POTENTIAL OF LITHIUM AS ANÆSTHETIC PREMEDICANT

1229 demonstrates that chemotherapy may be effective of the pineal region. It could be given instead of radiotherapy, at the start of treatment, as a diagnostic test. This

in

case

tumours

Neurosurgical Service and Department of Medicine, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland

N.

DE TRIBOLET L. BARRELET

FRACON GUT STERILISATION TO TREAT RECTAL FISTULA

SIR,-Dr Storring and colleagues (Oct. 22, p. 837) noted freedom from anorectal infection in neutropenic leuksemic patients given FRACON gut sterilisation (framycetin, colistin, nystatin). We found that the same regimen produced complete resolution of a high rectal fistula in a patient with aplastic anaemia. A 27-year-old man presented in May, 1975, with severe aplastic anaemia after hepatitis. He showed a transient improvement with androgen treatment but then had a series of bacterial infections including pneumonia, pharyngitis, pseudomonas septicsemia, and an ischiorectal abscess which subsequently formed a fistula-in-ano. Bone-marrow transplantation was not possible because he had no histocompatible sibling. He was given a course of antilymphocyte globulin in November, 1975, in an attempt to treat the aplasia. He was nursed with reverse-barrier precautions and given FRACON gut sterilisation with sterile food. Although he had no further serious bacterial infection after this time he still remained aplastic (typical neutrophil-count 0.4x109/1, typical platelet-count 30x 109/1). The patient was examined under general anxsthetic and the fistula was found to have a high internal opening above the levator ani. Surgery was not attempted and the patient continued to take FRACON; but the reverse barrier nursing and provision of sterile food were discontinued. Over the next 2 months the fistula slowly healed and FRACON was then stopped (figs. 1 and 2). The patient remains well and has had no further anorectal infection. This response suggests that gut decontamination with FRACON reduced the fxcal flora sufficiently to permit the fistula to

Fig. 2-Healing after

2 months of FRACON gut decontamina-

tion.

heal, despite the neutropenia. We suggest that gut decontamination may be an alternative to surgery for anorectal fissures" and fistular in neutropenic patients, and in haematologically normal patients where more rapid healing might be antici-

pated. Royal

Marsden

Hospital,

A. J. BARRETT

Sutton, Surrey SM2 5PT

M. NAUNTON MORGAN

Westminster Hospital, London SW1

K. A. NEWTON

POTENTIAL OF LITHIUM AS ANÆSTHETIC PREMEDICANT

SiR,—The objectives of anxsthetic premedication are to sedation and/or relaxation, analgesia, and reduction

produce

of metabolic rate to diminish oxygen needs and the dosage of anaesthetic required and to avoid autonomic-nervous-system effects such as secretions and stress.l Anxsthetic premedicants include the minor tranquillisers (e.g., diazepam), major tranquillisers (e.g., droperidol), barbiturates, and opiates, but all possess undesirable side-effects. Little work has been done on the interactions between anaesthetics and lithium, a mood-stabilising drug used in the treatment of manic-depressive illness. However, lithium potentiates ethanol-induced sleeping-time2 and neuromuscular blockade by muscle relaxants,3 so we have done some animal studies to compare the efficacy of lithium chloride with that of droperidol. We compared the actions of droperidol (1-33mg/kg intraperitoneally) and chronically administered (8 days) lithium (45

mg/kg intraperitoneally)

on

pentobarbitone-induced sleeping-

time and in the maximal electroshock and hot-plate analgesic tests in albino male Swiss mice. Compared with droperidol (3-41±0-23) lithium significantly decreased the latency to pentobarbitone-induced narcosis (time to loss of righting reflex) to 2-90+0-19 min as compared with saline control (3-56+0-21 min) and increased the duration of narcosis (time between loss

Fig. I-Rectal fistula

before gut decontamination.

1. Collins, V. J. Principles of Anesthesiology. Philadelphia, 1976. 2. Messiha, F. S. Pharmacology, 1976, 14, 153. 3. Hill, G. E., Wong, K. C., Hodges, M. R. Anesthesiology, 1977, 46, 122.

1230 and

with 82% of animals sleeping than 60 min (saline control duration 37-8±3-6min). Analgesia was measured as the latency before the mouse jumped from a plate maintained at 55 °C. Chronic administration of lithium exerted analgesic effects (median latency 9.0 s) when compared with saline (2.75 s), morphine 5 mg/kg

regaining of righting reflex)

more

intraperitoneally (6-0 s), or droperidol (3-0 s). Furthermore, lithium potentiated morphine analgesia (80% of animals went to the 45 s cut-off time). In electroshock, pentobarbitone 40 mg/kg intraperitoneally protected 20% of animals from full tonic seizures, whereas lithium protected 10% of animals. However, the combination of these two drugs produced a synergistic effect, protecting 46% of animals from full tonic seizures. The potentiation by lithium of pentobarbitone actions in the electroshock test parallels lithium potentiation of pentobarbitone narcosis as well as morphine analgesia. Moreover, we find that the mood-stabilising antimanic properties of lithium antagonise the excitatory induction phase of pentobarbitone narcosis in mice. Lithium is widely used as a mood stabiliser in psychiatry in manic-depressive disorders and would thus be expected to produce a smooth induction into and emergence from anesthesia. Moreover, plasma-lithium concentrations are easily monitored, and, with judicious administration, lithium is virtually free from side-effects (e.g., central depression, hypotension, and dysphoria) that are problems with every other premedicant. Furthermore, its stabilising action upon the release of thyroid hormone may make it an important adjunct in thyroid surgery. BRUCE I. DIAMOND Anesthesiology Department, HENRI S. HAVDALA Mount Sinai Hospital Medical Center, RICHARD L. BORISON Chicago, Illinois 60608 U.S.A.

SUCROSE OR GLUCOSE FOR DIARRHŒA

SIR,-Chatterjee et al.suggest that sucrose can replace gluin oral sugar-electrolyte therapy of diarrhoea and that the sodium content can be lowered. Since this research is intended to affect international distribution of prepacked oral-therapy powders, we would like to point out some of its limitations. The solution was delivered by nasogastric tube with rate and volume controlled by physicians over a 14-hour period. In practice, oral fluid is administered by mothers and drunk by children, usually quite rapidly. Since sugar intolerance is related both to concentration of the sugar and to load per unit time, the likelihood of intolerance to sucrose (more likely in diarrhoea than intolerance to glucose2) increases for children managed at home. Sucrose causes greater output of stool than does glucose,3.4 presumably because of impaired sucrase activity in diarrhoea.s Unlike glucose, the fructose generated by sucrose hydrolysis does not enhance absorption during diarrhoea.6 Chatterjee et al. gave few balance data, but the excess of intake over weight gain for the initial 12-hour period of rehydration may represent, in part, excessive stool output (intake 180 g/kg, weight cose

gain 70, excess 110). The children, as a group, remained hyponatraemic while gaining weight. Undoubtedly the hypotonic solution (with respect to. electrolytes) fostered water absorption. The linear representation of specific-gravity change is misleading, since the successive dilution of a fixed amount of plasma protein follows a logarithmic curve7-i.e., it takes considerably more Chatterjee, A., Mahalanabis, D., Jalan, K. N., Maitra, T. K., Agarwal, S. K., Bagchi, D. K. Lancet, 1977, i, 1333. 2. Lancet, 1975, i, 79. 3. Nalin, D. R. ibid. p. 1400. 4. Moenginah, P. A., Suprapto, Soenarto, J., Bachtin, M., Sutrisno, D., Sutaryo, Rohde, J. E. ibid. 1975, ii, 323. 5. Hirschhorn, N., Molla, A., Molla, A. M. Johns Hopkins med. J. 1969, 125, 1.

291. 6. Hirschhorn, N.,

Kinzie, J. S., Sachar, D. B., Northrup, R. S., Taylor, J. O., Ahmad, S. Z., Phillips, R. A. New Engl. J. Med. 1968, 279, 176.

7.

Carpenter, C. C. J. Bull. N.Y. Acad. Med. 1971, 47, 1192.

to go from a specific gravity of 1.026 to 1.023 (as Chatterjee et al. indicate) than from 1.029 (the average on admission) to 1.026. The children were therefore considerably over-

fluid

hydrated. The choice of sugar and electrolyte composition is particuin serious cases. But these children are the ones we believe we can most benefit with oral rehydration. Any national or international programme of distribution of powder packets for oral therapy ought not, therefore, to compromise the formula now in use. The data presented do not compel

larly important

change. Management Sciences for Health, Cambridge, Massachusetts 02142, U.S.A. University of Maryland School of Medicine, Baltimore, Maryland

NORBERT HIRSCHHORN DAVID R. NALIN

LATE WITHDRAWAL SYMPTOMS IN BABIES BORN TO METHADONE ADDICTS

SIR,-We have seen two babies, born to heroin addicts who had been weaned onto methadone during the pregnancy, who had no evidence of withdrawal until the end of the first week of life. A 26-year-old woman, on 40 mg methadone daily throughout pregnancy, gave birth to a baby girl at 34 weeks’ gestation, weighing 2-58 kg. The baby was well for the first 6 days. On the seventh day she was very irritable, sucking vigorously yet losing weight (2.06 kg). The bsby was sedated with chlorpromazine 0.5mg 4-hourly, and gained weight. However, on reduction of the dose of chlorpromazine to 0.5 mg 8-hourly on the eleventh day, the baby became restless, tachypnceic, and pyrexial. Chlorpromazine was required for 7

days. The second baby was born after 38 weeks’ gestation and weighing 2.85 kg to a 34-year-old woman with an 8-year history of heroin addiction. For the first 5 months of pregnancy the mother was taking 80 mg heroin and 60 mg methadone daily, but subsequently the doses were reduced, and at delivery she was taking 20 mg methadone daily and no heroin. The baby was carefully watched, and on the fourth day showed signs of hyperactivity and excessive sneezing. On day six, despite avid feeding the baby’s weight was static (2.62 kg) and she was started on 0-5 mg chlorpromazine 4-hourly. On the elevventh day, following reduction of the dose of chlorpromazine, the baby had a generalised convulsion, lasting 1 min, attributed to withdrawal, other investigations having proved negative. Previous reports have been restricted to babies born to heroin-addicted mothers. Zelson’ reported that of 384 babies born to such mothers, 67-4% had signs of withdrawal within the first 4 days and only 2 babies had withdrawal later than this. Methadone and heroin differ in their pharmacokinetics,z which may contribute to the later withdrawal signs in our babies born to methadone addicts. The half-life of methadone in adults is 18-97 h, and withdrawal does not develop in the addict for 72-96 h after the last dose. 85% of the drug is protein bound, and its slow onset and prolonged duration of action are thought to be due to its conversion to an active metabolite which is slowly excreted by the liver. The half-life of heroin metabolites is 10-44 h, 35% of the drug is protein bound, and it is conjugated with glucuronic acid and excreted primarily in the urine. These cases emphasise the need for close observation of all babies born to methadone addicts for at least 7 days. Pædiatric Unit, St. Thomas’s Hospital Medical School, London SE1 7EH 1. 2.

Zelson, C. Pediatrics, 1971, 48, 178. Way, E. L. Pharmac. Rev. 1960, 12, 383.

R. E. CHALLIS

J. W. SCOPES