[Central anticholinergic syndrome during postoperative period]. / Syndrome anticholinergique central en période postopératoire.

The central anticholinergic syndrome (CAS) includes central signs (somnolence, confusion, amnesia, agitation, hallucinations, dysarthria, ataxia, delirium, stupor, coma) and peripheral signs (dry mouth, dry skin, tachycardia, visual disturbances and difficulty in micturition). It occurs when central cholinergic sites are occupied by specific drugs and also as a result of an insufficient release of acetylcholine. The CAS can be caused by atropine sulphate, hyoscine (scopolamine), promethazine, benzodiazepines, opioids, halothane, influrane, ketamine. The incidence of CAS during the postoperative period depends on choice and dose of anaesthetic agents, type of surgery, patient's condition and diagnostic criteria. It is close to 10% following general anaesthesia and 4% following regional anaesthesia with sedation. The differential diagnosis of CAS includes an overdose of anaesthetic drugs or an alteration in pharmacokinetics, altered hydratation, electrolyte or acid-base state, hypoglycaemia, hypoxia, hypercapnia, hypocapnia, hyperthermia, hypothermia, hormonal disorders, neurological damage resulting from surgery, embolism, haemorrhage or trauma. The diagnosis of CAS is often determined by a process of exclusion and not actually made until a positive therapeutic response to physostigmine, a centrally active anticholinesterase agent has taken place.

No effect of doxapram during enflurane-nitrous oxide anesthesia.

Doxapram was administered to 50 spontaneously breathing patients receiving enflurane and nitrous oxide for surgical anesthesia. A similar group acted as control. Significant depression of ventilation did not occur in the control group of patients, nor did doxapram produce a reduction of end tidal CO2 concentrations. It is suggested that surgical stimulation and concomitant nitrous oxide administration reduced the ventilatory depressant effect of enflurane and that the effect of doxapram was attenuated by the actions of enflurane on the peripheral chemoreceptors.

[Physostigmine--recent pharmacologic data and their significance for practical use]. / Physostigmin--Neuere pharmakologische Befunde und ihre Bedeutung für den Einsatz in der Praxis.

Physostigmine is widely used for treatment of the central anticholinergic syndrome during recovery from anaesthesia. The drug is also very useful in treatment of intoxicated patients, in differential-diagnostic procedures of coma of unknown origin, and in restoration of vigilance after prolonged sedation for mechanical ventilation. Besides the specific central cholinergic action of physostigmine, several new pharmacological actions have now been established. Analgesic action is dependent on the interaction with the 5-HT (serotoninergic) system and is independent of narcotic or cholinergic agonists. The antianalgetic stress hormone, ACTH, also does not interfere with this action. Physostigmine does not interfere with the anaesthetic state when given during general anaesthesia. It attenuates several withdrawal states, especially alcohol delirium, opiate and nitrous oxide withdrawal syndromes. The drug may offer a protective mechanism against hypoxic damage of the brain and may also be beneficial in amnestic syndromes and sleep disorders. Physostigmine produces central and peripheral cardiovascular stimulation. It has been shown that physostigmine can be useful in prevention and treatment of postanaesthetic behavioural disturbances following anaesthesia with propofol. Number of indications for use of physostigmine has increased considerably.

Atropine methylbromide and glycopyrrolate. A comparative study during reversal of neuromuscular block.

Two quaternary anticholinergics, atropine methylbromide (methylatropine bromide, MAB) and glycopyrrolate (ROBINUL) were compared as adjuncts to neostigmine for the reversal of residual nondepolarising neuromuscular block. MAB 0.75 mg in combination with neostigmine 2 mg produced a marked initial rise in heart rate. This was significantly greater than that produced by the administration of glycopyrrolate 0.4 mg with neostigmine. The antisialogogue effects of the two anticholinergics were identical and the central nervous system status of the patients was similar. It is concluded that, with the doses used in this study, glycopyrrolate is a superior alternative to MAB and is the drug of choice if a quaternary ammonium anticholinergic is required.

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 degree 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.

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 micrograms 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.

Absence of electroencephalographic excitation pattern under isoflurane anesthesia.

In twelve patients the EEG was recorded under isoflurane--nitrous oxide inhalation anesthesia. A quiet EEG pattern was registered, without suppressions and seizures of spike activity which are often observed under enflurane. This was the case even when end expiratory CO2 shifted to low values (3-3.6 Vol%). In one patient the induction with N2O/O2 and thiopentone, resulted in spikes and suppression bursts on the EEG. After isoflurane was added, these changes disappeared. In another patient, epileptic EEG patterns were observed prior to the induction (confirmed by the history of the patient). During isoflurane anesthesia the epileptic waves disappeared and remained absent.

Methyl atropine bromide versus atropine sulphate. A clinical comparison.

In a double blind clinical investigation we compared methyl atropine bromide to atropine sulphate in equivalent doses for their effects on changes in the heart rate and dryness of the mouth. Drugs were administered five minutes before the induction of anesthesia. Methyl atropine bromide appeared to have a stronger positive chronotropic effect on the heart rate and a more pronounced mouth drying action. Less dysrhythmias were observed after the methyl congener. Both drugs failed to alter blood pressure significantly. We concluded that methyl atropine bromide is superior to atropine sulphate because it does not produce side effects which may cause the central anticholinergic syndrome. For clinical use, however, methyl atropine bromide should be administered only in half-equivalent dose of atropine sulphate to prevent excessive tachycardia and dryness of the mouth.

Electrocorticographic changes in cats after intoxication with anticholinergic drugs.

Atropine sulphate or atropine-methyl-bromide were administered to cats intravenously in a dose of 0.0115 mmol/kg (i.e 4 mg/kg). Electrocorticogram changes were studied. Atropine sulphate caused the classical shift of the electrocorticogram from high-frequency-low-voltage pattern to a low-frequency-high-voltage pattern. We observed no changes of the electrocorticogram after the administration of atropine-methyl-bromide.

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 patient's well-being by a withdrawal syndrome.

Practical experiences with flunitrazepam in anesthesia.

Flunitrazepam was used in general and local anesthesia. Little effect was noted on the respiratory and cardiovascular systems. In our patients there was an impressive period of amnesia and often we observed a central anticholinergic syndrome, which could be reversed by the use of physostigmine salicylate (0.04/kg body weight).

Central anticholinergic syndrome in anesthetic practice.

Anticholinergic agents may lead to a syndrome described by Longo as the Central Anticholinergic Syndrome (CAS). Patients with this syndrome exhibit one or more of the following: though impairement, disturbance of recent memory, hallucinations, ataxia, excitement, drowsiness of coma. We have reviewed our use of anticholinergics and tried to correlate it with the occurrence of the above symptomatology and have treated 200 cases in which the CAS was diagnosed with physostigmine salicylate (0.04 mg/kg). We also successfully treated 2 cases of apparently central anticholinergic hyperpyrexia in the same way. We would suggest that physostigmine be included in the armamentarium of every anesthetist to combat anticholinergic poisoning by the wide range of presently used anticholinergic drugs. (Act anaesth. belg., 1976, 27, 45-60).