Effects Of High-dose Fentanyl Research Articles

Effects of high dose Fentanyl in combination with hypoxia or ketamine in adult female goats

The worsening opioid epidemic in the United States continues to claim >80,000 lives each year. Synthetic opioids such as fentanyl are highly useful in the clinical management of pain but at high doses are thought to cause death through opioid-induced respiratory depression (OIRD), impairment of the alveolar to arterial oxygen (A-a O2) gradient and though upper airway and respiratory pump muscles activation causing airway dysfunction and/or Wooden Chest Syndrome (WCS). These negative effects of high dose opioids may be exacerbated when individuals use additional drugs such as ketamine or by an existing hypoxia. We have shown previously that low (sub-lethal) doses of fentanyl (25-125 μg/kg; IV) cause transient apnea (<30 sec), a brief suppression of breathing frequency (FB; <5 min), increased tidal volume (VT), upper airway and pump muscle activity, and an increased A-a O2 gradient with an overall stimulatory effect on ventilation for up to 90 min post-injection (PMID: 37885800). Here we tested the hypothesis that the physiological effects of high doses of fentanyl will be exacerbated when combined with pre-treatment of either mild hypoxia (FIO2=0.12) or IV ketamine (10 mg/kg). Adult female goats (n=3) were surgically instrumented with electromyographic (EMG) wires in airway (genioglossus and thyropharyngeal) and respiratory pump (diaphragm, transverse abdominus and intercostal) muscles and the carotid arteries relocated subcutaneously and allowed 2 weeks for recovery. Arterial blood samples were obtained through a carotid catheter and all injections were via a catheter in the jugular. Following a 30-minute control period, goats were given IV saline (vehicle) or fentanyl (50–500 μg/kg). In most goats, fentanyl doses of 200-250 μg/kg cause immediate apnea up to 60 sec in duration and decreased FB (~40%) and PaO2 (~35 mmHg) while increasing PaCO2 (~70mmHg) along with an EMG activation and increased A-a O2 gradient. These effects tended to be less severe at a given dose when injections were performed during mild hypoxia (15 min; n=2) but were exacerbated by pretreatment with ketamine (n=1). These data suggest high doses of fentanyl in goats cause similar life-threatening features as in humans, and that these effects seem to be mitigated by hypoxic ventilatory stimulation but exacerbated by polypharmacy with ketamine. NIH DA050571. 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.

620 COMPARISION OF INTRAOPERATIVE ANALGESIC EFFECT OF HIGH DOSE FENTANYL AND LOW DOSE FENTANYL PLUS RECTAL ACETAMINOPHEN IN PEDIATRIC CLEFT LIP AND PALATE SURGERIES

European Journal of PainVolume 10, Issue S1 p. S162d-S163 620 COMPARISION OF INTRAOPERATIVE ANALGESIC EFFECT OF HIGH DOSE FENTANYL AND LOW DOSE FENTANYL PLUS RECTAL ACETAMINOPHEN IN PEDIATRIC CLEFT LIP AND PALATE SURGERIES L. Kalami, L. Kalami Anesthesiology, Medical Faculty/Children General Hospital, Tabriz, IranSearch for more papers by this authorA. Kianfar, A. Kianfar Anesthesiology, Medical Faculty/Children General Hospital, Tabriz, IranSearch for more papers by this authorM. Seyed Hejazi, M. Seyed Hejazi Anesthesiology, Medical Faculty/Children General Hospital, Tabriz, IranSearch for more papers by this author L. Kalami, L. Kalami Anesthesiology, Medical Faculty/Children General Hospital, Tabriz, IranSearch for more papers by this authorA. Kianfar, A. Kianfar Anesthesiology, Medical Faculty/Children General Hospital, Tabriz, IranSearch for more papers by this authorM. Seyed Hejazi, M. Seyed Hejazi Anesthesiology, Medical Faculty/Children General Hospital, Tabriz, IranSearch for more papers by this author First published: 13 January 2012 https://doi.org/10.1016/S1090-3801(06)60623-XRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume10, IssueS1September 2006Pages S162d-S163 RelatedInformation

The Efficacy of Epinephrine-Containing Test Dose during Propofol-Nitrous Oxide Anesthesia with High Dose Fentanyl

Background: The aim of this study is to determine the effect of high dose fentanyl on the test dose containing 15 epinephrine during propofol anesthesia. Methods: One hundred patients with ASA physical status 1 were randomized to receive 2 mg/kg propofol with or without 10/kg fentanyl at the induction of anesthesia (n = 50 each). Anesthesia was maintained with propofol 8 mg/kg/h and 67% nitrous oxide in oxygen. Each group of patients were further divided into a test dose group receiving 1.5% lidocaine 3 ml plus epinephrine 15 or a saline group receiving 3 ml of isotonic saline (n = 25 each). Heart rate (HR) and systolic blood pressure (SBP) were monitored for 4 min after intravenous injection of the study drugs. Results: In the propofol and the propofol-fentanyl group, the intravenous injection of the test dose produced a HR increase 20 bpm (conventional HR criterion) in 25 and 23 out of the total 25 patients, respectively. Therefore, in the propofol-fentanyl group, sensitivity, specificity, positive predictive value, and negative predictive value were 82%, 100%, 100%, and 92.6%. According to the modified HR criterion (HR increase 10 bpm), all the values were 100%. All patients receiving test dose developed SBP increase 15 mmHg. Conclusions: Our results indicate that both HR increase 10 bpm or SBP increase 15 mmHg are clinically applicable during propofol-nitrous oxide anesthesia with 10/kg fentanyl.

High-dose fentanyl does not adversely affect outcome from forebrain ischemia in the rat.

Fentanyl citrate has properties, including agonism of the mu-opioid receptor and proconvulsant activity, that theoretically could pose adverse effects in ischemic brain. This study examined the effects of high-dose fentanyl on outcome in rats subjected to transient near-complete forebrain ischemia. Rats were anesthetized with halothane and surgically prepared for ischemia. In one group (fentanyl; n = 15), intravenous fentanyl (400 micrograms/kg followed by an infusion of 16 micrograms/kg/min for 20 min) was administered and halothane was discontinued. In the remaining rats (control: n = 15), halothane administration was continued and no fentanyl was given. Following 10 min of bilateral carotid artery occlusion and profound systemic hypotension, animals were maintained normocapnic, normothermic, and mildly hyperoxemic for 8 h. Four days later, histologic and neurologic outcomes were assessed. In another group of rats also administered halothane (uncontrolled recovery; n = 15), no attempt was made to control physiologic variables during recovery from ischemia. Fentanyl caused preischemic evidence of epileptoid activity but decreased the percentage of neurons that died in the CA1 sector of the hippocampus relative to control (p = 0.0005). Damage in the cortex or caudoputamen was not different from that in the control group. Rats with an uncontrolled recovery had decreased damage in the cortex (p = 0.005) and caudoputamen (p = 0.00015) relative to control. In this model of forebrain ischemia, fentanyl caused no worsening of histologic damage in the cortex or caudoputamen and decreased hippocampal CA1 injury despite major electroencephalographic activation in the immediate preischemic period.

Effects of high-dose fentanyl on fluid and vasopressor requirements after cardiac surgery

The effects of two different anesthetic techniques on postoperative cardiopulmonary events, fluid and vasopressor requirements, and overall intensive care unit (ICU) course were studied in patients undergoing elective myocardial revascularization (CABG) (N = 20) or single cardiac valve replacement (N = 20). Patients were randomized to receive either high-dose fentanyl (F, 75 μg/kg followed by 0.3 μg/kg/min) or diazepam-ketamine (0.8 mg/kg D and 2 mg/kg K followed by 0.07 mg/kg/h D and 1 mg/kg/h K). No significant differences in preoperative demographics, prebypass hemodynamics, ischemic crossclamp, or total cardiopulmonary bypass times were noted. Patients receiving F had lower systemic arterial pressures and vascular resistances and required more vasopressors during the first 12 hours postoperatively. They also had a more positive cumulative fluid balance at 24 and 48 hours postoperatively, despite a higher incidence of postoperative diuretic use in CABG patients receiving F. Rectal temperature was significantly higher at four and eight hours postoperatively in F patients. Time until arousal and length of ICU stay were significantly greater with F, although duration of intubation did not differ between anesthetic techniques. Although the data does not provide an explanation for these differences, it indicates that these two techniques produce quite different physiologic responses in the postoperative period following cardiac surgery. In summary, it was found that F for cardiac surgery was accompanied by increased postoperative fluid and vasopressor requirements with increased Qsp/Qt and longer ICU stays compared to diazepam and ketamine. This study suggests that some anesthetic techniques may provide less complicated and less costly postoperative courses than others, with the same outcome after cardiac surgery. Information on the postoperative effects of long-acting anesthetic agents is sparse and more studies of these effects and their mechanisms are necessary because they may affect patient management after cardiac surgery.

The Effect of High-Dose Fentanyl on Human Median Nerve Somatosensory-Evoked Responses

Median nerve somatosensory evoked responses (MnSSERs) were recorded in nine neurologically normal adult cardiac patients before and during the administration of high-dose fentanyl. MnSSERs were recorded prior to induction and at t = 20 win and t = 45 min postinduction. Fentanyl was administered as a slow bolus (53.2 ± 9.1 μg·kg-1), followed by a continuous infusion at 10-20 μg·kg-1·hr-1 (total dose 63.6 ± 10.1 μg·kg-1). All MnSSER waveform components remained recordable and easily identifiable during anaesthesia. The effect of fentanyl was more pronounced on cortical waveform components, leaving subcortical components largely unaffected. There was a significant increase in the latency of the cortical MnSSER at t = 20 min, e.g., for the initial negative cortical wave, N1, the latency was 21.18 ± 1.55 ms preinduction versus 22.18 ± 1.42 ms at t = 20 min. There was also a significant decrease in the amplitude of the cortical response at t = 20 min, i.e., 2.04 ± 1.30 μV preinduction versus 1.31 ± 0.74 μV at t = 20 min. However, the degree of change was quite variable (range = 0-65 per cent). No further changes occurred at t - 45 min. The authors conclude that MnSSERs can be consistently and reliably monitored during high-dose fentanyl anaesthesia. However, fentanyl produces modest but significant changes in the MnSSER which should be taken into account lest they be ministerpreted as neurologic injury in evolution.

The effect of high-dose fentanyl on human median nerve somatosensory-evoked responses.

Median nerve somatosensory evoked responses (MnSSERs) were recorded in nine neurologically normal adult cardiac patients before and during the administration of high-dose fentanyl. MnSSERs were recorded prior to induction and at t = 20 min and t = 45 min postinduction. Fentanyl was administered as a slow bolus (53.2 +/- 9.1 micrograms X kg-1), followed by a continuous infusion at 10-20 micrograms X kg-1 X hr-1 (total dose 63.6 +/- 10.1 micrograms X kg-1). All MnSSER waveform components remained recordable and easily identifiable during anaesthesia. The effect of fentanyl was more pronounced on cortical waveform components, leaving subcortical components largely unaffected. There was a significant increase in the latency of the cortical MnSSER at t = 20 min, e.g., for the initial negative cortical wave, N1, the latency was 21.18 +/- 1.55 ms preinduction versus 22.18 +/- 1.42 ms at t = 20 min. There was also a significant decrease in the amplitude of the cortical response at t = 20 min, i.e., 2.04 +/- 1.30 microV preinduction versus 1.31 +/- 0.74 microV at t = 20 min. However, the degree of change was quite variable (range = 0-65 per cent). No further changes occurred at t = 45 min. The authors conclude that MnSSERs can be consistently and reliably monitored during high-dose fentanyl anaesthesia. However, fentanyl produces modest but significant changes in the MnSSER which should be taken into account lest they be misinterpreted as neurologic injury in evolution.

Fentanyl- and Sufentanil-Oxygen-Pancuronium Anesthesia for Cardiac Surgery in Infants

The safety and efficacy of fentanyl-oxygen (50 and 75 micrograms/kg) and sufentanil-oxygen (5 and 10 micrograms/kg) were studied in 40 infants undergoing repair of complex heart defects. When fentanyl or sufentanil was given simultaneously with pancuronium, induction of anesthesia was rapid and smooth with only mild and clinically insignificant hemodynamic changes. Hemodynamic responses to tracheal intubation were completely blocked, whereas hemodynamic responses to surgical incision and sternotomy were partially and variably blocked. Except for somewhat more effective blocking of responses to surgical stimulation by sufentanil, the effects of both narcotics were similar. No significant differences in effects were found between the two dose levels of either drug. Transcutaneous oxygen tensions increased with induction, intubation, and surgical stimulation with both fentanyl and sufentanil, even in cyanotic patients with right to left shunts. Fentanyl- and sufentanil-oxygen-pancuronium anesthesia were both safe and effective for cardiac surgery in infants. This study raises the question of possible beneficial effects of high dose fentanyl and sufentanil in blunting stress responses in the pulmonary circulation, a critical aspect of anesthesia and intensive care in the infant and neonate.

The Effect of High-Dose Fentanyl on Cardiac Metabolic Balance and Coronary Circulation in Patients Undergoing Coronary Artery Surgery

The Effect of High-Dose Fentanyl on Cardiac Metabolic Balance and Coronary Circulation in Patients Undergoing Coronary Artery Surgery

Fentanyl and Cerebral Vascular Responsivity in Dogs

The effect of high-dose fentanyl on the cerebral vascular response to alterations in mean arterial blood pressure, arterial O2 tension (PaO2), and arterial CO2 tension (PaCO2) was studied in 28 mongrel dogs using the cerebral venous outflow technique. In 13 animals anesthetized with sodium pentobarbital (30 mg/kg, iv), bolus injection of fentanyl (25 micrograms/kg, iv) decreased mean arterial blood pressure (MABP) without a change in cerebral blood flow (CBF). In these animals, the response of the cerebral circulation to changes in PaO2, PaCO2, and MABP was determined before and after fentanyl administration. Fentanyl did not alter the increase in CBF caused by hypoxic hypoxia or hypercapnia. The lower and upper limit of cerebral autoregulation determined by hypovolemic hypotension and norepinephrine infusion, respectively, also were unaltered by fentanyl administration. The CBF response to alterations of MABP, PaO2, and PaCO2 were studied in another group of 15 dogs anesthetized with fentanyl (100 micrograms/kg) plus small doses (3-5 mg/kg) of pentobarbital. The CBF response to PaO2, and PaCO2 in these animals was not different from that observed in animals anesthetized with barbiturates only. The lower and upper limit of cerebral autoregulation also were not different from that observed in animals anesthetized with barbiturates only. These data suggest that fentanyl in doses sufficient to cause profound analgesia and anesthesia did not alter cerebral responsivity to changes in PaO2, and PaCO2, and MABP.

Effects of high-dose fentanyl on renal haemodynamics in conscious dogs.

The renal haemodyrumic effects of high doses of fentanyl were examined in 17 unanaesthethed, chronically implanted dogs, in order to avoid the confusing effects of superimposed anaesthesia and acute surgical procedures. Ten to fourteen days prior to the study, a Doppler flow probe was positioned around the left renal artery and u Tygon catheter was placed into the lower abdominal aorta through a lumbar arterial side branch. During the experiments, the trained animals were lying quietly on their right side. Following steady-state awake baseline measurements, an intravenous fentanyl infusion, 25µg-kg (lower dose), or50µg.kg (higher dose) was administered over a ten-minute period. Arterial pressure, renal blood flow, calculated renal vascular resistance and arterial blood gases were measured for 20 minutes following the infusion. Observations were made during spontaneous and controlled ventilation, with FIO2 = 0.21 or 1.0. Fentanyl increased arterial pressure 10–40 per cent in all groups and did not, as a rule, significantly affect renal blood flow. Thus renal vascular resistance was increased. There were no significant differences between effects of the 25 µg.kg and the 50 µg- kg doses of fentanyl. It is concluded that these doses of fentanyl, given to the conscious, normovolaemic dog, result in renal vasoconstriction. Renal blood flow does not decrease, however, implying that autoregulation remains intact. These changes are a result of fentanyl, per se, rather than secondary to changes in oxygenation and carbon dioxide levels in the blood and do not appear to have a dose response relationship in the dosage range studied.

The effects of high-dose fentanyl on cerebral circulation and metabolism in rats.

There is considerable controversy with respect to the effects of narcotics on the cerebral blood flow (CBF) and the cerebral metabolic rate for oxygen (CMRo2). The present study examined the effects of high doses of intravenous fentanyl (25-400 micrograms/kg) on the CBF and CMRo2 in rats. Cerebral cortical blood flow and metabolism were measured using the 133Xenon modification of the Kety-Schmidt technique. Fentanyl produced a dose-related decrease in both the CBF and the CMRo2. CBF and CMRo2 were maximally depressed by 50 and 35%, respectively, in rats given fentanyl 100 micrograms/kg compared with nitrous oxide-oxygen ventilated controls. The values for CBF and CMRo2 were 168 +/- 15 ml . 100 g-1 . min-1 and 10.3 +/- 0.7 ml . 100 g-1 . min-1, respectively in the nitrous oxide controls compared with 85 +/- 3 ml . 100 g-1 . min-1 and 7.1 +/- 0.1 ml . 100 g-1 . min-1 in animals receiving fentanyl 100 micrograms/kg. Higher doses of fentanyl did not further decrease either CBF or CMRo2 (108 +/- 12 ml . 100 g-1 . min-1 and 7.0 +/- 0.4 ml . 100 g-1 . min-1, respectively for fentanyl 400 micrograms/kg); however, seizures activity was noticed in about 25% of the rats receiving either 200 or 400 micrograms/kg fentanyl. The seizures seemed to be related to the narcotic in that they could be abolished by injections of naloxone. The seizure activity appeared to increase the CMRo2 relative to animals who received the same dose of fentanyl but did not have seizures. The CBF was not affected. The results confirm that narcotics in high enough doses may depress the CBF and CMRo2.

High dose Fentanyl anesthesia for aorto-coronary bypass surgery

The adverse effects of high dose Fentanyl were compared with those of Morphine, given to 48 patients undergoing aorto-coronary bypass surgery from January to August 1981. In ten patients among the Fentanyl group, their cardiovascular dynamics during the induction of Fentanyl anesthesia were evaluated using Swan-Ganz catheters at the dose of 25μg/kg, 50μg/kg, 70μg/kg.M.A.P., C.I., S.V.I., L.V.S.W.I. were decreased significantly at each dose, therefore the cardiovascular depressant effect by high dose Fentanyl was revealed. But the more stable cardiovascular conditions during anesthesia, were given by high dose Fentanyl anesthesia than Morphine anesthesia, although 33% of patients anesthetized by Fentanyl, became hypotensive during the induction, and 36% of those had hypertension and/or tachycardia on pulling epicardium.Despite of them, the high dose Fentanyl anesthesia is recommended for the aorto-coronary bypass surgery.