Administration Of Fentanyl Research Articles

Physiological effects of fentanyl in goats: acute withdrawal and known and novel reversal agents

Synthetic opioids alter several vital physiological functions and discontinuation of its use can cause acute withdrawal symptoms. In this and three adjoining posters we present data on the dose-dependent physiologic and behavioral effects of intravenous (IV) fentanyl in adult awake goats. Here, we tested two hypotheses: 1) that fentanyl will lead to acute, dose-dependent withdrawal symptoms, and 2) that co-administration of a known reversal agent (naloxone (NAL)) or novel respiratory stimulant (D-cysteine ethyl ester; D-CYSee) can mitigate the acute physiological and behavioral effects of fentanyl. Acute withdrawal was measured for 4 hrs. beginning 90 min post-injection of IV vehicle or fentanyl (n=5-7) using a wearable activity tracking device (Biopac) and subjective videographic observations. Animal movement (Vector Magnitude; g) was lowest with vehicle across all time points but was increased (p<0.05) in a dose-dependent manner from 90-210 min after fentanyl administration. Additional behaviors such as pawing, vocalization, hyperphagia, itching and rearing also appeared dose-dependent and were increased from 90-210 min post-injection but waned across the 4h observation period (n=4). Based on the demonstrated efficacy of D-CYSee in reversing OIRD in rats (Getsy et al., 2022), we next tested if fentanyl-induced physiological dysfunction or withdrawal symptoms were mitigated by co-administration of either D-CYSee (500 μmol/kg) or NAL (0.06 mg/kg). Transient suppression of minute ventilation (V I ) and breathing frequency was followed by a secondary increase >10 min after 50 μg/kg fentanyl, where co-administration of D-CYSee stimulated V I and NAL prevented the secondary increase in V I (n=5-6). Fentanyl alone moderately decreased HR where D-CYSee prevented this effect, whereas NAL exacerbated the fentanyl-induced bradycardia for up to 45 min. Mean, systolic and diastolic blood pressures were increased with fentanyl for >90 min post-injection, where D-CYSee had no additional effect but NAL prevented the hypertension. Finally, NAL but not D-CYSee reversed sedation (n=7), but neither NAL or D-CYSee appeared to mitigate withdrawal behaviors. These preliminary data suggest that: 1) fentanyl causes withdrawal behaviors in goats, and 2) NAL and D-CYSee have differential effects on fentanyl-induced physiological dysfunction suggesting D-CYSee has a distinctly different mechanism of action as a potential OIRD countermeasure. Supported by NIH DA050571. 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.

Neural and physiological state dependency of opioid induced respiratory depression

Opioid induced respiratory depression (OIRD) is the major cause of death associated with opioid overdose. Within the brainstem, respiratory activity is generated within the ventrolateral medulla in an opioid-sensitive region known as the PreBötzinger Complex (PreBötC). Within the PreBötC a heterogenous network of neurons under continuous influence by excitatory and inhibitory neuromodulators culminate to form synchronized bursting that results in inspiratory activity. Additionally, the PreBötC network dynamically interacts with the physiological processes that give rise to ventilation. Understanding the interplay between neural and physiological states of the in-vivo system will be key to overcoming OIRD. Here, we tested whether increasing the excitatory state of the PreBötC in-vivo by non-specific K + channel inhibition, or elevated norepinephrine destabilizes breathing, but creates a network state resistant to OIRD. Further, we tested whether the state of upper airway patency following opioid administration influences sensitivity of the PreBötC to OIRD. Following microdialysis into the PreBötC of the non-specific K + channel antagonist, tetraethylammonium (TEA)(10mM), or 1mM norepinephrine ventilation increased and breathing became erratic with variable frequency and tidal volume. However, following 150mg/kg morphine, breathing re-stabilized and returned to near control levels. These results demonstrate that determining the neuromodulatory state of excitability within the PreBötC prior to opioid administration may help to better predict and prevent OIRD. To determine whether the physiological state of the upper-airway following opioid administration can affect sensitivity of the PreBötC to OIRD we tested the ventilatory response to opioids in both airway-intact and tracheostomized mice in-vivo. For these experiments we utilized fentanyl, due to it’s known effects on disrupting upper airway function. Following administration of 500μg/kg fentanyl airway in-tact mice displayed increased upper airway resistance with regular periods of obstructive apnea, severe hypoxemia and reduced breathing frequency that eventually resulted in complete cessation of respiratory activity. Conversely, mice receiving 500μg/kg fentanyl following tracheostomy showed significantly less respiratory suppression and no apneic periods, compared to airway in-tact mice. However, following administration of a hypoxic gas mixture (10% O2) tracheostomized mice experienced terminal apnea in the presence of 500μg/Kg fentanyl. These results demonstrate that hypoxemia experienced following fentanyl administration, which is exacerbated by upper airway constriction may increase the risk of fatal OIRD in-vivo. Together our data suggest that understanding OIRD within the in-vivo system requires the careful investigation of integrative mechanisms between the neural and physiological processes that give rise to overall ventilation. This work was supported by NIH grants: HL154558 (NJB), HL145004 (NEB), HL126523 (JMR), HL144801 (JMR) 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.

Modulation of opioid overdose susceptibility due to context-dependent tolerance

The US is in the midst of an opioid epidemic, which is primarily being driven by repeat opioid use (ROU). The primary cause of opioid overdose is opioid-induced respiratory depression (OIRD). It has been shown that the risk of overdosing, and subsequently death, can change depending on the environment in which the user takes the drug. This phenomenon is called context-dependent tolerance. However, how OIRD changes depending on the location of drug delivery is not known. The objective of this pilot study is to investigate context-dependent respiratory tolerance to OIRD and overdose. We repeatedly paired an injection of fentanyl (0.7 mg/kg/day i.p.) with a distinctive environmental context (fentanyl-paired (FP) environment) and saline with another distinctive context (saline-paired (SP) environment) in adult mice for five days while monitoring breathing via unrestrained whole-body plethysmography. The ROU protocol was followed by two test days where fentanyl was administered in both environments and breathing was measured. We found that minute ventilation was greater during OIRD in the FP environment as compared to the SP environment (n=4). In the second set of mice (n=6?), we tested overdose susceptibility following ROU by administering a high dose of fentanyl (5mg/kg) in both contexts. In contrast to the FP environment where no mice overdosed (n=0/6), n=4/6 mice overdosed in the SP environment. These data suggest a greater susceptibility to OIRD and overdose when in an environment not previously paired with fentanyl administration. This context-dependent effect on OIRD may be a significant psychophysiological factor driving opioid-related deaths in the ongoing opioid epidemic. NIH: R01NS107421; R01HL163965; R01DA057767. 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.

Comparison of Changes in Chest Wall Mechanics and Respiratory Timing Between Patient-Controlled Epidural Analgesia and Intravenous Patient-Controlled Analgesia After Laparoscopic Gastrectomy: A Randomized Controlled Trial.

Upper abdominal surgery is associated with postoperative diaphragmatic dysfunction. Whether patient-controlled epidural analgesia (PCEA) is superior to intravenous patient-controlled analgesia (IV-PCA) in preventing postoperative diaphragmatic dysfunction is still unclear in laparoscopic gastric surgery. Sixteen patients undergoing laparoscopic gastrectomy randomly received either PCEA or IV-PCA. The primary outcomes were the change in chest wall mechanics and respiratory timing, measured by respiratory inductive plethysmography(Respitrace; Ambulatory Monitoring Inc., Ardsley, New York, United States) before and after surgery, and analyzed by a data acquisition system (PowerLab; ADInstruments, Dunedin, New Zealand). Inspiratory time (Ti), expiratory time (Te), total respiratory cycle time (Ttot), proportion of inspiratory time over total respiratory cycle time (Ti/Ttot), respiratory rate (RR), and abdominal contribution to tidal volume (AB/VT [%]) were calculated from the stored data. AB/VT, relative volume contribution of diaphragm to tidal breathing, represents an index of diaphragmatic function.Because the diaphragm is the main contributor to tidal volume, decreases in AB/VT indicate diaphragm dysfunction. Changes in outcomes over time between the two groups were analyzed using a linear mixed model, and two-sided p values < 0.05 were considered statistically significant. The secondary outcomes were postoperative pain score(visual analog scale (VAS)), bowel function recovery, and hospital stay duration. Postoperative AB/VT in the IV-PCA group was significantly decreased compared to preoperative levels. AB/VT in the PCEA group was significantly higher than the IV-PCA group on postoperative day (POD) 1. Change in AB/VT over time between the PCEA group and the IV-PCA group differed significantly (p = 0.01). A decrease of AB/VT during POD 1 to 3 was observed in the IV-PCA group but not in the PCEA group. As for respiratory timing, there were significant increases in RR with a reduction of Te and Ttot compared to preoperative levels on POD 1 in the PCEA group. There were significant decreases in RR and Ti/Ttot with an increase of Te and Ttot compared to preoperative levels on POD 1 in the IV-PCA group. There was a significant difference in the change of the Ttot over time between the two groups (p = 0.046). There were no significant differences in the changes of Te, Ti/Ttot, Ti, and RR over time between the two groups. There was no significant difference in VAS over time at rest and mobilization, recovery of bowel function, and hospital stay between the two groups. Continuous ropivacaine infusion with PCEA partially attenuated diaphragmatic dysfunction after laparoscopic gastrectomy, while pain relief by continuous intravenous administration of fentanyl could not attenuate diaphragmatic dysfunction. This suggests that PCEA might ameliorate postoperative diaphragmatic dysfunction after laparoscopic gastrectomy.

Comparison of Quality of Recovery (QoR-15) following the administration of intravenous lignocaine and fentanyl in patients undergoing septoplasty under general anaesthesia: A double-blinded, randomised, controlled trial.

Recovery from surgery and anaesthesia is usually observed through conventional indicators. The Quality of Recovery (QoR-15) score was specially designed to measure psychometric and functional recovery from the patient's perspective. This study aimed to evaluate QoR-15 following the administration of intravenous (IV) lignocaine or IV fentanyl in patients undergoing septoplasty surgery. This randomised, controlled trial was conducted on 64 patients of American Society of Anesthesiologists (ASA) physical status I and II, of either sex, of ages between 18 and 60 years, and who were scheduled for septoplasty. The primary end point was to compare the quality of recovery following the administration of IV lignocaine(group L) and IV fentanyl (group F) using the QoR-15 score in patients undergoing septoplasty. Secondary end points were to compare postoperative analgesia, recovery characteristics, and adverse effects in both groups. Statistical analysis was done using the Shapiro-Wilk test, paired t test/ Wilcoxon signed-rank test, and unpaired t test/Mann-Whitney U test. A P-value <0.05 was considered statistically significant. There was a significant improvement in the postoperative QoR-15 score than in the preoperative score in both groups (P < 0.000). However, the postoperative QoR-15 score was significantly higher in group L compared to group F (P < 0.001). Total consumption of analgesic doses were reduced in group L (P=0.000). Time taken to achieve an Aldrete score >9 and gastrointestinal recovery was shorter in group L compared to group F. Both IV lignocaine and IV fentanyl improved postoperative QoR-15 score; however, lignocaine had a higher postoperative QoR-15 score than fentanyl, in addition to showing early discharge readiness, better analgesia, and better recovery profile in patients following septoplasty surgery.

Surgical pleth index monitoring in perioperative pain management: usefulness and limitations.

Surgical pleth index (SPI) monitoring is a representative, objective nociception-monitoring device that measures nociception using photoplethysmographic signals. It is easy to apply to patients and the numerical calculation formula is intuitively easy to understand; therefore, its clinical interpretation is simple. Several studies have demonstrated its efficacy and utility. Compared with hemodynamic parameters, the SPI can detect the degree of nociception during surgery under general anesthesia with greater accuracy, and therefore can provide better guidance for the administration of various opioids, including remifentanil, fentanyl, and sufentanil. Indeed, SPI-guided analgesia is associated with lower intraoperative opioid consumption, faster patient recovery, and comparable or lower levels of postoperative pain and rates of adverse events compared with conventional analgesia. In addition, SPI monitoring allows for the degree of postoperative pain and analgesic requirements to be predicted through the SPI values immediately before patient arousal. However, because patient age, effective circulating volume, position, concomitant medication and anesthetic regimen and level of consciousness may be confounding factors in SPI monitoring, clinicians must be careful when interpreting SPI values. In addition, as SPI values can differ depending on anesthetic and analgesic regimens and the underlying disease, an awareness of the effects of these variables with an understanding of the advantages and disadvantages of SPI monitoring compared to other nociception monitoring devices is essential. Therefore, this review aimed to help clinicians perform optimal SPI-guided analgesia and to assist with the establishment of future research designs through clarifying current usefulness and limitations of SPI monitoring in perioperative pain management.

Effects of sevoflurane and propofol on hemodynamics during cardiac surgery: A randomized controlled clinical trial

The anaesthetic support for various types of cardiac surgery such as coronary artery bypass grafting, heart valve repair or replacement is essential for success of a surgery. The planning of anaesthesia depends on the intended surgical procedure. The traditional approach is total intravenous anesthesia with propofol and inhalation with sevoflurane.&lt;br /&gt; &lt;b&gt;Objectives: &lt;/b&gt;To identify the advantages and disadvantages of propofol and sevoflurane when cardiac surgery in adults. &amp;nbsp;&lt;br /&gt; &lt;b&gt;Material and methods: &lt;/b&gt;A total of&lt;b&gt; &lt;/b&gt;40 patients were assigned randomly into two groups to receive: in Group 1 - propofol and in Group 2 - sevoflurane. The induction to general anesthesia started with intravenous fractional administration of 1-1.5 mg/kg propofol, 5-7 µg/kg fentanyl and 1.5-2 mg/kg ketamine. Pipecuronium bromide 0.07-0.1 mg/kg was used as a myorelaxant in all patients in both groups. The anaesthesia in group P was supported with propofol 4-6 mg/kg/min intravenously by means of a perfusor as anaesthetic. In group 2, sevoflurane at a dose of 1.7-1.9 MAC was used as an anaesthetic. To maintain anaesthesia in both groups, there was a fractional administration of fentanyl at a dose of 100 µg intravenously when the heart rate and blood pressure increase, piperonium bromide in a dose of 2 mg intravenously was used for muscle relaxation.&lt;br /&gt; &lt;b&gt;Results: &lt;/b&gt;The mean arterial pressure, oxygen demand, energy expenditure, cardiac index, total peripheral resistance showed statistically significant differences between propofol and sevoflurane groups. Through the correlation analysis, the relationship between cardiac index and oxygen consumption was moderately relevant, as R was 0.4 and P&amp;gt;0.05.&lt;br /&gt; &lt;b&gt;Conclusion&lt;/b&gt;: When the use of sevoflurane for anesthesia, the hemodynamic parameters were stable. The oxygen consumption, energy expenditure in patients were significantly lower compared to propofol using the sevoflurane anesthesia.

Heroin- and Fentanyl-Induced Respiratory Depression in a Rat Plethysmography Model: Potency, Tolerance, and Sex Differences.

The opioid overdose death toll in the United States is an ongoing public health crisis. We characterized the magnitude and duration of respiratory depression, the leading cause of death in opioid overdose cases, induced by heroin or fentanyl and the development of tolerance in male and female rats. We used whole-body plethysmography to first establish dose-response curves by recording breathing for 60 minutes post-intravenous opioid injection. We then tested the development of respiratory tolerance to acute heroin or fentanyl over several weeks and to chronic fentanyl with acute fentanyl or heroin challenge. Heroin and fentanyl each provoked dose-dependent respiratory depression. Heroin caused prolonged (45-60 minute) respiratory depression in female and male rats, characterized by decreased frequency, tidal volume, and minute ventilation and increased inspiratory time and apneic pause. Fentanyl produced similar changes with a shorter duration (10-15 minutes). High-dose heroin or fentanyl produced robust respiratory depression that was slightly more severe in females and, when given intermittently (acute doses 2 to 3 weeks apart), did not lead to tolerance. In contrast, chronic fentanyl delivered with an osmotic minipump resulted in tolerance to acute fentanyl and heroin, characterized by a shorter duration of respiratory depression. This effect persisted during withdrawal in males only. Our model and experimental design will allow for investigation of the neurobiology of opioid-induced respiratory depression and for testing potential therapeutics to reverse respiratory depression or stimulate breathing. SIGNIFICANCE STATEMENT: Fentanyl was more potent and had shorter duration in producing respiratory depression than heroin in both sexes, whereas female rats were more sensitive than males to heroin-induced respiratory depression. Tolerance/cross-tolerance develops in chronic fentanyl administration but is minimized with long interadministration intervals.

Nociception Level Index-Guided Intraoperative Analgesia for Improved Postoperative Recovery: A Randomized Trial.

Nociception is the physiological response to nociceptive stimuli, normally experienced as pain. During general anesthesia, patients experience and respond to nociceptive stimuli by increasing blood pressure and heart rate if not controlled by preemptive analgesia. The PMD-200 system from Medasense (Ramat Gan, Israel) evaluates the balance between nociceptive stimuli and analgesia during general anesthesia and generates the nociception level (NOL) index from a single finger probe. NOL is a unitless index ranging from 0 to 100, with values exceeding 25 indicating that nociception exceeds analgesia. We aimed to demonstrate that titrating intraoperative opioid administration to keep NOL <25 optimizes intraoperative opioid dosing. Specifically, we tested the hypothesis that pain scores during the initial 60 minutes of recovery are lower in patients managed with NOL-guided fentanyl than in patients given fentanyl per clinical routine. We conducted a randomized, single-center trial of patients having major abdominal open and laparoscopic surgeries. Patients were randomly assigned 1:1 to intraoperative NOL-guided fentanyl administration or fentanyl given per clinical routine. The primary outcome was pain score (0-10 verbal response scale) at 10-minute intervals during the initial 60 minutes of recovery. Our secondary outcome was a measure of adequate analgesia, defined as a pain score <5, assessed separately at each interval. With a planned maximum sample size of 144, the study was stopped for futility after enrolling 72 patients from November 2020 to October 2021. Thirty-five patients were assigned to NOL-guided analgesic dosing and 37 to routine care. Patients in the NOL group spent significantly less time with a NOL index >25 (median reduction [95% confidence interval {CI}] of 14 [4-25] minutes) were given nearly twice as much intraoperative fentanyl (median [quartiles] 500 [330, 780] vs 300 [200, 330] µg), and required about half as much morphine in the recovery period (3.3 [0, 8] vs 7.7 [0, 13] mg). However, in the primary outcome analysis, NOL did not reduce pain scores in the first 60 minutes after awakening, assessed in a linear mixed effects model with mean (standard error [SE]) of 4.12 (0.59) for NOL and 4.04 (0.58) for routine care, and estimated difference in means of 0.08 (-1.43, 1.58), P = .895. More intraoperative fentanyl was given in NOL-guided patients, but NOL guidance did not reduce initial postoperative pain scores.

Usefulness and Reliability of the Bispectral Index during Balanced Anesthesia for Neurovascular Surgery in New Zealand White Rabbits.

Few data about the electroencephalogram and its calculated indices, such as the bispectral index (BIS), have been reported in rabbits. We aimed to evaluate whether a clinically stable anesthesia was mirrored by consistent and stable BIS values and to investigate the effects of modified cerebral blood supply, due to bilateral carotid clamping and re-opening, on BIS values. We also investigated the effects of fentanyl, as an antinociceptive drug, on the BIS. Sixty-eight rabbits undergoing general anesthesia for surgical creation of carotid bifurcation aneurysms were enrolled. The BIS values were recorded at nine selected time points (TPs) during each procedure and before and after fentanyl administration. The BIS values over time were compared with two-way repeated-measures analysis of variance followed by Tukey test, while the Wilcoxon signed rank test was performed to compare values at clamping and re-opening of the carotids as well as before and after fentanyl administration. The BIS values were significantly lower during anesthesia than at the end of anesthesia and at tracheal extubation; no significant differences were found among other TPs. Adequate depth of anesthesia was mirrored by consistent BIS values among rabbits, and alteration of cerebral blood supply did not modify BIS values, except once. Following fentanyl, BIS values did not change in a clinically relevant way.

Safety of nurse-directed triage intranasal fentanyl protocol for acute pain management in a European pediatric emergency department: A retrospective observational analysis.

Nurse-directed pain protocols for intranasal fentanyl administration are not widely implemented in European (EU) pediatric emergency departments (PED). Barriers include perceived safety concerns for intranasal (IN) fentanyl. The aim of this study is to describe our experience with a nurse-directed triage IN fentanyl protocol with a focus on safety in a tertiary EU PED. We conducted a retrospective analysis of patient records of children aged 0-16 years who received nurse-directed IN fentanyl between January 2019 and December 2021 at the PED of the University Children's Hospital of Bern, Switzerland. Extracted data points included demographics, presenting complaint, pain score, IN fentanyl dosage, concomitant pain medication use, and adverse events. A total of 314 patients were identified with ages ranging from 9 months to 15 years. The main indication for nurse-directed fentanyl administration was musculoskeletal pain due to trauma (n = 284, 90%). Mild adverse events (vertigo) were reported in two patients (0.6%), without a correlation to concomitant pain medication or protocol violation. The only reported severe adverse event of syncope and hypoxia in a 14-year-old adolescent occurred in a setting where the institutional nurse-directed protocol was violated. In accordance with previous studies outside of Europe, our data support the case that when appropriately used, nurse-directed IN fentanyl is a safe potent opioid analgesic for pediatric acute pain management. We strongly encourage the introduction of nurse-directed triage fentanyl protocols Europe-wide in order to provide effective and adequate acute pain management in children.

Use of Liquid Chromatography--Tandem Mass Spectrometry to Quantify and Confirm the Fentanyl Metabolite N-[1-(2-Phenethy-4-Piperidinyl)] Maloanilinic Acid in Equine Urine for Doping Control.

Fentanyl, a powerful synthetic mu opioid receptor agonist, is banned in equine sports by the Association of Racing Commissioners International and the Fédération Équestre Internationale. The presence of fentanyl in equine blood has been confirmed during routine post-race screening for doping substances in the authors' laboratory. While fentanyl can be detected and confirmed in blood, it is rapidly metabolized, and screening for the metabolite N-[1-(2-phenethy-4-piperidinyl)] maloanilinic acid (PMA) in equine urine is expected to allow for a longer detection time. In this study, a quantitative and confirmatory liquid chromatography--tandem mass spectrometry (LC-MS-MS) method was developed for PMA analysis in equine urine. PMA was extracted by solid phase extraction, separated on a C18 column and detected using a triple quadrupole mass spectrometer. The mass spectrometer was operated in positive-ion mode, and multiple reaction monitoring was used to monitor product ions m/z 188, m/z 281 and m/z 323. The method was validated for extraction recovery, matrix effect, specificity, sensitivity, precision and accuracy, carryover and processed sample stability according to the guidelines of the US Food and Drug Administration for bioanalysis. The limits of detection and quantification were 5 and 10 pg/mL, respectively. Linearity was obtained over the concentration range of 10-10,000 pg/mL. To confirm PMA in equine urine, LC retention time, diagnostic product ions (m/z 188, m/z 281 and m/z 323) and product ion ratio were used as the criteria. The lowest concentration for confirmatory analysis was validated at 50 pg/mL. The method was applied to measure the PMA concentrations in equine urine following intravenous administration of fentanyl to a research horse and has confirmed the presence of PMA in post-race urine samples. This method is a valuable addition to the arsenal of equine doping control methods to combat illegal doping and protect racehorse health.

The Role of Analgesia in the Identification and Treatment of Digestive Tract Lesions: A Randomized, Prospective, Double-Blind Study.

The association of sedation with analgesia in endoscopic procedures represents the ideal combination of anesthetic drugs, which allows these exploratory procedures to be carried out safely, in an outpatient setting. The aim of this study is to compare the results of the use of simple Propofol or Propofol associated with Fentanyl in order to ensure optimal sedation necessary for the detection of benign or malignant lesions of the digestive tract. In this study, 80 patients aged between 18 and 80 years were included, 40 in Group 1 who were administered Propofol alone and 40 in Group 2 in which Propofol was administered associated with Fentanyl. The onset of anesthetic sleep was 19.3±5.1 seconds in Lot 2 versus 29.6±9.1 seconds in Lot 1. The average dose of Propofol used was 203.6±82.8 mg in Lot 1 and in Lot 2 it was lower, 166.3±8.3mg. Cardio respiratory changes were more frequent in Lot 2. The wake-up time was 3.2±1.2 minutes in Lot 1 as a result of the administration of Propofol alone and 7±1.4 minutes in Lot 2. The discharge time was equal for patients in both groups. The degree of postanesthesia safisfaction was 10 for all patients from Lot 2, due to the analgesia provided by the administration of Fentanyl. The use of Propofol associated with Fentanyl in gastrointestinal endoscopic procedures is associated with a rapid recovery of cognitive function at the time of discharge and minimal adverse events, ensuring optimal conditions of analgesia and stability of vital functions.

Striatal μ-opioid receptor activation triggers direct-pathway GABAergic plasticity and induces negative affect.

Withdrawal from chronic opioid use often causes hypodopaminergic states and negative affect, which may drive relapse. Direct-pathway medium spiny neurons (dMSNs) in the striatal patch compartment contain μ-opioid receptors (MORs). It remains unclear how chronic opioid exposure and withdrawal impact these MOR-expressing dMSNs and their outputs. Here, we report that MOR activation acutely suppressed GABAergic striatopallidal transmission in habenula-projecting globus pallidus neurons. Notably, withdrawal from repeated morphine or fentanyl administration potentiated this GABAergic transmission. Furthermore, intravenous fentanyl self-administration enhanced GABAergic striatonigral transmission and reduced midbrain dopaminergic activity. Fentanyl-activated striatal neurons mediated contextual memory retrieval required for conditioned place preference tests. Importantly, chemogenetic inhibition of striatal MOR+ neurons rescued fentanyl withdrawal-induced physical symptoms and anxiety-like behaviors. These data suggest that chronic opioid use triggers GABAergic striatopallidal and striatonigral plasticity to induce a hypodopaminergic state, which may promote negative emotions and relapse.

Nociception Control of Bilateral Single-Shot Erector Spinae Plane Block Compared to No Block in Open Heart Surgery-A Post Hoc Analysis of the NESP Randomized Controlled Clinical Trial.

Background and Objectives: The erector spinae plane block (ESPB) is an analgesic adjunct demonstrated to reduce intraoperative opioid consumption within a Nociception Level (NOL) index-directed anesthetic protocol. We aimed to examine the ESPB effect on the quality of intraoperative nociception control evaluated with the NOL index. Materials and Methods: This is a post hoc analysis of the NESP (Nociception Level Index-Directed Erector Spinae Plane Block in Open Heart Surgery) randomized controlled trial. Eighty-five adult patients undergoing on-pump cardiac surgery were allocated to group 1 (Control, n = 43) and group 2 (ESPB, n = 42). Both groups received general anesthesia. Preoperatively, group 2 received bilateral single-shot ESPB (1.5 mg/kg/side 0.5% ropivacaine mixed with dexamethasone 8 mg/20 mL). Until cardiopulmonary bypass (CPB) was initiated, fentanyl administration was individualized using the NOL index. The NOL index was compared at five time points: pre-incision (T1), post-incision (T2), pre-sternotomy (T3), post-sternotomy (T4), and pre-CPB (T5). On a scale from 0 (no nociception) to 100 (extreme nociception), a NOL index > 25 was considered an inadequate response to noxious stimuli. Results: The average NOL index across the five time points in group 2 to group 1 was 12.78 ± 0.8 vs. 24.18 ± 0.79 (p < 0.001). The NOL index was significantly lower in the ESPB-to-Control group at T2 (12.95 ± 1.49 vs. 35.97 ± 1.47), T3 (13.28 ± 1.49 vs. 24.44 ± 1.47), and T4 (15.52 ± 1.49 vs. 34.39 ± 1.47) (p < 0.001) but not at T1 and T5. Compared to controls, significantly fewer ESPB patients reached a NOL index > 25 at T2 (4.7% vs. 79%), T3 (0% vs. 37.2%), and T4 (7.1% vs. 79%) (p < 0.001). Conclusions: The addition of bilateral single-shot ESPB to general anesthesia during cardiac surgery improved the quality of intraoperative nociception control according to a NOL index-based evaluation.

Transient loss of consciousness immediately after total pancreatectomy for pancreatic metastases from renal cell carcinoma: a case report

BackgroundTotal pancreatectomy (TP) is often selected for treatment of various pancreatic diseases. However, the resultant lack of autoregulation of glycometabolism necessitates careful postoperative management.Case presentationA 77-year-old man who had undergone right nephrectomy for renal cell carcinoma 11 years previously presented with multiple histologically diagnosed pancreatic metastases. The patient had no notable comorbidities, including diabetes. Because no extrapancreatic organ metastasis was identified, he underwent TP as a curative treatment. He awoke from anesthesia and was extubated without any problems in the operating room. However, 15 min after entering the intensive care unit, he suddenly lost consciousness and became apneic, resulting in reintubation. Blood gas analysis revealed an increased glucose concentration (302 mg/dL) and mixed acid–base disorder (pH of 7.21) due to insulin insufficiency and fentanyl administration. After induction of continuous intravenous insulin infusion and termination of fentanyl, the glucose concentration and pH gradually improved. He regained clear consciousness and spontaneous ventilation and was extubated the next day with no difficulties or complications.ConclusionThis case highlights the importance of active monitoring of the glycemic state and pH after TP because of the possibility of deterioration due to TP itself as well as the lingering effects of anesthesia.

Comparison of Pain Control and Inflammatory Profile in Cesarean Section Patients Treated with Multimodal Analgesia Utilizing Paracetamol and Ibuprofen

AIM: This single-blind study aimed to compare the combination of paracetamol with various doses of ibuprofen as multimodal analgesia in C-section surgery patients under spinal anesthesia. Levels of interleukin (IL)-6 and C-reactive protein (CRP) were analyzed as markers of inflammation. METHODS: Treatment groups (20 patients each) were: Group A, 750 mg paracetamol and 400 mg ibuprofen; Group B, 750 mg paracetamol and 600 mg ibuprofen; and Group C, 750 mg paracetamol and 800 mg ibuprofen. Degree of pain (movement and rest), scored using the numeric rating scale (NRS) and levels of IL-6 and CRP were assessed at various time points within 24 h of surgery. Side effects and numbers of subjects requiring rescue fentanyl administration were also recorded. RESULTS: Group C showed a rest NRS score of 1.00 ± 0.00 6 h postoperatively, compared with 2.00 ± 0.00 in Group B and 2.35 ± 0.87 in Group A. 4 h postoperatively, movement NRS scores were 1.00 ± 0.00 for Group C, compared to 3.00 ± 1.77 for Group B, and 4.85 ± 1.81 for Group A. At 12 h, IL-6 levels hours were 2.66 ± 0.04 pg/mL for Group A, 2.39 ± 0.02 pg/mL for Group B, and 2.05 ± 0.01 pg/mL for Group C. At 6 h, CRP levels were 1.18 ± 0.04 mg/L for Group A, 0.95 ± 0.01 mg/L for Group B, and 0.70 ± 0.02 mg/L for Group C. Overall, Group C showed the lowest values for all parameters analyzed, compared with other groups, and the differences were significant (p &lt; 0.05). In addition, none of the patients in Group C required rescue fentanyl (p &lt; 0.05), and no patients in any of the groups showed any side effects. CONCLUSION: For pain management after C-section surgery, the combination of 750 mg paracetamol and 800 mg ibuprofen yielded the best results as assessed by NRS scores, levels of IL-6 and CRP, and fentanyl rescue.

A Comparative Study of Epidural Butorphanol and Epidural Fentanyl for Postoperative pain relief in Lower Limb Orthopaedic Surgeries.

Background: Epidural narcotic agonists like fentanyl, and morphine has been studied as an adjunct to Bupivacaine for intraoperative and to provide epidural postoperative analgesia. Side effects like pruritus, nausea, vomiting, respiratory depression, and urinary retention occur with their use. The search for an effective analgesic with no or low incidence of side effects is continuing. Aims and objective: To evaluate the onset of anaesthesia, duration of analgesia with epidural administration of Butorphanol and fentanyl in 2 groups. Observe and compare side effects between these groups during post-operative period. Material and Methods: We had done this study on 60 patients with Orthopaedic fractures (lowerlimb), which are treated with IM IL nailing femur and tibia distributed to two groups of 30 each. Surgery was done under CSE technique, with Group A receiving butorphanol and Group B Fentanyl as adjuvant. The onset, duration of analgesia and side effects were recorded in each group. Results: The onset of analgesia was rapid in Fentanyl group (3.26+/- 0.95) than Butorphanol group (6.54 +/-1.10). Duration of analgesia was longer in Butorphanol group (330 +/- 62 minutes) in comparison to Fentanyl group (210 +/- 32 minutes). Quality of analgesia is better in Butorphanol group (80%) than Fentanyl group (43 %). Side effects were more in Group B than Group A. Conclusion: Epidural Fentanyl has faster onset of analgesia. Epidural Butorphanol has longer duration of analgesia with better quality of analgesia. Epidural butorphanol has fewer side effects when compared to Fentanyl.

Two syringes technique for spinal anesthesia to prevent hypotension in patients undergoing elective cesarean section

Aims: To compare the incidence of hypotension after intrathecal administration of hyperbaric bupivacaine and fentanyl in two different syringes against standard injection of mixed fentanyl with hyperbaric bupivacaine.&#x0D; Methods: This was a prospective comparative study conducted in 174 parturients undergoing elective caesarean section at Paropakar Maternity &amp; Women’s Hospital. Hemodynamic effects and characteristics of block were monitored and recorded and compared between the two groups, group S (single syringe) and group D (double syringe).&#x0D; Results: The incidence of hypotension was almost similar in the two groups but the drop in systolic blood pressure and mean arterial pressure at 5 minutes and 7.5 minutes after subarachnoid block was significant in group S as compared to group D (p&lt;0.005 and p&lt;0.005 respectively).&#x0D; Conclusion: Hyperbaric bupivacaine with fentanyl, which when injected separately without mixing, is associated with lesser incidence of hypotension following subarachnoid block.

Opioid antagonism in fentanyl antinociception experimental

Among the most commonly used drugs to reduce pain and inflammation are nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids. Opioids are a wide group of drugs including fentanyl a fully synthetic opioid that is more potent that morphine. The aim of the present study was to evaluate the fentanyl antinociception in two pain murine tests, the acetic acid writhing (WT) and the formalin hind paw (FHP). Likewise, the involvement of opioids antagonists: naltrexone, naltrindole and nor-binaltorphimine in the induced activity of fentanyl was estimated. The antinociceptive activity of fentanyl was evaluated from dose-response curves. The intraperitoneal administration of fentanyl induced a dose related antinociceptive effects with different potencies in both tests. The data revealed a significant decrease in the analgesic effect of fentanyl by action of naltrexone, naltrindole and nor-binaltorphimine in the WT and FHP tests with the exception of nor-binaltorphimine in the WT. The effect of opioids antagonist in reducing the efficacy of fentanyl could possibly be related to other multiple mechanisms added to the inhibition of the activation of the MOR, DOR, and KOR opioid receptors. This study demonstrates that there is a functional interaction modulatory between fentanyl antinociception fentanyl and naltrexone, naltrindole and nor-binaltorphimine in the murine assays of acetic acid writhing and formalin hind paw. This modulation seems to be mediated by the multiple mechanisms of action of fentanyl. These results suggest than fentanyl is able to be effective in models of nociception and the inflammatory pain.