Remifentanil Infusion Research Articles

P2Y1 purinergic receptor inhibition attenuated remifentanil-induced postoperative hyperalgesia via decreasing NMDA receptor phosphorylation in dorsal root ganglion

BackgroundRemifentanil-induced postoperative hyperalgesia is an intractable side effect of the clinical use of remifentanil, the mechanism of which remains obscure, especially in the peripheral nervous system. N-methyl-D-aspartate receptor (NMDAR) phosphorylation in dorsal root ganglion (DRG) plays a pronociceptive role in neuropathic pain. The contribution of the P2Y1 purinergic receptor (P2Y1R) in DRG to pain hypersensitivity derived from various origins and P2Y1R upregulation-induced NMDAR activation in neurons have also been uncovered. This study aimed to investigate whether P2Y1R participates in nociceptive processing in the DRG and spinal cord in remifentanil-induced postoperative hyperalgesia. MethodsRats with remifentanil-induced postoperative hyperalgesia were intrathecally injected with NMDAR antagonist MK801 or P2Y1R antagonist MRS2179 at 10 min prior to remifentanil infusion. Mechanical allodynia, heat hyperalgesia, and cold hyperalgesia were measured at −24 h, 2 h, 6 h, 24 h, and 48 h following remifentanil infusion. The P2Y1R expression and NMDAR expression and phosphorylation in DRG ipsilateral to the incision were detected by Western blot and immunofluorescence. ResultsIncision and remifentanil induced mechanical allodynia, heat hyperalgesia, and cold hyperalgesia accompanied by upregulated P2Y1R expression, increased NMDAR subunit NR1 expression and phosphorylation at Ser896, and NR2B expression and phosphorylation at Tyr1472 in DRG. Inhibition of NMDAR phosphorylation by MK801 effectively attenuated remifentanil-induced postoperative hyperalgesia. Furthermore, P2Y1R blockade by MRS2179 not only lessened remifentanil-evoked postoperative hypersensitivity to mechanical, heat, and cold stimuli, but also suppressed the increases in NR1 and NR2B expression and phosphorylation in DRG induced by incision and remifentanil. ConclusionThe process by which P2Y1R mediates NMDAR expression and phosphorylation represents a mechanism of remifentanil-induced postoperative hyperalgesia in the DRG and/or spinal cord.

Opioid-free anesthesia versus opioid-inclusive anesthesia for breast cancer surgery: a retrospective study

BackgroundBreast cancer surgery is usually managed using opioid-inclusive anesthesia (OIA), although opioids are associated with several adverse events, including nausea, vomiting, and constipation. Multimodal opioid-free anesthesia (OFA) has been introduced to reduce the incidence of these side effects. In this single-center retrospective study, we investigated whether ketamine, combined with magnesium and clonidine, could effectively control postoperative pain in patients undergoing quadrantectomy, while reducing postoperative nausea and vomiting (PONV).ResultsA total of 89 patients submitted to quadrantectomy were included and divided into an OFA group (38 patients) and an OIA group (51 patients) according to the received anesthetic technique. Analgesia in the OIA group was based on an intraoperative infusion of remifentanil, and analgesia in the OFA consisted of an intraoperative infusion of ketamine and magnesium sulfate. Postoperative pain in both groups was managed with nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol. Postoperative pain, assessed with the numeric rating scale (NRS), requirements for additional analgesics, the incidence of PONV, and patient satisfaction evaluated using a QoR-40 questionnaire were compared between the two groups. Levels of pain at 30 min and 6, 12, and 24 h after surgery; number of paracetamol rescue doses; and the incidence of PONV were lower in the OFA group (p <0.05). Patient satisfaction was comparable in the two groups.ConclusionsA combination of ketamine, magnesium, and clonidine could be more effective than opioid-based analgesia in reducing postoperative pain and lowering PONV occurrence after quadrantectomy for breast cancer.

Store-Operated Calcium Channels Contribute to Remifentanil-Induced Postoperative Hyperalgesia via Phosphorylation of CaMKIIα in Rats.

PurposeThe mechanisms of remifentanil-induced postoperative hyperalgesia (RIPH) remain unclear. Store-operated calcium channels (SOCCs) are mainly comprised of stromal interaction molecules 1 (STIM1) and pore-forming subunits (Orai1). They were found to take a pivotal part in Ca2+-dependent procedures and involved in the development of central sensitization and pain. Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα), regulated by Ca2+/calmodulin complex, has been shown to have a crucial role in RIPH. This study aims to determine whether SOCCs contribute to RIPH via activating CaMKIIα.Materials and MethodsIntra-operative infusion of remifentanil (1.0 µg kg−1 min−1, 60 min) was used to establish a RIPH rat model. The SOCCs blocker (YM-58483) was applied intrathecally to confirm the results. Animal behavioral tests including paw withdrawal thermal latency (PWTL) and paw withdrawal mechanical threshold (PWMT) were performed at −24, 2, 6, 24, 48 h after incision and remifentanil treatments. The protein expression of STIM1, Orai1, CaMKIIα, and p-CaMKIIα was assayed with Western blot, and the number of STIM1 and Orai1 positive cells was shown by immunofluorescence.ResultsRemifentanil administration significantly induced postoperative mechanical and thermal hyperalgesia, as well as increased STIM1 and Orai1 protein expression in the spinal dorsal horn. Furthermore, the intrathecal administration of YM-58483 effectively alleviated remifentanil-induced postoperative mechanical and thermal hyperalgesia according to the behavioral tests. In addition, YM-58483 suppressed the phosphorylation of CaMKIIα but had no effect on the expression of STIM1 and Orai1.ConclusionOur study demonstrated that SOCCs are involved in RIPH. The over-expressed STIM1 and Orai1 in the spinal cord contribute to RIPH via mediating the phosphorylation of CaMKIIα. Blockade of SOCCs may provide an effective therapeutic approach for RIPH.

Cardiovascular Safety and Hemostatic Efficacy of Topical Epinephrine in Children Receiving Zirconia Crowns.

The primary aim of this study was to determine the cardiovascular safety of topical racemic epinephrine pellets by measuring heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure in children receiving dental care under general anesthesia. The secondary aim was to assess clinical efficacy by measuring time to reach adequate hemostasis. For this pilot study utilizing a split-mouth randomized design, 13 patients requiring prefabricated zirconia crowns on both primary maxillary first molars were recruited. Patients received continuous infusions of propofol and remifentanil with 50-70% inhaled nitrous oxide and oxygen. After randomization and tooth preparation, either saline pellets (control) or racemic epinephrine pellets (experimental) were applied directly to gingival tissue. Vital signs were recorded for 5 minutes. The procedure was repeated on the contralateral side using the alternative (control or experimental) treatment. Topical racemic epinephrine compared to saline produced a significantly larger decrease in mean diastolic blood pressure (-11.1% vs -3.9%; P < .01) and mean arterial pressure (-8.1% vs -2.1%; P < .01), although all noted decreases in cardiovascular variables were clinically insignificant. All experimental treatment teeth achieved adequate hemostasis after 2.2 minutes. Only 5 of the 13 control treatment teeth achieved adequate hemostasis during the 5-minute observation period (1.6 vs 4.2 minutes; P = .01). Overall, we conclude that use of topical racemic epinephrine pellets did not result in adverse cardiovascular effects and hemostasis was reached more quickly and predictably compared to saline pellets.

Effects of changes in end-tidal carbon dioxide tension on oral tissue blood flow and tissue oxygen tension during remifentanil infusion in rabbits.

The aim of this study was to investigate the effects of end-tidal carbon dioxide tension (ETCO2) changes during remifentanil infusion on mandibular bone marrow tissue blood flow (BBF), masseter muscle tissue blood flow (MBF), mandibular bone marrow tissue oxygen tension (PbO2) and masseter muscle tissue oxygen tension (PmO2) in rabbits. Ten male tracheotomized Japan White rabbits were anesthetized and ventilated with sevoflurane. ETCO2 was adjusted to 30mmHg. After baseline measurement, CO2 was added to the inhaled air, and ETCO2 was increased to 40 and 60mmHg. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), BBF, MBF, PbO2, and PmO2 were recorded with and without remifentanil infusion at 0.4µg/kg/min. Two-way repeated measures analysis of variance showed no interaction between ETCO2 and remifentanil in all variables. Remifentanil infusion produced decreases in HR, SBP, MAP, BBF and MBF compared with those without remifentanil infusion, while it did not affect DBP, PbO2 and PmO2. Elevation of ETCO2 from 30 to 60mmHg produced decreases in HR and MBF, and increases in SBP, DBP, MAP and BBF, while it did not affect PbO2 and PmO2. PbO2 and PmO2 remained unchanged despite changes in BBF and MBF during ETCO2 change with or without remifentanil infusion.

Comparison of Intraoperative Infusion of Remifentanil Versus Fentanyl on Pain Management in Patients Undergoing Spine Surgery: A Double Blinded Randomized Clinical Trial.

BackgroundRemifentanil is an ultra-short-acting opioid which facilitates hemodynamic management. However, there are concerns about postoperative Remifentanil hyperalgesia because of its potent fast onset and offset.ObjectivesThe aim of this study was to determine visual analog scale (VAS), postoperative pain, and morphine used in two groups after spine surgery.MethodsIn this randomized clinical trial study, 60 patients aged 18 - 60 years old, according to the American Society of Anesthesiology (ASA) I - II, who underwent spinal canal stenosis or scoliosis surgery, were divided into two groups. In the control group, patients received 0.07 - 0.1 µg/kg/h intraoperative Fentanyl infusion, and in the intervention group 0.1 - 0.2 µg/kg/min remifentanil was infused during the surgery. Both groups received 15 mg/kg intravenous Acetaminophen 20 minutes before the end of the surgery. Postoperative pain score and morphine consumption were measured 6, 12, 24, and 48 hours after discharge from the post-anesthesia care unit (PACU).ResultsDuring the first 12 hours, VAS and morphine consumption were significantly higher in remifentanil group (P < 0.001). However, no significant difference was found between the two groups in morphine consumption 12 - 48 hours after surgery.ConclusionsThese findings suggest that Remifentanil infusion during surgery may increase postoperative pain. Also, VAS and morphine consumption were higher during the first 12 hours.

The Comparison of Two Different Techniques of Remifentanil Administration During Implantable Vascular Access Device Procedures

PurposeThe aim was to compare analgesic efficacy and adverse effects of two different techniques of intravenous remifentanil administration in patients undergoing vascular; access device procedures with monitored anesthesia care. DesignA randomized, single-blinded controlled study. MethodsThe patients (N = 92) were 30-80 years old and of American Society of Anesthesiologists Physical Status I-III. The first group was the continuous infusion group (group CI). Intravenous continuous remifentanil was infused after starting at a dosage of 0.1 mcg/kg/min, and the dose was raised incrementally up to 1 mcg/kg/min if required. The second group was intravenous bolus patient-controlled sedation analgesia (PCSA) with remifentanil infusion at a dose of 0.05 mcg/kg per minute and bolus of 0.1 mcg/kg with lock-out time of 3 minutes. In both groups, a bolus dose of 0.1 mcg/kg remifentanil was administered. The data evaluated include level of pain and sedation, total amount of remifentanil consumption, bolus doses of remifentanil, patient and surgeon satisfaction, hemodynamic data, and adverse events. FindingsIn comparison between techniques, pain and sedation scores during procedure, duration of procedure, patient and surgeon satisfaction, additional rescue medication, and bolus doses were not statistically different (P > .05). The total amount of remifentanil administered was significantly lower in the infusion group than that in the bolus group (P = .031). ConclusionsFor central venous access device procedures under monitored anesthesia care, remifentanil use in both infusion and bolus techniques could provide sufficient sedation and analgesia without serious adverse effects. Total remifentanil consumption amount in infusion group is lower than that in the bolus group.

Comparison of the Sedative and Analgesic Effects of Dexmedetomidine-Remifentanil and Dexmedetomidine-Sufentanil for Liposuction: A Prospective Single-Blind Randomized Controlled Study.

Dexmedetomidine had sedative and analgesic effects and did not produce significant respiratory depression at therapeutic doses. To compare the sedative and analgesic effects and safety of dexmedetomidine combined with remifentanil or sufentanil in patients undergoing liposuction. A total of 100 subjects were randomized 1:1 to two groups: Group R and Group S. First, patients were administered midazolam 0.02mg·kg-1. Anesthesia was induced with an intravenous infusion of dexmedetomidine 1µgkg-1 (15min) and remifentanil 0.1µgkg-1min-1 (Group R) or sufentanil 0.1µgkg-1h-1 (Group S). Anesthesia was maintained with an intravenous infusion of dexmedetomidine 1.0µgkg-1h-1, midazolam 0.015mgkg-1h-1, remifentanil 0.1µgkg-1min-1 (Group R), or sufentanil 0.1µgkg-1h-1 (Group S). Hemodynamic and respiratory changes, modified OAA/S score and BIS values, postoperative Visual Analogue Scale pain scores, satisfaction of the patient and surgical team with the procedure, and adverse events and recovery time were recorded. Group R received significantly less midazolam and midazolam per hour compared to Group S (Group R vs. Group S: 3.4 ± 1.7mg vs. 5.1 ± 2.0mg, P <0.0001; 1.5 ± 0.7mg/h vs. 1.9 ± 0.6mg/h, P = 0.002). The incidence of physical or verbal expressions of pain at the start of surgery was significantly lower in Group R compared to Group S (2 [4.3%] vs. 12 [26.7%], P = 0.003). Patient satisfaction with the procedure was significantly higher in Group R compared to Group S (3.9 ± 0.3 vs. 3.1 ± 0.3, P <0.0001). Dexmedetomidine-remifentanil and dexmedetomidine-sufentanil were effective and safe sedative and analgesic agents for liposuction. Hemodynamic stability was maintained. Dexmedetomidine-remifentanil might be associated with improved analgesic effects compared to dexmedetomidine-sufentanil. Evidence was obtained from at least one properly designed randomized controlled trial. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Evaluation of the impact of deep neuromuscular blockade on surgical conditions for laryngeal microsurgery with High Frequency Jet Ventilation. A comparison with no block during intravenous general anesthesia with topical lidocaine

ObjectiveLaryngeal transoral surgery classically requires a neuromuscular block (NMB) to facilitate tracheal intubation and to improve surgical conditions. However, the short duration of most procedures and the potential complications of residual NMB lead to consider a no block approach. The hypothesis that intravenous anesthesia (remifentanil and propofol infusions) without NMB but including glottis topical lidocaine anesthesia would allow clinically acceptable laryngeal exposure and good surgical conditions was tested in the specific context of procedures undergone with High Frequency Jet Ventilation (HFJV). Study designA prospective randomized clinical comparison. Methods66 consenting patients were planned to receive 0.6 mg·kg−1 rocuronium or saline at random. The outcome measurements included the time and conditions to complete suspended laryngoscopy, and the surgical conditions rated by the surgeon. Any vocal cord movement or coughing was recorded. Data were compared using a Wilcoxon rank-sum test for numerical variables and chi-square test for categorical ones. Treatment failure was defined as an impossible laryngoscopy or a grade 4 surgical field occurring at any time during surgery and was compared to its null theoretical value by a general z-test. An interim analysis after completion of 50% patients was performed using Pocock boundaries at 0.0294 significance levels. ResultsA significant failure rate occurred in the non paralysed group (27%, p < 0.001). No coughing and no vocal cords movement occurred in the NMB group. Poorer surgical conditions were obtained without NMB (p = 0.011). ConclusionInducing a deep NMB ensured improved conditions during direct laryngeal microsurgery with HFJV.

Postoperative Drip-Infusion of Remifentanil Reduces Postoperative Pain—A Retrospective Observative Study

Development of remifentanil-induced hyperalgesia (RIH) postoperatively is an unpleasant experience that requires further treatment. This study assessed the effects of gradual withdrawal combined with drip infusion of remifentanil on postoperative pain and the requirement for rescue analgesics. A total of 559 patients receiving total intravenous anesthesia with propofol and remifentanil were enrolled. All patients either underwent gradual withdrawal of remifentanil (GWR) or gradual withdrawal combined with drip infusion (GWDR) with a dose of 1 mcg·kg−1 for 30 min after extubation. The numeric rating scale (NRS) and the requirement of rescue analgesics were assessed. The requirement for rescue analgesics was significantly lower in the GWDR group than in the GWR group (13.2% vs. 35.7%; p < 0.001). At the post-anesthetic care unit (PACU), patients in the GWDR group had a lower NRS pain score (p < 0.001). In addition, in the postoperative 2nd hour, patients in the GWDR group had a significantly lower NRS than the GWR group (beta, −0.31; p = 0.003). No remifentanil-related adverse effects were observed. We found that gradual withdrawal combined with drip infusion of remifentanil required less rescue analgesics and reduced pain scores. The new way of remifentanil administration may be effective to prevent RIH.

Prospective evaluation of remifentanil-propofol mixture for total intravenous anesthesia: A randomized controlled study.

Application of total intravenous anesthesia (TIVA) may be considered as unpractical when compared with inhalational anesthesia. Although it is mostly not recommended, mixing intravenous agents is popular in clinical practice. The aim of the present study was to investigate the suitability of using remifentanil-propofol mixture (MIXTIVA) for TIVA. Adult patients with an American Society of Anesthesiologists grade of I-II scheduled for elective thyroidectomy were randomly allocated to 3 groups (n=32 for each) to receive TIVA with remifentanil and propofol infusions separately (control group, Group I) or with MIXTIVA infusion that contained remifentanil/propofol at a proportion of 2/1,000 or 3/1,000 (remifentanil concentration, 20 or 30 µg/ml in 1% propofol in Group II or Group III, respectively). The extubation time (the primary outcome of the study), the orientation time and number of patients in whom intraoperative hypotension, hypertension or bradycardia episodes were encountered during anesthesia were comparable among the groups. The mean remifentanil infusion rate in Group III was significantly higher than that in the other groups. The mean propofol infusion rates and mean bispectral index (BIS) scores during anesthesia were comparable among groups. Hypotension accompanied with a high BIS was encountered in one patient in Group III. In conclusion, compared to the standard TIVA technique using separate drug infusions, MIXTIVA infusion used for thyroidectomies did not result in any statistically significant difference in recovery and clinical outcomes. This technique may be considered as a practical implementation for busy ambulatory centers performing general anesthesia. The present study was retrospectively registered at clinicaltrials.gov (trial registration no. NCT04394897).

Effects of Thoracic Epidural Anesthesia on Systemic and Local Inflammatory Responses in Patients Undergoing Lung Cancer Surgery: A Randomized Controlled Trial

Inflammatory responses play major roles in the development of acute lung injury following lung cancer surgery. The authors tested the hypothesis that thoracic epidural anesthesia (TEA) during surgery could attenuate both systemic and local inflammatory cytokine productions in patients undergoing lung cancer surgery. A prospective randomized controlled trial. At Keio University Hospital, Tokyo, Japan. Patients scheduled for lung cancer surgery. Sixty patients were randomly allocated into two groups (n = 30 each group): the epidural group (group E), in which anesthesia was maintained with propofol, fentanyl, rocuronium, and epidural anesthesia with 0.25% levobupivacaine; or the remifentanil group (group R), in which a remifentanil infusion was used as a potent analgesia instead of epidural anesthesia. The lung epithelial lining fluid (ELF) and blood sampling were collected prior to one-lung ventilation (OLV) initiation (T1) and at 30 minutes after the end of OLV (T2). The concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in the ELF at T2 were increased significantly compared with those at T1 in both groups. The ELF concentration of IL-6 in group E was significantly lower than that in group R at T2 (median [interquartile range]: 39.7 [13.8-80.2] versus 76.1 [44.9-138.2], p = 0.008). Plasma IL-6 concentrations at T2, which increased in comparison to that at T1, were not significantly different between the two groups. The plasma concentrations of TNF-α did not change in both groups. This randomized clinical trial suggested that TEA could attenuate local inflammatory responses in the lungs during lung cancer surgery.

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

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. 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%). 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 < 0.001), and 25 (22 to 28) breaths/min (n = 11, P < 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 < 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. 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.

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

PurposeRemifentanil has been shown to increase the bioavailability of nasally administered naloxone. The aim of this study was to explore the nature of this observation.MethodsWe 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).ResultsUnder 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.ConclusionRemifentanil increases the bioavailability of naloxone after nasal administration by reducing the pre-systemic metabolism of the swallowed part of the nasal dose.

Effects of food restriction on the conditioned reinforcing properties of an opioid-associated stimulus.

Food restriction promotes drug self-administration; however, the effects of food restriction on the conditioned reinforcing properties of drug-associated stimuli are less clear. We tested the extent to which food restriction modified the conditioned reinforcing properties of a remifentanil-associated stimulus following conditioning with 3.2 or 1.0 μg/kg/infusion of remifentanil. First, we provided restricted (20 g/day standard chow) or ad libitum access to standard chow to rats. Second, within each feeding condition, we exposed rats to 20 intravenous infusions of remifentanil and 20 stimulus presentations that were delivered response independently each day for 5 days. For the experimental group (paired Pavlovian), the remifentanil infusions and stimulus presentations were delivered concurrently. The control group (random control) received the same number of infusions and stimulus presentations, but were not paired. For 28 sessions, we tested the extent to which the stimulus functioned as a conditioned reinforcer by allowing rats to freely respond for presentations of the remifentanil-associated stimulus. Following conditioning with 3.2 μg/kg/infusion of remifentanil, we found that rats that in the Paired Pavlovian group responded for the remifentanil-associated stimulus significantly more than rats in the Random control group, regardless of feeding condition. Following conditioning with 1.0 μg/kg/infusion of remifentanil, the remifentanil-associated stimulus was not associated with conditioned reinforcing properties, regardless of feeding condition. These findings confirm previous research demonstrating that a remifentanil-associated stimulus takes on conditioned reinforcing properties in a dose-dependent manner.

Effects of depth of neuromuscular blockade on the BIS-guided propofol requirement: A randomized controlled trial.

Background:Deep neuromuscular blockade is considered beneficial for improving the surgical space condition during laparoscopic surgery. Adequacy of the surgical space condition may affect the anesthetists’ decision regarding titration of depth of anesthesia. We investigated whether deep neuromuscular blockade reduces the propofol requirement under bispectral index monitoring compared to moderate neuromuscular blockade.Methods:Adult patients undergoing elective laparoscopic colorectal surgery were randomly allocated to a moderate or deep group. A train-of-four count of 1–2 in the moderate group, and a post-tetanic count of 1–2 in the deep group, were maintained by continuous infusion of rocuronium. The induction and maintenance of anesthesia were achieved by target-controlled infusion of propofol and remifentanil. The dose of propofol was adjusted to maintain the bispectral index in the range of 40–50. The remifentanil dose was titrated to maintain the systolic blood pressure to within 20% of the ward values.Results:A total of 82 patients were included in the analyses. The mean±SD dose of propofol was 7.54 ± 1.66 and 7.42 ± 1.01 mg·kg−1·h−1 in the moderate and deep groups, respectively (P = .104). The mean±SD dose of remifentanil was 4.84 ± 1.74 and 4.79 ± 1.77 μg kg−1 h−1 in the moderate and deep groups, respectively (P = .688). In comparison to the moderate group, the deep group showed significantly lower rates of intraoperative patient movement (42.9% vs 22.5%, respectively, P = .050) and additional neuromuscular blocking agent administration (76% vs 53%, respectively, P = .007). Postoperative complications, including pulmonary complications, wound problems and reoperation, were not different between the two groups.Conclusion:Deep neuromuscular blockade did not reduce the bispectral index-guided propofol requirement compared to moderate neuromuscular blockade during laparoscopic colon surgery, despite reducing movement of the patient and the requirement for a rescue neuromuscular blocking agent.Trial registration:Clinicaltrials.gov (NCT03890406)

Practice Patterns and Variability in Intraoperative Opioid Utilization: A Report From the Multicenter Perioperative Outcomes Group.

Opioids remain the primary mode of analgesia intraoperatively. There are limited data on how patient, procedural, and institutional characteristics influence intraoperative opioid administration. The aim of this retrospective, longitudinal study from 2012 to 2016 was to assess how intraoperative opioid dosing varies by patient and clinical care factors and across multiple institutions over time. Demographic, surgical procedural, anesthetic technique, and intraoperative analgesia data as putative variables of intraoperative opioid utilization were collected from 10 institutions. Log parenteral morphine equivalents (PME) was modeled in a multivariable linear regression model as a function of 15 covariates: 3 continuous covariates (age, anesthesia duration, year) and 12 factor covariates (peripheral block, neuraxial block, general anesthesia, emergency status, race, sex, remifentanil infusion, major surgery, American Society of Anesthesiologists [ASA] physical status, non-opioid analgesic count, Multicenter Perioperative Outcomes Group [MPOG] institution, surgery category). One interaction (year by MPOG institution) was included in the model. The regression model adjusted simultaneously for all included variables. Comparison of levels within a factor were reported as a ratio of medians with 95% credible intervals (CrI). A total of 1,104,324 cases between January 2012 and December 2016 were analyzed. The median (interquartile range) PME and standardized by weight PME per case for the study period were 15 (10-28) mg and 200 (111-347) μg/kg, respectively. As estimated in the multivariable model, there was a sustained decrease in opioid use (mean, 95% CrI) dropping from 152 (151-153) μg/kg in 2012 to 129 (129-130) μg/kg in 2016. The percent of variability in PME due to institution was 25.6% (24.8%-26.5%). Less opioids were prescribed in men (130 [129-130] μg/kg) than women (144 [143-145] μg/kg). The men to women PME ratio was 0.90 (0.89-0.90). There was substantial variability in PME administration among institutions, with the lowest being 80 (79-81) μg/kg and the highest being 186 (184-187) μg/kg; this is a PME ratio of 0.43 (0.42-0.43). We observed a reduction in intraoperative opioid administration over time, with variability in dose ranging between sexes and by procedure type. Furthermore, there was substantial variability in opioid use between institutions even when adjusting for multiple variables.

Intraoperative awareness during laparoscopic sleeve gastrectomy

Objectives: The aim of this study is to determine the incidence of intraoperative awereness (IA) in our patients who underwent laparoscopic sleeve gastrectomy (LSG) and the factors affecting the formation of this complication. Methods: Four hundred ten patients who underwent LSG between March 2018 and September 2020 were included in the study. By April 2019, we started using the Bispectral index (BIS) monitoring, which measures the depth of anesthesia in all of our LSG cases (n = 167). Patients with and without BIS monitorization were divided into two groups and compared. Results: In our series, IA was seen in 3 patients (2 males) in two different hospitals (0.7%; n = 410). They were all in the non BIS group (n = 243). The median duration of anesthesia was 120 minutes (ranging 90-180) in the non-BIS, and 113 minutes (ranging, 90-140) in the BIS group (p &amp;lt; 0.001). Hypotension developed in 63 patients in non-BIS and 12 patients in BIS group at the beginning of the operation (&amp;lt; 90/60 mm Hg). The total remifentanil infusion dose administered during the anesthesia period in the BIS group was 1310 ± 351 mcg, and 1330 ± 270 mcg in the non BIS group (p = 0.002). The effect of BIS monitorization between groups on IA, did not show statistical significance (p = 0.27). Conclusions: Anesthesia techniques that work well for patients with normal weight may not be safe and appropriate for obese patients. Especially in patients with intraoperative hypotension, it is necessary to be more careful about dose adjustment of anesthetic drugs.

Comparison of three intraoperative analgesic strategies in laparoscopic bariatric surgery: a retrospective study of immediate postoperative outcomes

Introduction and objectivesMultimodal Analgesia (MMA) has shown promising results in postoperative outcomes across a broad spectrum of surgeries, including bariatric surgery. We compared the analgesic effect immediately after Laparoscopic Bariatric Surgery (LBS) of the combined effect of MMA and methadone against two techniques that were based mainly on the use of high-potency medium-acting opioids. MethodsTwo hundred seventy-one patients were retrospectively reviewed. The primary outcome was postoperative pain score > 3/10 measured by the Verbal Numeric Scale (VNS) during the Postanesthetic Care Unit (PACU) stay. The three protocols of intraoperative analgesia were: (P1) sufentanil at anesthetic induction followed by remifentanil infusion; (P2) sufentanil at induction followed by dexmedetomidine infusion; and (P3) remifentanil at induction followed by MMA including dexmedetomidine, magnesium, lidocaine, and methadone. Only P1 and P2 patients received morphine toward the end of surgery. Poisson regression was used to adjust confounding factors and calculate Prevalence Ratio (PR). ResultsPostoperative VNS > 3 was recorded in 135 (49.81%) patients, of which 93 (68.89%) were subjected to P1, 25 (18.56%) to P2, and 17 (12.59%) to P3. In the final adjusted model, both anesthetic techniques (P3) (PR = 0.10; 95% CI [0.03–0.28]), and (P2) (PR = 0.42%; 95% CI [0.20–0.90]) were associated with lower occurrence of VNS > 3, whereas age range 20–29 was associated to higher occurrence of VNS > 3 (PR = 3.21; 95% CI [1.22–8.44]) in PACU. Postoperative Nausea and Vomiting (PONV) was distributed as follows: (P1) 20.3%, (P2) 31.25% and (P3) 6.77%; (P3 < P1, P2; p < 0.05). Intraoperative hypotension occurred more often in P3 (39%) compared to P2 (20.31%) and P1 (17.46%) (p < 0.05). ConclusionMMA + methadone was associated with higher incidence of intraoperative hypotension and lower incidence of moderate/severe pain in PACU after LBS.

Oxidative Stress in Controlled Hypotension: Assessment with A Novel Oxidative Stress Marker

Objectives: The aim of this study was to evaluate the effects of oxidative stress on thiol-disulfide homeostasis caused by hypotensive anesthesia in mastoidectomy-tympanoplasty cases undergoing controlled hypotension. Methods: Fifty adult patients scheduled for mastoidectomy and tympanoplasty were included in the study. Anesthesia was induced with lidocaine, propofol, rocuronium, and remifentanil. The maintenance of anesthesia was continued with remifentanil infusion (target mean arterial pressure as 60-65 mmHg) along with 2% sevoflurane/40% O2/air mixture. Blood samples were taken 5 times at the t0 (before induction), t1 (intraoperatively after intubation), t2 (first hour) and t3 (second hour of the operation) and t4 (following recovery). Total thiol (TT) and Native Thiol (NT) levels were measured, and thus, Di-Sulphide (SS), Di-Sulphide/Native Thiol (SSNT), Di-Sulphide/Total Thiol (SSTT), and Native Thiol/Total Thiol (NTTT) values were estimated. Results: During the operation, progressive decrease was observed in thiol levels of patients. There was a significant decrease in t3 thiol values when compared with t0 value. Thiol values were observed to have returned to baseline values after recovery from anesthesia (p&amp;gt;0.05). SS, SSNT and SSTT levels were found as increased in t1 blood samples, but increase in SSNT and SSTT levels was significant. Throughout the operation, values were observed to have dropped and reverted back to initial values. Conclusion: Since the measurement of thiol-disulfide blood values is able to show the instantaneous state of oxidative stress, it can be used in anesthesia practice in which every event occurs very quickly.