Heart rate variability and cardiac autonomic function in men with chronic alcohol dependence.

Cardiac autonomic function was studied in 23 alcohol dependent men by standard tests of autonomic function and measurement of 24 hour heart rate variability. In all there was peripheral or central nervous system damage or both. Standard tests of autonomic function showed vagal neuropathy in seven. The remainder had normal autonomic function tests. Twenty four hour heart rate variability was measured as the standard deviation of the successive differences between RR intervals from an ambulatory electrocardiogram recording. Twenty four hour heart rate variability was significantly lower in both alcohol dependent groups than in controls, but the results in the two alcohol dependent groups were not significantly different from each other. The results of standard tests of autonomic function did not distinguish between the alcohol dependent men with normal autonomic function and controls. The differences in heart rate variability between this group and the controls may have been the result of the ability of this method to detect small changes in autonomic integrity. Cardiomyopathy may also account for some of these differences and such abnormalities should be excluded before results are to be regarded as a reflection of vagal function. Twenty four hour measurement of heart rate variability may be a more useful index of cardiac vagal neuropathy than currently available tests of autonomic function.

Sleep apnoea in alcoholic patients after withdrawal.

Respiration during sleep was studied in 16 withdrawn alcoholic patients and in 12 control subjects. The alcoholic patients had increased numbers of central (P less than 0.01) and of obstructive (P less than 0.05) apnoea and of hypopnoea episodes (P less than 0.01) as compared with controls. Significant positive associations were found between the frequencies of central apnoea (P less than 0.05) or hypopnoea (P less than 0.01) and clinical evidence of central nervous system damage in the alcoholic patients. Hypopnoea also showed a significant association with vagal neuropathy (P less than 0.05), assessed by tests of cardioreflexes. We conclude that abnormal respiratory events are common in abstinent alcoholic patients and that they are likely to be at least partly related to nervous damage.

Plasma catecholamine responses to change of posture in alcoholics during withdrawal and after continued abstinence from alcohol.

Plasma catecholamine, blood pressure and heart rate responses to standing were measured in ten alcoholics during withdrawal, ten alcoholics after 2-7 weeks of abstinence from alcohol, six abstinent alcoholics with orthostatic hypotension and ten normal control subjects. Withdrawing alcoholics had supine and standing heart rates and plasma noradrenaline and adrenaline concentrations that were higher than in abstinent alcoholics or control subjects. Supine blood pressures were also higher in withdrawing alcoholics than in abstinent alcoholics or control subjects, but on standing blood pressures in withdrawing alcoholics fell, four patients having a fall of more than 30/5 mmHg. Abstinent alcoholics without orthostatic hypotension had higher basal and standing concentrations of noradrenaline than control subjects but normal heart rates and adrenaline concentrations. Abstinent alcoholics with orthostatic hypotension showed a wide range of basal plasma noradrenaline concentrations and were found to have variable plasma noradrenaline responses to standing, three subjects having normal responses and three subjects having no or little increase in plasma noradrenaline on standing. It is concluded that alcohol withdrawal is associated with increased sympathetic nervous activity, as reflected by raised supine and standing plasma concentrations of catecholamines, and that even after 2-7 weeks of abstinence from alcohol plasma noradrenaline concentrations may be higher than in control subjects. Despite increased sympathetic nervous responses to standing, alcoholics during withdrawal have impaired blood pressure control and some may exhibit orthostatic hypotension. Orthostatic hypotension may also be observed in alcoholics during continuing abstinence from alcohol; in some of these patients failure of reflex noradrenaline release in response to standing may contribute to orthostatic hypotension.

Alcoholic vagal neuropathy: recovery following prolonged abstinence.

Cardiac vagal reflexes were studied in 11 alcoholic subjects, 1 to 6 weeks after withdrawal and again after up to 27 months of continued abstinence. On initial investigation six subjects had vagal neuropathy. On the second occasion only two subjects had vagal neuropathy and significant improvement was seen in the total patient group with regard to heart rate responses to standing, Valsalva's manoeuvre and atropine infusion. Vagal neuropathy in alcoholics may be reversible with abstinence and/or improved nutrition.

Erectile impotence in chronic alcoholics.

Erectile impotence is a common complaint in alcoholics, but its mechanism is unknown. We have studied nocturnal penile erection in 13 alcoholics who complained of impotence. Seven had normal erections and their impotence was therefore psychogenic. Six were found to have diminished or absent nocturnal erections. Plasma concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were elevated in this latter group, with the exception of one patient who had only raised FSH. They also had more evidence of neurological damage than the other seven alcoholics, and two had evidence of damage to the parasympathetic nervous system. Investigation of erection during sleep in alcoholic patients with impotence may be useful in differentiating clinically between patients with psychogenic causes and patients with organic causes of impotence.

Parasympathetic denervation of the iris in alcoholics with vagal neuropathy.

Parasympathetic innervation of the pupil was studied in 30 alcoholics. Twelve alcoholics had cardiac vagal neuropathy. The resting pupillary diameters in this group were larger, and pupil responses to methacholine were greater, than in control subjects or alcoholics without vagal neuropathy. These observations imply that lesions in the parasympathetic supply to the pupil may occur in alcoholics with other evidence of autonomic neuropathy involving the parasympathetic system.

Mortality associated with alcoholism in New Zealand.

Rates of mortality were determined in patients attending an alcoholic assessment centre. The study group comprised 1068 patients, studied for a mean of 1.5 years after referral. A total of 50 deaths occurred, being four times the expected death rate in the general population. Significantly increased mortality rates were found for deaths from cirrhosis, other digestive disease, cardiovascular disease, neoplasms, trauma and alcoholism. In 15 patients death was due to definite alcohol-related causes.

Release of glucagon in male alcoholics with vagal neuropathy.

There is evidence supporting involvement of the parasympathetic nervous system in the control of glucagon secretion. We have investigated the possible role of vagal neuropathy in alcoholics as a cause of alcoholic hypoglycemia. Slow infusions of insulin (2.4 U/hr) were carried out in ten male alcoholics, four with and six without evidence of vagal neuropathy, and in six male controls. The fall in blood glucose levels and the rise in serum glucagon levels in the alcoholics with or without vagal neuropathy were not significantly different from controls. We conclude that vagal neuropathy in alcoholics has no effect on the glucagon response to hypoglycemia.

Deficient catecholamine release as the basis of orthostatic hypotension in pernicious anaemia.

A patient with peripheral neuropathy and orthostatic hypotension was found to have pernicious anaemia. Symptoms improved after vitamin B12 replacement therapy. Insulin tolerance testing showed that the patient lacked catecholamine, heart rate, and sweating responses to hypoglycaemia. This indicates that pernicious anaemia may cause orthostatic hypotension owing to failure of noradrenaline release.

Evidence of vagal neuropathy in chronic alcoholics.

Autonomic function was tested in healthy control subjects and 20 chronic alcoholic patients with varying degrees of alcohol-related peripheral and central neurological damage. The alcoholics were divided into two groups according to the severity of their symptoms and signs. The alcoholic subjects had no postural hypotension. However, heart-rate responses to Valsalva's manoeuvre, deep breathing, change in posture, baroreceptor stimulation, and atropine were lower in those alcoholics with a greater degree of peripheral and central nervous damage than in the less severely affected alcoholics and the controls. These results suggest that chronic vagal damage may be a feature of alcoholic polyneuropathy.

Sodium valproate in the treatment of the alcohol withdrawal syndrome.

The value of sodium valproate in the management of patients during withdrawal from alcohol dependence has been assessed. Alcoholic inpatients were randomly allocated to two groups - one treated with sodium valproate and the other acting as a control. All patients received multivitamins and fluid and electrolyte replacement, and some received chlormethiazole or other tranquillisers. Treatment with sodium valproate (1200 mg daily) was continued for one week. The occurrence of seizures and other withdrawal symptoms (tremulousness, nausea, sweating, disorientation) were noted daily. Forty-nine episodes of withdrawal have been included in the trial - 22 in the sodium valproate group and 27 in the control group. Five patients, all in the control group, had seizures. Other withdrawal symptoms disappeared more quickly in the sodium valproate group even though fewer patients were receiving chlormethiazole.

Intravenous phenobarbital therapy in barbiturate and other hypnosedative withdrawal reactions: a kinetic approach.

Phenobarbital (0.03 to 0.04 mg/kg/min) was infused intravenously in 7 patients with clinical hypnosedative withdrawal reaction until patients slept but were arousable. The infusion time to reach this clinical end point was 7.8 +/- 1.1 hr (mean +/- SEM), the total dose was 992 +/- 144 mg, and the peak serum phenobarbital concentration was 26.1 +/- 5.1 micrograms/ml. A user of minimal hypnosedatives required 54% less phenobarbital and 65% lower concentration than any of the abusers to reach an equivalent state of intoxication. The mean serum half-life (t 1/2) was 57.5 +/- 4.9 hr for hypnosedative abusers and 86 +/- 3 hr for 8 normal volunteers (p less than 0.001). Only the patient with the shortest t 1/2 (36.4 hr) required oral phenobarbital supplements to prevent withdrawal symptoms. Dosage supplements required can be calculated from the postinfusion rate of fall of serum phenobarbital. Slow infusion of large amounts of phenobarbital provides a safe, efficacious single-dose treatment.