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Safety and effectiveness of fentanyl administration for prehospital pain management.

OBJECTIVE: To determine the safety and effectiveness of fentanyl administration for prehospital pain management. METHODS: This was a retrospective chart review of patients transported by ambulance during 2002-2003 who were administered fentanyl citrate in an out-of-hospital setting. Pre- and post-pain-management data were abstracted, including vital signs, verbal numeric pain scale scores, medications administered, and recovery interventions. In addition, the emergency department (ED) charts of a subgroup of these patients were reviewed for similar data elements. RESULTS: Of 2,129 patients who received fentanyl for prehospital analgesia, only 12 (0.6%) had a vital sign abnormality that could have been caused by the administration of fentanyl. Only one (0.2%) of the 611 patients who had both field and ED charts reviewed had a vital sign abnormality that necessitated a recovery intervention. There were no admissions to the hospital, nor patient deaths, attributed to fentanyl use. There was a statistically significant improvement in subjective pain scale scores (8.4 to 3.7). Clinically, this correlates with improvement from severe to mild pain. CONCLUSION: This study showed that fentanyl was effective in decreasing pain scores without causing significant hypotension, respiratory depression, hypoxemia, or sedation. Thus, fentanyl citrate can be used safely and effectively for pain management in the out-of-hospital arena.

Adolescent↗

Steady-state plasma fentanyl in the rabbit.

Linear pharmacokinetic models were obtained for fentanyl in anaesthetized rabbits. A composite model was used to predict the bolus dose and infusion rates necessary to achieve rapidly a steady-state concentration of fentanyl in plasma. When this was tested in a further six rabbits, steady-state concentrations were greater than predicted. The most likely reasons for this are imperfect mixing between plasma and the central compartment, and substantial uptake of fentanyl by the lung. These sources of error were allowed for in modifications to the model. On further testing, a 4-h infusion set to achieve a plasma fentanyl concentration of 10 ng ml-1 yielded actual concentrations ranging from a mean low of 8.7 ng ml-1 to a mean high of 18.0 ng ml-1. The second model described more precisely the disposition of fentanyl, although a tendency to overestimate dosing requirement remained. This tendency is probably a consequence of continuing lung uptake of fentanyl. The demonstrated ability to obtain rapidly and maintain for 4h "steady" blood fentanyl concentrations suggests that the methods merits further investigation with other drugs both in animals and man.

Anesthesia, General↗

Transfer of fentanyl across the rabbit placenta. Effect of umbilical flow and concurrent drug administration.

The transfer of fentanyl has been studied in the perfused in situ rabbit placenta. Does were infused with fentanyl and, subsequently, with fentanyl plus bupivacaine and pethidine. Antipyrine was infused throughout as an index of materno-fetal exchange. The fetal side of one placenta was perfused artificially with Krebs buffer containing dextran, and the effluent collected from the umbilical vein (uv). Drug concentrations were measured in maternal arterial blood (ma) and uv. Maternal plasma protein binding was also measured. Transfer of fentanyl was intermediate between that of pethidine and bupivacaine (Cuv:Cma for fentanyl was 0.25, for bupivacaine, 0.11 and for pethidine was 0.44), while placental clearance (Cuv X umbilical flow/Cma) increased with umbilical flow between 0.5 and 4.0 ml min-1 for all drugs. When clearances of unbound drugs were calculated, those of bupivacaine, pethidine and antipyrine were similar, but that of fentanyl was higher. The clearance of fentanyl was not affected by the presence of bupivacaine and pethidine.

Analgesics↗

Vecuronium induced bradycardia following induction of anaesthesia with etomidate or thiopentone, with or without fentanyl.

To define the role of vecuronium in the occurrence of bradyarrhythmia, haemodynamic changes after the induction of anaesthesia were studied in 96 patients undergoing coronary artery bypass grafting. Patients were assigned to one of six groups according to different combinations of induction agents (etomidate 0.3 mg kg-1 or thiopentone 3 mg kg-1, with fentanyl 0.003 mg kg-1; etomidate 0.4-0.5 mg kg-1 or thiopentone 4-6 mg kg-1, without fentanyl) and neuromuscular blocking drugs (vecuronium 0.112 mg kg-1, pancuronium 0.112 mg kg-1 or suxamethonium 1 mg kg-1). Anaesthesia was maintained with enflurane and nitrous oxide in oxygen. After initial diverse changes, heart rate decreased in all groups. Thirty minutes after intubation, the reduction of heart rate showed statistically significant differences between the different combinations of drugs: fentanyl-etomidate-vecuronium (group I) (the largest reduction) greater than etomidate-vecuronium (II) = fentanyl-thiopentone-vecuronium (IV) greater than thiopentone-vecuronium (V) = fentanyl-thiopentone-suxamethonium (VI) = fentanyl-etomidate-pancuronium (III). Five patients in group I, two in group IV and one each in groups II and V had a heart rate slower than 45 beat min-1, whereas a similar value was never seen in groups III and VI. These results indicate that vecuronium has a bradycardic effect. This effect is more pronounced in association with etomidate than in association with thiopentone, and is augmented by the addition of fentanyl.

Adult↗

Pharmacokinetics of fentanyl in the elderly.

The pharmacokinetics of fentanyl were determined in seven elderly (71-82 yr) and seven younger adults (18-41 yr) anaesthetized with thiopentone, nitrous oxide in oxygen and morphine. Fentanyl was administered as a 2-min i.v. infusion at doses of 15 micrograms kg-1 for elderly patients and 20 micrograms kg-1 for the younger patients. Plasma samples were obtained for 4 h and fentanyl concentrations determined by radioimmunoassay. Fentanyl concentration, per microgram kg-1 administered, was higher in elderly than in young patients at 2 min (7.73 +/- 3.14 v. 4.54 +/- 1.83 ng ml-1 (mean +/- SD), respectively) and at 4 min after the start of infusion (3.26 +/- 1.44 v. 1.78 +/- 0.72 ng ml-1, respectively). Concentrations were similar at all other sampling times. Pharmacokinetic variables were determined by non-compartmental techniques. Total plasma clearance was similar for the two age groups. Volume of distribution at steady-state (VDss) was smaller in elderly patients (1.36 +/- 0.44 v. 2.27 +/- 0.82 litre kg-1). Despite age-related changes in VDss, plasma fentanyl concentrations for the two groups were similar throughout the 4-h sampling period except immediately following administration. These results suggest that, if there are age-related differences in response to fentanyl, the likely pharmacokinetic explanation is the higher concentration of fentanyl in the elderly immediately following its administration.

Adult↗

Addition of clonidine or fentanyl to local anaesthetics prolongs the duration of surgical analgesia after single shot caudal block in children.

Caudal anaesthesia is indicated for surgical procedures lasting less than 90 min. Fentanyl and clonidine are known to prolong postoperative caudal analgesia, but there are no data on their effect on duration of surgical analgesia. We evaluated if the addition of clonidine or fentanyl to local anaesthetics prolonged the duration of surgical analgesia after single shot caudal block in children in a randomized, double-blind study. We studied 64 children, aged 6-108 months, undergoing bilateral correction of vesicoureteral reflux which was expected to last more than 90 min. Patients were allocated to one of four groups: group O received 1 ml kg-1 of a mixture of 0.25% bupivacaine with epinephrine and 1% lidocaine in equal parts; group F received the same mixture of local anaesthetics in addition to fentanyl 1 microgram kg-1; group C received the same mixture of local anaesthetics in addition to clonidine 1.5 micrograms kg-1; and group C + F received the same mixture of local anaesthetics in addition to fentanyl 0.5 microgram kg-1 and clonidine 0.75 microgram kg-1. Single shot caudal block was sufficient in only 57% of children in group O compared with 93% in groups C and F and 86% in group C + F (P = 0.035). Global assessment of anaesthesia, defined as the time from caudal injection to the first administration of analgesic (either during or after surgery), was significantly longer in the three groups of children who received additives compared with local anaesthetics alone (P = 0.035), but there were no differences between the three additive groups. Vomiting was observed only in children who received fentanyl. Addition of clonidine or fentanyl to local anaesthetics prolonged the duration of surgical analgesia of caudal block, allowing single shot caudal anaesthesia to be recommended for surgery lasting 90-150 minutes. Clonidine had some advantages over fentanyl as it did not produce clinically significant side effects.

Adrenergic alpha-Agonists↗

Comparison of alfentanil, fentanyl and sufentanil for total intravenous anaesthesia with propofol in patients undergoing coronary artery bypass surgery.

We have studied the pharmacokinetics and pharmacodynamics of alfentanil, fentanyl and sufentanil together with propofol in patients undergoing coronary artery bypass graft surgery (CABG). Sixty patients (age 40-73 yr, 56 male) were assigned randomly to receive alfentanil, fentanyl or sufentanil and propofol. Plasma concentrations of these drugs and times for the plasma concentration to decrease by 50% (t50) and 80% (t80) after cessation of the infusion were determined. Times were recorded to awakening and tracheal extubation. Total dose and plasma concentrations of propofol were similar in all groups. Mean total doses of alfentanil, fentanyl and sufentanil were 443, 45 and 4.4 micrograms kg-1, respectively. Time to awakening did not differ significantly. In patients receiving fentanyl, the trachea was extubated on average 2 h later than in those receiving sufentanil and 3 h later than in those receiving alfentanil (P < 0.05). The t80 of fentanyl was longer (P < 0.05) than that of alfentanil or sufentanil, and there was a linear correlation between the t80 of the opioid and the time to tracheal extubation (r = 0.51; P < 0.01). However, the t50 values for these opioids were similar and did not correlate with recovery time. In conclusion, patients undergoing CABG and who were anaesthetized with fentanyl and propofol needed mechanical ventilatory support for a significantly longer time than those receiving alfentanil or sufentanil and propofol. On the basis of the interindividual variation observed, the time to tracheal extubation was most predictable in patients receiving alfentanil and most variable in patients receiving fentanyl, a finding which may be important if the patients are transferred to a step-down unit on the evening of the operation.

Adult↗

Relation between fentanyl dose and predicted EC50 of propofol for laryngeal mask insertion.

BACKGROUND: This study sought to determine the effective concentration for 50% of the attempts to secure laryngeal mask insertion (predicted EC(50LMA)) of propofol using a target-controlled infusion (Diprifusor) and investigated whether fentanyl influenced these required concentrations, respiratory rate (RR) and bispectral index (BIS). METHODS: Sixty-four elective unpremedicated patients were randomly assigned to four groups (n = 16 for each group) and given saline (control) or fentanyl 0.5, 1 or 2 micro g kg(-1). Propofol target concentration was determined by a modification of Dixon's up-and-down method. Laryngeal mask airway insertion was attempted without neuromuscular blocking drugs after equilibration had been established for >10 min. Movement was defined as presence of bucking or gross purposeful muscular movement within 1 min after insertion. EC(50LMA) values were obtained by calculating the mean of 16 patients in each group. RESULTS: Predicted EC(50LMA) of the control, fentanyl 0.5, 1 and 2 micro g kg(-1) groups were 3.25 (0.20), 2.06 (0.55), 1.69 (0.38) and 1.50 (0.54) micro g ml(-1) respectively; those of all fentanyl groups were significantly lower than that of control. RR was decreased in relation to the fentanyl dose up to 1 micro g kg(-1). BIS values after fentanyl 1 and 2 micro g kg(-1) were significantly greater than in the control and 0.5 micro g kg(-1) groups. CONCLUSIONS: A fentanyl dose of 0.5 micro g kg(-1) is sufficient to decrease predicted EC(50LMA) with minimum respiratory depression and without a high BIS value.

Adjuvants, Anesthesia↗

Comparison of the respiratory effects of intravenous buprenorphine and fentanyl in humans and rats.

BACKGROUND: There is evidence from animal studies suggesting the existence of a ceiling effect for buprenorphine-induced respiratory depression. To study whether an apparent ceiling effect exists for respiratory depression induced by buprenorphine, we compared the respiratory effects of buprenorphine and fentanyl in humans and rats. METHODS: In healthy volunteers, the opioids were infused i.v. over 90 s and measurements of minute ventilation at a fixed end-tidal PCO2 of 7 kPa were obtained for 7 h. Buprenorphine doses were 0.7, 1.4, 4.3 and 8.6 microg kg(-1) (n=20 subjects) and fentanyl doses 1.1, 2.1, 2.9, 4.3 and 7.1 microg kg(-1) (n=21). Seven subjects received placebo. In rats, both opioids were infused i.v. over 20 min, and arterial PCO2 was measured 5, 10, 15 and 20 min after the start of fentanyl infusion and 30, 150, 270 and 390 min after the start of buprenorphine infusion. Doses tested were buprenorphine 0, 100, 300, 1000 and 3000 microg kg(-1) and fentanyl 0, 50, 68 and 90 microg kg(-1). RESULTS: In humans, fentanyl produced a dose-dependent depression of minute ventilation with apnoea at doses > or = 2.9 microg kg(-1); buprenorphine caused depression of minute ventilation which levelled off at doses > or = 3.0 microg kg(-1) to about 50% of baseline. In rats, the relationship of arterial PCO2 and fentanyl dose was linear, with maximum respiratory depression at 20 min (maximum PaCO2 8.0 kPa). Irrespective of the time at which measurements were obtained, buprenorphine showed a non-linear effect on PaCO2, with a ceiling effect at doses > 1.4 microg kg(-1). The effect on PaCO2 was modest (maximum value measured, 5.5 kPa). CONCLUSIONS: Our data confirm a ceiling effect of buprenorphine but not fentanyl with respect to respiratory depression.

Adult↗

Intra-cervical versus i.v. fentanyl for abortion.

BACKGROUND: The majority of abortions are performed using a para-cervical block (without general anaesthesia) and involve a significant amount of pain. If fentanyl was given with the lidocaine in the para-cervical block, it potentially could improve pain control while decreasing side effects and avoiding i.v. access for women having abortions. METHODS: This was a randomized double-blind placebo-controlled trial of two treatment arms: (i) para-cervical block with 100 microg of fentanyl i.v; or (ii) para-cervical block with 100 microg of fentanyl intra-cervically (i.c.) for first trimester abortion. The setting was a free-standing urban abortion clinic. The outcome measures were pain scores and side effects. RESULTS: A total of 104 women received the fentanyl i.v. and 98 received the fentanyl i.c. The two groups were similar with respect to age, gestational age, obstetric history, anxiety and depression. Pain scores (0-10) were 4.7 and 5.7 for dilation (P = 0.01) and 3.8 and 5.6 for suctioning (P < 0.001) in the i.v. and i.c. groups, respectively. Side effects were similar, but more women in the i.v. group received anti-emetics. More women in the i.c. group were dissatisfied with the pain control. CONCLUSION: I.v. fentanyl is more effective than i.c. fentanyl for pain control in abortion.

Abortion, Induced↗

Fentanyl-related deaths in Ontario, Canada: toxicological findings and circumstances of death in 112 cases (2002-2004).

In order to characterize fentanyl-related deaths in the province of Ontario, Canada, a retrospective study of all cases in which fentanyl was quantitated in blood was conducted for the time period between 2002 and 2004. A total of 112 fentanyl-related deaths were identified. Decedents ranged in age from 4 to 93 years and comprised 63 men and 49 women. A variety of routes of administration of the drug were identified: transdermal application of Duragesic patches, intravenous injection of patch contents or fentanyl citrate solution, oral/transmucosal administration, and volatilization and inhalation of Duragesic systems. Blood fentanyl concentrations were determined for all modes of drug administration and are provided. There were 54 cases in which death was attributed solely to fentanyl intoxication; the mean blood concentration was 25 microg/L (range: 3.0-383 microg/L). This concentration range overlapped with blood fentanyl concentrations measured among cases where the presence of the drug was considered incidental. For example, a mean blood concentration of 12 microg/L was observed among 12 cases of natural death (range: 2.7-33 microg/L). Detailed case reports of six individuals are also included and provide additional insight into the use of this drug for both therapeutic and illicit means.

Adolescent↗

The effects of ketorolac and fentanyl on postoperative vomiting and analgesic requirements in children undergoing strabismus surgery.

Fifty-four ASA I and II children 1 to 10 yr of age undergoing strabismus surgery were randomized to receive in a double-blind fashion intravenous ketorolac (0.9 mg/kg), fentanyl (1 microgram/kg), or saline placebo (2 mL) during a standardized general anesthetic. Patients received no analgesic or antiemetics intraoperatively except for the study drug. Patients receiving ketorolac or placebo compared to fentanyl had a significantly lower incidence of postoperative vomiting in the day surgery unit (DSU) (P = 0.03) and overall (DSU plus home) (P = 0.005). The severity (number of episodes) of post-operative vomiting was significantly lower in the DSU, at home (first 24 h after hospital discharge), and overall for patients receiving ketorolac or placebo compared to fentanyl (P < 0.01). Postoperative pain scores and frequency of acetaminophen administration did not differ among the study groups, suggesting that the intraoperative use of ketorolac or fentanyl during pediatric strabismus surgery is unnecessary. No patients required fentanyl postoperatively, indicating that rectal acetaminophen administered in the postanesthesia recovery room provides sufficient analgesia for pediatric strabismus surgery. In conclusion, neither ketorolac nor fentanyl was associated with less postoperative vomiting or analgesic requirements compared to saline placebo administered during pediatric strabismus surgery. Fentanyl should be avoided, as it was associated with a significantly greater incidence of postoperative vomiting compared to ketorolac or placebo.

Acetaminophen↗

Recovery after propofol with and without intraoperative fentanyl in patients undergoing ambulatory gynecologic laparoscopy.

This prospective, randomized double-blind study was conducted to examine the effect of intraoperative opioid (fentanyl) supplementation on postoperative analgesia, emesis, and recovery in ambulatory patients receiving propofol-nitrous oxide anesthesia. Eighty patients undergoing ambulatory gynecologic laparoscopy participated. Confounding variables that could influence the incidence of postoperative emesis were controlled. Patients received either fentanyl 100 micrograms (Group I) or ketorolac 60 mg (Group II) intravenously (IV) at the time of anesthetic induction. No further analgesic supplements were given intraoperatively. Anesthesia was induced with propofol and maintained with propofol-nitrous oxide. Atracurium was used for muscle relaxation and reversed with neostigmine and glycopyrrolate. Postoperative pain during early recovery was treated with IV fentanyl 25-50 micrograms (Group I) or IV ketorolac 15-30 mg (Group II). Subsequent breakthrough pain in both groups was treated with IV fentanyl 25 micrograms increments as needed (rescue analgesia). Eighty-four percent of patients in Group I required analgesics during early recovery versus 56% of patients in Group II (P < 0.05). Maintenance dose of propofol was significantly lower in Group I (129 +/- 35 micrograms.kg-1.min-1 than in Group II (170 +/- 63 micrograms.kg-1.min-1. Immediate recovery (emergence) in the two groups was comparable, despite different propofol requirements. Although the incidence of emetic sequelae in the postanesthesia care unit was not significantly different between the two treatment groups, a significantly larger number of patients in Group I (fentanyl group) had emetic sequelae that required therapeutic intervention (Group I 29% versus Group II 10%). Patients in Group I also took a significantly longer time to ambulate and meet criteria for home discharge. These results indicate that, in patients undergoing ambulatory gynecologic laparoscopy, the practice of administering a small dose of fentanyl at the time of anesthetic induction reduces maintenance propofol requirement, but fails to provide effective postoperative analgesia. Fentanyl administration at anesthetic induction increased the need for rescue antiemetics. The relative severity of emetic sequelae could have contributed to delay in ambulation and discharge.

Adult↗

Contribution of the spinal cord to arousal from inhaled anesthesia: comparison of epidural and intravenous fentanyl on awakening concentration of isoflurane.

UNLABELLED: To investigate the contribution of modulation of afferent nociceptive inputs by an opioid in the spinal cord to arousal from inhaled anesthesia, we determined the awakening concentration of isoflurane in 50 unpremedicated patients scheduled for abdominal hysterectomy. Patients were assigned randomly to three groups. Group I received bolus injections of both epidural and intravenous (I.V.) saline, followed by both epidural and I.V. infusions at the rate of 0.2 mL x kg(-1) h(-1). Group II received an I.V. injection of fentanyl 2 microg/kg, followed by an infusion at the rate of 25 ng x kg(-1) x min(-1), and Group III received an epidural injection and infusion in the same administration regimen as Group II. Anesthesia was induced with and maintained by isoflurane in an air/oxygen mixture (fraction of inspired oxygen = 0.5) with no adjuvant drugs. The study drug was administered at the start of retroperitoneal suturing. The awakening concentrations of isoflurane in Groups I, II, and III (mean +/- SD) were 0.32% +/- 0.07%, 0.31% +/- 0.06%, and 0.24% +/- 0.06%, respectively. At that time, plasma fentanyl concentrations in Groups II and III were 1.12 +/- 0.09 ng/mL and 0.65 +/- 0.04 ng/mL, respectively. Epidural fentanyl infusion reduced the awakening concentration of isoflurane more (P < 0.01) than I.V. fentanyl infusion, despite the lower plasma concentration (P < 0.01) in the epidural group. These findings suggest that epidural fentanyl delays arousal from inhaled anesthesia by modulating the afferent nociceptive inputs in the spinal cord. The spinal cord may contribute to arousal from inhaled anesthesia through the regulation of afferent inputs by opioids along with the supraspinal region of the central nervous system (CNS), even if the effects of subarachnoid fentanyl on the higher CNS via the cephalad migration is taken into consideration. IMPLICATIONS: The present study revealed that the spinal cord, the lower level of central nervous system, contributed to arousal from general anesthesia, along with the higher central nervous system, by comparing the concentrations of an inhaled anesthetic, isoflurane, in the expiration of patients receiving systemic or regional administration of an opioid, fentanyl.

Adult↗

Small-dose fentanyl: optimal time of injection for blunting the circulatory responses to tracheal intubation.

UNLABELLED: This study was designed to examine the optimal time of injection of a small dose of fentanyl during anesthetic induction to attenuate circulatory responses to laryngoscopy and tracheal intubation. One hundred seventy patients were randomly assigned to one of five groups. In Groups II, III, IV, and V, patients received fentanyl (2 microg/kg) 1, 3, 5, or 10 min before tracheal intubation, respectively. Group I patients did not receive fentanyl and served as the control group. In Groups III and IV, blood pressures were not increased, except diastolic pressure in Group III, significantly postintubation compared with preinduction values; but Groups I, II, and V showed a significant increase (P < 0.05). The 1-min postintubation values of systolic, diastolic, and mean arterial pressure in Groups III and IV were less than those in the control group (P < 0.05). Increases of heart rate in Group IV were less (P < 0.05) than those in the control group, but significant differences were not observed in Groups II, III, and V. The number of patients with tachycardia and dysrhythmia was significantly smaller in Group IV than in the control group (P < 0.05). We conclude that the most effective time to administer fentanyl to protect circulatory responses to laryngoscopy and tracheal intubation is 5 min before tracheal intubation. IMPLICATIONS: Fentanyl is often used to reduce the hemodynamic response to tracheal intubation. However, large doses may cause unwanted side effects. Administration of fentanyl at the optimal time reduces the dose required. Our results indicate that optimal injection time of fentanyl for intubation is 5 min before intubation.

Adult↗

Anesthesia for in vitro fertilization: the addition of fentanyl to 1.5% lidocaine.

UNLABELLED: Ultrasonically guided transvaginal oocyte retrieval is relatively short procedure that is performed on an out-patient basis. The optimal anesthetic technique should allow good surgical anesthesia with minimal side effects, a short recovery time, and, if possible, a high rate of successful pregnancy. Spinal anesthesia is often used in this institution, as well as many others, for this procedure. The addition of fentanyl may be effective for both intraoperative and postoperative pain relief. We assessed the effect of adding fentanyl to 1.5% lidocaine in women undergoing ultrasonically guided oocyte retrieval. Seventy-eight women were randomized to receive 45 mg of hyperbaric 1.5% lidocaine with or without 10 microg of fentanyl. Visual analog scale (VAS) pain scores were lower in the operating room (OR) (P < 0.05) and postanesthesia care unit (PACU) (P < 0.0005) for the group that received fentanyl. In addition, the amount of narcotic required in the PACU was less in the fentanyl group (P < 0.005). There was no difference in VAS scores the evening of or 24 h after the procedure. The amount of analgesics and narcotics required after discharge was the same for both groups. Timed variables, such as time to urination, ambulation, and discharge, were the same for both groups of women. The addition of fentanyl to lidocaine for transvaginal oocyte retrieval results in a more comfortable patient in the OR and PACU. IMPLICATIONS: This study demonstrates that when fentanyl is added to a local anesthetic, lidocaine, with spinal anesthesia for egg retrieval procedures, patients are more comfortable during the procedure compared with those who receive lidocaine alone. In addition, the narcotic requirements of patients are less in the postanesthesia care unit.

Adult↗

Intraoperative localization of an epileptogenic focus with alfentanil and fentanyl.

UNLABELLED: We evaluated the effectiveness of alfentanil and fentanyl in stimulating epileptogenic activity during surgery for intractable temporal lobe epilepsy under general anesthesia. Ten patients received a standardized anesthetic induction with i.v. fentanyl 5 microg/kg, propofol 3-5 mg/kg, and atracurium 0.5 mg/kg. Maintenance was with isoflurane, 70% N2O/30% O2, and an atracurium infusion. After dural opening, droperidol 0.02 mg/kg was administered i.v.. Both inhaled anesthetics were discontinued and verified to be at 0 end-tidal concentration before the study. Baseline electrocorticography over the surface of the temporal lobe and depth electrode recordings in the amygdala and hippocampus were obtained, followed by 10 min of recording before and after the i.v. administration of both alfentanil 50 microg/kg and fentanyl 10 microg/kg. Any changes in cardiovascular variables were documented. The number of interictal epileptiform spikes at the most active site for each patient was tabulated before and after the administration of each drug. Both alfentanil and fentanyl induced an increase in spike activity in all patients. Alfentanil was more potent, increasing the median number of spikes per epoch from 18 to 58, compared with fentanyl (20 to 42 spikes) (P < 0.05). Alfentanil had a shorter duration of action (4.9+/-1.3 min) compared with fentanyl (8.5+/-2 min) (P < 0.009). In nine patients, the most active site was the hippocampus or amygdala. There was a decrease in mean blood pressure, but only after the administration of alfentanil (P < 0.05). Two patients had electrographic evidence of seizure activity. These opioids can be used to assist in the localization of the epileptogenic focus during surgery. IMPLICATIONS: Both alfentanil and fentanyl activate epileptiform activity in patients with temporal lobe epilepsy. These opioids can be used to assist in the localization of the epileptogenic focus during surgery.

Adult↗

Analgesia, pruritus, and ventilation exhibit a dose-response relationship in parturients receiving intrathecal fentanyl during labor.

UNLABELLED: Several studies have characterized the 50% and 95% effective doses (ED50 and ED95, respectively) of intrathecal sufentanil for labor analgesia. Few have investigated these same criteria for the less expensive alternative, fentanyl. In addition, the ventilatory effects of intrathecal fentanyl at clinically relevant doses are unclear. We performed this study to establish the dose-response relationship of intrathecal fentanyl for both analgesia and ventilatory depression. Ninety parturients in active early labor (< or = 5 cm dilation) received intrathecal fentanyl 5, 7.5, 10, 15, 20, or 25 micrograms in a double-blinded, randomized fashion (n = 15 patients in each group). Parturients were monitored for degree of pain (measured using a 100-mm visual analog pain scale), blood pressure, arterial oxygen saturation (SaO2), respiratory rate, ETCO2, and fetal heart rate 0, 1, 5, 10, 15, 20, 25, and 30 min after the administration of intrathecal fentanyl. An absolute visual analog pain scale score < or = 25 mm was defined a priori as analgesic success. The percentage of parturients who achieved analgesic success was used to construct quantal dose-response curves, from which the ED50 and ED95 values were derived for the total population (mixed parity) and the nulliparous and multiparous subpopulations separately. Overall ED50 and ED95 values (95% CI) were 5.5 (3.4-7.2) and 17.4 (13.8-27.1) micrograms, respectively. Nulliparous values were lower (5.3 and 15.9 micrograms, respectively) than multiparous values (6.9 and 26.0 micrograms, respectively) but were within the 95% CIs of the total population. Pruritus incidence in parturients with analgesic success displayed a dose-response relationship identical to that seen for analgesia. ETCO2 displayed a dose-related increase, particularly at doses > or = 15 micrograms, without concomitant changes in respiratory rate or SaO2, which suggests a decrease in tidal volume. Even in the absence of overt signs or symptoms of somnolence, intrathecal fentanyl at doses within the effective analgesic range induced a change in ventilation that may last longer than the 30-min period we studied. IMPLICATIONS: Intrathecal fentanyl induces rapid and satisfying dose-dependent analgesia in early labor; however, it also produces dose-related decreases in ventilation in the absence of overt somnolence.

Adult↗