Low-dose Fentanyl Research Articles

Depression of cortical neuronal activity after a low-dose fentanyl in preterm infants.

Opioids might be harmful to the developing brain and dosing accuracy is important. We aimed at investigating fentanyl effects on cortical activity in infants using computational re-analysis of bedside recorded EEG signals. Fifteen infants born at median 26.4 gestational weeks (range 23.3-34.1), with a birth weight 740 grams (530-1420) and postnatal age 7 days (5-11) received fentanyl 0.5 or 2 μg/kg intravenously before a skin-breaking procedure or tracheal intubation, respectively. Cortical activity was continuously recorded using amplitude-integrated electroencephalography (aEEG). Analyses using three computational EEG features representing cortical synchrony and signal power, were conducted five minutes pre- and 10 minutes post the drug administration. Visual assessment of trends displayed from the EEG metrics did not indicate systematic changes. However, the magnitude of the changes in the parietal and right hemisphere signals after the dose was significantly correlated (ρ < -0.5, p < 0.05) to the EEG amplitude and frequency power level before drug administration. This effect started after 3-4 min. Fentanyl, even in small doses, may affect cortical activity in the preterm brain. The effect is robustly related to the state of cortical activity prior to drug treatment, which must be taken into account when analysing the effects of sedative drugs.

Oxygen fluctuations in the brain and periphery induced by intravenous fentanyl: effects of dose and drug experience.

Fentanyl is the leading contributor to drug overdose deaths in the United States. Its potency, rapid onset of action, and lack of effective reversal treatment make the drug much more lethal than other opioids. Although it is understood that fentanyl is dangerous at higher doses, the literature surrounding fentanyl's physiological effects remains contradictory at lower doses. To explore this discrepancy, we designed a study incorporating electrochemical assessment of oxygen in the brain (nucleus accumbens) and subcutaneous space, multisite thermorecording (brain, skin, muscle), and locomotor activity at varying doses of fentanyl (1.0, 3.0, 10, 30, and 90 µg/kg) in rats. In the nucleus accumbens, lower doses of fentanyl (3.0 and 10 µg/kg) led to an increase in oxygen levels while higher doses (30 and 90 µg/kg) led to a biphasic pattern, with an initial dose-dependent decrease followed by an increase. In the subcutaneous space, oxygen decreases started to appear at relatively lower doses (>3 µg/kg), had shorter onset latencies, and were stronger and prolonged. In the temperature experiment, lower doses of fentanyl (1.0, 3.0, and 10 µg/kg) led to an increase in brain, skin, and muscle temperatures, while higher doses (30 and 90 µg/kg) resulted in a dose-dependent biphasic temperature change, with an increase followed by a prolonged decrease. We also compared oxygen and temperature responses induced by fentanyl over six consecutive days and found no evidence of tolerance in both parameters. In conclusion, we report that fentanyl's effects are highly dose-dependent, drawing attention to the importance of better characterization to adequately respond in emergent cases of illicit fentanyl misuse.NEW & NOTEWORTHY By using electrochemical oxygen sensors in freely moving rats, we show that intravenous fentanyl induces opposite changes in brain oxygen at varying doses, increasing at lower doses (<10 µg/kg) and inducing a biphasic response, decrease followed by increase, at higher doses (>10-90 µg/kg). In contrast, fentanyl-induced dose-dependent oxygen decreases in the subcutaneous space. We consider the mechanisms underlying distinct oxygen responses in the brain and periphery and discuss naloxone's role in alleviating fentanyl-induced brain hypoxia.

Safety and efficacy of remimazolam tosilate combined with low-dose fentanyl for procedural sedation in obese patients undergoing gastroscopy: study protocol for a single-centre, double-blind, randomised controlled trial

IntroductionObese patients are susceptible to hypoxaemia during procedural sedation. Propofol combined with low-dose opioids is commonly used as a sedation strategy, but it can exacerbate hypoxaemia by causing cardiopulmonary depression...

Pain Control and Hemodynamic Changes due to Moderate Sedation during Cardiac Catheterization

Background: Moderate sedation is a practice of promoting patient comfort during cardiac catheterization. However, few studies have evaluated the effectiveness of moderate sedation in patients undergoing cardiac catheterization. Objective: To determine the efficacy of moderate sedation in patients undergoing cardiac catheterization. Materials and Methods: The authors retrospectively analyzed patients undergoing cardiac catheterization. They were divided into the moderate sedation group, which received midazolam, fentanyl, or combined midazolam and fentanyl, and the control group, which received no sedative medication. The primary endpoint was self-reported pain score during the procedure. The secondary endpoint was a hemodynamic variation during the procedure. Propensity-score matching was used to reduce confounding biases. Results: One hundred ninety-six patients were included, with 111 patients in the moderate sedation group and 85 patients in the control group. The proportion of patients who experienced any pain was significantly lower in the moderate sedation group than in the control group at 3.6% versus 11.8% (p=0.028). No significant difference was found in the average change in the systolic blood pressure at –9 mmHg versus –4 mmHg (p=0.097) and the heart rate at –1 bpm versus –2 bpm (p=0.289) obtained at baseline and that at the end of the procedure between the moderate sedation group and the control group. However, the change in the diastolic blood pressure (DBP) measured at baseline and at the end of the procedure was significantly lower in the moderate sedation group than in the control group at –4 mmHg versus –1 mmHg (p=0.039). Conclusion: Moderate sedation by using a low-dose fentanyl, midazolam, or combined fentanyl and midazolam is associated with fewer episodes of pain and better DBP stability during cardiac catheterization. Keywords: Conscious sedation; Midazolam; Coronary angiography; Percutaneous coronary intervention; Cardiac catheterization

Pain assessment in fentanyl-propofol combination: two dosage levels

Background. In the field of intravenous anesthesia, propofol is widely utilized as an induction agent. However, Propofol injection pain is a frequent adverse event that may result in discomfort for patients. Various strategies have been investigated to prevent or alleviate this pain, considering the presence of opioid receptors in the primary afferent nerve endings of peripheral tissues, which suggests a potential role of opioids in mitigating propofol-induced pain. Fentanyl, a short-acting pure opioid agonist commonly used for systemic analgesia during intraoperative and postoperative periods, has been found to possess peripherally mediated analgesic properties within its clinical dosage range. Therefore, the objective of this study was to evaluate the efficacy of a low dose of fentanyl in the fentanyl-propofol combination for reducing propofol injection pain.The objective of our study was to evaluate and compare the efficacy of two distinct doses of fentanyl in mitigating the pain associated with propofol injection.Materials and methods. The study enrolled 90 patients classified as ASA I–II who were scheduled for elective surgery. The study spanned over 4 months, from November 2022 to April 2023, and included patients aged 19 to 65 years. Patients were divided into three groups, each comprising 30 patients. The control group received only 5 ml (50 mg) of propofol. The group M1 received only 5 ml of a mixture of fentanyl and propofol, prepared with 20 ml (200 mg) of propofol and 2 ml (100 μg) of fentanyl, while the group M2 received only 5 ml of a mixture of fentanyl and propofol, prepared with 20 ml (200 mg) of propofol and 4 ml (200 μg) of fentanyl, at an injection speed of 0.5 ml/s. After 10 seconds of medication, patients were asked a standard question about the comfort of the injection, and a verbal rating scale (VRS) was used to assess propofol injection pain. Anesthesia induction was then continued following standard protocols. Statistical significance was set at p &lt; 0.05 for all analyses.Results. The three groups were found to be similar in terms of patient characteristics. In the control group, the incidence of severe pain upon propofol injection was 46.7%, whereas it was 0% in both groups M1 and M2 (p &lt; 0.05).Conclusion. The combination of fentanyl and propofol has been shown to effectively reduce the incidence of propofol injection pain. Interestingly, in this study, no significant difference was observed between the two different doses of fentanyl used in the mixture. This suggests that a low dose of fentanyl may be sufficient in achieving a pain-free environment during propofol induction, thereby offering a cost-effective approach in clinical practice.

Successful Use of Low-Dose Combination Propofol and Fentanyl in Cataract Surgery Phacoemulsification.

The combination between sedatives and opioids is one of the recommended anesthetic options in ophthalmic procedures and regimens are more advantageous as smaller amounts of each drug can be administered to reduce side effects and have proper outcomes due to the synergistic effects. This study aims to observe the use of low-dose propofol and fentanyl for patients undergoing phacoemulsification surgery. This observational study involves a sample of 125 adult patients who underwent elective cataract procedures using the phacoemulsification technique and had an American Society of Anesthesiologists (ASA) physical status of 1 to 3. Dose amount of fentanyl and propofol, Ramsay score, hemodynamic parameter, side effects, and patient satisfaction were evaluated, recorded, and analyzed using a 5-point Likert scale. The result showed the mean absolute dose of propofol was 12.46±4.376 mg, with a range between 10 and 30 mg, while the mean per body weight was 0.21±0.075 mg. Similarly, the mean absolute dose for fentanyl was 25.04±3.012 mcg within the range of 10-50 mcg, and the per-body weight dose was 0.43±0.080 mcg. About 90.4% and 9.6% of the patients reached Ramsay 2 and 3, respectively. The analysis of systolic, diastolic blood pressure, mean arterial pressure, and pulse rate showed that the combination of low-dose fentanyl and propofol was significantly lower than before therapy administration in all four values (p < 0.05). The combination of low-dose propofol and fentanyl in cataract surgery using phacoemulsification successfully reached the targeted sedation level and a significant decrease in blood pressure, MAP, pulse rate, minimal side effects, and high satisfaction rate.

Chronic inflammatory pain promotes place preference for fentanyl in male rats but does not change fentanyl self-administration in male and female rats

The current opioid epidemic is a national health crisis marked by skyrocketing reports of opioid misuse and overdose deaths. Despite the risks involved, prescription opioid analgesics are the most powerful and effective medications for treating pain. There is a clear need to investigate the risk of opioid misuse liability in male and female adults experiencing chronic pain. In the present study, we tested the hypothesis that chronic inflammatory pain would increase fentanyl intake, motivation to acquire fentanyl, and drug seeking in the absence of fentanyl in rats. Fentanyl intake, motivation for fentanyl, and drug seeking were tested under limited and extended access conditions using intravenous fentanyl self-administration. Fos activity in ventral tegmental area (VTA) dopamine neurons following intravenous fentanyl challenge (35 μg/kg) was examined using immunohistochemistry. Finally, we tested whether low-dose fentanyl supports development of conditioned place preference under an inflammatory pain state in rats. Contrary to our hypothesis, fentanyl self-administration and VTA Fos activity were unaffected by inflammatory pain status. During acquisition, males exhibited increased fentanyl intake compared to females. Animals given extended access to fentanyl escalated fentanyl intake over time, while animals given limited access did not. Males given extended access to fentanyl demonstrated a greater increase in fentanyl intake over time compared to females. During the dose-response test, females given limited access to fentanyl demonstrated increased motivation to acquire fentanyl compared to males. Both sexes displayed significant increases in responding for fentanyl as unit fentanyl doses were lowered. Following fentanyl challenge, females exhibited higher numbers of Fos-positive non-dopaminergic VTA neurons compared to males. Using conditioned place preference, we found that chronic inflammatory pain promotes fentanyl preference in males, but not females. These findings suggest that established fentanyl self-administration is resistant to change by inflammatory pain manipulation in both sexes, but chronic inflammatory pain increases the rewarding properties of low-dose fentanyl in males.

Opioid-Induced Esophageal Dysmotility (OIED) - A Case Report.

Recent studies have shown that chronic opioid use is associated with an increased risk of symptomatic esophageal motility disorders. Opioid-induced esophageal dysfunction (OIED) is most often identified in patients taking high doses of opioids. This condition is associated with poorer treatment outcomes than primary motility disorders and management of these cases is further complicated by the presence of chronic pain, opioid addiction, and physical and psychological comorbidity.We present the case of a 68-year-old Caucasian woman with OIED, induced by the chronic intake of low-dose Fentanyl and Tramadol prescribed to treat severe back pain. The clinical course highlights the sometimes difficult diagnosis and management of this recently recognized condition.

The Effect of High-dose Versus Low-dose Epidural Fentanyl on Gastric Emptying in Nonfasted Parturients: A Double-blinded Randomized Controlled Trial

(Eur J Anaesthesiol. 2022;39:50–57. doi: 10.1097/EJA.0000000000001514) Aspiration of gastric contents is a risk for laboring women who may undergo general anesthesia. Although organizations regard the risk/benefit of eating during labor with varying approaches, it is still important to clarify factors that may contribute to pulmonary aspiration during childbirth. High-dose epidural fentanyl (≥100 µg) has been previously associated with delayed gastric emptying by paracetamol absorption test, but not low-dose fentanyl (&lt;100 µg). As paracetamol does not directly measure the volume of gastric contents, the previously validated gastric ultrasonography technique is used in this study to measure the cross-sectional area (CSA) of the antrum to observe the effects of epidural fentanyl on gastric emptying in nonfasted laboring women.

Postoperative analgesia for complex spinal surgery.

Complex spinal surgery is associated with significant postoperative pain. The purpose of this paper is to review recent literature on postoperative pain management in adult and adolescent patients having complex spinal surgery. We conducted a literature search using the Medline database for relevant publications from 2020 to 2022 on postoperative pain after complex spinal surgery. Although opioids remain the mainstay to manage pain after complex spinal surgery, they are associated with adverse effects. Multimodal analgesia may be used to reduce these adverse effects by combining different drugs targeting different parts of the pain pathway. Recent publications suggest continuous low dose fentanyl or morphine infusion, methadone, intravenous paracetamol and ibuprofen, ketorolac, ketamine, magnesium infusion, lidocaine infusion and dexmedetomidine appear to be effective and safe to manage pain after complex spinal surgery. Regional techniques including bilateral erector spinae block, interfascial plane block and intrathecal morphine also appear to be effective and safe. Pain management after complex spinal surgery remains challenging. Therefore, further studies are still required to determine the optimal multimodal analgesic regimen for these patients.

Dose of intra-operative opioids has no impact on recurrence or survival in primary liver cancer.

Intra-operative use of opioid analgesics might have an impact on cancer recurrence and survival after surgery. The objective of this study was to investigate the association between the intra-operative fentanyl equivalents and survival outcomes in patients with primary liver cancer after receiving hepatectomy. This was a retrospective single-center cohort study, and clinical data of 700 patients with primary liver cancer who underwent hepatectomy in Harbin Medical University Cancer Hospital from September 2013 to August 2018 were reviewed. After propensity matching, 376 patients were included. Patients were divided into high-dose and low-dose groups according to the median intra-operative fentanyl equivalents (1.500 mg). Kaplan Meier curve and Cox proportional hazards regression model were used. Results of univariable analysis showed there were no significant differences in recurrence-free survival (RFS) (p=0.136) and overall survival (OS) (p=0.444) between high-dose fentanyl equivalents and low-dose fentanyl equivalents group. The multivariable Cox regression analysis found that the dose of intra-operative fentanyl equivalents was not associated with RFS (HR: 1.119, 95%CI: 0.851-1.472, p=0.422) or OS (HR: 0.939, 95%CI: 0.668-1.319, p=0.715). The amounts of intra-operative fentanyl equivalents had no impact on recurrence-free or overall survival in patients with primary liver cancer after curative hepatectomy.

Usefulness of Continuous Low-Dose Fentanyl in Combination with Dexmedetomidine and Midazolam for Intravenous Sedation: A Randomised Controlled Trial.

Intravenous dexmedetomidine (DEX) and midazolam (MZ) are currently used to achieve sedation in dental surgery under local anaesthesia. However, the efficacy of low-dose fentanyl (FEN) in combination with DEX and MZ sedation remains unclear. Therefore, we implemented a prospective randomised controlled trial to investigate the intra- and postoperative analgesic effects, intraoperative respiratory and circulatory dynamics, and frequency of intra- and postoperative adverse events of continuous low-dose fentanyl administration with DEX and MZ sedation. Patients aged 20–64 years scheduled for dental surgery under sedation were randomly assigned to the DEX+MZ (DM) or DEX+MZ+FEN (DMF) group. DEX was administered at 4 μg/kg/h for 10 min and then reduced to 0.7 μg/kg/h until the end of surgery. MZ was administered at 0.04 mg/kg upon the initial administration of DEX and 0.02 mg/kg every hour thereafter. In the DMF group, FEN infusion was administered at 2 μg/kg/h during the initial administration of DEX and then reduced to 1 μg/kg/h after 10 min until the end of surgery. Primary outcomes were intra- and postoperative analgesic efficacies, whereas secondary outcomes were intraoperative respiratory and circulatory dynamics. The total amount of intraoperative local anaesthetic administered and the heart rate were significantly lower in the DMF group than in the DM group (P = 0.044 and P < 0.01, respectively). No significant difference was observed in the frequency of postoperative administration of analgesics and intra- and postoperative adverse events. These findings demonstrated that low-dose FEN infusion in combination with DEX and MZ sedation in dental surgery provides intraoperative analgesia and suppresses tachycardia with little effect on blood pressure and respiratory dynamics and without effect on postoperative analgesia.

Premedication with Fentanyl for Less Invasive Surfactant Application (LISA): A Randomized Controlled Trial.

Currently, there is no consensus regarding analgesic premedication before the surfactant administration by less invasive surfactant application (LISA) procedure. In this randomized controlled trial, we compared the level of comfort of preterm infants receiving fentanyl as analgesic and sedative versus no fentanyl during LISA procedure. We randomized 34 preterm infants of 28+0-33+6 weeks of gestation with respiratory distress syndrome (RDS) within 6 h of birth to receive either fentanyl (1 μg/kg intravenous) or no premedication during surfactant administration by LISA procedure. Primary objective was to assess the proportion of preterm infants to be comfortable during the procedure [revised premature infant pain profile (R-PIPP) score ≤12] and secondarily complications occurring during the procedure, hemodynamically significant patent ductus arteriosus (hsPDA), intraventricular hemorrhage (IVH) (≥ grade 3), bronchopulmonary dysplasia (BPD) and composite outcome of BPD/mortality. Proportion of preterm infants with a R-PIPP score ≤12 during LISA was significantly higher in the fentanyl group [15/17 (88.23%) vs. 8/17 (47.05%); p value 0.025]. There were no differences in secondary outcome parameters. Low-dose fentanyl during LISA procedure resulted in more comfort in preterm infants and without increased complication of both the LISA procedure and fentanyl administration. Further studies are needed to determine the safest and most effective pharmacologic measures to prevent pain and discomfort during LISA.

Low-dose fentanyl reduces pain perception, muscle sympathetic nerve activity responses, and blood pressure responses during the cold pressor test.

Our knowledge about how low-dose (analgesic) fentanyl affects autonomic cardiovascular regulation is primarily limited to animal experiments. Notably, it is unknown if low-dose fentanyl influences human autonomic cardiovascular responses during painful stimuli in humans. Therefore, we tested the hypothesis that low-dose fentanyl reduces perceived pain and subsequent sympathetic and cardiovascular responses in humans during an experimental noxious stimulus. Twenty-three adults (10 females/13 males; 27 ± 7 yr; 26 ± 3 kg·m-2, means ± SD) completed this randomized, crossover, placebo-controlled trial during two laboratory visits. During each visit, participants completed a cold pressor test (CPT; hand in ∼0.4°C ice bath for 2 min) before and 5 min after drug/placebo administration (75 μg fentanyl or saline). We compared pain perception (100-mm visual analog scale), muscle sympathetic nerve activity (MSNA; microneurography, 11 paired recordings), and beat-to-beat blood pressure (BP; photoplethysmography) between trials (at both pre- and postdrug/placebo timepoints) using paired, two-tailed t tests. Before drug/placebo administration, perceived pain (P = 0.8287), ΔMSNA burst frequency (P = 0.7587), and Δmean BP (P = 0.8649) during the CPT were not different between trials. After the drug/placebo administration, fentanyl attenuated perceived pain (36 vs. 66 mm, P < 0.0001), ΔMSNA burst frequency (9 vs. 17 bursts/min, P = 0.0054), and Δmean BP (7 vs. 13 mmHg, P = 0.0174) during the CPT compared with placebo. Fentanyl-induced reductions in pain perception and Δmean BP were moderately related (r = 0.40, P = 0.0641). These data provide valuable information regarding how low-dose fentanyl reduces autonomic cardiovascular responses during an experimental painful stimulus.

Low-dose fentanyl does not alter muscle sympathetic nerve activity, blood pressure, or tolerance during progressive central hypovolemia.

Hemorrhage is a leading cause of battlefield and civilian trauma deaths. Several pain medications, including fentanyl, are recommended for use in the prehospital (i.e., field setting) for a hemorrhaging solider. However, it is unknown whether fentanyl impairs arterial blood pressure (BP) regulation, which would compromise hemorrhagic tolerance. Thus, the purpose of this study was to test the hypothesis that an analgesic dose of fentanyl impairs hemorrhagic tolerance in conscious humans. Twenty-eight volunteers (13 females) participated in this double-blinded, randomized, placebo-controlled trial. We conducted a presyncopal limited progressive lower body negative pressure test (LBNP; a validated model to simulate hemorrhage) following intravenous administration of fentanyl (75 µg) or placebo (saline). We quantified tolerance as a cumulative stress index (mmHg·min), which was compared between trials using a paired, two-tailed t test. We also compared muscle sympathetic nerve activity (MSNA; microneurography) and beat-to-beat BP (photoplethysmography) during the LBNP test using a mixed effects model [time (LBNP stage) × trial]. LBNP tolerance was not different between trials (fentanyl: 647 ± 386 vs. placebo: 676 ± 295 mmHg·min, P = 0.61, Cohen's d = 0.08). Increases in MSNA burst frequency (time: P < 0.01, trial: P = 0.29, interaction: P = 0.94) and reductions in mean BP (time: P < 0.01, trial: P = 0.50, interaction: P = 0.16) during LBNP were not different between trials. These data, the first to be obtained in conscious humans, demonstrate that administration of an analgesic dose of fentanyl does not alter MSNA or BP during profound central hypovolemia, nor does it impair tolerance to this simulated hemorrhagic insult.

Adding a Low Dose of Fentanyl to Propofol in Patients Receiving Electroconvulsive Therapy: A Randomized Controlled Trial

Objective: To evaluate the effects of low-dose fentanyl combined with a reduced dose of propofol on seizure duration and hemodynamic response during electroconvulsive therapy (ECT). Materials and Methods: Twenty-two patients with the American Society of Anesthesiologist Physical Status II to III undergoing ECT were enrolled in the present study. One hundred and five bilateral ECT sessions randomized to receive thiopental 2 mg/kg, propofol 1 mg/kg, and fentanyl 0.3 mcg/kg, followed by propofol 0.5 mg/kg. Succinylcholine 0.5 mg/kg was used for muscle paralysis. Seizure duration, awakening time and hemodynamic changes were compared between groups. Results: One hundred and five bilateral ECT treatments were randomized into thiopental group (n=35), propofol group (n=35), and fentanyl plus propofol group (n=35). The thiopental and fentanyl plus propofol groups had longer EEG and motor seizure durations than the propofol group, but the differences were not statistically significant. There was no difference in stimulus intensity across groups. However, fentanyl plus propofol group had statistically significant prolonged awakening time compare with thiopental group [mean difference 2.71, (95% CI 0.37 to 5.06, p=0.019)] and propofol group (mean difference 2.77, 95% CI 0.42 to 5.12, p=0.016). Only systolic blood pressure in propofol group was significantly lower than thiopental group [mean difference –10.4, (95% CI –19.4 to –1.38, p=0.018)]. There were no significant differences in diastolic blood pressure (df=2, F=2.546, p=0.083), heart rate (df=2, F=0.596, p=0.553), or oxygen saturation across group (df=2, F=2.914, p=0.059). Conclusion: Using a combination of low-dose fentanyl and low-dose propofol during ECT could be beneficial. Further investigation is needed to establish the optimal dose of propofol and fentanyl. Keywords: Electroconvulsive therapy; Fentanyl, Hemodynamic response; Propofol; Thiopental; Seizure duration

Effect of Fentanyl Infusion on Heart Rate Variability and Anaesthetic Requirements in Isoflurane-Anaesthetized Horses.

Simple SummaryHistorically, the use of opioids in equine anaesthesia has been limited due to many reported adverse effects. Even though more research is being conducted, there is conflicting evidence on the efficacy of opioids and their behavioural effects in horses. The aim of this study was to investigate the effect of the synthetic opioid fentanyl on various parameters measured during general anaesthesia, as well as to determine its possible sparing-effect on inhalant anaesthetic.Controversy continues to surround the use of opioids in equine anaesthesia, with variable effects reported. This blinded clinical study aimed to investigate the influence of a low-dose fentanyl continuous rate infusion (CRI) on isoflurane requirements, parasympathetic tone activity (PTA), and anaesthetic parameters in horses during general anaesthesia. All of the twenty-two horses included in the research underwent a standard anaesthetic protocol. Eleven horses in the fentanyl group (Group F) received a loading dose of fentanyl at 6 µg/kg, followed by a CRI of 0.1 µg/kg/min during anaesthesia. A further 11 horses in the control group (Group C) received equivalent volumes of normal saline. Anaesthetic parameters and PTA index were recorded during anaesthesia. The achieved mean fentanyl plasma concentration was 6.2 ± 0.83 ng/mL. No statistically significant differences between groups were found in isoflurane requirements, MAP values, and mean dobutamine requirements. However, horses in Group F required a significantly lower dose of additional ketamine to maintain a sufficient depth of anaesthesia. Significantly higher PTA values were found in the fentanyl group. Further research is warranted to determine the limitations of PTA monitoring, and the influence of various anaesthetics on its values.

Takotsubo syndrome after liver transplantation: An association with intraoperatively administered epinephrine and fentanyl.

Takotsubo syndrome (TTS) can develop after liver transplant (LT), but its predisposing factors are poorly understood. In this study, we aimed to determine if perioperative factors were associated with posttransplant TTS. Adult patients who underwent primary LT between 2006 and 2018 were included. Patients with and without TTS were identified and matched by propensity scores. Of 2181 LT patients, 38 developed postoperative TTS with a mean left ventricular ejection fraction of 25.5% (±7.8%). Multivariable logistic regression revealed two preoperative risk factors (alcoholic cirrhosis and model for end-stage liver disease-sodium scores) for TTS. Post-propensity match analyses showed that TTS patients had significantly higher doses of epinephrine and lower doses of fentanyl during LT compared with non-TTS patients. A higher dose of epinephrine and a lower dose of fentanyl was associated with a higher predicted probability of TTS. All TTS patients had full recovery of cardiac function and had comparable 1-year survival. In conclusion, TTS occurred at a rate of 1.7% after LT and was associated with two pretransplant risk factors. The higher doses of epinephrine and lower doses of fentanyl administered during LT were associated with posttransplant TTS. More studies on the relationship between intraoperative medications and TTS are warranted.

Effect of pre-extubation low-dose fentanyl on attenuation of haemodynamic response and quality of extubation: A prospective randomised trial

BackgroundEmergence from anaesthesia, tracheal stimulation during extubation alters the hemodynamics, and coughing generates aerosol that needs to be avoided. AimThe study aimed to evaluate the effectiveness of low doses (0.5 μg/kg) of fentanyl at the end of the surgery in attenuating hemodynamic response and extubation quality. MethodsThis prospective, randomized, double-blind trial was conducted in a tertiary care center, with a total of 70 ASA PS I&II patients scheduled for elective laparoscopic cholecystectomy. Standard protocol followed for induction of the patients. At the end of the surgery, patients were randomly allocated to either Group-F and Group-C to receive intravenous fentanyl 0.5 μg/kg or an equal volume of normal saline respectively. Hemodynamic parameters before and after the drug, at awakening, while extubation (T0), one and minutes post-extubation (T1&T5 respectively) were measured. Airway reflex scores (ARS), extubation quality score (EQS), and Ramsay sedation scores (RSS) monitored during extubation. ResultsGroup-C patients had significantly higher mean arterial pressure at T1 (P = 0.021), higher incidence of agitation at T0(P = 0.002), T1(P = 0.002), and T5 (P = 0.009). Group-F patients had significantly better ARS at T0 and T1 (P < 0.001) and better EQS (P < 0.001). ConclusionLow-dose fentanyl at the time of extubation is an effective way to achieve smooth extubation, control unstable hemodynamics and agitation.

The synthetic opioid fentanyl enhances viral replication in vitro.

The US is in the midst of a major drug epidemic fueled in large part by the widespread recreational use of synthetic opioids such as fentanyl. Persons with opioid use disorder are at significant risk for transmission of injection-associated infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV). Commonly abused substances may antagonize immune responses and promote viral replication. However, the impact of synthetic opioids on virus replication has not been well explored. Thus, we evaluated the impact of fentanyl and carfentanil using in vitro systems that replicate infectious viruses. Fentanyl was used in cell lines replicating HBV or HCV at concentrations of 1 ng, 100 ng, and 10 ug. Viral protein synthesis was quantified by ELISA, while apoptosis and cell death were measured by M30 or MTT assays, respectively. HCV replicative fitness was evaluated in a luciferase-based system. RNAseq was performed to evaluate cellular gene regulation in the presence of fentanyl. Low dose fentanyl had no impact on HCV replication in Huh7.5JFH1 hepatocytes; however, higher doses significantly enhanced HCV replication. Similarly, a dose-dependent increase in HCV replicative fitness was observed in the presence of fentanyl. In the HepG2.2.15 hepatocyte cell line, fentanyl caused a dose-dependent increase in HBV replication, although only a higher doses than for HCV. Addition of fentanyl resulted in significant apoptosis in both hepatocyte cell lines. Cell death was minimal at low drug concentrations. RNAseq identified a number of hepatocyte genes that were differentially regulated by fentanyl, including those related to apoptosis, the antiviral / interferon response, chemokine signaling, and NFκB signaling. Collectively, these data suggest that synthetic opioids promote viral replication but may have distinct effects depending on the drug dose and the viral target. As higher viral loads are associated with pathogenesis and virus transmission, additional research is essential to an enhanced understanding of opioid-virus pathogenesis and for the development of new and optimized treatment strategies.