Postoperative pain relief with naloxone, Severe respiratory depression and pain after high dose buprenorphine

Buprenorphine 30 and 40 micrograms/kg was given as the sole intravenous analgesic in balanced anaesthesia to 12 patients undergoing cholecystectomy. Significant and severe respiratory depression was found 15 minutes after preoperative loading with buprenorphine. In the immediate postoperative period six patients were in pain. They were treated with naloxone 0.08-0.4 mg leading to a long lasting period of pain relief (median 22 hours).     

Reducing the haemodynamic responses to laryngoscopy and intubation

The effects of alfentanil and fentanyl on controlling the haemodynamic responses to laryngoscopy and intubation have been compared. Five groups of ten patients were studied. Induction was with thiopentone 4 mg/kg. Thirty seconds later group 1 received 1 ml/20 kg saline, group 2 received 15 micrograms/kg alfentanil, group 3 received 30 micrograms/kg alfentanil and group 4 received 5 micrograms/kg fentanyl one minute before induction. Suxamethonium was given 60 seconds after induction and intubation of the trachea was performed 150 seconds after the start of induction. Heart rate and mean arterial pressure were recorded every minute throughout and compared with pre-induction control values. Control patients (group 1) showed significant increases associated with tracheal intubation in all haemodynamic variables. No increases were noted in groups receiving 30 micrograms/kg alfentanil or 5 micrograms/kg fentanyl. The heart rate, but not blood pressure, increased with intubation after 15 micrograms/kg alfentanil. The mean time to movement in 50% of the control patients was 7 minutes. In those given 15 and 30 micrograms/kg alfentanil it was 11 and 12 minutes respectively. In those given 5 micrograms/kg fentanyl it was greater than 15 minutes. Alfentanil is shown to reduce the cardiovascular responses to laryngoscopy and intubation and the effect appears to have a shorter duration than that of fentanyl.     

Propofol and alfentanil infusion

In 42 patients undergoing major surgery, anaesthesia was induced by intravenous alfentanil 10 micrograms/kg together with methohexitone 1.5 mg/kg or propofol 2 mg/kg. An infusion of six times these doses per hour was then started; the rate was varied subsequently as indicated by the monitoring of arterial blood pressure, heart rate, EEG and frontalis electromyogram. The mean duration of infusion was 76.7 minutes for propofol and 74.5 minutes for methohexitone and the infusion was stopped about 10 minutes before the end of surgery in each group. The induction dose differed, but the total dose requirement for the two drugs was similar. In every case, anaesthesia was satisfactory. Methohexitone caused a significant rise in mean pulse rate throughout anaesthesia (p less than 0.05, paired t-test). There was no change in mean pulse rate during propofol infusion. The dose of alfentanil used provided excellent control of autonomic reflexes, with negligible respiratory depression. Naloxone was not required. Propofol provided better anaesthesia than methohexitone, with fewer side effects (p less than 0.05, Chi squared test), easier control of the level of narcosis and faster recovery (p less than 0.001, t-test after log transformation).     

Buprenorphine antagonism of ventilatory depression following fentanyl anaesthesia

In order to compare the effect of buprenorphine and naloxone on respiratory depression after fentanyl anaesthesia (25 micrograms/kg), 32 women scheduled for elective abdominal hysterectomy participated in a double-blind randomized investigation. At termination of anaesthesia, after antagonizing residual neuromuscular blockade, 20 normocapnic patients with a respiratory rate of 4 breaths/min or less entered the study, receiving either buprenorphine (0.6 mg in 20 ml NaCl) or naloxone (0.4 mg in 20 ml NaCl) 2 ml/min until 20 ml was given or until the respiratory rate exceeded 8 breaths/min. Respiratory rate, PaCO2, sedation score, and pain intensity were evaluated during a 3-h study period. Fifteen min after beginning the treatment, all the patients in both groups had their ventilatory depression antagonized. There were no statistically significant differences in respiratory rates between groups except at 15 min. On no occasion did either PaCO2 or a sedation score differ statistically significantly between the groups. At 15 min all patients in the buprenorphine group had no or mild pain, compared to the patients in the naloxone group, of whom 50% had moderate to severe pain (P less than 0.05). It seems as if buprenorphine is as effective as naloxone in antagonizing respiratory rate depression following fentanyl anaesthesia.     

Alfentanil infusions. Comparison of bolus administration of fentanyl with three alfentanil infusion regimens

Three different dosage regimens of alfentanil were compared with boluses of fentanyl in 80 patients who underwent a variety of surgical procedures. Alfentanil given by infusion at a rate of 7.5 micrograms/kg/minute for 10 minutes followed by 0.75 micrograms/kg/minute, was shown to provide a stable anesthetic which minimises the use of a volatile agent for surgery that lasts more than 45 minutes.     

Alfentanil used to supplement propofol infusions for oesophagoscopy and bronchoscopy

This randomised double-blinded study compared the cardiovascular stability and rate of recovery when propofol infusions with or without alfentanil were used to provide anaesthesia for rigid oesophagoscopy and (or) bronchoscopy. Forty-six patients were allocated randomly to receive either alfentanil 10 micrograms/kg or saline just before a rapid sequence induction with propofol. Suxamethonium 1 mg/kg was given and infusions of suxamethonium 10 mg/minute and propofol (10 mg/kg/hour for 10 minutes, 8 mg/kg/hour for 10 minutes and then 6 mg/kg/hour thereafter) were started. There were 23 patients in each group with no significant demographic differences between the groups. A significantly mean lower induction dose of propofol was needed in the alfentanil group (1.7 mg/kg compared to 2.2 mg/kg). Cardiovascular measurements were made on the ward pre-operatively, just before induction, just after induction, just after intubation, and at 3-minute intervals thereafter. Arterial pressure was significantly lower during the procedure in the patients who received alfentanil and there was a significant incidence of hypotension. There was no significant difference between the groups in respect of heart rate, with a significant increase in both groups just after intubation compared to the baseline values. Recovery from anaesthesia was assessed using the critical flicker fusion threshold. No differences were found between the groups and patients in both groups had returned to baseline values by 60 minutes. No patient had any recall of intra-operative events, and there were no other adverse effects of any significance.     

A comparison of nalbuphine with fentanyl for postoperative pain relief following termination of pregnancy under day care anaesthesia

A double-blind investigation was undertaken to compare the efficacy of nalbuphine and fentanyl in the prevention of pain after day case termination of pregnancy. Forty patients were allocated randomly to receive nalbuphine 0.25 mg/kg or fentanyl 1.5 micrograms/kg immediately before induction of anaesthesia. The patients completed scores for pain and nausea, and performed a reaction time test to assess recovery. An observer assessed patient appearance at 1, 2 and 4 hours postoperatively. Patients who received nalbuphine had significantly lower pain scores at 1 hour (p less than 0.01) and 2 hours (p less than 0.05) and required significantly (p less than 0.05) less postoperative analgesia. No significant differences were found between the groups for incidence of nausea or for observer assessment of appearance. There was some evidence of psychomotor impairment at 2 hours in the nalbuphine group. Freedom from Controlled Drug Act regulations and improved analgesia with nalbuphine, render it more satisfactory for day case surgery than the more commonly used fentanyl.     

The haemodynamic effects of bronchoscopy

The cardiovascular responses to bronchoscopy under general anaesthesia were investigated in 36 premedicated patients. Twelve patients acting as controls received a standard intravenous anaesthetic of intermittent thiopentone and suxamethonium. A further 24 patients were given either fentanyl 6 micrograms/kg or alfentanil 18 micrograms/kg intravenously, one minute prior to induction. There were significant rises in systolic arterial blood pressure (p less than 0.05) and in rate pressure product (p less than 0.05) in the patients in the control group, but these changes were not seen in those patients receiving either fentanyl or alfentanil. However, dysrhythmias and ST segment changes indicative of myocardial ischaemia were present in some patients in all three groups.     

Comparison of Alfentanil and Fentanyl as Supplements to Induction of Anaesthesia with Thiopentone

In 120 premedicated patients undergoing general surgery, anaesthesia was induced with thiopentone 3 mg kg-1, preceded by alfentanil 4.5, 9.0 or 13.5 micrograms kg-1 or fentanyl 1.5 micrograms kg-1. The largest alfentanil dose attenuated the arterial blood pressure response to laryngoscopy and intubation better than the smaller doses of alfentanil. Changes in frontal muscle electromyogram or plasma cortisol and prolactin levels were not dependent on the adjuvant used. After thiopentone, 30, 7 and 17% of the patients given alfentanil 9.0 and 13.5 micrograms kg-1 and fentanyl 1.5 micrograms kg-1, respectively, reacted to pinching of the lower abdomen. Patients given alfentanil 4.5 micrograms kg-1 did not tolerate the endotracheal tube after recovery from suxamethonium block and their heart rate was increased 12 min after alfentanil administration. We conclude that the antinociceptive effect of alfentanil is distinctly shorter than that of fentanyl. The analgesic potency of alfentanil is between one sixth and one ninth of that of fentanyl.     

Inhaled fentanyl as a method of analgesia

A study was undertaken to investigate the use of fentanyl by aerosol for postoperative analgesia. Seven patients had placebo, six received fentanyl 100 micrograms and seven were given fentanyl 300 micrograms. A significant improvement in postoperative pain, as assessed by linear visual analogue scale, was achieved in the higher dose group, and in both fentanyl groups the time to alternative analgesia was significantly longer than in the control group. Serum fentanyl levels after inhalation of 100 micrograms reached a plateau around 0.04 ng/ml and after 300 micrograms at around 0.1 ng/ml after 15 minutes. Inhaled fentanyl may have a useful analgesic effect despite these low serum levels; this supports the hypothesis that the mode of analgesia from inhaled opioids may be different from that after other routes of administration. There were no adverse effects such as respiratory depression, bronchospasm, nausea or drowsiness.     

Pretreatment with opioids

Pretreatment with small doses of fentanyl (100 micrograms) or alfentanil (300 micrograms) was found significantly to reduce the induction dose of thiopentone. Fentanyl 50 micrograms and alfentanil 150 micrograms also significantly reduced the onset time and increased the consistency of action of midazolam. Respiratory depression was not a problem when 50 micrograms fentanyl or 150 micrograms alfentanil were used.     

Alfentanil, a new, potent and very short-acting morphinomimetic for minor operative procedures. A pilot study

A recently developed derivative of fentanyl, alfentanil, which showed an extremely short lived activity in pharmacological studies was evaluated in 57 female patients undergoing short gynaecological operations. Anaesthesia was induced with 0.05 mg/kg alfentanil, followed by an injection of etomidate. Virtually no respiratory depression was seen: all patients resumed normal spontaneous respiration within 7 minutes after the operation and naloxone was not given. Blood pressure and heart rate remained stable. No complications occurred during the procedure and serious side-effects were absent.     

Human volunteer studies of Alfentanyl (R39209), a new short-acting narcotic analgesic

Alfentanyl is a new narcotic analgesic with a rapid onset and very short duration of effect, and a potency about one third of that of fentanyl. The respiratory effects of 1.6, 3.2 and 6.4 micrograms/kg Alfentanyl were studied in a randomised controlled trial in five volunteers. Alfentanyl 6.4 micrograms/kg induced a significant increase in respiration at 1 minute, then significant depression of mean minute volume 3 and 4 minutes after slow intravenous injection, compared with saline control, and pre-injection values. Mean end-expired carbon dioxide concentration was increased after Alfentanyl 6.4 micrograms/kg, significantly from 2 to 9 min after injection, and highly significantly at 3, 4 and 5 minutes. Examination of the effect on expired CO2 concentration at 4 minutes reveals a highly significant dose-response relationship with the three doses of Alfentanyl. The transient effect of ALfentanyl was confirmed by the fact that no change in mean ventilatory response to carbon dioxide was demonstrable 30 or 50 minutes after any dose. When Alfentanyl was given 1 minute before testing the ventilatory response to carbon dioxide the response curves showed a highly significant dose-related shift to the right. There were no significant changes in heart rate or blood pressure after Alfentanyl, but the drug produces the typical subjective effects of the opiates.     

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.     

The analgesic effect of a low dose of alfentanil

The effect of a single small dose of alfentanil (6 micrograms/kg) on postoperative pain was compared with saline using a double blind study. Pain was assessed using a linear analogue scale and shown to decrease at 2, 5 and 10 minutes after injection of alfentanil (p less than 0.01). The PE'CO2 was increased at 2 and 15 minutes (p less than 0.05) and 5 and 10 minutes (p less than 0.01) after injection of alfentanil. There were no changes in pain or PE'CO2 in the control group throughout the study. Intravenous alfentanil given to patients in pain provides quick effective analgesia for a short period of time, but respiratory depression may occur.     

Alfentanil in minor gynaecological surgery: use with etomidate and a comparison with halothane

Etomidate was used to induce anaesthesia in 50 healthy subjects undergoing minor gynaecological surgery who were randomly divided into two groups, one receiving alfentanil 8 micrograms/kg intravenously immediately prior to induction of anaesthesia with etomidate, and the other halothane as required to maintain adequate anaesthesia. There was a highly significant reduction in the incidence of myoclonia and involuntary movement and significant reduction of pain on injection in the alfentanil group. Tests of recovery performed in the 60 minutes following anaesthesia suggested that supplementation with alfentanil led to more rapid recovery than halothane.     

Clinical experiences with naloxone in neuroradiology

In 17 patients, the reversal by naloxone of a short duration narcotic anesthesia done for neuroradiology, was studied. Neuroleptanalgesic technique comprised d-hydrobenzperidol (5-10 mg) and fentanyl (+/- 0.4 mg) after barbiturate induction, and curarization with pancuronium, reversed by neostigmine. In group A 2 microgram/kg naloxone I.V. was given and 1 microgram/kg I.M. 30 min. later and in group B 1 micrometer/kg I.V. and 30 min. later 0.5 micrometer/kg. Reversal of narcotic depression was good and well maintained for 60 min. in both groups, as evidenced by respiratory rate, respiratory minute volume, pHa, PaCO2. Marginal temporarily cardiovascular stimulation occurred with arousal. Tolerance was good. It is concluded that antagonisation of respiratory depression due to narcotic anesthesia is possible with small titrated dosis of naloxone.     

The effects of continuous intravenous naloxone on epidural morphine analgesia

Forty-five patients undergoing Caesarean section under epidural anesthesia with bupivacaine were randomly allocated to three groups. Group 1 received 4 mg of epidural morphine immediately postoperatively and 2 mg naloxone by intravenous infusion for 12 hours postoperatively; group 2 was treated as group 1 but without naloxone infusion; group 3 received 10 mg morphine intramuscularly and 20 ml epidural saline after delivery of the baby. Epidural morphine 4 mg produced better postoperative analgesia than 10 mg of morphine intramuscularly (p less than 0.001) and the intravenous infusion of naloxone did not ablate the analgesic effects of epidural morphine. The incidence of itching and vomiting was higher in the epidural opioid groups (p less than 0.05) and intravenous naloxone, although it reduced the severity of the itching, did not reduce its overall incidence. Respiratory depression was not detected in any of the three groups.     

Respiratory effects of epidural fentanyl

Respiratory function following single bolus doses as well as continuous infusions of epidural fentanyl were studied in 21 patients. Respiratory rate decreased significantly and end-tidal CO2 showed a non-significant increase following single doses of epidural fentanyl (1.5 micrograms/kg). These changes occurred within minutes of injection, but could not be attributed solely to rapid systemic absorption of fentanyl from the epidural space. Prior administration of parenteral morphine resulted in significantly higher end-tidal CO2 concentrations and lower respiratory rates following epidural fentanyl. Continuous epidural fentanyl infusion (0.5 micrograms/kg/hour) started 60 minutes after the bolus dose had no effect on end-tidal CO2 concentration or respiratory rate for up to 18 hours. Infusions were continued after the study terminated for up to 9 days, during which there was no clinically significant respiratory depression.     

Comparison of midazolam and propofol in combination with alfentanil for total intravenous anesthesia

Hemodynamic function during induction of anesthesia, the alfentanil and naloxone requirements, and the speed of recovery from total intravenous anesthesia with alfentanil/midazolam (group M, n = 10) or alfentanil/propofol (group P, n = 10) were compared in patients undergoing lower limb surgery. Twenty patients were randomly assigned to receive either 2 mg/kg propofol in 5 min followed by 9 mg.kg-1.h-1 for 30 min and 4.5 mg.kg-1.h-1 until skin closure, or 0.42 mg/kg midazolam in 5 min followed by 0.125 mg.kg-1.h-1 until skin closure. Simultaneously, a variable-rate infusion of alfentanil was given. Patients were ventilated with 30% oxygen in air. In both groups blood pressure and heart rate decreased significantly (P less than 0.02) and to a similar extent during induction. The total dose of alfentanil was similar in both groups. No patient in group P and nine patients in group M needed naloxone (average dose 130 +/- 70 micrograms, P less than 0.001). Recovery, as judged by psychomotor tests (90% score was reached at 1 h in the P group and at about 4 h in the M group, P less than 0.001), sedative scores, and orientation in time and place, was shorter in group P than in group M. The conclusion is reached that propofol is superior to midazolam in total intravenous anesthesia with alfentanil.