J. Rupreht

REM sleep deprivation decreases the antinociceptive property of enkephalinase-inhibition, morphine and cold-water-swim

Rats treated with phosphoramidon (an enkephalinase-inhibitor 250 micrograms, i.c.v.), morphine (20 micrograms i.c.v.) or subjected to cold-water-swim (CWS, animals forced to swim in water at 5 degrees C for 5 min) showed consistent analgesia. The antinociceptive effect of phosphoramidon, morphine and CWS was antagonised by REM sleep deprivation (REMSD). It is suggested that normal duration of REM sleep is of importance for the anti-nociceptive activity of endogenous and exogenous opiates.

Tolerance to Nitrous Oxide in Volunteers

Nociception and loss of awareness during exposure to anaesthetic concentration of nitrous oxide (N2O) were studied in eight male medical students. The cold water nociception test, where a hand is immersed in 0°C stirred water, was used for measurement of nociception. At irregular intervals an auditory command was given to oppose two fingers, and this served to monitor consciousness. The selected inspiratory concentration of N2O used per individual was sufficient to induce a loss of consciousness for more than 2.5 min, within 10 min of exposure to N2O. This concentration of N2O varied from 60% to 80%. The experimental exposure to N2O lasted 3 h. In all volunteers significant antinociception was observed within 2 min of exposure to N2O. The maximal analgesic effect was observed between 20 and 30 min of exposure to N2O. The analgesic effect of N2O gradually decreased and was absent in all eight volunteers within 150 min. Two volunteers regained consciousness at 77 and 91 min of exposure, whilst still breathing 60 and 80% N2O. These results show that tolerance to antinociceptive effects of N2O in man rapidly develops and that awareness may occur in some volunteers during prolonged exposure to N2O.

An analgesic effect of enkephalinase inhibition is modulated by monoamine oxidase-B and REM sleep deprivations

SummaryBoth the MAO-B inhibitor deprenyl (2.5–10 mg/kg, ip, 60 min prior) and the MAO-B substrate β-phenylethylamine (PEA, 40 μg, icv) potentiated the analgesic action of the enkephalinase inhibitor phosphoramidon (250 μg, icv) in animals allowed normal sleep. The enhancing effect of PEA on phosphoramidon analgesia was further potentiated by deprenyl (5 mg/kg, ip) pretreatment. Deprenyl (5 mg/kg, ip) or PEA (40 μg, iv) given alone did not induce analgesia in animals allowed undisturbed sleep.REM sleep deprivation (REMSD) decreased the basal pain threshold and abolished the analgesic effect of phosphoramidon. The administration of deprenyl and/or PEA failed to restore the analgesic effect of phosphoramidon in REM sleep deprived animals.The results indicate that excess PEA has a stimulatory effect on the analgesic activity of endogenously released enkephalins in rats allowed undisturbed sleep but not in REM sleep deprived animals.It is suggested that the failure of phosphoramidon to induce analgesia after REMSD, is probably due to a functional insufficiency of an enkephalinergic system.

Effect of phosphoramidon — a selective enkephalinase inhibitor — on nociception and behaviour

Phosphoramidon (100-350 micrograms i.c.v.), a selective enkephalinase inhibitor, induced in the rat a decrease of nociception to pressure stimulation without evident respiratory depression. In addition, intensive behavioural changes such as grooming (licking the fur, face washing and scratching), mounting behaviour and wet dog shakes were observed. Naltrexone pretreatment (1 mg/kg i.p.) caused a significant decrease in the phosphoramidon-induced nociception and behavioural changes. Puromycin (30 micrograms i.c.v. or 7.5 mg/kg i.p.) caused no changes in nociception or behaviour.

Enkephalinase Inhibition Prevented Tolerance to Nitrous Oxide Analgesia in Rats

Tolerance to nitrous oxide (N2O) antinociception was studied in rats in accordance with the Randall‐Selitto pressure nociception test. Both N2O (70% in 30% O2) and the relatively selective enkephalinase inhibitor phosphoramidon (350 μg i.c.v.), which blocks the biotransformation of enkephalins, were administered. They both induced a significant analgesic effect which vanished within 45 min. The rapidly developed tolerance to N2O analgesia does not affect the anaesthetic state since the animals remained motionless for the duration of exposure lasting 3 h. In the animals treated with the enkephalinase inhibitor phosphoramidon, no development of tolerance to N2O‐antinociception occurred during the exposure lasting 3 h. The results indicate that tolerance to N2O analgesia can be abolished by activation of the enkephalinergic system, which might suggest a possible insufficiency of this system during tolerance to N2O.

The involvement of the central cholinergic and endorphinergic systems in the nitrous oxide withdrawal syndrome in mice.

The nitrous oxide withdrawal syndrome in mice was used as an experimental model to examine some of the factors which may play a role in postanesthetic excitation. Predisposition to nitrous oxide withdrawal convulsions as judged by duration of susceptibility was decreased significantly after pretreatment with the cholinesterase inhibitors, physostigmine and galanthamine, or with the opiate receptor blocking agent naloxone. Results are discussed in relation to the central anticholinergic syndrome, endorphin release, and disturbances which follow nitrous oxide anesthesia in humans and animals.

Physostigmine Versus Naloxone in Heroin -Overdose

Two groups of 10 chronically heroin addicted patients who were admitted to the Emergency Ward because of hypoventilation and coma, were treated random- aselectively with naloxone, 3 micrograms kg-1 BW iv, or with physostigmine salicylate 0,04 mg kg-1 BW iv. Patients in both groups completely regained consciousness and breathed spontaneously, regularly and adequately within 10 minutes. One essential difference in the treatment was that physostigmine caused no signs of acute opiate withdrawal, the patients felt fine and stayed for further control, in contrast with naloxone where the patients felt bad and occasionally escaped prematurely from the ward. Another difference is that the beneficial effect of one dose of physostigmine is shorter lived than that of naloxone. Authors emphasise the fact that treatment of heroin overdose in an addict need not jeopardize the patients well-being by a withdrawal syndrome.

Effect of aminophylline or physostigmine on recovery from nitrous oxide-enflurane anaesthesia

If facilities for recovery are limited, shortening the recovery time from general anaesthesia is important. A comparative study on the effect of 3 mg·kg‐1 aminophylline or 0.04 mg·kg‐1 physostigmine on duration and quality of the recovery time from nitrous oxide‐enflurane anaesthesia is presented. Three groups of 35 patients were observed, placebo being included for comparison in this double‐blind study. Without treatment, recovery from nitrous oxide‐enflurane inhalation anaesthesia lasted 18.8 ± 5.80 min. Aminophylline considerably shortened the recovery time (12.06 ± 3.52 min), whereas physostigmine did not (18.97 ± 9.18 min). In the physostigmine group, however, a remarkably calm recovery and early return of protective reflexes was observed. Although aminophylline shortens the recovery time, due to earlier incidence of pain and other disturbances, it cannot be recommended for general improvement of recovery, whereas physostigmine clearly improves the quality of recovery from nitrous oxide‐enflurane anaesthesia.

Awareness with amnesia during total intravenous anaesthesia with propofol

disturbances, but they might also have been aware during surgery. A recently published study by Flier et aL4 reported two of 140 patients with recall of awareness during general anaesthesia. These investigators used a somewhat different approach (adapted from Brice et a[.

Keuskamp and the Amsterdam Infant Ventilator

) to assess the number of patients with intra-operative memories. All patients were asked during a short postoperative interview three questions: What is the last thing you remember before going to sleep for your operation? What is the first thing you remember on waking up after your operation? Do you remember anything in between? A careful interview of patients, with direct questions about whether or not they have memories of intra-operative events, seems to be the appropriate strategy for assessing the incidence of awareness. If Pedersen and Johansen had used this method they would, without doubt, have found more patients with recollections of intra-operative events in their sample. Pedersen and Johansen have done valuable work in pursuing types and frequencies of complications attributable to anaesthesia, but we suggest that in future studies on the incidence of awareness patients should be interviewed with scrutiny.