High-dose Remifentanil Research Articles

Impact of Fentanyl on Recovery Times and Hypotensive Events in Ophthalmic Surgery: A Comparative Study

Background and Objectives: Remifentanil is a member of the fentanyl family and a short-acting, esterase-metabolized opioid that offers potential advantages over fentanyl in ophthalmic surgeries characterized by rapid patient turnover. This study aimed to compare two different analgesia induction regimes, remifentanil or fentanyl, with respect to intraoperative hypotensive events and perioperative process times in patients undergoing ophthalmic surgery under general anesthesia. Materials and Methods: Clinical data of 500 patients either receiving remifentanil infusion (R group, 0.4–0.5 μg/kg/min at induction, and then 0.1 µg/kg/min maintenance dose) or fentanyl bolus (F group, 1 μg/kg for induction followed by 0.1 μg/kg/min remifentanil maintenance dose) were analyzed in this retrospective study. All patients received a propofol injection as part of the induction and sevoflurane for the maintenance of anesthesia. We investigated hemodynamic events as defined by the administration of vasopressors, atropine and Akrinor (Theodrenaline and Cafedrine), as well as procedural times in the two groups. Results: There was no difference in hypotensive events between the two groups. However, there was a relationship between preoperative ASA (American Society of Anesthesiologists) status and vasopressor administration. The amount of propofol for the induction of anesthesia exhibited a significant correlation to the age of the patients (p < 0.05). The time from the end of anesthesia to discharge from the recovery room was significantly reduced by approximately 6 min per patient in the remifentanil group (p < 0.01). In conclusion, the induction of anesthesia with high-dose remifentanil combined with propofol can significantly shorten the time span to discharge from the recovery ward compared to fentanyl bolus administration, without an increase in the administration of vasopressors in patients undergoing ophthalmic surgery in general anesthesia. Conclusions: These findings suggest that remifentanil may be a more effective choice for anesthesia management in settings with high patient turnover.

Anesthesia for Bronchoscopy-An Update.

The field of interventional pulmonology has grown immensely and is increasingly recognized as a subspecialty. The new procedures introduced in the last decade pose unique challenges, and anesthesiologists need to readapt to their specific demands. In this review, we extensively discuss the pathophysiology, technical aspects, preprocedural preparation, anesthetic management, and postprocedural challenges of many new procedures such as navigational bronchoscopy, endobronchial valve deployment, and bronchial thermoplasty. Majority of these procedures are performed under general anesthesia with an endotracheal tube. Total intravenous anesthesia with rocuronium as a muscle relaxant seems to be the standard US practice. The easy availability and proven safety and efficacy of sugammadex as a reversal agent of rocuronium has decreased the need for high-dose remifentanil as an agent to avoid muscle relaxants. Additional research is available with regard to the utility of nebulized lidocaine and is discussed. Finally, two newer drugs administered for conscious sedation (typically without the need of an anesthesiologist) are likely to gain popularity in the future. Remimazolam is a new short-acting benzodiazepine with a relatively faster offset of clinical effects. Dexmedetomidine, a selective adrenergic agonist, is increasingly employed in bronchoscopy as a sedative during bronchoscopic procedures.

High-Dose Remifentanil Anesthesia With Minimal Sedation in Neonates: A Single-Center Retrospective Study.

Introduction Remifentanil is an opioid with rapid onset and elimination. Theoretically, reducing sedation using high-dose remifentanil may contribute to early emergence and prevention of postanesthetic complications related to residual anesthesia. However, there have been few reports of high-dose remifentanil anesthesia in neonatal surgery. This study aims to describe the techniques of high-dose remifentanil anesthesia in neonates and their safety outcomes. Methods This is a single-center, retrospective observational study from January 2016 to February 2022. Medical records from neonatal surgical procedures performed using high-dose remifentanil anesthesia were reviewed. "High dose" was defined as 0.5 mcg/kg/min or more. Patient profiles, anesthetic drugs used, and intra- and post-operative adverse events, including cardiopulmonary complications, were abstracted. Results There were 15 neonatal abdominal operations performed under high-dose (>0.5 mcg/kg/min) remifentanil anesthesia during the study period. The average remifentanil infusion rate was 1.9 (0.68-3.1) mcg/kg/min. Hypotension occurred in two patients (13%). Bradycardia was not observed in any patients. The mean time for tracheal extubation was 16 minutes. Five patients (33%) received naloxone administration before extubation, and two patients (13%) experienced hypoxemia immediately after extubation. No patient had cardiorespiratory complications after leaving the operating room. Conclusions High-dose remifentanil can be used without impairing hemodynamic stability in neonatal surgery, although there is concern about respiratory depression. Further research is needed on its potential impact on long-term outcomes.

Comparison of Two Anesthetic Regimens on Extubation Time and Postoperative Recovery in Children Undergoing Ambulatory Adenoidectomy: A Retrospective Study

PurposeThis aim of this study was to compare two anesthetic regimens in terms of extubation time and postoperative recovery in children undergoing ambulatory adenoidectomy. DesignA retrospective cohort study with propensity score matching. MethodsThe medical charts of 452 children aged between 3 and 8 years undergoing ambulatory adenoidectomy were retrieved for analysis, of which 438 were eligible to participate in this study. A majority (n = 327) were children exposed to a conventional propofol-pronounced general anesthetic regimen (high-dose propofol plus low-dose remifentanil, labeled as group P), while n = 111 were administered a modified remifentanil-pronounced anesthetic regimen (low-dose propofol plus high-dose remifentanil, namely group R). Propensity score matching was employed to adjust for confounders, resulting in 69 matched patients in each group. The primary endpoint of this study was extubation time. The secondary endpoints were total intraoperative fluid volume, length of stay in the postanesthesia care unit (PACU), postoperative pain rating, the incidence of emergence agitation, nausea and vomiting, as well as the level of consciousness (fully awake or waking by gentle patting) when transferred out of PACU, and any major complications (wound bleeding, reintubation, readmission, and overnight stay). FindingsNo major complications were observed in both groups. Compared to group P, group R had significantly shorter extubation time (8.2 ± 1.4 minutes vs 13.3 ± 2.4 minutes, P < .001), shorter length of stay in the PACU (14.1 ± 3.1 minutes vs 20.2 ± 3.4 minutes, P < .001), and a higher proportion of cases being fully awake when transferred out of the PACU (91% vs 46%, P < .001). Lastly, the pain rating, frequency of oropharyngeal airway usage, incidence of emergence agitation, and nausea and vomiting were comparable between the two groups (P > .05 for all). ConclusionsRemifentanil-pronounced anesthesia was superior to propofol-pronounced anesthesia in children undergoing ambulatory adenoidectomy, given that the former was associated with a faster recovery time from anesthesia without jeopardizing patient safety.

Association between intraoperative remifentanil use and postoperative hyperalgesia in adolescent idiopathic scoliosis surgery: a retrospective study

BackgroundThe liberal use of remifentanil in spine surgery has been associated with an increased incidence of postoperative hyperalgesia. Nevertheless, controversies remain as the existing evidence is inconclusive to determine the relationship between remifentanil use and the development of opioid-induced hyperalgesia. We hypothesized that intraoperative infusion of higher dose remifentanil during scoliosis surgery is associated with postoperative hyperalgesia, manifesting clinically as greater postoperative morphine consumption and pain scores.MethodsNinety-seven patients with adolescent idiopathic scoliosis (AIS) who underwent posterior spinal fusion surgery at a single tertiary institution from March 2019 until June 2020 were enrolled in this retrospective study. Anesthesia was maintained using a target-controlled infusion of remifentanil combined with volatile anesthetic desflurane in 92 patients, while five patients received it as part of total intravenous anesthesia. Intravenous ketamine, paracetamol, and fentanyl were administered as multimodal analgesia. All patients received patient-controlled analgesia (PCA) morphine postoperatively. Pain scores at rest and on movement, assessed using the numerical rating scale, and the cumulative PCA morphine consumption were collected at a six-hourly interval for up to 48 h. According to the median intraoperative remifentanil dose usage of 0.215 µg/kg/min, patients were divided into two groups: low dose and high dose group.ResultsThere were no significant differences in the pain score and cumulative PCA morphine consumption between the low and high dose remifentanil group. The mean duration of remifentanil infusion was 134.9 ± 22.0 and 123.4 ± 23.7 min, respectively.ConclusionIntraoperative use of remifentanil as an adjuvant in AIS patients undergoing posterior spinal fusion surgery was not associated with postoperative hyperalgesia.

Ventral and dorsal cervical spinal cord electrical epidural stimulation facilitated respiration differently in the presence of opioids in human via different neural circuits

Opioid overdose is one of the leading causes of overdose related deaths in the United States of America, accounting for 70.6% of overdose fatalities in 2019 alone. A leading cause of death among opioid overdoses is respiratory depression. Epidural electrical stimulation (EES) emerges as a novel approach of facilitating rhythmic motor activities such as locomotion and respiration. Previous studies conducted in humans and rodent models demonstrated respiratory augmentations induced by EES delivered to the dorsal cervical spinal cord. Importantly, EES at the dorsal cervical spinal cord opposes opioid-induced respiratory depression in human. To reveal the mechanism underpins how cervical EES modulate the respiratory neural circuit, we conducted this comparative study between dorsal cervical EES to the ventral EES in patients with opioid-induced respiratory suppression or depression. We hypothesize that the ventral cervical EES activates the local motor neuronal pools while the dorsal EES recruits both sensory and motor cervical circuits as well as accesses supraspinal structures such as medulla. We recruited and consented 25 patients who underwent anterior (ventral) cervical spinal cord surgery and compared the effect of ventral cervical EES to to the effect of dorsal cervical ESS in a dataset that we collected from 18 patients undergoing cervical spinal surgery. In the 25 patients, the EES was deliver to the ventral surface of spinal cord ranging from cervical level 3 to 7 (C3 to C7) for no more than 90 seconds at the optimal intensity ranging from 0.5 mA to 5 mA with stimulation frequencies 5 Hz or 30 Hz. In both the dorsal and ventral EES groups, the subjects were anesthetized with low dose or high dose remifentanil that partially or completely depressed voluntary respiration. We observed three main differences between the dorsal and ventral cervical EEST in regulating respiration in the presence of remifentanil. First, dorsal cervical EES induced the resetting of inspiratory rhythm while ventral cervical EES did not. Second, dorsal but not ventral cervical EES induced longer lasting respiratory modulation after the stimulation stopped. Third, dorsal cervical EES induced both frequency and amplitude changes of respiration while ventral cervical EES modulated the amplitude of the respiration more significantly. These observations suggest that the dorsal and ventral cervical EES facilitate respiration via different neural circuits. This work was supported by the National Institute of Drug Abuse in the National Institutes of Health: R01 DA047637, Louis and Harold Price Foundation, H &amp; H Evergreen Foundation, and J. Yang Family Foundation. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of Different Doses of Esketamine on Pain Sensitivity of Patients Undergoing Thyroidectomy: A Randomized Controlled Trial.

Several factors may lead to increased postoperative pain sensitivity, of which remifentanil-induced hyperalgesia (RIH) is one of the main factors. High-dose remifentanil exposure during anesthesia may induce RIH. Esketamine may prevent RIH by antagonizing N-methyl-D-aspartate (NMDA) receptors, thereby reducing the postoperative pain sensitivity. This study examined the effects of different esketamine doses on pain sensitivity in patients undergoing thyroidectomy and determined the optimal dose. This study included 117 patients who received elective thyroidectomy. They were randomized into four groups: saline group (group C), esketamine 0.2mg·kg-1 group (group RK1), esketamine 0.4mg·kg-1 group (group RK2), and esketamine 0.6mg·kg-1 group (group RK3). Five minutes before anesthesia induction, the same volume of study drugs were injected respectively in groups C, RK1, RK2, and RK3. Remifentanil was pumped at the same rate of 0.3µg·kg-1·min-1 during surgery to ensure uniformity. This study's primary outcomes were the mechanical pain thresholds measured before surgery, as well as at 30min, 6h, 24h, and 48h after surgery. Hyperalgesia, rescue analgesia, numerical rating scale (NRS) score, and adverse reactions were recorded. Compared with baseline, the mechanical pain threshold was significantly decreased in group C [(94.67 ± 22.85) versus (112.00 ± 36.62) versus (161.33 ± 53.28) g, P < 0.001 at 30min, P < 0.001 at 6h] and group RK1 [(102.86 ± 24.17) versus (114.29 ± 41.05) versus (160.00 ± 54.98) g, P < 0.001 at 30min, P < 0.001 at 6h] around the surgical incision, and in group C [(112.00 ± 31.78) versus (170.67 ± 56.26) g, P < 0.001 at 30min, (118.67 ± 34.42) versus (170.67 ± 56.26) g, P = 0.001 at 6h] and group RK1 [(114.29 ± 45.17) versus (175.71 ± 54.80) g, P = 0.001 at 30min, (121.43 ± 38.46) versus (175.71 ± 54.80) g, P = 0.002 at 6h] on the forearm at 30min and 6h after surgery; compared with group C, the mechanical pain threshold was higher in group RK2 [(142.76 ± 50.06) versus (94.67 ± 22.85) g, P < 0.001 at 30min, (145.52 ± 49.83) versus (112.00 ± 36.62) g, P < 0.001 at 6h] and group RK3 [(140.00 ± 40.68) versus (94.67 ± 22.85) g, P < 0.001 at 30min, (150.67 ± 56.50) versus (112.00 ± 36.62) g, P = 0.010 at 6h] around the surgical incision, and in group RK2 [(149.66 ± 39.50) versus (112.00 ± 31.78) g, P = 0.006 at 30min, (156.55 ± 47.23) versus (118.67 ± 34.42) g, P = 0.005 at 6h] and group RK3 [(145.33 ± 51.18) versus (112.00 ± 31.78) g, P = 0.018 at 30min, (154.67 ± 47.54) versus (118.67 ± 34.42) g, P = 0.008 at 6h] on the forearm at 30min and 6h after surgery. Group RK3 had more glandular secretions than the other three groups (P = 0.042). Intravenous injection of esketamine 0.4mg·kg-1 before anesthesia induction is a suitable dose to reduce pain sensitivity in patients undergoing thyroidectomy without increasing adverse reactions. However, future research needs to be extended to other populations. Registered at the Chinese Clinical Trials Registry http://www.chictr.org.cn/ (09/06/2022, ChiCTR-2200060741).

High-dose remifentanil exacerbates myocardial ischemia-reperfusion injury through activation of calcium-sensing receptor-mediated pyroptosis.

Background: The aim of this study was to investigate whether calcium-sensing receptor (CaSR) was involved in HRF-mediated exacerbation of MI/R injury through NLRP3 inflammasome activation and pyroptosis. Methods: In vivo, a rat MI/R model was established by ligating the left coronary artery, and short-term HRF exposure was induced during reoxygenation. Then, TUNEL, H&E, Masson staining, immunohistochemical (IHC) and serum levels of lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK), as well as the expression levels of CaSR and pyroptosis-related proteins in heart tissues, were measured. H9c2 cells were cultured to create a hypoxia/reoxygenation (H/R) model and exposed to different concentrations of RF. After pretreatment with the CaSR activator gadolinium chloride (GdCl3) and inhibitor NPS2143 in the H/R model and treatment with HRF, we compared cellular viability, TUNEL, cytosolic [Ca2+]i, the levels of LDH and CK, pyroptosis-related proteins and CaSR in H9c2 cells. We further researched the mechanisms of CaSR-mediated pyroptosis in the H/R+HRF model by CaSR-shRNA, Ac-YVAD-CMK, MCC950 and NAC. Results: We found that HRF significantly increased CaSR expression, rate of cell death, levels of CK and LDH, and exacerbated pyroptosis in MI/R model. In vitro, HRF increased CaSR expression, decreased viability, enhanced cytosolic [Ca2+]i and exacerbated pyroptosis in H/R cells. Pretreated with GdCl3 worsen these changes, and NPS2143, MCC950, Ac-YVAD-CMK, NAC and sh-CaSR can reversed these effects. Conclusion: Exposure to HRF for a short time exacerbates MI/R-induced injury by targeting CaSR to increase cytosolic [Ca2+]i and ROS levels, which mediate the NLRP3 inflammasome and pyroptosis.

Epidural electrical stimulation of the cervical spinal cord opposes opioid-induced respiratory depression.

Opioid overdose suppresses brainstem respiratory circuits, causes apnoea and may result in death. Epidural electrical stimulation (EES) at the cervical spinal cord facilitated motor activity in rodents and humans, and we hypothesized that EES of the cervical spinal cord could antagonize opioid-induced respiratory depression in humans. Eighteen patients requiring surgical access to the dorsal surface of the spinal cord between C2 and C7 received EES or sham stimulation for up to 90s at 5 or 30Hz during complete (OFF-State) or partial suppression (ON-State) of respiration induced by remifentanil. During the ON-State, 30Hz EES at C4 and 5Hz EES at C3/4 increased tidal volume and decreased the end-tidal carbon dioxide level compared to pre-stimulation control levels. EES of 5Hz at C5 and C7 increased respiratory frequency compared to pre-stimulation control levels. In the OFF-State, 30Hz cervical EES at C3/4 terminated apnoea and induced rhythmic breathing. In cadaveric tissue obtained from a brain bank, more neurons expressed both the neurokinin 1 receptor (NK1R) and somatostatin (SST) in the cervical spinal levels responsive to EES (C3/4, C6 and C7) compared to a region non-responsive to EES (C2). Thus, the capacity of cervical EES to oppose opioid depression of respiration may be mediated by NK1R+/SST+ neurons in the dorsal cervical spinal cord. This study provides proof of principle that cervical EES may provide a novel therapeutic approach to augment respiratory activity when the neural function of the central respiratory circuits is compromised by opioids or other pathological conditions. KEY POINTS: Epidural electrical stimulation (EES) using an implanted spinal cord stimulator (SCS) is an FDA-approved method to manage chronic pain. We tested the hypothesis that cervical EES facilitates respiration during administration of opioids in 18 human subjects who were treated with low-dose remifentanil that suppressed respiration (ON-State) or high-dose remifentanil that completely inhibited breathing (OFF-State) during the course of cervical surgery. Dorsal cervical EES of the spinal cord augmented the respiratory tidal volume or increased the respiratory frequency, and the response to EES varied as a function of the stimulation frequency (5 or 30Hz) and the cervical level stimulated (C2-C7). Short, continuous cervical EES restored a cyclic breathing pattern (eupnoea) in the OFF-State, suggesting that cervical EES reversed the opioid-induced respiratory depression. These findings add to our understanding of respiratory pattern modulation and suggest a novel mechanism to oppose the respiratory depression caused by opioids.

Pain after Interventional Radiology in Oncology: A Case-Control Study from a 5-Year Cohort.

Simple SummaryFew reports address post-procedural pain after interventional radiology in oncology. All patients treated from 2015 to 2019 in interventional radiology were included in a retrospective cohort study. In an additional case-control study, patients reporting strong or intolerable pain were compared to those with no pain. From 4411 procedures, severe pain was more frequent in women (6% vs. 4%) and the youngest patients, after general anesthesia, arterial embolization, limb cementoplasty, osteosynthesis, and abdominal tumor ablation. In the case-control study, long-term opioid use, duration >160 min, and high-dose remifentanil were risk factors for a high pain level. Intraoperative ketoprofen was associated with a decreased high pain level incidence. Immediate severe post-procedural pain was a risk factor for severe pain in wards until discharge. Severe post-procedural pain was observed, particularly after specific interventional radiology procedures, and may be prevented by injecting intraoperative analgesics.Background: Interventional radiology plays a major role in oncology both for curative and palliative treatment, but few reports address post-procedural pain. The purpose of this study was to quantify postoperative pain after interventional radiology procedures in oncology and to identify major pain-associated pre and intraoperative factors. Methods: From 2015 to 2019, all patients treated with interventional radiology were included retrospectively in a cohort study. Anesthetic protocols were standardized by the type of radiological procedure. Demographic data, preoperative treatments, analgesic agents, pain score levels, and morphine consumption from the post-anesthesia care unit (PACU) to hospital discharge were collected from databases. In an additional case-control study, patients reporting strong or intolerable pain in PACU were compared to those with no pain. Matching to control cases was based on the type of intervention, sex, and age. Results: From 4411 procedures, severe pain in PACU was more frequent in women (p < 0.04) and the youngest patients (p < 0.0001), after general anesthesia (p < 0.0001). Higher pain levels were associated with certain procedures, such as arterial embolization, limb cementoplasty, osteosynthesis, and abdominal tumor ablation, and when the intervention duration exceeded 160 min (p = 0.038). In the cohort study, high-dose remifentanil (≥0.055 µg/kg/min) was a risk factor for post-procedural high pain levels (p < 0.001). Intraoperative ketoprofen was associated with a decrease in high pain level incidence (p < 0.0001). Severe pain in PACU was a risk factor for severe pain in wards from day 0 until discharge. Conclusion: Severe pain depends on the type and duration of interventional radiology, type of anesthesia, and preoperative use of opiates. Limiting doses of remifentanil and injecting intraoperative analgesics, especially ketoprofen, may reduce the incidence of post-intervention severe pain.

Effects of Preoperative Electroacupuncture on Remifentanil-Induced Post-Infusion Hyperalgesia in Patients Undergoing Thyroidectomy: A Double-Blind Randomized Controlled Trial

ObjectiveElectroacupuncture (EA) delivered one day before surgery could reduce postoperative pain. Remifentanil-induced post-infusion hyperalgesia (RPH) was occurred after exposure to high-dose remifentanil. This study aimed to investigate the effects of preoperative EA on RPH in patients undergoing thyroidectomy.MethodsA total of 80 patients who were scheduled to undergo elective thyroidectomy were randomly assigned to two groups: an EA group and a sham EA (SEA) group. EA was delivered at the Zusanli (ST36) and Neiguan (PC6) acupoints 24 h before the surgery. To ensure uniformity across all patients, remifentanil was administered at the same set rate (0.3 μg/kg/min) to all patients. Mechanical pain thresholds were recorded by an electronic von Frey device around the skin incision and on the arm before surgery as well as at 30 min and 6, 24, and 48 h after surgery.ResultsAt 30 min and 6 h after surgery, the EA group showed considerably greater mechanical pain thresholds surrounding the surgical site compared with the SEA group. At 30 min and 6 h after surgery, the patients in the SEA group showed a greater incidence of postoperative hyperalgesia surrounding the surgical site than those in the EA group. At 24 and 48 h after surgery, no significant differences were found between the two groups, although the pain intensity of the EA group was less than that of the SEA group. There were also no substantial differences between the two groups in the frequency of postoperative adverse reactions and rescue analgesia needed.ConclusionEA administered 24 h before surgery could alleviate RPH in patients undergoing thyroidectomy.

Brain-based measures of nociception during general anesthesia with remifentanil: A randomized controlled trial.

BackgroundCatheter radiofrequency (RF) ablation for cardiac arrhythmias is a painful procedure. Prior work using functional near-infrared spectroscopy (fNIRS) in patients under general anesthesia has indicated that ablation results in activity in pain-related cortical regions, presumably due to inadequate blockade of afferent nociceptors originating within the cardiac system. Having an objective brain-based measure for nociception and analgesia may in the future allow for enhanced analgesic control during surgical procedures. Hence, the primary aim of this study is to demonstrate that the administration of remifentanil, an opioid widely used during surgery, can attenuate the fNIRS cortical responses to cardiac ablation.Methods and findingsWe investigated the effects of continuous remifentanil on cortical hemodynamics during cardiac ablation under anesthesia. In a randomized, double-blinded, placebo (PL)-controlled trial, we examined 32 pediatric patients (mean age of 15.8 years,16 females) undergoing catheter ablation for cardiac arrhythmias at the Cardiology Department of Boston Children’s Hospital from October 2016 to March 2020; 9 received 0.9% NaCl, 12 received low-dose (LD) remifentanil (0.25 mcg/kg/min), and 11 received high-dose (HD) remifentanil (0.5 mcg/kg/min). The hemodynamic changes of primary somatosensory and prefrontal cortices were recorded during surgery using a continuous wave fNIRS system. The primary outcome measures were the changes in oxyhemoglobin concentration (NadirHbO, i.e., lowest oxyhemoglobin concentration and PeakHbO, i.e., peak change and area under the curve) of medial frontopolar cortex (mFPC), lateral prefrontal cortex (lPFC) and primary somatosensory cortex (S1) to ablation in PL versus remifentanil groups. Secondary measures included the fNIRS response to an auditory control condition. The data analysis was performed on an intention-to-treat (ITT) basis. Remifentanil group (dosage subgroups combined) was compared with PL, and a post hoc analysis was performed to identify dose effects. There were no adverse events. The groups were comparable in age, sex, and number of ablations. Results comparing remifentanil versus PL show that PL group exhibit greater NadirHbO in inferior mFPC (mean difference (MD) = 1.229, 95% confidence interval [CI] = 0.334, 2.124, p < 0.001) and superior mFPC (MD = 1.206, 95% CI = 0.303, 2.109, p = 0.001) and greater PeakHbO in inferior mFPC (MD = −1.138, 95% CI = −2.062, −0.214, p = 0.002) and superior mFPC (MD = −0.999, 95% CI = −1.961, −0.036, p = 0.008) in response to ablation. S1 activation from ablation was greatest in PL, then LD, and HD groups, but failed to reach significance, whereas lPFC activation to ablation was similar in all groups. Ablation versus auditory stimuli resulted in higher PeakHbO in inferior mFPC (MD = 0.053, 95% CI = 0.004, 0.101, p = 0.004) and superior mFPC (MD = 0.052, 95% CI = 0.013, 0.091, p < 0.001) and higher NadirHbO in posterior superior S1 (Pos. SS1; MD = −0.342, 95% CI = −0.680, −0.004, p = 0.007) during ablation of all patients. Remifentanil group had smaller NadirHbO in inferior mFPC (MD = 0.098, 95% CI = 0.009, 0.130, p = 0.003) and superior mFPC (MD = 0.096, 95% CI = 0.008, 0.116, p = 0.003) and smaller PeakHbO in superior mFPC (MD = −0.092, 95% CI = −0.680, −0.004, p = 0.007) during both the stimuli. Study limitations were small sample size, motion from surgery, indirect measure of nociception, and shallow penetration depth of fNIRS only allowing access to superficial cortical layers.ConclusionsWe observed cortical activity related to nociception during cardiac ablation under general anesthesia with remifentanil. It highlights the potential of fNIRS to provide an objective pain measure in unconscious patients, where cortical-based measures may be more accurate than current evaluation methods. Future research may expand on this application to produce a real-time indication of pain that will aid clinicians in providing immediate and adequate pain treatment.Trial registrationClinicalTrials.gov NCT02703090

Association between the Remifentanil Dose during Anesthesia and Postoperative pain.

Remifentanil is an ultra-short-acting opioid that sometimes causes opioid-induced hyperalgesia, which has led to controversy regarding the association between intraoperative remifentanil administration and postoperative pain. This study aimed to assess the effects of the intraoperative remifentanil dose on postoperative pain. Patients undergoing esophageal, gastric/hepatobiliary, or intestinal/colon surgery and using postoperative patient-controlled epidural analgesia were analyzed. The patients were divided into two groups based on the average intraoperative remifentanil dose (high-dose remifentanil [HR] group: ≥0.1 μg/kg/min; low-dose remifentanil [LR] group: <0.1 μg/kg/min). In all, 406 patients met the inclusion criteria. A significant difference in the average dose of remifentanil was seen between the groups during the anesthesia period (0.14±0.05 vs. 0.07±0.02 μg/kg/min). However, no significant difference was seen in pre- or intraoperative patient characteristics. Numerical rating scale (NRS) scores on postoperative day 1 were similar between the groups (HR: 1.7±2.0; LR: 1.7±2.0; p=0.74). The incidence of poor pain control (NRS > 3/10) was also similar between the groups (HR: 14%; LR: 16%; p=0.57). Older age (> 60 years) and type of surgery (esophageal surgery) were associated with worse postoperative NRS scores. No significant association was seen between the intraoperative remifentanil dose and postoperative NRS scores following thoracoabdominal surgery with postoperative epidural pain management.

Remifentanil requirement for acceptable intubation conditions with two different doses of ketamine without a neuromuscular blocking agent in pediatric patients.

The optimal remifentanil concentration for improving intubation conditions when intubation is performed without neuromuscular blocking agents (NMBAs) but with ketamine as an induction agent remains unknown. Here, we aimed to identify the effective bolus doses of remifentanil required to achieve acceptable intubation conditions upon anesthesia induction with 1 or 2 mg/kg ketamine without NMBAs. In this prospective, double-blinded, randomized up-down sequential allocation study, we enrolled pediatric patients aged 3-12 years undergoing general anesthesia for inguinal hernia surgery. The patients were randomly allocated to one of two groups to receive either ketamine 1.0 mg/kg (K1 group) or 2.0 mg/kg (K2 group) intravenously until seven success-failure pairs were achieved. The remifentanil dose for each patient was determined using the modified Dixon's up-and-down method with an initial dose of 2.5 μg/kg and a step size of 0.5 μg/kg. In total, 51 patients (22 in the K1 group and 29 in the K2 group) were enrolled. The effective dose (ED)50s of remifentanil for obtaining clinically acceptable intubation conditions under anesthesia induction with ketamine but without NMBAs was 3.2 μg/kg in the K1 group and 1.6 μg/kg in the K2 group. High-dose remifentanil with 1 mg/kg ketamine was associated with more severe chest wall rigidity and lower mean blood pressure and heart rate than was low-dose remifentanil with 2 mg/kg ketamine. The ED50 of remifentanil required for clinically acceptable intubation conditions with anesthesia induction using 1 mg/kg ketamine without NMBAs in pediatric patients was twice that when using 2 mg/kg ketamine. The combination of 2 mg/kg ketamine and remifentanil was better at preventing chest wall rigidity.

Effect of Remifentanil on Postoperative Vomiting After Strabismus Surgery in Preschool Children: A Prospective Randomized Controlled Trial.

BackgroundStrabismus surgery and the use of opioid are risk factors of postoperative vomiting. We evaluated whether there is a dose-dependent effect of remifentanil on the incidence of postoperative vomiting.MethodsSixty pediatric patients who were scheduled for strabismus surgery were enrolled. Patients were randomly divided into three groups; Group H (high-dose remifentanil group), Group L (low-dose remifentanil group), and Group C (control group). After endotracheal intubation, patients in the Group H and L received an intravenous bolus dose of remifentanil of 1.0 μg/kg and 0.5 μg/kg over 2 min, respectively. Group H and L patients received a continuous infusion of remifentanil (0.1 μg/kg/min) during the surgery. The patients in Group C did not have any dose of remifentanil. Intravenous fentanyl (1 µg/kg) was administered to the patients for postoperative pain control.ResultsThe primary outcome was a difference of the incidence of postoperative vomiting within 24 hours after surgery. There was no significant difference in incidence of postoperative vomiting between three groups. The degree of emergence agitation and postoperative pain did not show any significant difference between three groups.ConclusionsThe intraoperative administration of remifentanil did not show dose-dependent effect on postoperative vomiting in pediatric strabismus surgery.

The effect of different doses of naloxone on postoperative hyperalgesia in patients who received high-dose remifentanil during hysterectomy procedures; a double-blind randomized clinical trial

BackgroundHyperalgesia is one of the adverse effects of remifentanil, an opioid drug used for reducing pain in surgical procedures. Naloxone is used for reversing the adverse effects of opioids and can reduce this acute and persistent pain after surgery. In the present study, we aimed to investigate the effect of two doses of naloxone (high and low doses) for reducing hyperalgesia after hysterectomy. MethodsIn this single-blinded randomized clinical trial, 72 patients who underwent hysterectomy with ASA class I and II were randomly divided into three groups of 24 participants. All three groups received an intraoperative infusion of 0.4 micrograms/kg/min of remifentanil.One group received 0.02 µg/kg/min naloxone, the other group received 0.05 µg/kg/min naloxone, and the third group received 0.2 cc/kg normal saline instead of naloxone. The results of the visual analogue scale, Ramsay score, and pressure algometry were completed for all participants half an hour before the surgery, one hour, two, and eight hours after the surgery, pethidine requirement, and postoperative nausea/vomiting and the Ramsay score were recorded. Comparison of variables among the groups was performed using one-way ANOVA and posthoc tests by SPSS software, version 21. ResultsThe mean age of the participants was 48.63±9.85 years. The pressure algometry of the right and left forearms and abdomen was different among the three groups after surgery (P<0.05). There was no difference in mean pethidine requirement at recovery and in general, visual analogue scale score, Ramsay score 1 hour and 8 h after the surgery, and the frequency of postoperative nausea and vomiting among the three groups (P>0.05). ConclusionThe similar efficacy and adverse effects of the two doses indicate that the low dose of naloxone is suggested for reducing remifentanil-induced hyperalgesia after hysterectomy.

Intraoperative Remifentanil Dosage in Surgery for Adolescent Idiopathic Scoliosis Does Not Increase Postoperative Opioid Consumption When Combined With Epidural Analgesia: A Retrospective Cohort Study.

BackgroundIn adults, high-dose remifentanil during surgery has been reported to increase postoperative opioid consumption, but this has not been well documented in children. Multimodal analgesia is recommended in the perioperative period for adolescent idiopathic scoliosis (AIS), but no report has examined opioid consumption under epidural analgesia, which is one of the most common types of analgesia.AimsTo investigate the association between intraoperative remifentanil dosage and postoperative opioid consumption in AIS in the setting of combined epidural analgesia for postoperative multimodal analgesia.MethodsIn this retrospective cohort study, patients aged 10-18 years who underwent surgery for scoliosis and epidural analgesia for postoperative pain between July 2012 and April 2019 were included. The primary endpoint was the association between intraoperative cumulative weight-adjusted remifentanil dosage and logarithmic transformation of cumulative weight-adjusted fentanyl consumption in the intensive care unit (ICU). Nonopioid analgesics were investigated as secondary endpoints. An epidural catheter was inserted by the surgeon intraoperatively, and a local anesthetic was administered at the end of the surgery. Multivariate linear regression analysis with adjustment for confounders was performed for all analyses.ResultsIn total, 142 patients were included, and the median intraoperative remifentanil dosage for all patients was 0.27 (interquartile range, 0.24-0.34) µg/kg/min. No association was observed between cumulative weight-adjusted intraoperative dosage of remifentanil and fentanyl, even after adjusting for potential confounders (slope = −1.25; 95% confidence interval [CI], −4.35 to 1.85; P = 0.43). No association was observed between nonopioid analgesic use and intraoperative remifentanil dosage.ConclusionNo association was noted between remifentanil dosage during surgery for AIS and postoperative opioid consumption with epidural analgesia. However, this study has limitations due to its retrospective design; thus, further prospective studies are warranted.

Rapid Sequence Intubation with Remifentanil During COVID-19 Pandemic

We greatly appreciate the interest that De Melo MS, et al. showed on the use of remifentanil in a rapid sequence intubation technique that we recently proposed for patients undergoing surgery during the current SARS-CoV-2 pandemic [1, 2]. The authors also reported the response that Tang and Wang wrote to comment on that paper [3]. Given the interest aroused by our article, we think it would be worth making some clarifications. In brief, in order to limit aerosolization, we proposed to systematically perform rapid induction and intubation in the surgical patient after he had reached a state of deep analgesia with a continuous infusion of high-dose remifentanil (0.2-0.3 g/kg/min) [2]. Although in the title of the article this method is labeled as a rapid sequence induction, in the text, we explain how this technique, far from being standard rapid sequence intubation, was a rather longer technique in which the patient, although in a state of profound analgesia and sedation induced by remifentanil, breathed spontaneously and at last on command, until hypnosis, and muscle paralysis was rapidly induced with a low dose of propofol (&lt;0.5 mg/kg) or midazolam (0.05-0.1 mg/kg) and a full dose of rocuronium (1 mg/kg) [2].

Pre-emptive remifentanil alleviates pain associated with tracheal suctioning in patients under mechanical ventilation and goal-directed sedation: A randomized controlled feasibility trial.

To investigate the efficacy of pre-emptive remifentanil in alleviating pain during tracheal suctioning in patients under mechanical ventilation. Goal-directed sedation is recommended for patients under mechanical ventilation by the current guidelines. Whether goal-directed sedation can prevent pain during tracheal suctioning in these patients is unknown. This was a two-centre, randomized, crossover, single-blind trial conducted between August and October 2019. Patients under mechanical ventilation received low-dose remifentanil, high-dose remifentanil or placebo prior to each tracheal suctioning in a random order. The primary outcomes were evaluated using the critical-care pain observation tool and Richmond agitation-sedation scale after tracheal suctioning. Adverse events were also documented. A total of 39 patients who underwent 117 tracheal suctions were enrolled. After the tracheal suction, changes in the critical-care pain observation tool and Richmond agitation-sedation scale scores were significantly lower in the low-dose and high-dose groups than in the placebo group (P<0.001). A non-significant increase in the absence of spontaneous breathing was observed in the high-dose group compared to that in the placebo group. A pre-emptive remifentanil bolus of 0.5μg/kg can mitigate the pain associated with tracheal suctioning.

Pharmacological strategies to prevent haemodynamic changes after intubation in parturient women with hypertensive disorders of pregnancy: A network meta-analysis.

Objective: This network meta-analysis (NMA) aimed to determine the relative efficacy and safety of pharmacological strategies used to mitigate haemodynamic instability by intubation for general anaesthesia in hypertensive parturient women undergoing caesarean section.Methods: We considered randomised controlled studies comparing the effects of pharmacological strategies used to alleviate haemodynamic instability during intubation in parturient women with hypertensive disorders of pregnancy. The primary endpoints were maximum blood pressure and heart rate after intubation, and secondary endpoints were the Apgar scores at 1 and 5 min. NMA allowed us to combine direct and indirect comparisons between strategies.Results: Twelve studies evaluating nine pharmacological strategies in 619 patients were included. According to the surface under the cumulative ranking curve, the maximal mean arterial pressure was lowest for high-dose remifentanil (99.4%) followed by nitroglycerin (73.6%) and labetalol (60.9%). The maximal heart rate was lowest for labetalol (99.9%) followed by high dose of remifentanil (81.2%) and fentanyl (61.6%). Apgar score at 1 min was higher with low-dose than with high-dose remifentanil (mean difference, 0.726; 95% confidence interval, 0.056 to 1.396; I2=0.0%).Conclusions: High-dose remifentanil produces minimum blood pressure changes, while labetalol is most effective in maintaining normal heart rate in parturient women with hypertensive disorders of pregnancy during caesarean section under general anaesthesia.