The relationship between the effect-site concentration of propofol and sedation scale in children: a pharmacodynamic modeling study

Background Continuous infusion of propofol has been used to achieve sedation in children. However, the relationship between the effect-site concentration (Ce) of propofol and sedation scale has not been previously examined. The objective of this study was to investigate the relationship between the Ce of propofol and the University of Michigan Sedation Scale (UMSS) score in children with population pharmacodynamic modeling. Methods A total of 30 patients (aged 3 to 6 years) who underwent surgery under general anesthesia with propofol and remifentanil lasting more than 1 h were enrolled in this study. Sedation levels were evaluated using the UMSS score every 20 s by a 1 μg/mL stepwise increase in the Ce of propofol during the induction of anesthesia. The pharmacodynamic relationship between the Ce of propofol and UMSS score was analyzed by logistic regression with nonlinear mixed-effect modeling. Results The estimated Ce50 (95% confidence interval) of propofol to yield UMSS scores equal to or greater than n were 1.84 (1.54–2.14), 2.64 (2.20–3.08), 3.98 (3.66–4.30), and 4.78 (4.53–5.03) μg/mL for n = 1, 2, 3, and 4, respectively. The slope steepness for the relationship of the Ce versus sedative response to propofol (95% confidence interval) was 5.76 (4.00–7.52). Conclusions We quantified the pharmacodynamic relationship between the Ce of propofol and UMSS score, and this finding may be helpful to predict the sedation score at the target Ce of propofol in children. Trial registration http://www.clinicaltrials.gov (No.: NCT03195686, Date of registration: 22/06/2017).

Impact of Palonosetron on Cough Suppression in Females Undergoing Sevoflurane-Remifentanil Anesthesia for Laparoscopic Cholecystectomy: A Randomized Trial

Remifentanil has been used to suppress peri-extubation cough. Palonosetron, a 5-HT3 receptor antagonist, is an effective antiemetic, and 5-HT receptors mediate the cough reflex. We assessed the impact of palonosetron on effect-site concentration (Ce) of remifentanil for preventing emergence cough in females. Forty-five female patients undergoing laparoscopic cholecystectomy randomly received 0.075 mg of palonosetron (n = 21) or normal saline (n = 24) intravenously at the end of surgery. The remifentanil Ce for 50% (EC50) and for 95% (EC95) of patients were estimated via Dixon’s up-and-down method or isotonic regression. Using Dixon’s method, EC50 in the control group (1.33 ± 0.38 ng/mL) was comparable to that of the palonosetron group (1.42 ± 0.75 ng/mL) (p = 0.813). Using isotonic regression, EC50 (83% CIs) and EC95 (95% CIs) did not reveal significant differences between the control and the palonosetron groups (1.17 (0.86–1.43) and 1.90 (1.45–1.96) ng/mL and 0.88 (0.78–1.23) and 2.43 (1.94–2.47) ng/mL, respectively). No difference was found in the remifentanil Ce to suppress emergence cough in the palonosetron group compared with the control group. It may indicate no effect of palonosetron on antitussive activity of remifentanil.

Comparison of remifentanil concentrations with and without dexmedetomidine for the prevention of emergence cough after nasal surgery: a randomized double-blinded trial

Background Preventing emergence cough after nasal surgery is critical. Emergence cough can provoke immediate postoperative bleeding, which leads to upper airway obstruction. In the present study, we compared the effect-site concentration (Ce) of remifentanil to prevent emergence cough after propofol anesthesia for nasal surgery when remifentanil was or was not combined with dexmedetomidine. Methods Forty-seven patients with propofol-remifentanil anesthesia for nasal surgery were randomly assigned to a dexmedetomidine group (Group D, n = 23) or a saline group (Group S, n = 24). Group D and Group S were infused with dexmedetomidine (0.5 μg/kg) and saline, respectively, for 10 min before the completion of surgery. A predetermined Ce of remifentanil was infused until extubation. Remifentanil Ce to prevent cough in 50 and 95% of patients (EC50 and EC95) was estimated using modified Dixon’s up-and-down method and isotonic regression. Hemodynamic and recovery parameters were recorded. Results The EC50 of remifentanil Ce was significantly lower in Group D than in Group S (2.15 ± 0.40 ng/mL vs. 2.66 ± 0.36 ng/mL, p = 0.023). The EC95 (95% CI) of remifentanil Ce was also significantly lower in Group D [2.75 (2.67–2.78) ng/mL] than in Group S [3.16 (3.06–3.18) ng/mL]. Emergence and recovery variables did not differ between the two groups. Conclusion The remifentanil EC50 to prevent cough after propofol-remifentanil anesthesia was significantly lower (approximately 19%) when a combination of remifentanil and 0.5 μg/kg dexmedetomidine was used than when remifentanil infusion alone was used in patients undergoing nasal surgery. Therefore, the Ce of remifentanil may be adjusted to prevent emergence cough when used in combination with dexmedetomidine. Trial registration ClinicalTrials.gov (NCT03622502, August 9, 2018).

Remifentanil-based propofol-supplemented vs. balanced sevoflurane-sufentanil anesthesia regimens on bispectral index recovery after cardiac surgery: a randomized controlled study

Background: The present study was to compare the potential impact of remifentanil-based propofol-supplemented anesthesia regimen vs. conventional sevoflurane-sufentanil balanced anesthesia on postoperative recovery of consciousness indicated by c) values in patients undergoing cardiac surgery.Methods: Patients undergoing cardiac surgery were randomly allocated to get the remifentanil-based propofol-supplemented anesthesia employing target-controlled infusion (TCI) of remifentanil and propofol (Group-PR, n = 15) or a balanced-anesthesia employing sevoflurane-inhalation and TCI-sufentanil (Group-C, n = 19). In Group-PR, plasma concentration (Cp) of TCI-remifentanil was fixed at 20 ng/ml, and the effect-site concentration of TCI-propofol was adjusted within 0.8–2.0 μg/ml to maintain BIS value of 40–60. In Group-C, sevoflurane dosage was adjusted within 1–1.5 minimum alveolar concentration to maintain BIS of 40–60, and Cp of TCI-sufentanil was fixed at 0.4 ng/ml. The inter-group difference in the time for achieving postoperative BIS > 80 (T-BIS80) in the intensive care unit was determined as the primary outcome. The inter-group difference in the extubation time was determined as the secondary outcome.Results: T-BIS80, was shorter in Group-PR than Group-C (121.4 ± 64.9 min vs. 182.9 ± 85.1 min, respectively; the difference of means –61.5 min; 95% CI –115.7 to –7.4 min; effect size 0.812; P = 0.027). The extubation time was shorter in Group-PR than in Group-C (434.7 ± 131.3 min vs. 946.6 ± 393.3 min, respectively, P < 0.001).Conclusions: Compared with the conventional sevoflurane-sufentanil balanced anesthesia, the remifentanil-based propofol-supplemented anesthesia showed significantly faster postoperative conscious recovery in patients undergoing cardiac surgery.

Comparison of Remifentanil Concentrations with and without Dexmedetomidine for the Prevention of Emergence Cough after Nasal Surgery: A Randomized Double Blinded Trial

Background: After nasal surgery, preventing emergence cough is critical. Emergence cough can provoke immediate postoperative bleeding, which leads to upper airway obstruction. In the present study, we compared the effect-site concentration (Ce) of remifentanil for preventing emergence cough after propofol anesthesia when remifentanil was or was not combined with dexmedetomidine after nasal surgery.Methods: Forty-seven patients who underwent nasal surgery with propofol-remifentanil anesthesia were randomly divided into a dexmedetomidine group (Group D, n=23) or a saline group (Group S, n=24). Group D and Group S were infused dexmedetomidine (0.5 μg/kg) or saline for 10 min before the completion of surgery. Remifentanil was infused a predetermined Ce until extubation. Remifentanil Ce for the prevention of cough in 50% of patients (EC50) and 95% of patients (EC95) was estimated using modified Dixon's up-and-down method and isotonic regression. Hemodynamic and recovery parameters were observed.Results: The EC50 of remifentanil Ce in Group D was significantly lower than that in Group S (2.15 ± 0.40 ng/mL vs. 2.66 ± 0.36 ng/mL, p = 0.023). The EC95 (95% CI) of remifentanil Ce was also significantly lower in Group D [2.75 (2.67-2.78) ng/mL] than in Group S [3.16 (3.06-3.18) ng/mL]. Emergence and recovery parameters were comparable between the two groups. Conclusion: The remifentanil EC50 for the prevention of cough after propofol-remifentanil anesthesia was significantly lower (approximately 19%) when a combination of remifentanil and 0.5 μg/kg dexmedetomidine was used than when remifentanil infusion alone was used in patients undergoing nasal surgery. Therefore, the Ce of remifentanil may be adjusted for the prevention of emergence cough when used in combination with dexmedetomidine.Trial registration: ClinicalTrials.gov, NCT03622502, Registered August 9, 2018, https://clinicaltrials.gov

Masseter Muscle Rigidity After Initiating Monitored Anaesthesia Care of Propofol and Remifentanil

Masseter muscle rigidity can be seen following administration of opioids, succinylcholine, and nondepolarizing muscle relaxants. We report a case of a 56-year-old male patient in a “Cannot Intubate Cannot Ventilate Situation” due to masseter muscle rigidity after initiating monitored anaesthesia care (MAC) with remifentanil and propofol using target-controlled infusion in procedural cardiology. For rapid effect and equilibrium between plasma-concentration and effect site-concentration using target-controlled infusion, remifentanil overdose is possible during the induction period of MAC. Moreover, the presence of propofol could result in a significantly greater remifentanil concentration. To manage masseter muscle rigidity, muscle relaxants and emergent ventilation systems should be prepared to secure airway maintenance. In addition, alternative airway management devices and techniques should be on hand even if no airway difficulties are expected.