[Distraction osteogenesis in the head and neck region]. / Distractieosteogenese in het hoofd-halsgebied.

Distraction osteogenesis is used in oral and maxillofacial surgery for the purpose of lengthening or widening an upper or lower jaw or to reposition the jaw to such an extent as cannot be achieved with normal osteotomy. This technique moves the parts of an osteomised bone slowly apart. Subsequently, new trabecular bone growth occurs between the separate bone parts that is then turned into bone with a normal mineralised architecture. Extraoral distractors can be fitted, activated, positioned and removed fairly easily. Distractors for intraoral placement do not cause any extraoral scars and are less burdensome in their daily use. Some distractors can impede access to the larynx and the trachea. For elective surgical procedures, the accessibility of the larynx can be judged with a laryngoscope for the induction and ending of anaesthesia. Should the intraoral or extraoral distractors form any obstruction in this process, then they should be removed. The alternatives are fibroscopic intubation and emergency tracheotomy.

[Physostigmine for the immediate treatment of a patient with the central anticholinergic syndrome induced by cocaine cut with atropine]. / Fysostigmine als acute behandeling van een patiënt met het centraal anticholinerg syndroom na gebruik van cocaïne versneden met atropine

A 34-year-old man was admitted in a coma after a nightlong abuse of cocaine and alcohol, whereupon he fell and convulsed at home. There was a fracture of the nose, hyperpyrexia, tachycardia and hypertension. Dry mouth and mydriasis were suggestive of anticholinergic poisoning. Physostigmine 3 mg were slowly administered intravenously, followed by complete neurological recovery and normalisation of the body temperature. There was no brain damage. Cocaine and atropine were found in the patient's urine. Several users of cocaine in various European countries have recently developed a central anticholinergic syndrome due to adulteration of cocaine with atropine. In the presence of indications for such an intoxication, physostigmine is the antidote of first choice.

Monitoring cobalamin inactivation during nitrous oxide anesthesia by determination of homocysteine and folate in plasma and urine.

The effects of nitrous oxide-induced cobalamin inactivation on homocysteine and folate metabolism have been investigated. Plasma levels of cobalamin, folate, homocysteine, and methionine were determined in 40 patients before and after operation under nitrous oxide anesthesia (range of exposure time, 70 to 720 minutes). Twelve patients anesthetized with total intravenous anesthesia served as control subjects (range of exposure time, 115 to 600 minutes). Postoperative plasma levels of folate and homocysteine increased (p less than 0.001) up to 220% and 310%, respectively, in nitrous oxide-exposed patients, whereas plasma levels of methionine decreased (p less than 0.025). Response occurred after 75 minutes of nitrous oxide exposure. The percentage increase of plasma folate and homocysteine correlated significantly with exposure time (p less than 0.025 and p less than 0.0001, respectively). In eight patients receiving nitrous oxide anesthesia plasma homocysteine levels had not returned to preoperative levels within 1 week (p less than 0.01). Urinary excretion of folate and homocysteine increased during and after nitrous oxide exposure (p less than 0.01 and p less than 0.002, respectively) and correlated with exposure time (p less than 0.01 and p less than 0.005, respectively). It can be concluded that disturbance of homocysteine and folate metabolism by nitrous oxide develops with little delay and return to normal levels requires several days. Elevation of plasma homocysteine levels may therefore be used for monitoring nitrous oxide-induced cobalamin inactivation.

The effects of orally active enkephalinase inhibitors on morphine withdrawal syndrome.

Considerable evidence has accumulated to suggest that intracerebroventricular administration of enkephalinase inhibitors, which do not penetrate the blood-brain barrier, significantly attenuates opioid withdrawal syndrome. Therefore, the aim of this study was to examine the effect of intraperitoneal (i.p.) administration of orally active enkephalinase inhibitors, acetorphan (2.5-20 mg kg-1) and SCH 34826 (15-120 mg kg-1). These drugs significantly decreased the severity of the naloxone precipitated withdrawal syndrome in morphine dependent rats and mice. It therefore appears that these orally active enkephalinase inhibitors are promising tools in studying modulation of opioid dependence phenomena.

Effects of eseroline on the ventilatory response to CO2.

The effect of eseroline on the normoxic hypercapnic ventilatory response was assessed in nine alpha-chloralose-urethane-anaesthetized cats. The ventilatory responses to step changes in end-tidal PCO2 were determined before (control), during i.v. infusion of eseroline (bolus of 1.2 mg.kg-1 followed by 0.65 mg.kg-1 x h-1) and 1 h after the end of the infusion. Each response was separated into central and peripheral chemoreflexes, characterized by CO2 sensitivity, time constant, time delay and apnoeic threshold. We found that eseroline depressed ventilation by affecting both tidal volume and breathing frequency. The ventilatory response to CO2 was depressed due to a decrease in the CO2 sensitivity of peripheral chemoreceptors from 0.20 to 0.12 l.min-1 x kPa-1 and in the CO2 sensitivity of central chemoreceptors from 1.04 to 0.50 l.min-1 x kPa-1 (P < 0.01). However, the ratio of these sensitivities was not changed, like the apnoeic threshold. The depressant effect was reversed by naloxone. We conclude that the depressant effect of eseroline on ventilatory response to CO2 is mainly due to an action on the respiratory integrating centres in the brainstem rather than on the CO2 sensitivity of peripheral and central chemoreceptors.

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.

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

Both the MAO-B inhibitor deprenyl (2.5-10 mg/kg, ip, 60 min prior) and the MAO-B substrate beta-phenylethylamine (PEA, 40 micrograms, icv) potentiated the analgesic action of the enkephalinase inhibitor phosphoramidon (250 micrograms, 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 micrograms, 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.

Behavioral and electrophysiological aspects of nitrous oxide dependence.

We examined the effect of 70% nitrous oxide (N2O) on locomotion and visual-evoked potentials (VEP) in rats. The animals exposed to N2O showed an initial decrease of locomotion, followed by development of tolerance and unaltered motor activity during N2O withdrawal. Similarly, an initial decrease of VEP amplitudes was followed by tolerance to N2O. In addition, some amplitudes (N2-P3, P3-N3, and N3-P4) exceeded the control values, indicating an increase of neuronal excitability of the visual system during a long lasting exposure to N2O. The increase of VEP amplitudes was further potentiated by cessation of this gas. The VEP latencies after initial increase, returned to normal and remained unaltered during N2O withdrawal suggesting that the speed of neurotransmission is not essentially changed during chronic exposure to N2O. However, a significant increase of neuronal excitability during chronic N2O exposure, which further increased by cessation of N2O, could be of clinical importance. Therefore, monitoring of VEP, particularly the amplitude values, may significantly improve a detection of altered neuronal excitability during anaesthesia and drug withdrawal.

Tolerance to N2O-induced alterations in somatosensory evoked potentials.

The effect of nitrous oxide (N2O) on somatosensory evoked potentials from the cortical (CEP) and spinal cord (SCP) regions in response to forepaw stimulation was studied in ketamine-anesthetized and mechanically ventilated rats. The CEP was recorded from the skull over the contralateral somatosensory area; the SCP was recorded from the supraspinous ligament at C57-6 and L1-2 levels of the spine. Rats were exposed to 70% N2O for 5 h, whereupon N2O was withdrawn for 2 h. Thereafter, the rats were re-exposed to N2O for 10 min. The N13-P21 component of the CEP, the slow positive wave (P2) of the segmental SCP, and the heterosegmental positive cord dorsum potential (HSP) were significantly suppressed by N2O, while the large negative (N1) component of the segmental SCP remained unchanged. A partial recovery of the CEP and HSP was observed during the 5 h of N2O anesthesia, while significant recovery of the P2 component of the SCP was not observed. The withdrawal from N2O following 5 h exposure caused an augmentation of the CEP (When compared to the control values). Re-exposure of rats to N2O again caused the suppression of these potentials as in the initial exposure. The results suggest that the phenomenon of tolerance to N2O in terms of evoked potentials develops within 5 h in the brain but not in the spinal cord.

Decrease of beta-endorphin in the brain of rats following nitrous oxide withdrawal.

beta-Endorphin levels in the whole rat brain were not changed during acute (25 min) or chronic (48 h) exposure of rats to N2O. However, a significant decrease of beta-endorphin was found in the whole brain, brain stem and subcortex during the withdrawal from chronic exposure to N2O. It has been suggested that decrease of beta-endorphin levels during N2O withdrawal could be ascribed to unspecific stress accompanying drug withdrawal. Decrease of central beta-endorphin during N2O withdrawal might have a significant modulatory effect on transmitter balance, neuronal excitability and corresponding withdrawal behaviour. Furthermore, the decrease of beta-endorphin levels in the whole brain during N2O withdrawal might contribute to the postanaesthesia N2O-excitatory syndrome in humans. This might explain the known therapeutic effect of the opioid drug, meperidine on the excitatory N2O withdrawal phenomena during recovery from N2O anaesthesia in man.

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).

Central anticholinergic syndrome (CAS) in anesthesia and intensive care.

Many of the drugs used in anesthesia and intensive care may cause blockade of the central cholinergic neurotransmission. Acetylcholine is of significance in modulation of the interaction among most other central transmitters. The clinical picture of the central cholinergic blockade, known as the central anticholinergic syndrome (CAS), is identical with the central symptoms of atropine intoxication. This behaviour consists of agitation including seizures, restlessness, hallucinations, disorientation or signs of depression such as stupor, coma and respiratory depression. Such disturbances may be induced by opiates, benzodiazepines, phenothiazines, butyrophenones, ketamine, etomidate, propofol, nitrous oxide, and halogenated inhalation anesthetics as well as by H2-blocking agents such as cimetidine. There is an individual predisposition for CAS--but unpredictable from laboratory findings or other signs. Reports of postanesthetic occurrence of the CAS requiring treatment are not unanimous, varying between 1 and 40%. Differential diagnosis of the CAS includes disorders of glucose and electrolyte metabolism, severe hormonal imbalance, respiratory disorders (hypoxia, hypercarbia), hypothermia, hyperthermia and neuropsychiatric diseases (cerebral hypoxia, stroke, catatony, acute psychosis). The CAS may considerably impair the postanesthetic period especially when agitation is prevalent, which may endanger the patient or the surgical results. The diagnosis is confirmed ex iuvantibus by the sudden increase in the acetylcholine level in the brain. This is achieved with physostigmine, a cholinesterase inhibitor able to easily cross the blood-brain barrier. Its peripheral muscarinic effects are minimal. Postanesthetic CAS can be prevented by administration of physostigmine during the anesthesia procedure. During intensive care (IC), agitated forms of CAS may occur in patients undergoing mechanical ventilation, particularly during prolonged high-dose sedation. Artificial ventilation of such patients becomes very difficult and muscle relaxation may be necessary. In these cases of IC-CAS, physostigmine is of value and has proven beneficial during weaning from mechanical ventilation. Dealing with the CAS for more than a decade has improved knowledge of the central cholinergic transmission. For example, it can be said that CAS occurs alongside general anesthesia, being no more than a frequent side-effect. Furthermore, acetylcholine is involved in nociception through the endorphinergic and the serotoninergic systems. There is a close relation between the central cholinergic transmission and actions of nitrous oxide. Moreover, cholinergic transmission is involved in withdrawal from (among others) alcohol, opiates, hallucinogens and nitrous oxide. In some intoxications with psychoactive agents, physostigmine is useful for reversal of the central nervous symptoms of the acute intoxication itself. In addition it can be used for prevention of some withdrawal states. In

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.

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.

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.

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.

[Fatal arrhythmia following administration of suxamethonium in a postpartum woman subsequently found to have dystrophia myotonica]. / Fatale hartritmestoornis na toediening van suxamethonium aan een kraamvrouw die achteraf dystrophia myotonica bleek te hebben.

A 28-year-old woman died of irreversible ventricular fibrillation after administration of succinylcholine because of post partum curettage. Afterwards it became known she had undiagnosed myotonic dystrophy. She also had metabolic acidosis because of haemorrhagic hypovolaemia resulting in a probably elevated serum K+ concentration preoperatively. Succinylcholine given to patients with myotonic dystrophy may lead to life threatening hyperkalaemia and cardiac arrest. Therapy should be aimed at immediate lowering of serum K+ concentration with calcium, sodium bicarbonate and hyperventilation.

[Submental intubation: surgical and anesthesiological aspects]. / Submentaal intuberen: chirurgische en anesthesiologische aspecten.

In patients with cranio-maxillofacial trauma and in corrections of cranio-facial anomalies submental intubation may be used during surgery and postoperatively. In the period June 2001-May 2002 submental intubation was performed on five patients with cranio-maxillofacial trauma and on two patients with cranio-facial anomalies (Dubowitz syndrome (LeFort II osteotomy and distraction) in one patient and cheilognathopalatoschisis (Le Fort I osteotomy and distraction) in the other). In accordance with the literature the submental intubation technique was a useful, fast and safe technique which provides a secure airway during surgery. No postoperative intubation-related complications were seen in the group of patients. It provides the surgeon with an excellent view of the operation field and permits optimal intra-operative control of the dental occlusion. Combined procedures by the surgeon and the anaesthetist must be planned beforehand.

[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.

Stimulus processing during apparent unconsciousness in anesthetized volunteers.

Return of motor-responses upon request as an indicator of stimulus processing during apparent unconsciousness in general anesthesia was studied in 8 healthy, male volunteers during prolonged inhalation of nitrous oxide. First the minimal effective concentration of nitrous oxide was established for each volunteer, based upon continued absence of motor-responses to repeated verbal commands. One week later this concentration of nitrous oxide was administered for a 3-hr. period; return of motor-responses after at least 30 min. of absence was considered a sign of so-called unconscious perception. Four volunteers showed return of motor-response within the 3 hr. of exposure, but two of these had been rather restless throughout the session. Results indicate that unexpected processing of information by patients may occur during presumed unconsciousness after a prolonged inhalation of nitrous oxide in general anesthesia.