Reversal of high-dose fentanyl anesthesia by naloxone: analysis of factors attenuating respiratory and hemodynamic responses to naloxone

The respiratory and hemodynamic responses to postoperative reversal by naloxone of high-dose fentanyl anesthesia were studied in 101 patients after open heart surgery. Respiratory and hemodynamic changes after drip infusion of naloxone were minimum. Change of systolic blood pressure (BPs), mean blood pressure (BPm), CVP and PO2 were statistically significant. BPs increased for 3.8 +/- 14.0 mmHg, BPm increased for 1.6 +/- 8.2 mmHg. CVP decreased for 0.4 +/- 2.1 mmHg, and PO2 decreased for 8.6 +/- 3.4 mmHg. Severe side effect was not observed. Multi-factorial analysis revealed that the abrupt recovery of consciousness from anesthesia and acidosis were the most important factors that attenuate hemodynamic response to naloxone.     

Plasma concentration of fentanyl with xenon to block somatic and hemodynamic responses to surgical incision

BACKGROUND: Although anesthesia with xenon has been supplemented with fentanyl, its requirement has not been established. This study was conducted to determine the plasma concentrations of fentanyl necessary to suppress somatic and hemodynamic responses to surgical incision in 50% patients in the presence of 0.7 minimum alveolar concentration (MAC) xenon. METHODS: Twenty-five patients were allocated randomly to predetermined fentanyl concentration between 0.5 and 4.0 ng/ml during 0.7 MAC xenon anesthesia. Fentanyl was administered using a pharmacokinetic model-driven computer-assisted continuous infusion device. At surgical incision each patient was monitored for somatic and hemodynamic responses. A somatic response was defined as any purposeful bodily movement. A positive hemodynamic response was defined as a more than 15% increase in heart rate or mean arterial pressure more than the preincision value. The concentrations of fentanyl to prevent somatic and hemodynamic responses in 50% of patients were calculated using logistic regression. RESULTS: The concentration of fentanyl to prevent a somatic response to skin incision in 50% of patients in the presence of 0.7 MAC xenon was 0.72 +/- 0.07 ng/ml and to prevent a hemodynamic response was 0.94 +/- 0.06 ng/ml. CONCLUSIONS: Comparing these results with previously published results in the presence of 70% nitrous oxide, the fentanyl requirement in xenon anesthesia is smaller than that in the equianesthetic nitrous oxide anesthesia.     

Plasma Concentration of Fentanyl with Xenon to Block Somatic and Hemodynamic Responses to Surgical Incision

Background: Although anesthesia with xenon has been supplemented with fentanyl, its requirement has not been established. This study was conducted to determine the plasma concentrations of fentanyl necessary to suppress somatic and hemodynamic responses to surgical incision in 50% patients in the presence of 0.7 minimum alveolar concentration (MAC) xenon.

Methods: Twenty-five patients were allocated randomly to predetermined fentanyl concentration between 0.5 and 4.0 ng/ml during 0.7 MAC xenon anesthesia. Fentanyl was administered using a pharmacokinetic model-driven computer-assisted continuous infusion device. At surgical incision each patient was monitored for somatic and hemodynamic responses. A somatic response was defined as any purposeful bodily movement. A positive hemodynamic response was defined as a more than 15% increase in heart rate or mean arterial pressure more than the preincision value. The concentrations of fentanyl to prevent somatic and hemodynamic responses in 50% of patients were calculated using logistic regression.

Results: The concentration of fentanyl to prevent a somatic response to skin incision in 50% of patients in the presence of 0.7 MAC xenon was 0.72 +/- 0.07 ng/ml and to prevent a hemodynamic response was 0.94 +/- 0.06 ng/ml.     

Comparison of sufentanil and fentanyl to supplement N2O-halothane anesthesia for total hip arthroplasty in elderly patients.

Sufentanil was compared with fentanyl as a supplement to nitrous oxide-halothane anesthesia in a double-blind study of 30 elderly patients undergoing total hip arthroplasty. Comparisons were made with respect to (a) hemodynamic (heart rate and blood pressure) and adrenergic (plasma norepinephrine and epinephrine levels) responses during surgery and recovery; (b) time to extubation after the end of surgery; and (c) postoperative analgesia. No difference was observed between the two groups with respect to demographic data, blood gas tensions, or hemodynamic and adrenergic responses to surgery and recovery. Total doses of opioids used were 0.7 +/- 0.3 micrograms/kg of sufentanil and 6 +/- 2.6 micrograms/kg of fentanyl. Times between end of surgery and extubation were not different (60 +/- 54 min in the fentanyl group and 58 +/- 52 min in the sufentanil group). The number of patients needing postoperative analgesia did not differ between the two groups, but use of analgesia was significantly delayed in the sufentanil group (168 +/- 25 vs 127 +/- 29, P less than 0.05). This study suggests that in elderly patients sufentanil confers a greater residual analgesia than fentanyl in the immediate postoperative period.     

Epidural anesthesia with high dose fentanyl for abdominal surgery

An epidural catheter was inserted at T9-L2 interspace and 10 micrograms.kg-1 fentanyl with (E+) or without (E-) epinephrine 1:100,000 was given for 82 elective abdominal surgeries. N2O 66%, enflurane and muscle relaxant were used as needed. The onset and the duration of the action were estimated to be approximately 15 minutes and 4 hours, respectively. Anesthesia was maintained with enflurane below 0.4% (0.22 +/- 0.09%) in 70 patients (85.4%). E+ group needed significantly lower concentration of enflurane than E- group. There was no severe hemodynamic change during the operation. Systolic pressure, diastolic pressure and heart rate during the operation were 115.2 +/- 16.0 mmHg, 69.4 +/- 10.8 mmHg and 74.2 +/- 11.4 min-1, respectively, each of which was about 18% less than the values on arrival in the operating room. Sixty-one patients (82.5%) woke rapidly. Almost all patients felt well and had no pain during the recovery period. Naloxone 0.05-4 mg was administered intravenously in 21 patients (31.7%) whose respiratory rate was below 10 min-1. The patients with shorter operation time (shorter than 2.5 hours) needed more naloxone. Troubles of respiratory depression did not occur in the recovery room and in the ward in both naloxone and non-naloxone groups. This anesthesia method which induces mild depression of blood pressure and heart rate may be indicated for patients with ischemic heart disease or with poor cardiac function, but has no advantages in patients with poor respiratory function who need early extubation after a short operation.     

Use of intranasal fentanyl in children undergoing myringotomy and tube placement during halothane and sevoflurane anesthesia

BACKGROUND: Many children are restless, disoriented, and inconsolable immediately after bilateral myringotomy and tympanosotomy tube placement (BMT). Rapid emergence from sevoflurane anesthesia and postoperative pain may increase emergence agitation. The authors first determined serum fentanyl concentrations in a two-phase study of intranasal fentanyl. The second phase was a prospective, placebo-controlled, double-blind study to determine the efficacy of intranasal fentanyl in reducing emergence agitation after sevoflurane or halothane anesthesia. METHODS: In phase 1, 26 children with American Society of Anesthesiologists (ASA) physical status I or II who were scheduled for BMT received intranasal fentanyl, 2 microg/kg, during a standardized anesthetic. Serum fentanyl concentrations in blood samples drawn at emergence and at postanesthesia care unit (PACU) discharge were determined by radioimmunoassay. In phase 2, 265 children with ASA physical status I or II were randomized to receive sevoflurane or halothane anesthesia along with either intranasal fentanyl (2 microg/kg) or saline. Postoperative agitation, Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores, and satisfaction of PACU nurses and parents with the anesthetic technique were evaluated. RESULTS: In phase 1, the mean fentanyl concentrations at 10 +/- 4 min (mean +/- SD) and 34 +/- 9 min after administering intranasal fentanyl were 0.80 +/- 0.28 and 0.64 +/- 0.25 ng/ml, respectively. In phase 2, the incidence of severe agitation, highest CHEOPS scores, and heart rate in the PACU were decreased with intranasal fentanyl. There were no differences between sevoflurane and halothane in these measures and in times to hospital discharge. The incidence of postoperative vomiting, hypoxemia, and slow respiratory rates were not increased with fentanyl. CONCLUSIONS: Serum fentanyl concentrations after intranasal administration exceed the minimum effective steady state concentration for analgesia in adults. The use of intranasal fentanyl during halothane or sevoflurane anesthesia for BMT is associated with diminished postoperative agitation without an increase in vomiting, hypoxemia, or discharge times.     

Effective therapeutic infusions produced by closed-loop feedback control of methohexital administration during total intravenous anesthesia with fentanyl

A combined pharmacokinetic and pharmacodynamic model of methohexital was used to establish and evaluate feedback control of methohexital delivery during total intravenous anesthesia with fentanyl in 11 surgical patients. The median frequency of the EEG power spectrum served as the pharmacodynamic variable constituting feedback. Based on previous investigations a median frequency from 2-3 Hz was chosen as the desired EEG set point. In addition to methohexital, patients were given a 10-min loading infusion of 0.5 mg of fentanyl followed by a constant-rate infusion of 0.22 mg/h. In agreement with an earlier similar study in volunteers given only methohexital and aiming at the same set point, identical distribution of EEG power was achieved in the current study. The decrease of median EEG frequency to 2-3 Hz was primarily induced by an increase in fractional power in the 0.5-2- Hz frequency band to 46 +/- 4%. The average requirement of methohexital during the first 2 h was 675 +/- 250 mg. The authors conclude that model-based feedback control of intravenous methohexital delivery can help establish and quantitate methohexital requirements during total intravenous anesthesia with fentanyl.     

EEGs during high-dose fentanyl-, sufentanil-, or morphine-oxygen anesthesia

In 49 patients undergoing open-heart surgery we compared the electroencephalographic (EEG) effects of high-dose morphine, fentanyl, or sufentanil with O2, using two computerized analysis and display techniques: a period analysis (the Klein method) and an aperiodic analysis (the Neurometrics monitor). During fentanyl or sufentanil anesthesia, both techniques revealed a general decrease in frequency, shown by the aperiodic analysis primarily as a marked increase in the very low frequency range: an increase in the 1-Hz bin (TP1, in muv2) from 2.80 X 10(4) +/- 3.20 X 10(4) (SD) to 45.1 X 10(4) +/- 27.2 X 10(4) for fentanyl and from 3.11 X 10(4) +/- 2.83 X 10(4) to 52.8 X 10(4) for sufentanil. The cumulative percent power at 3 Hz (CP3) increased from 27.2 +/- 6.8 to 83.0 +/- 11.0 for fentanyl and from 22.7 +/- 5.2 to 85.1 +/- 10.4 for sufentanil, while the frequency at 90% cumulative percent power (F90, in Hz) decreased from 17.8 +/- 2.9 to 7.9 +/- 2.8 for fentanyl and 16.4 +/- 5.2 to 5.6 +/- 4.3 for sufentanil. The changes with morphine were less obvious, with some attenuation of high-frequency power shown by the Klein method, and an increase from 24.1 +/- 8.6 to 59.3 +/- 20.7 with CP3, but no change in TP1. Low-frequency power with the period analysis and TP1 with the aperiodic analysis decreased between laryngoscopy and the incisions with fentanyl and sufentanil.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of desflurane and isoflurane in patients undergoing coronary artery surgery

Animal studies indicate that desflurane and isoflurane have similar hemodynamic effects when administered in equipotent anesthetic concentrations. The authors compared desflurane and isoflurane, used as primary anesthetics for patients undergoing elective coronary artery bypass surgery whose left ventricular ejection fractions were greater than 0.34. After induction of anesthesia with thiopental (dose 180 +/- 45 mg [mean +/- standard deviation]) and fentanyl, 10 micrograms.kg-1, either desflurane or isoflurane was administered to maintain systolic blood pressure within 70-120% of, and heart rates less than 120% of, the patients' average preoperative values. If adjusting the end-tidal anesthetic concentration within the range of 0-2.0 MAC could not maintain these predefined hemodynamic limits, additional fentanyl or vasoactive drugs were used. Induction and maintenance of anesthesia was accompanied by a significant decrease in mean arterial pressure in both groups (desflurane 97 +/- 12 mmHg at control, decreasing to 71 +/- 5 mmHg during skin preparation; isoflurane 95 +/- 9 mmHg at control, 74 +/- 9 mmHg during skin preparation). One minute after sternotomy, mean arterial pressure in the isoflurane group had returned to control, 97 +/- 9 mmHg, which was significantly greater than in the desflurane group, 87 +/- 12 mmHg. Systolic arterial pressure was also significantly greater in the isoflurane group 1 min after intubation, during skin preparation, and 1 min after sternotomy. Otherwise, the hemodynamic effects of these volatile agents were similar. There were no differences between groups in the incidence of ECG changes indicative of myocardial ischemia prior to cardiopulmonary bypass, perioperative myocardial infarction, or perioperative mortality.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of sufentanil on cerebral blood flow, cerebral metabolism and the CO2 reactivity of the cerebral vessels in man]

Sufentanil, a synthetic opioid that is 5-10 times as potent as fentanyl, has been suggested for use during neurosurgical procedures because it maintains cardiovascular stability and produces hypnosis without the use of additional anesthetic agents. Doses as low as 2.5 micrograms.kg-1 are reported to create deep levels of anesthesia as demonstrated by EEG changes to high-amplitude delta-waves. However, there are no reports concerning the effects of sufentanil on blood flow and metabolism in the human brain. The present study was designed to investigate the influence of high-dose sufentanil-O2 anesthesia on the cerebral circulation, metabolism, and the cerebrovascular response to CO2 in man. METHODS. Nine male and 2 female patients between 41 and 60 years of age who were scheduled for coronary artery bypass surgery were studied. Premedication consisted of flunitrazepam 2 mg orally and piritramide 15 mg and promethazine 50 mg i.m. 1 h before arrival in the induction room. Measurements were performed with the patients awake (I), after sufentanil 10 micrograms.kg-1 as an induction dose followed by 0.15 micrograms.kg-1.min-1 as an infusion with normocapnia (pa CO2 42.1 +/- 2 mmHg) (II), during hypercapnia (pa CO2 53.7 +/- 3.5 mmHg) (III), and during hypocapnia (pa CO2 31.7 +/- 2 mmHg) (IV). Cerebral blood flow (CBF) was measured using the argon wash-in technique. Cerebral venous blood was obtained from a catheter in the superior bulb of the right internal jugular vein. Cerebral metabolic rates of oxygen (CMRO2) glucose (Mgluc) lactate (CMlac) were calculated by multiplying the arterial-cerebral venous oxygen and substrate differences by CBF. The Anaerobic Index was calculated from the equation avD lactate x 100/2 x avD glucose = ANI (%) Cerebral electrical activity was recorded by aperiodic analysis of the EEG (Lifescan). RESULTS AND DISCUSSION. In the EEG sufentanil anesthesia was characterized by a decrease in the number of high-frequency waves and an increase in the number and amplitude of delta-waves, a pattern that did not change throughout the study period. Concomitantly, under normocapnic conditions high-dose sufentanil led to the significant decrease in CBF by 29% accompanied by an 18% increase in cerebral vascular resistance (CVR). CMRO2 decreased by 22% while CMRgluc and CMRlac changed only insignificantly such that the ANI, which represents the percentage of anaerobically metabolized glucose, essentially remained unchanged. Mean perfusion pressure declined by 18% but stayed within the range of autoregulation. Hypoventilation (III) was followed by an 82% increase in CBF as a result of a 55% reduction in CVR, whereas cerebral metabolic parameters did not show important changes when compared to measurement II. Hyperventilation (IV), on the other hand, produced a distinct fall in CBF by 56% to a value that was 21% below the one obtained under normocapnia. This was due to an increase in CVR of the same magnitude. There was a 31% rise in CMRO2, resulting in a decrease in cerebral venous oxygen tension, but in no case did it fall below the critical value of 20 mmHg at which tissue hypoxia becomes severe. Although CMRlac increased and CMRgluc did not significantly change, the ANI remained essentially unchanged, which suggests a predominantly aerobic metabolism. The increase in metabolic activity with sufentanil during hypocapnia might be caused by an alkalosis-induced stimulation of glycolysis. It might also be related to a reduction in the depth of anesthesia, although neither the EEG nor the hemodynamic parameters indicated this. This study shows that the coupling between CBF and metabolism is well maintained and that the cerebrovascular response to CO2 is unimpaired during high-dose sufentanil anesthesia.     

Continuous Spinal Anesthesia/Analgesia for Perioperative Management of Morbidly Obese Patients Undergoing Laparotomy for Gastroplastic Surgery

Background: The authors determined prospectively the safety of continuous spinal anesthesia combined with general anesthesia and the efficacy of postoperative pain relief with continuous spinal analgesia for morbidly obese patients undergoing vertical banded gastroplasty. Methods: 27 patients (13 men, 14 women) with a mean body mass index (BMI) of 50.4 ± 7.8 and several co-morbidities were studied. All patients were anesthetized with the same anesthetic regimen, which included midazolam, fentanyl, propofol, muscle relaxants, N₂O, isoflurane and intrathecal bupivacaine. Postoperative pain relief was provided for 5 days and all patients received the same regimen, which included intrathecal bupivacaine, fentanyl and intravenous tenoxicam. The intrathecal analgesic regimen was administered continuously through a pump which had the facility of providing bolus doses when requested in predetermined lockout intervals. Intra-operative monitoring included hemodynamic and respiratory parameters. Additional postoperative monitoring included respiratory rate, degree of sedation, sensory level of anesthesia, motor response and intensity of pain. Results: Intraoperative anesthetic technique was safe and provided satisfactory results in the immediate postoperative period. Furthermore, the postoperative analgesia regimen provided effective analgesia in all patients.The mean doses of fentanyl and bupivacaine infused intrathecally for the first 24 postoperative hours were 14.1 ± 2.0 μg.h^-1 and 0.7 ± 0.1 mg.h^-1 respectively, while the requirements of anal gesia decreased progressively with time. The technique provided effective analgesia with low pain scores, which was reflected by ease in mobilizing and performing physical exercises with the physiotherapist. Only minor complications related to anesthesia and analgesia were encountered. Conclusion: To our knowledge, this technique of anesthesia and postoperative analgesia has not been described before in morbidly obese patients. This regimen merits further controlled trials to establish its place in the perioperative management of morbidly obese patients.     

Comparison of Remifentanil and Fentanyl in Patients Undergoing Craniotomy for Supratentorial Space-occupying Lesions

Background: Remifentanil hydrochloride is an ultra-short-acting, esterase-metabolized micro-opioid receptor agonist. This study compared the use of remifentanil or fentanyl during elective supratentorial craniotomy for space-occupying lesions.

Methods: Sixty-three adults gave written informed consent for this prospective, randomized, double-blind, multiple-center trial. Anesthesia was induced with thiopental, pancuronium, nitrous oxide/oxygen, and fentanyl (n = 32; 2 micro gram [center dot] kg [center dot] sup -1 min sup -1) or remifentanil (n = 31; 1 micro [center dot] kg sup -1 [center dot] min sup -1). After tracheal intubation, infusion rates were reduced to 0.03 micro gram [center dot] kg sup -1 [center dot] min sup -1 (fentanyl) or 0.2 micro gram [center dot] kg sup -1 [center dot] min sup -1 (remifentanil) and then adjusted to maintain anesthesia and stable hemodynamics. Isoflurane was given only after specified infusion rate increases had occurred. At the time of the first burr hole, intracranial pressure was measured in a subset of patients. At bone flap replacement either saline (fentanyl group) or remifentanil ([nearly equal] 0.2 micro gram [center dot] kg sup -1 [center dot] min sup -1) were infused until dressing completion. Hemodynamics and time to recovery were monitored for 60 min. Analgesic requirements and nausea and vomiting were observed for 24 h. Neurological examinations were performed before operation and on postoperative days 1 and 7.

Results: Induction hemodynamics were similar. Systolic blood pressure was greater in the patients receiving fentanyl after tracheal intubation (fentanyl = 127 +/- 18 mmHg; remifentanil = 113 +/- 18 mmHg; P = 0.004). Intracranial pressure (fentanyl = 14 +/- 13 mmHg; remifentanil = 13 +/- 10 mmHg) and cerebral perfusion pressure (fentanyl = 76 +/- 19 mmHg; remifentanil = 78 +/- 14 mmHg) were similar. Isoflurane use was greater in the patients who received fentanyl. Median time to tracheal extubation was similar (fentanyl = 4 min: range = -1 to 40 min; remifentanil = 5 min: range = 1 to 15 min). Seven patients receiving fentanyl and none receiving remifentanil required naloxone. Postoperative systolic blood pressure was greater (fentanyl = 134 +/- 16 mmHg; remifentanil = 147 +/- 15 mmHg; P = 0.001) and analgesics were required earlier in patients receiving remifentanil. Incidences of nausea and vomiting were similar.     

A comparison of fentanyl and buprenorphine in total intravenous anesthesia using propofol during spinal surgery

A retrospective study was performed to compare the hemodynamic effect and postoperative pain relief of fentanyl (Group F, n = 11) and buprenorphine (Group B, n = 11) in total intravenous anesthesia (TIVA) using propofol during spinal surgery. All patients were premedicated with midazolam (3-5 mg) i.m. Anesthesia was maintained with propofol infusion, and increments of fentanyl or single dose of buprenorphine with 40% oxygen in air. Total doses of fentanyl and buprenorphine were 7.6 +/- 1.0 micrograms.kg-1 and 2.0 +/- 0.4 micrograms.kg-1, respectively. Maintenance doses of propofol (Group F: 5.5 +/- 0.8 mg.kg-1.h-1, Group B: 5.9 +/- 1.1 mg.kg-1.h-1) and vecuronium were not significantly different. Mean arterial pressures from 2 hours after incision to the end of surgery were elevated significantly in Group F than in Group B. Recovery time (Group F 12.5 +/- 6.1 min vs Group B 11.8 +/- 6.1 min) and extubation time (Group F 19.5 +/- 10.3 min vs Group B 15.0 +/- 7.0 min) were not different. At the end of anesthesia, seven patients in Group F and one patient in Group B (P < 0.01) complained of severe pain. All patients in Group F, and only two in Group B (P < 0.02) received analgesics within 20 hours. Neither nausea nor respiratory depression was found in both groups. This study suggests that buprenorphine would provide a more stable hemodynamic state and better postoperative pain relief than fentanyl in TIVA using propofol.     

Effect-site concentration of propofol for recovery of consciousness is virtually independent of fentanyl effect-site concentration

Fentanyl reduces the amount of propofol necessary to prevent responses to surgical stimuli. However, opioids have relatively little effect on consciousness. We, therefore, tested the hypothesis that fentanyl minimally alters the effect-site concentration of propofol associated with awakening. Fifty women having gynecologic laparotomy with propofol anesthesia were randomly allocated into the following target effect-site fentanyl concentrations: 0.8, 1.0, 1.4, 2.0, and 3.0 ng/mL. Fentanyl was continued at the designated rate through the initial postoperative phase. The propofol effect-site concentration associated with eye opening in response to verbal command was regarded as the awakening concentration. The estimated propofol effect-site concentrations at awakening did not differ significantly among the groups and were 1.9 +/- 0.5 micro g/mL with a fentanyl effect-site concentration of 0.8 ng/mL; 1.6 +/- 0.4 micro g/mL with 1.0 ng/mL of fentanyl; 1.6 +/- 0.2 micro g/mL with 1.4 ng/mL of fentanyl; 1.7 +/- 0.4 micro g/mL with 2.0 ng/mL of fentanyl; and 1.6 +/- 0.34 micro g/mL with 3.0 ng/mL of fentanyl (mean +/- SD). Seventy percent of the subjects in the 0.8 ng/mL fentanyl group spontaneously complained of pain, whereas none of the patients in the 2 or 3 ng/mL groups did. Five (56%) of 9 women in the 3 ng/mL group had a postoperative respiratory rate <6 breaths/min. Heart rate in one of these women decreased to <40 bpm. These data suggest that the optimal fentanyl effect-site concentration in patients recovering from gynecologic laparoscopy is between 1.4 and 2.0 ng/mL. IMPLICATIONS:The effect-site concentration for propofol at awakening was virtually independent of the fentanyl effect-site concentration over the range of 0.8 to 3.0 ng/mL; however, 0.8 ng/mL of fentanyl was associated with inadequate postoperative analgesia, and 3.0 ng/mL of fentanyl was associated with respiratory toxicity. The optimal postoperative fentanyl effect-site concentration during recovery from propofol general anesthesia for laparotomy thus appears to be near 2 ng/mL.     

Respiratory depression by tramadol in the cat: involvement of opioid receptors

BACKGROUND: Tramadol hydrochloride (tramadol) is a synthetic opioid analgesic with a relatively weak affinity at opioid receptors. At analgesic doses, tramadol seems to cause little or no respiratory depression in humans, although there are some conflicting data. The aim of this study was to examine whether tramadol causes dose-dependent inhibitory effects on the ventilatory carbon dioxide response curve and whether these are reversible or can be prevented by naloxone. METHODS: Experiments were performed in cats under alpha-chloralose-urethane anesthesia. The effects of tramadol and naloxone were studied by applying square-wave changes in end-tidal pressure of carbon dioxide (Petco2; 7.5-11 mmHg) and by analyzing the dynamic ventilatory responses using a two-compartment model with a fast peripheral and a slow central component, characterized by a time constant, carbon dioxide sensitivity, time delay, and a single offset (apneic threshold). RESULTS: In five animals 1, 2, and 4 mg/kg tramadol (intravenous) increased the apneic threshold (control: 28.3 +/- 4.8 mmHg [mean +/- SD]; after 4 mg/kg: 36.7 +/- 7.1 mmHg; P < 0.05) and decreased the total carbon dioxide sensitivity (control: 109.3 +/- 41.3 ml x min(-1) x mmHg(-1) ) by 31, 59, and 68%, respectively, caused by proportional equal reductions in sensitivities of the peripheral and central chemoreflex loops. Naloxone (0.1 mg/kg, intravenous) completely reversed these effects. In five other cats, 4 mg/kg tramadol caused an approximately 70% ventilatory depression at a fixed Pet co2 of 45 mmHg that was already achieved after 15 min. A third group of five animals received the same dose of tramadol after pretreatment with naloxone. At a fixed Petco of 45 mmHg, naloxone prevented more than 50% of the expected ventilatory depression in these animals. CONCLUSIONS: Because naloxone completely reversed the inhibiting effects of tramadol on ventilatory control and it prevented more than 50% of the respiratory depression after a single dose of tramadol, the authors conclude that this analgesic causes respiratory depression that is mainly mediated by opioid receptors.     

COMPARISON BETWEEN HIGH-DOSE SUFENTANIL-OXYGEN AND HIGH-DOSE FENTANYL-OXYGEN FOR NEUROANAESTHESIA

The cardiovascular responses to anaesthesia, neurosurgery andthe postoperative administration of naloxone were studied in20 patients. Ten patients were anaesthetized with sufentanil20 µ kg^–1 and 10 with fentanyl 100 µg kg^–1,and oxygen. At 30-min intervals, sufentanil 50 µg or fentanyl250 µg was given to maintain anaesthesia. Mean arterialpressure and heart rate did not increase following intubation,incision of the scalp or infusion of naloxone. Because of inadequateanaesthesia, thiopentone was administered at the end of surgeryto one patient who had received sufentanil and seven patientswho received fentanyl. Apart from one patient in each groupthe tracheal tubes were removed within 1 h of the start of theadministration of naloxone. Recall of tracheal intubation orsurgery was not reported by any patient. High-dose sufentanil-oxygenanaesthesia, like high-dose fentanyl- oxygen anaesthesia, wassatisfactory for use in neurosurgery. However, high-dose narcoticanaesthesia, followed by the postoperative administration ofnaloxone, requires that skilled nursing care be available formany hours after surgery.     

Influence of perioperative nalbuphine and fentanyl on postoperative respiration and analgesia

In a double-blind study the relative postoperative respiratory and analgesic effects of perioperatively administered nalbuphine and fentanyl were compared in 60 females undergoing gynecological surgery under i.v. anesthesia. One milliliter (10 mg) nalbuphine was considered equipotent to 1 ml (100 micrograms) fentanyl. In the recovery period pain was assessed by visual analog score (VAS) and recovery by Pegboard scoring. Respiratory function was evaluated by continuous monitoring of respiratory frequency and end-tidal CO2 (ETCO2) and by frequent arterial blood gas analyses. The total volume of analgesic required for surgical analgesia was similar in the two groups. Patients in the nalbuphine group showed mild to moderate increases in pulse rate during the intubation phase and in blood pressure during surgery. Fentanyl was more effective in suppressing these cardiovascular responses. Within the first 15 min following recovery, increasing PaCO2 and ETCO2 as well as respiratory rates below 10/min were noted in 8 patients, who all belonged to the fentanyl group; in 4 of these patients i.v. naloxone had to be administered to reverse respiratory depression. Prolonged sedation was a common feature in patients receiving nalbuphine. It was concluded that fentanyl was superior to nalbuphine in attenuating the pressor responses to intubation and surgery. However, fentanyl was associated with respiratory depression in a considerable number of patients. The quality and duration of postoperative analgesia were similar in the two groups.     

The cardiovascular effects of naloxone administration after fentanyl anesthesia in hypercapnic patients

Hemodynamic changes and plasma catecholamine levels after naloxone administration were studied in seventeen postoperative patients who received nitrous oxide, oxygen, and fentanyl anesthesia combined with epidural block. Group I consisted of ten postoperative hypercapnic (Pa_{CO 2} = 55.2 ± 2.4 torr) and group II seven postoperative normocapnic patients (Pa_{CO 2} = 38.4 ± 2.1 torr), respectively. In group I, naloxone reversal resulted in significant increases in heart rate (13.5%), mean arterial pressure (46.6%), systemic vascular resistance (32.1%), and rate pressure product (68.8%), whereas mean pulmonary artery pressure and pulmonary vascular resistance were significantly decreased. No significant hemodynamic changes after naloxone administration were observed in group II. There were no significant differences in arterial norepinephrine and epinephrine levels either before or after naloxone administration in the both groups. This study indicates that the postoperative hypercapnia elicits the cardiovascular stimulation after fentanyl reversal by naloxone.(Kishikawa K, Namiki A, Iwasaki H: The cardiovascular effects of naloxone administration after fentanyl anesthesia in hypercapnic patients. J Anesth 3: 48–53, 1989)     

Low-dose enflurane as adjunct to high-dose fentanyl in patients undergoing coronary artery surgery: stable hemodynamics and maintained myocardial oxygen balance

The effects of enflurane (end-tidal concentration 0.7%) on central and coronary hemodynamics and myocardial oxygenation were studied during steady state, high-dose fentanyl anesthesia in ten patients undergoing coronary artery bypass grafting operations. Compared with the response in ten patients receiving the same fentanyl anesthesia (100 micrograms/kg) without enflurane supplementation, enflurane caused a moderate reduction in mean arterial pressure, systemic vascular resistance, and left ventricular stroke work index. No patient showed signs of myocardial ischemia, and mean coronary sinus flow and calculated coronary resistance remained unchanged. Surgical stimulation induced no central or coronary hemodynamic responses in the enflurane-fentanyl group. No coronary hemodynamic changes occurred in the fentanyl group, but a marked increase in arterial pressure and systemic vascular resistance was seen. Myocardial oxygen extraction decreased in the enflurane supplemented group although it increased in the fentanyl group after surgical stimulation. Three fentanyl group patients and one enflurane-fentanyl group patient had a low myocardial lactate extraction as a sign of myocardial ischemia during surgery. We conclude that a 0.7% enflurane supplementation of 100 micrograms/kg fentanyl anesthesia does not endanger myocardial oxygenation and effectively prevents central and coronary hemodynamic responses to skin incision and sternotomy in patients undergoing coronary artery surgery.