with systemic clearance of 0.18 (95% CI, 0.07 to 0.27) l/min, distributional clearance of 1.25 (95% CI, 1.03 to 1.56) l/min, central volume of 10.9 (95% CI, 9.3 to 12.6) l, and peripheral volume of 16.5 (95% CI, 12.5 to 24.7) l. After adjusting for the dose ratio, calcium gluconate and calcium chloride had identical time courses. A 1-g infusion of calcium chloride resulted in a peak increase in serum ionized calcium concentration of 0.39 (0.38 to 0.42 mM), which decreased by half (29 [23 to 40] min) after initiation of the 10-min infusion.

Conclusions: This study confirmed a 3:1 dose ratio of calcium gluconate to calcium chloride and estimated the pharmacokinetics over the first hour after intravenous delivery. These data inform clinical care and may guide future trials assessing calcium efficacy to reduce bleeding in obstetric patients.

Editor’s perspective:

Background: A brachial plexus block plays an important role in providing perioperative analgesia for shoulder surgery; however, the inherent risk of phrenic nerve block and resulting hemidiaphragmatic paralysis may limit its use in patients with compromised pulmonary function. This study aimed to evaluate the safety, efficacy, maximum tolerated volume, and optimal biologic volume of 0.5% ropivacaine used in a single-injection retroclavicular brachial plexus block for arthroscopic shoulder surgery.

Methods: In this seamless single-arm exploratory phase I/II trial, a novel Bayesian optimal interval design was used to guide volume escalation for determination of the maximum tolerated volume, followed by sequential volume expansion using Bayesian optimal phase 2 design to establish the optimal biologic volume. Fifty-four patients who underwent arthroscopic shoulder surgery received a single-injection retroclavicular brachial plexus block with 0.5% ropivacaine ranging from 15 to 40 ml. The primary outcomes were complete or partial hemidiaphragmatic paralysis in phase I, measured using ultrasound 30 min after block completion, and the block success in phase II, defined as achieving a total sensorimotor score 12 points or greater and the total sensory score 3 points or greater, measured through manual sensorimotor testing.

Results: The maximum tolerated volume for the single-injection retroclavicular brachial plexus block was determined to be 35 ml of 0.5% ropivacaine, with a hemidiaphragmatic paralysis rate of 0.09 (95% credible interval, 0 to 0.29). The optimal biologic volume was found to be 25 ml, with a block success rate of 1.0 (95% credible interval, 0.95 to 1.0) and a negligible hemidiaphragmatic paralysis rate of 0.01 (95% credible interval, 0 to 0.06).

Conclusions: A single-injection retroclavicular brachial plexus block using 25 ml of 0.5% ropivacaine produced consistent block success with a minimal hemidiaphragmatic paralysis rate, suggesting the need for further studies to confirm this result in arthroscopic shoulder surgery.

Editor’s perspective:

Background: Fentanyl is a synthetic opioid that is widely used in anesthesiology, but its illicit use is rapidly increasing. At high doses fentanyl induces unconsciousness and muscle rigidity, the mechanisms of which are poorly understood. Since animal models are needed to study these effects, the aim of this study was to establish a rat model of fentanyl abuse and investigate the effects of repeated high-dose fentanyl injections on loss of righting reflex, heart rate, respiratory depression, muscle, and brain activity.

Methods: Male and female Sprague-Dawley rats were studied (n=40). A bolus of 100µg/kg fentanyl was administered intravenously twice a week for five consecutive weeks. Time to return of righting reflex (RORR) after fentanyl injection and changes in EMG/EEG activity as well as heart rate were analyzed. Additionally, arterial blood gas analysis for evaluation of ventilation was performed. Mixed-effect models with Dunnet's test and effect sizes were used for statistical analysis.

Results: Repeated injections resulted in a U-shaped change in time to RORR with the longest latency after the first exposure (median: 50[1st-3rd quartile:36-56]min) and the shortest after the fifth exposure (16[13-33]min). Following fentanyl administration, heart rate dropped immediately by 225[95%CI: 179, 271]bpm (F=3952.16, p<.001), while EMG activity increased by 291[95%CI: 212, 370]% (F=27.51, p<0.001) and PaCO2 inclined by 49.4[95%CI: 40.6, 58.2]mmHg (F=75.97, p<0.001) within 5 minutes after injection. Additionally, pH decreased by 0.48[95%CI: 0.41, 0.54] (F=142.00, p<0.01), and PaO2 decreased by 50.4[40.8, 60.0]mmHg (F=57.90, p<0.001). Repeated fentanyl exposures did not significantly affect the extent of these changes (EMG: F=1.63, p=0.237; PaCO2: F=1.23, p=0.312; HR: F=1.05, p=0.400; pH: F=3.05, p=0.066; pO2: F=3.35, p=0.052). EEG analysis revealed that repeated fentanyl exposures elicited significantly higher absolute power in frequencies >20Hz as indicated by an area under the receiver operator characteristics curve >0.7.

Conclusion: We established a rodent model of repeated, high-dose fentanyl administration. Overall, significant evidence of tolerance was not observed after ten exposures of high-dose fentanyl for any of the analyzed parameters. These results suggest that tolerance does not develop for fentanyl-induced unconsciousness, muscle rigidity, or respiratory depression.