A potentially hazardous interaction between erythromycin and midazolam.

Interaction between erythromycin and midazolam was investigated in two double-blind, randomized, crossover studies. In the first study, 12 healthy volunteers were given 500 mg erythromycin three times a day or placebo for 1 week. On the sixth day, the subjects ingested 15 mg midazolam. In the second study, midazolam (0.05 mg/kg) was given intravenously to six of the same subjects, after similar pretreatments. Plasma samples were collected, and psychomotor performance was measured. Erythromycin increased the area under the midazolam concentration-time curve after oral intake more than four times (p < 0.001) and reduced clearance of intravenously administered midazolam by 54% (p < 0.05). In psychomotor tests (e.g., saccadic eye movements), the interaction between erythromycin and orally administered midazolam was statistically significant (p < 0.05) from 15 minutes to 6 hours. Metabolism of both erythromycin and midazolam by the same cytochrome P450IIIA isozyme may explain the observed pharmacokinetic interaction. Prescription of midazolam for patients receiving erythromycin should be avoided or the dose of midazolam should be reduced by 50% to 75%.

The effect of narcotic analgesics on the uptake of 5-hydroxytryptamine and (-)-metaraminol by blood platelets.

1. The effects of narcotic analgesic and related drugs were studied on the uptake of 5-hydroxytryptamine (5-HT) and (-)-metaraminol by blood platelets.2. The most potent drug in inhibiting the uptake of 5-HT (10 muM) by human platelets was methadone, followed by pentazocine>piminodine approximately pethidine approximately anileridine approximately cyclazocine approximately thebaine > dextropropoxyphene. Alphaprodine, papaverine, apomorphine, nalorphine, codeine, and morphine were almost without effect. Methadone was slightly less active than desipramine, and had 10% of the activity of imipramine under similar conditions. Naloxone did not antagonize the effect of methadone on 5-HT uptake.3. The most potent inhibitor of metaraminol (3 muM) uptake by human platelets was piminodine, followed by pentazocine>/=anileridine>cyclazocine=methadone > dextropropoxyphene approximately thebaine >/= papaverine approximately alphaprodine >pethidine>morphine. The activity of morphine was 1% of that of piminodine. Piminodine was more potent than desipramine and protriptyline under similar conditions. The order of potency of drugs studied in inhibiting the uptake of metaraminol by rabbit platelets was similar to that obtained with human platelets.4. The effects of the analgesics studied on inhibiting uptake of monoamines did not correlate with their pain-relieving properties.

Comparison of alfentanil and morphine in the prehospital treatment of patients with acute ischaemic-type chest pain.

Patients with acute myocardial ischaemic pain would benefit from rapid pain relief. The clinical usefulness of alfentanil, which has a rapid onset of action, was therefore assessed as the initial pain relieving opioid in patients suffering from acute myocardial ischaemic pain. The effects of alfentanil were compared with those of morphine in the prehospital treatment of 40 haemodynamically stable patients suffering from acute ischaemic-type chest pain. After initial assessment, the patients were given either 0.5 mg alfentanil or 5 mg morphine intravenously in a randomized double-blind fashion. The dose was repeated 2 minutes later if severe pain persisted. Arterial pressure, heart rate, respiratory rate and pain expressed on a visual analogue scale was measured before and at 2, 4, 6, 10 and 15 minutes after administration of drugs. After randomization, four patients were excluded. Sixteen patients received alfentanil and 20 patients morphine. Pain relief was faster (p < 0.005) in the alfentanil group than in the morphine group. Alfentanil was found to provide effective analgesia during the follow-up period of 15 minutes. No haemodynamic or respiratory side effects occurred. It is concluded that alfentanil is an effective analgesic in the prehospital treatment of myocardial ischaemic pain.

Effect of esmolol on the hemodynamic and electrocardiographic changes during laryngomicroscopy under propofol-alfentanil anesthesia.

Laryngomicroscopy is a short-lasting procedure, which causes considerable hemodynamic and ECG changes. Therefore it sets specific demands on anesthetic care. In this double-blind randomized work, we studied hemodynamic and ECG changes in patients during laryngomicroscopy in jet ventilation under propofol-alfentanil anesthesia with and without esmolol, a short-acting beta1-adrenergic receptor blocking agent. Forty ASA class I-II patients were allocated to receive either esmolol 1 mg.kg-1 + 200 micrograms.kg-1.min-1 (the esmolol group) or saline (the control group) (mean age +/- SD 36 +/- 12 yrs in the esmolol group and 39 +/- 9 yrs in the control group). The heart rate and arterial pressure were measured non-invasively and ECG was analyzed with the aid of a microcomputer. In the control group, neither the heart rate nor the QTc interval of the ECG did change significantly when compared with the baseline values. In the presence of esmolol, the heart rate decreased and the QTc interval shortened during the procedure. Arterial pressure increased in the control group, but not in the esmolol group, when compared with the baseline values. No cardiac arrhythmias occurred in either of the groups. On the basis of the present study, propofol-alfentanil anesthesia combined with esmolol is a satisfactory method to meet specific demands of laryngomicroscopy in young and middle-aged ASA I-II patients. However, a combination of propofol and esmolol showed a tendency to decrease both the heart rate and arterial pressure and a caution is necessary when the combination were used in elderly patients.

Comparison of thiopentone, Althesin and ketamine in anaesthesia for otolaryngological surgery in children.

Thiopentone 4 mg/kg, Althesin 0.055 ml/kg and ketamine 2 mg/kg were compared in 157 children undergoing minor otolaryngological surgery, mostly adenotonsillectomy. Premedication was with pethidine and atropine and anaesthesia was maintained with nitrous oxide in oxygen and halothane. Tracheal intubation was facilitated with suxamethonium. In each group half of the children received pethidine 0.7 mg/kg after intubation and the remainder received saline. Ketamine increased arterial pressure after induction. The cardiovascular responses to intubation were more obvious after thiopentone and Althesin than after ketamine. Operating conditions, cardiovascular changes during operation and the course of extubation were similar in all groups. The recovery after ketamine was longer than after thiopentone and Althesin. Thiopentone was associated with significantly less vomiting immediately after operation than was Althesin and ketamine. In the period immediately after operation Althesin was associated with a higher need for analgesics compared with thiopentone and ketamine. Pethidine prolonged the recovery after thiopentone, decreased the incidence of vomiting immediately after operation associated with Althesin and increased that associated with ketamine.

Comparison of paracetamol and pentazocine suppositories for pain relief after tonsillectomy in adults.

The pain-relieving effect of paracetamol 500 mg or pentazocine 50 mg suppositories was studied in 91 voluntary adult patients after tonsillectomy in halothane or enflurane anaesthesia. Both suppositories were studied after both anaesthetics. Thus the patients were randomly allocated to four study groups. At 60 min after administration of coded suppositories, 46-50% of the patients in various groups needed extra analgesic and received pethidine 1 mg/kg i.m. Thereafter, the pain relief was satisfactory in all groups until the end of the observation period (120 min). The incidence of vomiting, the most common side effect, ranged from 5 to 14% in the groups. Bleeding from the operation site was most common (14%) in the patients treated with pentazocine after enflurane anaesthesia and did not occur in the patients treated with pentazocine after halothane anaesthesia. The incidence of bleeding in both paracetamol groups was 9%. In all cases, bleeding stopped without any special treatment. The results suggest that both paracetamol 500 mg and pentazocine 50 mg suppositories in the doses used were weak analgesics for throat pain after tonsillectomy in adults in the early postoperative period. The incidence of side effects was relatively low.

Comparison of halothane and enflurane anaesthesia for tonsillectomy in adults.

Halothane and enflurane in combination with N2O/O2 were compared in 103 adults undergoing tonsillectomy. Anaesthesia was induced with thiopental, and intubation was facilitated with suxamethonium. During halothane anaesthesia the mean heart rate ranged from 91 to 106 beats/min and the mean systolic arterial pressure from 111 to 127 mmHg. The values did not differ significantly from the corresponding values during enflurane anaesthesia. Electrocardiographic changes occurred in 56% and 31% of the patients anaesthetized with halothane or enflurane, respectively. the incidence of junctional rhythm, the most common ECG change, was 46% in the halothane group and 29% in the enflurane group. 19% of the patients in the halothane group and 31% in the enflurane group responded to surgical stimulus by swallowing or coughing. The responses were mostly short-lasting and did not much disturb the surgeon. The incidence of laryngospasm was 6% after halothane and 2% after enflurane anaesthesia. The mean total recovery score (0-10) was 6.1 after halothane and 6.3 after enflurane at arrival in the recovery room and 9.8 in both groups 30 min later. After halothane, nausea and vomiting occurred in 8 and 12% of the patients, respectively. The corresponding figures after enflurane were 2 and 8%. It is concluded that both halothane and enflurane are suitable anaesthetics for tonsillectomy in adults. The most striking difference between the anaesthetics was the significantly more common occurrence of ECG changes during halothane than enflurane anaesthesia.

Enflurane inhibits muscle fasciculations caused by suxamethonium in children.

Eighty-three children with a mean age of 2.7 years were anaesthetized with either thiopental 5 mg/kg followed by suxamethonium 1.5 mg/kg i.v. or with enflurane 5 vol% in 70% nitrous oxide in oxygen via a face mask. In the enflurane group, venepuncture was performed when the children were unconscious, 1.8 +/- 0.05 (s.e.) min after the start of anaesthesia. After enflurane, suxamethonium 1, 1.5 or 2 mg/kg was administered i.v. for endotracheal intubation. The incidence and duration of muscle fasciculations after suxamethonium were significantly lower (P less than 0.01) in the enflurane groups than in the thiopental group. The fasciculation index was significantly lower (P less than 0.01) in the enflurane groups than in the thiopental group. In the enflurane groups, intubating conditions were better (P less than 0.05) in the children treated with suxamethonium 2 mg/kg than in those treated with suxamethonium 1 mg/kg.

[Interactions between lithium/rubidium and six muscle relaxants. A study on the rat phrenic nerve-hemidiaphragm preparation]. / Wechselwirkungen zwischen Lithium/Rubidium und sechs Muskelrelaxanzien. Studie zum halbseitigen Nervus phrenicus--Zwerchfellpräparat der Ratte.

The cumulative concentration-response curves for alcuronium, metocurine, d-tubocurarine, suxamethonium, pancuronium and vecuronium alone or in combination with lithium or rubidium were measured using indirectly evoked twitch tension in the isolated rat phrenic nerve-hemidiaphragm preparation. In the experiments with lithium and rubidium, 10% and 2% of the sodium ions (118 mmol/l) of Krebs solution were replaced by lithium (11.8 mmol/l = 0.082 g/l) or rubidium (2.36 mmol/l = 0.202 g/l) ions, respectively. At these concentrations, neither lithium nor rubidium alone affected twitch tension. Lithium led to a statistically significant enhancement of the myoneural blocking effects of suxamethonium, pancuronium and vecuronium, but not of the other myoneural blocking drugs. Rubidium behaved similarly to lithium, except that enhancement of the effect of vecuronium was not statistically significant. At higher concentrations, lithium and rubidium alone depressed twitch tension in a dose-dependent manner. Neither myoneural blocking drugs nor lithium and rubidium affected the directly evoked twitch tension. It is concluded that myoneural blocking drugs, especially the newer ones, should be used with caution in patients receiving lithium or other alkali metal therapy as it is not known what interactions may arise.

Injection pain, cardiovascular changes and recovery following induction of anaesthesia with propofol in combination with alfentanil or lignocaine in children.

The effect of pretreatment with alfentanil 10 (Alf10), 15 (Alf15) or 20 (Alf20) micrograms.kg-1 on reducing injection pain caused by propofol was compared with lignocaine 10 mg mixed with propofol (Lign). This double-blind, double-dummy and randomized study included 100 children with a mean age of 4.3 +/- 0.6 years, 25 children in each group, undergoing minor otolaryngological surgery. The children were premedicated orally with midazolam 0.5 mg.kg-1 and atropine 0.03 mg.kg-1. Injection pain occurred in 4% in the Lign group. The corresponding figures were 40, 16 and 20% in the Alf10, Alf15 and Alf20 groups, respectively. Both 1% lignocaine 10 mg and alfentanil 15 micrograms.kg-1 reduced injection pain significantly compared with alfentanil 10 micrograms.kg-1. Pretreatment with alfentanil significantly diminished haemodynamic responses to tracheal intubation. Furthermore, the concomitant use of alfentanil and propofol caused transient severe bradycardia and a significant decrease in heart rate after laryngoscopy.

Increase in intragastric pressure during suxamethonium-induced muscle fasciculations in children: inhibition by alfentanil.

Changes in intragastric pressure after the administration of suxamethonium 1.5 mg kg-1 i.v. were studied in 32 children (mean age 6.9 yr) pretreated with either physiological saline or alfentanil 50 micrograms kg-1. Anaesthesia was induced with thiopentone 5 mg kg-1. The incidence and intensity of muscle fasciculations caused by suxamethonium were significantly greater in the control than in the alfentanil group. The intragastric pressure during muscle fasciculations was significantly higher in the control group (16 +/- 0.7 (SEM) cm H2O) than in the alfentanil group (7.7 +/- 1.5 (SEM) cm H2O). The increase in intragastric pressure was directly related to the intensity of muscle fasciculations (regression line: y = 0.5 + 4.78x with r of 0.78). It is concluded that intragastric pressure increases significantly during muscle fasciculations caused by suxamethonium in healthy children. Alfentanil 50 micrograms kg-1 effectively inhibits the incidence and intensity of suxamethonium-induced muscle fasciculations; moreover, intragastric pressure remains at its control value.

The effect of instrumentation with a telescope during bronchoscopy on arterial oxygen tension and acid-base balance.

The effect of instrumentation with a telescope during bronchoscopy on the arterial oxygen tension and acid-base status was studied in 17 unselected, anaesthetized patients using a ventilating technique based on Sanders' method (1). After ventilating the patients with a bronchoscope and a telescope in the trachea, in the left main bronchus or in the right main bronchus, the PaO2 value was always statistically significantly higher than after ventilating only with a bronchoscope. During the course of the bronchoscopy as well as after 1 h in the recovery room, the arterial acid-base status was within normal limits and the mean PaO2 value during bronchoscopy ranged from 175 to 240 mmHg (23.3-31.9 kPa) and was 138 mmHg (18.4 kPa) in the recovery room when the patients breathed about 35% oxygen in air. The present results suggest that instrumentation with a telescope during bronchoscopy ameliorates rather than impairs the ventilation and oxygenation of the patients.

Cardiovascular responses to enflurane induction followed by suxamethonium in children.

Induction of anaesthesia with enflurane 5 vol% plus 70% nitrous oxide in oxygen was followed by suxamethonium 1, 1.5 or 2 mg kg-1 i.v. and the cardiovascular changes studied in 58 children. The eyelash reflex disappeared in 44 +/- 1.2 (SEM)s and the venepuncture could be performed 1.8 +/- 0.05 (SEM) min after the start of enflurane anaesthesia. The increase in systolic arterial pressure after tracheal intubation was less marked after enflurane than after thiopentone (taken from an earlier study). Heart rate increased significantly after all doses of suxamethonium, but no cardiac arrhythmias were seen. The QT interval was significantly prolonged by enflurane (P less than 0.001), but remained unchanged after suxamethonium.

Effect of competitive myoneural blockade and fentanyl on muscle fasciculation caused by suxamethonium in children.

The effects of tubocurarine 0.06 mg kg-1, alcuronium 0.03 mg kg-1, pancuronium 0.01 mg kg-1, and fentanyl 1 or 2 micrograms kg-1 on the muscle fasciculations associated with suxamethonium were studied in 171 children undergoing otolaryngological surgery. The mean fasciculation index in all pretreatment groups was significantly smaller than in the control group. The most effective pretreatment was fentanyl 2 micrograms kg-1 followed, in order, by alcuronium, fentanyl 1 microgram kg-1, tubocurarine and pancuronium. The rate of the onset of the fasciculations after the injection of suxamethonium ranged from 8 s after pancuronium to 20 s after tubocurarine. There was evidence of respiratory depression in the children receiving fentanyl 2 micrograms kg-1 if the duration of anaesthesia was less than 30 min.