Adequacy of Anesthesia and Pupillometry for Endoscopic Sinus Surgery

Inadequate intraoperative analgesia causes the deterioration of the condition of the surgical field (CSF) as a result of hemodynamic instability. Analgesia monitors are used to guide remifentanil) infusion to optimize intraoperative analgesia. The main aim of the current randomized controlled trial was to investigate the potential advantages of intraoperative analgesia monitoring using surgical Pleth index (SPI)- or pupillometry (PRD)-guided remifentanil administration for managing the volume of total intraoperative blood loss (TEIBL), CSF, and length of operation (LOP) in comparison with the standard practice in patients undergoing endoscopic sinus surgery (ESS). The 89 patients in our study were grouped as follows: 30 patients were assigned to the general analgesia (GA) group, 31 patients were assigned to the SPI group, and 28 patients were assigned to the PRD group. The speed of remifentanil infusion was accelerated by 50% when SPI, PRD, or BSS were increased by >15 points, >5%, or >2, respectively, in adjacent groups until their normalization. The SPI group showed significantly lower TEIBL in comparison to the GA group (165.2 ± 100.2 vs. 283.3 ± 193.5 mL; p < 0.05) and a higher mean arterial pressure (MAP; 73.9 ± 8 vs. 69.2 ± 6.8 mmHg; p < 0.05). In the PRD group, a shorter LOP compared with the GA group was observed (63.1 ± 26.7 min vs. 82.6 ± 33.1 min; p < 0.05). It was noted that the PRD group had a lower total remifentanil consumption than the SPI group (1.3 ± 1.4 vs. 1.8 ± 0.9 mg; p < 0.05). In ASA I-III patients undergoing ESS, intraoperative monitoring based on state entropy and SPI values can optimize the CSF and reduce TEIBL, whereas monitoring based on state entropy and PRD measurements can optimize the cost effectiveness of anesthetic drugs and the use of the operation room.

Predictors for time to awake in patients undergoing awake craniotomies

OBJECTIVE Awake craniotomies are often characterized by alternating asleep-awake-asleep periods. Preceding the awake phase, patients are weaned from anesthesia and mechanical ventilation. Although clinicians aim to minimize the time to awake for patient safety and operating room efficiency, in some patients, the time to awake exceeds 20 minutes. The goal of this study was to determine the average time to awake and the factors associated with prolonged time to awake (> 20 minutes) in patients undergoing awake craniotomy. METHODS Records of patients who underwent awake craniotomy between 2003 and 2020 were evaluated. Time to awake was defined as the time between discontinuation of propofol and remifentanil infusion and the time of extubation. Patient and perioperative characteristics were explored as predictors for time to awake using logistic regression analyses. RESULTS Data of 307 patients were analyzed. The median (IQR) time to awake was 13 (10–20) minutes and exceeded 20 minutes in 17% (95% CI 13%–21%) of the patients. In both univariate and multivariable analyses, increased age, nonsmoker status, and American Society of Anesthesiologists (ASA) class III versus II were associated with a time to awake exceeding 20 minutes. BMI, as well as the use of alcohol, drugs, dexamethasone, or antiepileptic agents, was not significantly associated with the time to awake. CONCLUSIONS While most patients undergoing awake craniotomy are awake within a reasonable time frame after discontinuation of propofol and remifentanil infusion, time to awake exceeded 20 minutes in 17% of the patients. Increasing age, nonsmoker status, and higher ASA classification were found to be associated with a prolonged time to awake.

Dose-dependent Respiratory Depression by Remifentanil in the Rabbit Parabrachial Nucleus/Kölliker–Fuse Complex and Pre-Bötzinger Complex

Background Recent studies showed partial reversal of opioid-induced respiratory depression in the pre-Bötzinger complex and the parabrachial nucleus/Kölliker–Fuse complex. The hypothesis for this study was that opioid antagonism in the parabrachial nucleus/Kölliker–Fuse complex plus pre-Bötzinger complex completely reverses respiratory depression from clinically relevant opioid concentrations. Methods Experiments were performed in 48 adult, artificially ventilated, decerebrate rabbits. The authors decreased baseline respiratory rate ~50% with intravenous, “analgesic” remifentanil infusion or produced apnea with remifentanil boluses and investigated the reversal with naloxone microinjections (1 mM, 700 nl) into the Kölliker–Fuse nucleus, parabrachial nucleus, and pre-Bötzinger complex. In another group of animals, naloxone was injected only into the pre-Bötzinger complex to determine whether prior parabrachial nucleus/Kölliker–Fuse complex injection impacted the naloxone effect. Last, the µ-opioid receptor agonist [d-Ala,2N-MePhe,4Gly-ol]-enkephalin (100 μM, 700 nl) was injected into the parabrachial nucleus/Kölliker–Fuse complex. The data are presented as medians (25 to 75%). Results Remifentanil infusion reduced the respiratory rate from 36 (31 to 40) to 16 (15 to 21) breaths/min. Naloxone microinjections into the bilateral Kölliker–Fuse nucleus, parabrachial nucleus, and pre-Bötzinger complex increased the rate to 17 (16 to 22, n = 19, P = 0.005), 23 (19 to 29, n = 19, P &lt; 0.001), and 25 (22 to 28) breaths/min (n = 11, P &lt; 0.001), respectively. Naloxone injection into the parabrachial nucleus/Kölliker–Fuse complex prevented apnea in 12 of 17 animals, increasing the respiratory rate to 10 (0 to 12) breaths/min (P &lt; 0.001); subsequent pre-Bötzinger complex injection prevented apnea in all animals (13 [10 to 19] breaths/min, n = 12, P = 0.002). Naloxone injection into the pre-Bötzinger complex alone increased the respiratory rate to 21 (15 to 26) breaths/min during analgesic concentrations (n = 10, P = 0.008) but not during apnea (0 [0 to 0] breaths/min, n = 9, P = 0.500). [d-Ala,2N-MePhe,4Gly-ol]-enkephalin injection into the parabrachial nucleus/Kölliker–Fuse complex decreased respiratory rate to 3 (2 to 6) breaths/min. Conclusions Opioid reversal in the parabrachial nucleus/Kölliker–Fuse complex plus pre-Bötzinger complex only partially reversed respiratory depression from analgesic and even less from “apneic” opioid doses. The lack of recovery pointed to opioid-induced depression of respiratory drive that determines the activity of these areas. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

The pharmacokinetic interaction between nasally administered naloxone and the opioid remifentanil in human volunteers

Purpose Remifentanil has been shown to increase the bioavailability of nasally administered naloxone. The aim of this study was to explore the nature of this observation. Methods We analysed samples from three pharmacokinetic studies to determine the serum concentrations of naloxone-3-glucuronide (N3G), the main metabolite of naloxone, with or without exposure to remifentanil. To enable direct comparison of the three studies, the data are presented as metabolic ratios (ratio of metabolite to mother substance, N3G/naloxone) and dose-corrected values of the area under the curve and maximum concentration (Cmax). Results Under remifentanil exposure, the time to maximum concentration (Tmax) for N3G was significantly higher for intranasal administration of 71 min compared to intramuscular administration of 40 min. The dose-corrected Cmax of N3G after intranasal administration of naloxone under remifentanil exposure was significantly lower (4.5 ng/mL) than in subjects not exposed to remifentanil (7.8–8.4 ng/mL). The metabolic ratios after intranasal administration rose quickly after 30–90 min and were 2–3 times higher at 360 min compared to intravenous and intramuscular administration. Remifentanil exposure resulted in a much slower increase of the N3G/naloxone ratio after intranasal administration compared to intranasal administration with the absence of remifentanil. After remifentanil infusion was discontinued, this effect gradually diminished. From 240 min there was no significant difference between the ratios observed after intranasal naloxone administration. Conclusion Remifentanil increases the bioavailability of naloxone after nasal administration by reducing the pre-systemic metabolism of the swallowed part of the nasal dose.

Comparison of the Effect of Dexmedetomidine and Remifentanil on Pain Control After Spinal Surgery: A Double-Blind, Randomized Clinical Trial

Background: A variety of spinal surgery procedures are performed on patients with different cardiac, vascular, and respiratory comorbidities. Postoperative pain management is a major determinant of hemodynamic and respiratory status in these patients and promotes clinical results, prevents complications, saves health services, and improves the quality of life of patients. Objectives: We compared the effects of dexmedetomidine and remifentanil on pain control after spinal surgery. Methods: Sixty patients aged 18 - 65 years undergoing spinal surgery were randomized into the two groups of dexmedetomidine and remifentanil. The dexmedetomidine group (group D, n = 30) received dexmedetomidine infusion (0.6 mcg/kg/h), and the remifentanil group (group R, n = 30) received remifentanil infusion (0.1 mcg/kg/min) from induction of anesthesia until extubation. Propofol (1.5 mg/kg) and fentanyl (2mcg/kg) were used to initiate anesthesia, and propofol (100 - 150 mcg/kg/min) was infused to maintain anesthesia. Postoperative pain, hemodynamic parameters, and recovery characteristics were evaluated after surgery. Results: The mean pain intensity in the dexmedetomidine group was significantly lower than in the remifentanil group (2.98 ± 1.29 vs. 3.80 ± 1.1; P < 0.001). Hemodynamic changes in the dexmedetomidine group (MAP: 92.60 ± 5.56, HR: 73.07 ± 7) were less, and their condition was significantly more stable than in the remifentanil group (MAP: 93.85 ± 4.78, HR: 79.15 ± 7.03; P < 0.05). The mean arterial oxygen saturation (O2 sat) in the dexmedetomidine group was significantly higher and more stable than in the remifentanil group (98.87 ± 0.51 vs. 97.92 ± 0.46; P < 0.05). The incidence of nausea and vomiting was significantly lower in the dexmedetomidine group compared to the remifentanil group (P < 0.05). The administration of analgesics in the post-anesthetic care unit (PACU) was significantly higher in the remifentanil group than the dexmedetomidine group (P = 0.016). Conclusions: Anesthetic maintenance with either dexmedetomidine or remifentanil infusion until extubation provided more smooth and hemodynamically stable conditions, without complications. However, dexmedetomidine provides better analgesia, causes a more stable hemodynamic state, and reduces postoperative nausea-vomiting, shivering, and the need for analgesics.

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).

Lateralized Periodic Discharges During Remifentanil Infusion

Lateralized periodic discharges (LPDs) are a common electroencephalographic (EEG) pattern in the neurointensive care unit setting. LPDs are typically observed in association with acute structural lesions of the brain with different etiologies. There are no reports describing a link between the occurrence of LPDs and the administration of remifentanil. Remifentanil is a rapid-acting pure μ-opioid receptor agonist, which is indicated to provide analgesia and sedation in mechanically ventilated patients in intensive care units. We present a case of an 84-year-old man with neuroglycopenia who developed LPDs while sedated with remifentanil. We report, for the first time, a potential relationship between remifentanil and the induction of LPDs.

Pupillary unrest, opioid intensity, and the impact of environmental stimulation on respiratory depression

Opioid-induced respiratory depression (OIRD) confers significant morbidity, but its onset can be challenging to recognize. Pain or stimulation effects of conversation may mask or attenuate common clinical manifestations of OIRD. We asked whether pupillary unrest could provide an objective signal of opioid exposure, and whether this signal would be independent from the confounding influence of extrinsic stimulation. We conducted a cross-over trial of healthy volunteers using identical remifentanil infusions separated by a washout period; in both, pupillary unrest in ambient light (PUAL) was measured at 2.5-min intervals. During one infusion, investigators continuously engaged the subject in conversation, while in the other, a quiet environment was maintained; measures of respiratory depression were compared under each condition. We tested PUAL’s relationship to estimated opioid concentration under quiet conditions, measured PUAL’s discrimination of lower versus higher opioid exposure using receiver operating characteristic (ROC) analysis, and assessed the effect of stimulation on PUAL versus opioid using mixed effects regression. Respiratory depression occurred more frequently under quiet conditions (p < 0.0001). Under both conditions, PUAL declined significantly over the course of the remifentanil infusion and rose during recovery (p < 0.0001). PUAL showed excellent discrimination in distinguishing higher versus absent-moderate opioid exposure (AUROC = 0.957 [0.929 to 0.985]), but was unaffected by interactive versus quiet conditions (mean difference, interactive – quiet = − 0.007, 95% CI − 0.016 to 0.002). PUAL is a consistent indicator of opioid effect, and distinguishes higher opioid concentrations independently of the stimulating effects of conversational interaction. Under equivalent opioid exposure, conversational interaction delayed the onset and minimized the severity of OIRD.Clinical trial registration: NCT 04301895