Single Dose Of Fentanyl Research Articles

The impact of repeat opioid use (ROU) on fentanyl-induced respiratory depression

Objective: Repeat opioid use (ROU) is a primary driver for the ongoing opioid epidemic, and while a substantial understanding exists for the impact of ROU on behavioral neurophysiology, the consequences of ROU on respiratory-related physiology including opioid-induced respiratory depression (OIRD) remain poorly understood. Hypothesis: ROU leads to respiratory tolerance to fentanyl that is characterized by the blunting of respiratory depression and improvement of O2 consumption (VO2). Methods: We utilized a pre-clinical rodent model. Breathing was measured via whole body-plethysmography in freely behaving adult mice (P>90) prior to and immediately following fentanyl administration. A single dose of fentanyl (0.7 mg/kg, i.p.) was given for up to 6 consecutive days. In a subset of experiments, O2 consumption was measured simultaneously using whole-body plethysmography. Results: We identified two distinct respiratory phenotypes in response to OIRD following ROU. Type 1 phenotype (n=18) adapted over time where breathing during OIRD is greater on day 5 versus day 1. In contrast, the Type 2 phenotype (n=5) showed no such adaptation, with unchanged or worsened breathing by day 5. In a subset of animals (n=12) the relationship between breathing (i.e. minute ventilation (Ve)) and oxygen consumption (VO2) was examined before and following ROU. Under baseline conditions the Ve to VO2 relationship positively correlated on day 1 and 5. During OIRD on day 1 this correlation became negative, but began to normalize by day 5, resembling the baseline relationship. These phenomena also coincided with an increase in the ventilatory drive observed at the whole-animal level and in the isolated preBötzinger complex following ROU. Conclusions: ROU leads to two distinct respiratory phenotypes in response to OIRD, where the majority of subjects show a blunted respiratory depression. Additionally, ROU improves the relationship between breathing and oxygen consumption and enhances inspiratory drive in the presence of fentanyl. These findings suggest that fentanyl-induced hypoxia experienced by repeat opioid users vastly differ from naïve users. Such differences may contribute to the unpredictable occurrence of overdose amongst repeat users. This work was supported by NIH: R01 HL163965 and DA057767. This is the full abstract presented at the American Physiology Summit 2024 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 incisional, transverse abdominis plane, and rectus sheath blocks in dogs undergoing ovariohysterectomy.

To compare the analgesia provided by incisional (Incisional), transverse abdominis plane (TAP), and rectus sheath (RS) blocks in dogs submitted for ovariohysterectomy (OHE). 22 female mixed-breed dogs were allocated into 3 treatments of Incisional (n = 7), TAP (n = 7), and RS (n = 8) and underwent OHE from April 4 to December 6, 2022. After premedication with acepromazine (0.05 mg/kg) and morphine (0.5 mg/kg), anesthesia was induced (6 mg/kg) and maintained (0.4 mg/kg/min) with propofol. Each dog randomly received either an incisional (blind technique), TAP, or RS (ultrasound-guided) block. Intraoperative analgesia was assessed using cardiorespiratory variables. Postoperative analgesia was evaluated up to 6 hours after the operation with a Short Form of Glasgow Pain Scale (SF-GCPS) and Visual Analog Scale (VAS). Fentanyl was administered as a rescue analgesic when needed. During surgery, all data remained within normal limits without any significant differences. Fentanyl was administered to 1 dog in the Incisional and 1 in the TAP. Post-operatively, a single dose of fentanyl was given to 1 dog in the TAP and 1 in the RS. Four dogs in the Incisional and 3 in the RS received both doses of fentanyl. There was no significant difference regarding postoperative rescue analgesia among treatments. All 3 techniques demonstrated acceptable intra- and post-operative analgesia efficacy in dogs undergoing OHE. Further studies are warranted to confirm these findings.

Comparison of the Effect of Intravenous Fentanyl with Low-Dose Ketamine on Pain Relief in Patients Taking Methadone and Suffering from Limb Fractures.

Given the significance of pain control in addicted patients and the prominence of not using opioids due to patient's drug dependence, the present study aimed at comparing and evaluating the effect of intravenous fentanyl with low-dose ketamine on pain relief in patients taking methadone and suffering from limb fractures. The present double-blind randomized clinical trial was performed on 100 patients taking methadone and suffering from limb fractures. The patients were divided into two groups receiving 1 μg/kg single dose of fentanyl and 0.3 mg/kg single dose of ketamine (low-dose ketamine). Patients' pain scores and the incidence rate of complications were recorded before the intervention, and 15, 30, and 60 min after drug administration and were then compared between the two groups. The mean pain score of patients 15 min after the intervention was significantly lower in the low-dose ketamine group with a mean of 2.50 ± 1.34 as compared with the fentanyl group with a mean of 7.10 ± 1.43 (P < 0.001). However, the mean pain score was not significantly different between the two groups 30 and 60 min after the intervention (P > 0.05). In addition, the incidence rate of complications was not significantly different between the two groups (P > 0.05). According to the results of this study, low-dose ketamine as compared with fentanyl relieves pain in the mentioned patients with a faster effect and in a shorter time although no difference can be found between the pain scores of the two groups 30 and 60 min after the intervention.

An assessment of opioids on respiratory depression in children with and without obstructive sleep apnea.

Obstructive sleep apnea is a risk factor for respiratory depression following opioid administration as well as opioid-induced hyperalgesia. Little is known on how obstructive sleep apnea status is associated with central ventilatory depression in pediatric surgical patients given a single dose of fentanyl. This was a single-center, prospective trial in children undergoing surgery requiring intubation and opioid administration. Sixty patients between the ages of 2-8years presenting for surgery at Texas Children's Hospital were recruited. Twenty non-obstructive sleep apnea controls and 30 patients with moderate to severe obstructive sleep apnea met inclusion criteria. Following induction of general anesthesia and establishment of steady-state ventilation, participants received 1mcg/kg intravenous fentanyl. Ventilatory variables (tidal volume, respiratory rate, end-tidal CO2 , and minute ventilation) were assessed each minute for 10min. The primary outcome was the extent of opioid-induced central ventilatory depression over time by obstructive sleep apnea status when compared with baseline values. Secondary aims assessed the impact of demographics and SpO2 nadir on ventilatory depression. We found no significant difference in percent decrease in respiratory rate (38.1% and 37.1%; p=.950), tidal volume (6.4% and 5.4%; p=.992), and minute ventilation (35.0L/min and 35.0L/min; p=.890) in control and obstructive sleep apnea patients, respectively. Both groups experienced similar percent increases in end-tidal CO2 (4.0% vs. 2.2%; p=.512) in control and obstructive sleep apnea patients, respectively. In pediatric surgical patients, obstructive sleep apnea status was not associated with significant differences in central respiratory depression following a single dose of fentanyl (1mcg/kg). These findings can help determine safe opioid doses in future pediatric obstructive sleep apneapatients.

SPECTRAL ENTROPY FOR ASSESSING THE PATIENT RESPONSIVENESS DURING PROPOFOL/FENTANYL SEDATION IN DAY CARE SURGERIES

Background: For day care surgery under monitored anesthetic care, precise monitoring of sedation depth facilitates optimization of dosage and prevents adverse complications from over sedation. Conventionally subjective sedation scales, such as the Modified observer’s assessment of alertness/ sedation scale (MOAA/S) have been widely utilized for sedation monitoring. The newer monitoring called entropy is considered to be beneficial for objective assessment with combined use of opioids and hypnotics if applied. The primary objective is to determine measurement of entropy as a marker for measuring depth of anaesthesia.&#x0D; Methods: Two groups P and PF ( with 25 patients each) received either propofol 1mg/kg followed by maintenance infusion of 250 mic/ kg/hr whereas “PF”group received additional single dose of fentanyl 2 mic/kg respectively. The values of response entropy (RE) and state entropy (SE) corresponding to each MOAA/S (5 to 0) were determined.&#x0D; Results: The patient’s demographic profile and clinical characteristics were comparable in both the groups. No difference observed in duration of anaesthesia and surgery in both groups. No difference observed in MOAA/S in both groups. The results shows a highly significant differences in the observed means of SE, RE, MAP and HR with considerably higher mean values in group P (p&lt;0.0001). However other parameter such as SPO2, ETCO2 and RR were almost comparable in both groups.&#x0D; Conclusion: The mean value of SE and RE in group P and PF indicates that deeper plane of anaesthesia is observed in PF group. It is concluded that in assessing the level of hypnosis during intra-operative sedation in MAC, entropy corresponds to MOAA/S and increases or decreases proportionately depending upon increase or decrease level of sedation. Hence from these results it is proposed that entropy monitoring is a reliable monitoring index of anaesthesia depth in MAC.&#x0D; Keywords: Entropy, Propofol, Sedation, Day care surgery, Observer’s assessment of alertness/ sedation scale, Monitored anaesthesia Care

Pharmacokinetics of Sublingually Delivered Fentanyl in Head and Neck Cancer Patients Treated with Curatively Aimed Chemo or Bioradiotherapy.

Over 90% of patients treated for head and neck cancer with curatively aimed chemo or bioradiotherapy will develop painful mucositis and xerostomia. Sublingually delivered fentanyl (SDL) is a rapid acting opioid to treat breakthrough pain. It is unclear how SDL is absorbed by the mucosa of these patients. Therefore, the aim of this study was to investigate the effects of mucositis and xerostomia on the absorption of SDL. Thirteen patients who received chemo or bioradiotherapy (RT), were given a single dose of fentanyl: Before start of RT, 3 and 6 weeks after start of RT, and 6 weeks after finishing RT. Pharmacokinetic samples were taken. The primary endpoint was the relative difference (RD) between systemic exposure to fentanyl (area under the curve; AUC) at baseline (AUCbaseline) and fentanyl AUC in the presence of mucositis grade ≥2. The secondary endpoint was the RD between AUCbaseline and fentanyl AUC in the presence of xerostomia, which were analyzed by means of a paired t-test on log-transformed data. Mucositis resulted in a 12.7% higher AUC (n = 13; 95% CI: −10.7% to +42.2%, p = 0.29) compared to baseline levels and xerostomia resulted in a 22.4% lower AUC (n = 8; 95% CI: −51.9% to +25.3%, p = 0.25) compared to baseline levels. Mucositis grade ≥2 or xerostomia caused by chemo or bioradiotherapy does not significantly alter the systemic exposure to SDL. Patients with pain during and after chemo or bioradiotherapy may be safely treated with SDL.

Can liver cirrhosis patients benefit from target controlled infusion of propofol for conscious sedation during endoscopic variceal ligation?

Background: The aim of the present study was to evaluate the feasibility of conscious sedation using target controlled infusion of propofol combined with a single dose of fentanyl during endoscopic variceal ligation in patients with liver cirrhosis.Methods: Forty-eight patients with liver cirrhosis scheduled for endoscopic variceal ligation were randomly assigned to deep sedation group (DS group) with intravenous bolus of propofol and conscious sedation group (CS group) with target controlled infusion of propofol, 1 μg/kg fentanyl was intravenously injected in each patient before administration of propofol. Cardiorespiratory parameters were monitored, and the side-effects were recorded. The depth of sedation was assessed by both of the sale of observer′s assessment of alertness/sedation (OAA/S) and the bispectral index (BIS). The quality of sedation/analgesia was evaluated by the endoscopist and patients using Visual Analog Scores (VAS). The recovery level was evaluated with the Aldrete scales.Results: No significant differences were found on demographic data and initial parameters in the two groups. Compared with the CS group, the changes of mean arterial pressure (MAP) and heart rate (HR) and the signs of respiratory depression were significant in the DS group (p&lt;0.05). The recovery time in DS group (16.7±2.7 minutes) was much longer than that in the CS group (9.3±3.0 minutes, p&lt;0.01). There was no difference in Visual Analogue Scale scores for endoscopist’s satisfaction between the two groups (9.2±0.6 versus 9.0±0.6, p&gt;0.05), but a higher degree of satisfaction for patient was found in the DS group (9.3±0.6 versus 7.9±0.7, p&lt;0.01).Conclusions: Conscious sedation with target controlled infusion of propofol combined with a single bolus of fentanyl for endoscopic variceal ligation in patients with liver cirrhosis had better hemodynamic stability, less respiratory depression and shorter recovery time.

Comparative study between prophylactic single dose of fentanyl and dexmedetomidine in the management of agitation after sevoflurane anesthesia in children

ObjectiveThe higher incidence of post sevoflurane agitation presents a great dilemma. This controlled study was performed to test the hypothesis that the prophylactic single dose of either dexmedetomidine or fentanyl reduces the incidence of emergence agitation post sevoflurane anesthesia in children.Patients and methodsNinety pediatric patients were scheduled for elective surgical procedures under general anesthesia and caudal block. They were randomized to one of three groups (each one is 30 patients); fentanyl group (1 μg/kg), dexmedetomidine (DEX) group (0.15 μg/kg), and control group. Recovery was assessed by time until eye opening on command, pain was evaluated by the children’s and infants’ postoperative pain scale (CHIPPS) and adequacy of recovery was assessed using a Modified Aldert score. Both were recorded every 15 min. Behavior score was recorded in the pre- and postoperative periods.Main resultsPatients in control group obtained higher values (9.65 ± 0.34) in the modified Aldert score than patients who received fentanyl (9.58 ± 0.30) and dexmedetomidine (9.37 ± 0.37). There was significant difference between dexmedetomidine and fentanyl groups For pain assessment, patients in control group suffered from pain when measured by CHIPPS (0.93 ± 0.56) more than patients in dexmedetomidine group (0.48 ± 0.45) and fentanyl group (0.13 ± 0.35), with more significant pain in dexmedetomidine group when compared to fentanyl group (p < 0.05). As regard behavior during emergence, there were significant differences between the placebo with 40% agitation and both fentanyl group with 21.4% agitation (p = 0.002) and dexmedetomidine group with 16.7% agitation (p = 0.001), while there were no significant differences between fentanyl and dexmedetomidine group.ConclusionsIncidence of postoperative agitation in pediatric patients receiving sevoflurane was decreased from 40% with placebo to 16.7% with dexmedetomidine and 21.4% with fentanyl with no significant differences between dexmedetomidine and fentanyl groups.

A Computer-Assisted Personalized Sedation System to Administer Propofol Versus Standard-of-Care Sedation for Colonoscopy and Esophagogastroduodenoscopy: A 1,000-Subject Randomized, Controlled, Multicenter, Pivotal Trial

A Computer-Assisted Personalized Sedation System to Administer Propofol Versus Standard-of-Care Sedation for Colonoscopy and Esophagogastroduodenoscopy: A 1,000-Subject Randomized, Controlled, Multicenter, Pivotal Trial

A single dose of fentanyl and midazolam prior to Cesarean section have no adverse neonatal effects

A single dose of fentanyl and midazolam prior to Cesarean section have no adverse neonatal effects

A single dose of fentanyl and midazolam prior to Cesarean section have no adverse neontal effects

Analgesia and sedation, routinely used as adjunct medications for regional anesthesia, are rarely used in the pregnant patient because of concerns about adverse neonatal effects. In an effort to obtain more information about maternal analgesia and sedation we studied neonatal and maternal effects of iv fentanyl and midazolam prior to spinal anesthesia for elective Cesarean section. In this double-blinded, randomized, placebo-controlled trial, 60 healthy women received either a combination of 1 microg x kg(-1) fentanyl and 0.02 mg x kg(-1) midazolam intravenously or an equal volume of iv saline at the time of their skin preparation for a bupivacaine spinal anesthetic. Sample size was based on a non-parametric power analysis (power > 0.80 and alpha = 0.05) for clinically important differences in Apgar scores. Fetal outcome measures included Apgar scores, continuous pulse oximetry for three hours, and neurobehavioural scores. Maternal outcomes included catecholamine levels, and recall of anesthesia and delivery. There were no between-group differences of neonatal outcome variables (Apgar score, neurobehavioural scores, continuous oxygen saturation). Mothers in both groups showed no difference in their ability to recall the birth of their babies. Maternal analgesia and sedation with fentanyl (1 microg x kg(-1)) and midazolam (0.02 mg x kg(-1)) immediately prior to spinal anesthesia is not associated with adverse neonatal effects.

Breath interval as a measure of dynamic opioid effect

We measured breath interval to characterize the time course of opioid effect in anaesthetized patients breathing spontaneously during knee replacement surgery with concurrent regional nerve blockade. Breath interval was recorded before and after a single dose of fentanyl 0.75 microgram kg-1 i.v. Breath interval was measured between the start of successive inspirations, identified by a decrease in carbon dioxide concentration, sampled at the laryngeal mask connection. Nineteen patients were admitted to the study, of whom nine were withdrawn (there was a recording failure for one patient, five patients had inadequate block and three were excessively depressed by the fentanyl). Using MKMODEL software, the mean (SD) dynamic elimination half-life and dynamic mean brain residence time of fentanyl were 15.3 (7.8) and 24.1 (8.1) min, respectively. The times to detection of change from baseline, and peak effect of fentanyl on breath interval were 0.9 (0.6) and 5.2 (1.4) min, respectively. Breath interval increased from 2.9 (1.0) s to a maximum of 9.0 (5.7) s. There were no differences between the time course of changes in breath interval and end-tidal carbon dioxide concentrations. End-tidal carbon dioxide concentrations increased from a baseline of 6.6 (0.9)% to a peak of 8.2 (0.8)%. Breath interval was a useful and reproducible method of monitoring the duration of opioid effect in anaesthetized patients breathing spontaneously when surgical stimulation was not affecting the CNS. The data provide information on the duration of action of fentanyl and could guide dosage.

Selective spinal anaesthesia in ambulatory surgery

Background and objectives: selective spinal anaesthesia (SSA) is preferable in day hospital surgery. The present investigation aims to confirm the usefulness and safety of this technique. Methods: 250 patients (ASA I–II, mean age 42 ± 3 years) scheduled for day-hospital surgery were enrolled in our study. The puncture was performed with the patients in a lateral position, the ill side down; for proctological surgery the puncture was performed in a sitting position. A 27G Whitacre needle was always used and 1% hyperbaric bupivacaine was administered in 30 s or more, preceded by a single dose of fentanyl (20 μg) injected very slowly. The position was maintained for 10 min. Hemodynamic parameters (SBP, DBP, HR) and pulsoximetry were recorded before anaesthesia (T 0), 5 min after subarachnoid injection (T 1) and then every 15 min (T n) up to the completion of the surgical procedure. In the last 100 patients enrolled in our study haemodynamic data (CI, EF, SVRI, MAP,HR) were recorded by using a non invasive bioimpedenzometric method, before anaesthesia (T a), after 15 min (T b), 60 min (T c) and 240 min (T d). The postoperative course was evaluated from the end of surgery on, with regard to analgesic consumption and residual analgesic degree. The incidence of adverse effects was evaluated. Results: the level and degree of anaesthesia was excellent in 183 and good in 67 patients. SBP, DBP, HR and pulsoximetry showed an excellent stability during the study. Haemodynamic stability was confirmed by data obtained with bioimpedenzometry that showed significant variations in CI ( P < 0.001), SVN ( P < 0.0001) at T b and T c as to basal five values. Postoperative analgesia was excellent and the incidence of side effects very low. Conclusions: we believe that the method is suitable for day-hospital surgery because it is easy to execute and provides an excellent degree of surgical anaesthesia, cardiovascular stability, postoperative analgesia and patient safety.

Manual compared with target-controlled infusion of propofol

We studied 160 ASA I-II patients, anaesthetized with propofol by infusion, using either a manually controlled or target-controlled infusion system. Patients were anaesthetized by eight consultant anaesthetists who had little or no previous experience of the use of propofol by infusion. In addition to propofol, patients received temazepam premedication, a single dose of fentanyl and 67% nitrous oxide in oxygen. Each consultant anaesthetized 10 patients in sequential fashion with each system. Use of the target-controlled infusion resulted in more rapid induction of anaesthesia and allowed earlier insertion of a laryngeal mask airway. There was a tendency towards less movement in response to the initial surgical stimulus and significantly less movement during the remainder of surgery. Significantly more propofol was administered during both induction and maintenance of anaesthesia with the target-controlled system. This was associated with significantly increased end-tidal carbon dioxide measurements during the middle period of maintenance only, but recovery from anaesthesia was not significantly prolonged in the target-controlled group. With the exception of a clinically insignificant difference in heart rate, haemodynamic variables were similar in the two groups. Six of the eight anaesthetists found the target-controlled system easier to use, and seven would use the target-controlled system in preference to a manually controlled infusion. Anaesthetists without prior experience of propofol infusion anaesthesia quickly became familiar with both manual and target-controlled techniques, and expressed a clear preference for the target-controlled system.