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Disulfiram intoxication in a child
Clinical and laboratory observations Disulfiram intoxication in a child William E. Benitz, M.D., and David S. Tatro, Pharm.D.
DISULFIRAM INHIBITS acetaldehyde dehydrogenase, which catalyzes the oxidation of acetaldehyde, the initial product of ethanol metabolism. Ingestion of ethanol while this e n z y m e is inhibited results in accumulation of acetaldehyde, causing flushing, diaphoresis, vomiting, tachycardia, headache, chest pain, dyspnea, a n d anxiety, which persist for hours. These unpleasant symptoms are the basis for use of disulfiram in alcohol rehabilitation programs, reinforcing motivation to avoid ethanol use. Disulfiram is relatively nontoxic, but untoward effects have been observed after large doses or extended periods of treatment. T h e widespread use of disulfiram (200,000 patients in the U n i t e d States at any given time; Ayerst Laboratories, telephone c o m m u n i c a t i o n , 1983) in settings associated with accidental poisoning in children (unemployment, marital discord and instability, and alcoholic family m e m bers) leads us to suspect that this intoxication m a y b e underdiagnosed in this country. W e found only six reports of childhood intoxication? -7 W e report a n additional case of disulfiram intoxication in a child, and discuss the distinctive features of this syndrome in children. CASE REPORT This 6-year-old white boy had increasing lethargy and somnolence for 3 days. Four days previously, he had complained of a sore throat, which was treated with "ampio'llin" (prescribed for a previous episode of tonsillitis) four times a day. The next day, he was mildly lethargic but alert and communicative. Two days prior to admission he vomited several times. The day before admission he had had blurred vision, difficulty walking, and drowsiness. On
From the Department of Pediatrics and the Drug Information Center, Stanford University Medical Center. Submitted for publication Nov. 17, 1983; accepted Feb. 24, 1984. Reprint requests." William E. Benitz, M.D., Division of Neonatology, Rm. $222, Stanford University Medical Center, 300 Pasteur Dr,, Stanford, CA 94305.
Stanford, California
the morning of admission he fell asleep while eating breakfast and could be aroused only with difficulty. Inspection of the bottle from which the prescribed "ampicillin" had been dispensed reveaied that, although labeled as ampicillin, it contained only disulfiram (Antabuse) 250 mg tablets. A total of 13 tablets (3250 rag) had been ingested. On further questioning, the child's mother recalled that she had transferred the disulfiram tablets to this bottle while consolidating the contents of the medicine cabinet prior to moving. Administration of ethanol (in alcoholic beverages or medicinal elixirs) and availability of other psychoactive drugs were denied. Flushing, headache, tachycardia, diaphoresis, hallucinations, bizarre ideation, and confusion were specifically denied. There had been numerous previous hospitalizations for asthma, but the child had not recently been given medication for this. Several recent episodes of tonsillitis had been treated with ampicillin. Adenoidectomy and tympanostomy had been performed at age 5 years. The patient, his mother, and her boyfriend had recently moved from another state. Neither adult was employed. His mother had taken disulfiram after a divorce 1 year previously, but was currently neither taking disulfiram nor abusing alcohol. The patient's vital signs were normal. Abnormal physical findings were limited to the neurologic examination, which revealed a somnolent child who became alert in response to painful ,stimuli or when his name was called loudly, but who quickly lapsed back into a sleeplike state. He was oriented to place, but would not state his name and was irritable when aroused. The cranial nerves were intact. The optic fundi were normal. Muscle tone was diffusely decreased. Deep-tendon reflexes were symmetric but weak. Plantar reflexes were downward. Strength, coordination, gait, and fine motor skills could not be assessed. Sensation, assessed by withdrawal in response to light pinprick, was intact. Blood counts, serum electrolytes, glucose, urea nitrogen, and creatinine values were normal. Urinalysis showed a specific gravity of 1.034, ketonuria (3+), and pH 6.0. Blood and urine toxicology screens revealed only small amounts (20 mg/dl) of acetone in the blood. He was admitted to the hospital, given maintenance fluids intravenously, and observed. The next day he was briefly spontaneously alert, answered direct questions, and was fully oriented. His muscle tone and deep-tendon reflexes returned to normal. On the second hospital day he intermittently obeyed commands and
The Journal of P E D I A T R I C S Vol. 105, No. 3, September 1984
487
488
Clinical and laboratory observations
had some spontaneous speech, but remained lethargic, irritable, and occasionallyconfused. On the third hospital day he was alert, oriented, and cooperative. Findings of neurologic examination were normal except for weakness, which was most evident while walking. At 1 and 12 weeks after discharge he had no apparent sequelae. DISCUSSION Disulfiram intoxication in childhood is characterized by lethargy or somnolence, weakness, hypotonia, and vomiting, beginning approximately 12 hours after ingestion and progressing to stupor or coma. Dehydration, moderate tachycardia, and marked tachypnea are frequently seen. Muscle tone is greatly decreased, and deep-tendon reflexes are usually weak or absent, but may be normal. Moderately stuporous or drowsy patients may manifest weakness or an apparently ataxic gait, which may be manifestations of peripheral neuropathy. There are no consistent effects on vital signs, and no focal or specific neurologic manifestations have been reported. Ketosis, often disproportionate to the degree of dehydration, has been the only consistent laboratory finding. In two patients, electroencephalograms demonstrated diffuse toxic encephalopathic changes. The presentation may mimic that of Reye syndrome, but serum transaminase and ammonia levels are normal. Several factors contribute to difficulty in diagnosis. This syndrome is distinct from the ethanol-disulfiram interaction (acetaldehyde syndrome) t and acute disulfiram intoxication in adults, in whom depression, agitation, bizarre ideation, and hallucinations are frequently seen? These were observed only in the oldest (10 years) reported child? In contrast, stupor, coma, hypotonia, and weakness are rare in adults but universal in children. Chronic intoxication in adults has been associated with ataxia, weakness, optic neuritis, peripheral neuropathy, fluctuating ptosis, anisocoria, positive Babinski reflexes, hyperreflexia, and behavioral changes similar to those seen in acute intoxications.9 Failure to recognize these distinctions may result in dismissal of the diagnosis, because the symptoms and signs observed in an intoxicated child do not conform to the pattern expected in one of these related syndromes. Because of the social stigma associated with alcoholism, the family may not acknowledge the availability of disulfiram in the home. Incorrect identification of an ingested drug is also frequent. This compromises the accuracy of the history, and it is therefore essential to examine both the container from which the potential intoxicant was dispensed and its contents. Unless the possibility of disulfiram intoxication is specifically considered, the diagnosis will not be made, even when toxic encephalopathy is suspected. Disulfiram is not detected by routine "toxic screen" studies, so laboratory
The Journal of Pediatrics September 1984
diagnosis requires specific measurement of levels of disulfiram or its metabolites in blood, urine, or exhaled air? ~ Disulfiram determinations, available from regional commercial medical laboratories, may be misleading, because the drug is very rapidly reduced in vivo and may be undetectable in serum soon after ingestion,t~ Measurement of disulfiram metabolites is not routinely available, and would be useful only for confirmation of suspected ingestion. In addition, predictions of the severity of intoxication based on measurements of levels of disulfiram or its metabolites are not reliable. These considerations underscore the importance of a carefully obtained history. There is no specific treatment. Emetics, activated charcoal, and cathartics are most useful before the onset of symptoms, but may be of some value later because a portion of the absorbed drug may be bound by the charcoal in the intestinal lumen and excreted. Exchange transfusion, dialysis, and charcoal hemoperfusion hav,e also been suggested, 7 but rapid absorption and distribution of disulfiram into fatty tissues ~~make it unlikely that these would be of significant benefit. The similarity to Reye syndrome suggests that attention to cerebral perfusion and intracranial pressure also may be appropriate. The prognosis is poor. Of the seven reported patients, only three made apparently complete recoveries. One child died after a stormy course that resembled rapidly progressive Reye syndrome.4 Three survivors had moderate or severe brain damage (mental retardation and gait abnormalities.3, 5.~,This poor outlook is also in distinct contrast to the intoxication in adults, in whom withdrawal of the drug results in complete recovery? Increased awareness of the signs and symptoms of disulfiram intoxication in children may result in more frequent diagnosis of this condition, which may allow assessment of specific therapeutic measures. REFERENCES 1. Ritchie JM: The aliphatic alcohols. In Gilman AG, Goodman LS, Gilman A, editors: The pharmacological basis of therapeutics, ed 6. New York, 1980, Macmillan, pp 387-388. 2. Wokittel E: Vergiftung mit Antabuse bei einem 10 jahrigen Madchen (Antabuse poisoning in a 10-year-old girl), Arch Kinderheilk 161:145, 1960. 3. Buksowicz C: Zespol Mozgowy u Dzriecka w Nastepstevie Ostrego Zatrucia Antabusem (Cerebral syndrome in a child following acute' Antabuse poisoning). Neurol Neurochir I Psychiatria Pol 12:293, 1962. 4. Gyntelberg AF, Hansen JPH, Steentoft A, Thamdrup E: Disulfiram-forgiftning (Disulfiram [Antabuse] poisoning). Ugeskr Laeger 130:1235, 1968. 5. Schmoigl S: Akute Disulfiram-Vergiftung bei einem Kleinkind (Acute disulfiram poisoning in a small child). Nervenarzt 41:89, 1970. 6, Brzozowska-JakowickaM, Krasowska 1: Zatrucia Antikolem u 3-Letnieg6.Chlopca(Anticol poisoningin a 3-year-old boy). Wiad Lek 24:1957, 1971.
Volume 105 Number 3
7. Reichelderfer TE: Acute disulfiram Poisoning in a child. J Studies Alcohol 30:724, 1969. 8. Hotson JR, Langston JW: Disulfiram-inducedencephalopathy. Arch NeuroI 33:141, 1976. 9. Rainey JM Jr: Disulfiram toxicity and carbon disulfide poisoning. Am J Psychiatry 134:371, 1977.
Clinical and laboratory observations
48 9
10. Brien JF, Loomis CW: Disposition and pharmacokinetics of disulfiram and calcium carbimide. Drug Metab Rev 14:113, 1983.
Effect of low-dose dopamine therapy on catecholamine values in cerebrospinal fluid in preterm neonates I. Seri, M.D., T. Tulassay, M.D., J. Kiszel, M.D., E. Sulyok, M.D., T. Ertl, M.D., J. B6dis, M.D., and S. Csiim~ir, M.D. Budapest and Pbcs, Hungary
ALTHOUGH SOME DATA ARE AVAILABLE on the effect of dopamine on neonatal cardiovascular and renal functions, ~-6its exact mechanism of action is far from clear and no information on its effect on the central nervous system monoamine metabolism and on the dopamine-mediated endocrine system can be found. Because monoamines are intimately involved in the regulation of brain growth and functions in human neonates, 7 it seemed important to investigate whether intravenously administered dopamine crosses the blood-brain barrier in preterm sick neonates, and if itdoes, whether it causes any alterations in CNS monoamine metabolism. The importance of this question is stressed by the observations that in preterm infants given dopamine for systemic hypotension5 or oliguria,6 there is marked reduction in apneic episodes (unpublished data), and decreased urinary catecholamine excretion has been reported in premature neonates with apnea) Our study was conducted to determine the effect of low-dose dopamine infusion on the dopamine and noradrenaline levels in cerebrospinal flhid in preterm infants with perinatal infections.
METHODS Patients undergoing repeat lumbar puncture were enrolled in the study. Babies with symptoms of severe C N S lesions, postasphyxia, or hemorrhage were excluded. AI~i From the 1st Department of Gynecology and Obstetrics, Neonatal Intensive Care Unit, Semmelweis University Medical School; and Clinic of Gynecology and Obstetrics, University of Pbcs. Submitted for publication Aug. 5, 1983; accepted Feb. 17, 1984. Reprint requests." lstvhn Seri, M.D., Ist Department of Gynecology and Obstetrics, Neonatal Intensive Care Unit, Semmelweis University Medical School, H-I088 Budapest, Baross U 27, Hungary.
infants studied had perinatal infections. The reason for repeated spinal taps was to reveal CNS involvement (i.e., meningitis). In patients in whom the first lumbar puncture did not verify meningitis, but with clinical symptoms suspect of CNS involvement, repeat spinal tap was performed. Three infants were found to have meningitis at the first spinal tap, and two at the second lumbar puncture. These five infants were excluded from the study, and only neonates with repeatedly negative CSF samples were finally enrolled. Among them, l0 babies had not been given dopamine before the first lumbar puncture, but DA NA
Dopamine Noradrenaline
]
dopamine infusion (1 to 4 #g/kg/min) was later initiated for oliguria or systemic hypotension; the second CSF sample was obtained during dopamine treatment. The control group consisted of seven preterm neonates who did not receive dopamine infusion either before or after the first spinal tap. The average time between the two lumbar punctures in the treated and control groups was 18 and 17.7 hours, respectively. The CSF samples were frozen immediately and stored at - 2 5 ~ C until analyzed. DA and NA concentrations were determined by the spectrofluorimetric aluminum oxide adsorption procedure as modified by Hahn, 9 as follows. A high-pressure centrifugal filtration device, constructed from a disposable syringe, was used for solid-liquid separation, and facilitated considerably the aluminum oxide adsorption method of catecholamine determination: practically 100% recovery from the adsorbent in as little as 100 tzl eluent was achieved, and the total amount of catecholamines was transferred into the microcuvette of a fluorimeter. This resulted in a significant increase of sensitivity: the detection limit for both DA and NA was 0.1 ng/ml; the
DISULFIRAM INHIBITS acetaldehyde dehydrogenase, which catalyzes the oxidation of acetaldehyde, the initial product of ethanol metabolism. Ingestion of ethanol while this e n z y m e is inhibited results in accumulation of acetaldehyde, causing flushing, diaphoresis, vomiting, tachycardia, headache, chest pain, dyspnea, a n d anxiety, which persist for hours. These unpleasant symptoms are the basis for use of disulfiram in alcohol rehabilitation programs, reinforcing motivation to avoid ethanol use. Disulfiram is relatively nontoxic, but untoward effects have been observed after large doses or extended periods of treatment. T h e widespread use of disulfiram (200,000 patients in the U n i t e d States at any given time; Ayerst Laboratories, telephone c o m m u n i c a t i o n , 1983) in settings associated with accidental poisoning in children (unemployment, marital discord and instability, and alcoholic family m e m bers) leads us to suspect that this intoxication m a y b e underdiagnosed in this country. W e found only six reports of childhood intoxication? -7 W e report a n additional case of disulfiram intoxication in a child, and discuss the distinctive features of this syndrome in children. CASE REPORT This 6-year-old white boy had increasing lethargy and somnolence for 3 days. Four days previously, he had complained of a sore throat, which was treated with "ampio'llin" (prescribed for a previous episode of tonsillitis) four times a day. The next day, he was mildly lethargic but alert and communicative. Two days prior to admission he vomited several times. The day before admission he had had blurred vision, difficulty walking, and drowsiness. On
From the Department of Pediatrics and the Drug Information Center, Stanford University Medical Center. Submitted for publication Nov. 17, 1983; accepted Feb. 24, 1984. Reprint requests." William E. Benitz, M.D., Division of Neonatology, Rm. $222, Stanford University Medical Center, 300 Pasteur Dr,, Stanford, CA 94305.
Stanford, California
the morning of admission he fell asleep while eating breakfast and could be aroused only with difficulty. Inspection of the bottle from which the prescribed "ampicillin" had been dispensed reveaied that, although labeled as ampicillin, it contained only disulfiram (Antabuse) 250 mg tablets. A total of 13 tablets (3250 rag) had been ingested. On further questioning, the child's mother recalled that she had transferred the disulfiram tablets to this bottle while consolidating the contents of the medicine cabinet prior to moving. Administration of ethanol (in alcoholic beverages or medicinal elixirs) and availability of other psychoactive drugs were denied. Flushing, headache, tachycardia, diaphoresis, hallucinations, bizarre ideation, and confusion were specifically denied. There had been numerous previous hospitalizations for asthma, but the child had not recently been given medication for this. Several recent episodes of tonsillitis had been treated with ampicillin. Adenoidectomy and tympanostomy had been performed at age 5 years. The patient, his mother, and her boyfriend had recently moved from another state. Neither adult was employed. His mother had taken disulfiram after a divorce 1 year previously, but was currently neither taking disulfiram nor abusing alcohol. The patient's vital signs were normal. Abnormal physical findings were limited to the neurologic examination, which revealed a somnolent child who became alert in response to painful ,stimuli or when his name was called loudly, but who quickly lapsed back into a sleeplike state. He was oriented to place, but would not state his name and was irritable when aroused. The cranial nerves were intact. The optic fundi were normal. Muscle tone was diffusely decreased. Deep-tendon reflexes were symmetric but weak. Plantar reflexes were downward. Strength, coordination, gait, and fine motor skills could not be assessed. Sensation, assessed by withdrawal in response to light pinprick, was intact. Blood counts, serum electrolytes, glucose, urea nitrogen, and creatinine values were normal. Urinalysis showed a specific gravity of 1.034, ketonuria (3+), and pH 6.0. Blood and urine toxicology screens revealed only small amounts (20 mg/dl) of acetone in the blood. He was admitted to the hospital, given maintenance fluids intravenously, and observed. The next day he was briefly spontaneously alert, answered direct questions, and was fully oriented. His muscle tone and deep-tendon reflexes returned to normal. On the second hospital day he intermittently obeyed commands and
The Journal of P E D I A T R I C S Vol. 105, No. 3, September 1984
487
488
Clinical and laboratory observations
had some spontaneous speech, but remained lethargic, irritable, and occasionallyconfused. On the third hospital day he was alert, oriented, and cooperative. Findings of neurologic examination were normal except for weakness, which was most evident while walking. At 1 and 12 weeks after discharge he had no apparent sequelae. DISCUSSION Disulfiram intoxication in childhood is characterized by lethargy or somnolence, weakness, hypotonia, and vomiting, beginning approximately 12 hours after ingestion and progressing to stupor or coma. Dehydration, moderate tachycardia, and marked tachypnea are frequently seen. Muscle tone is greatly decreased, and deep-tendon reflexes are usually weak or absent, but may be normal. Moderately stuporous or drowsy patients may manifest weakness or an apparently ataxic gait, which may be manifestations of peripheral neuropathy. There are no consistent effects on vital signs, and no focal or specific neurologic manifestations have been reported. Ketosis, often disproportionate to the degree of dehydration, has been the only consistent laboratory finding. In two patients, electroencephalograms demonstrated diffuse toxic encephalopathic changes. The presentation may mimic that of Reye syndrome, but serum transaminase and ammonia levels are normal. Several factors contribute to difficulty in diagnosis. This syndrome is distinct from the ethanol-disulfiram interaction (acetaldehyde syndrome) t and acute disulfiram intoxication in adults, in whom depression, agitation, bizarre ideation, and hallucinations are frequently seen? These were observed only in the oldest (10 years) reported child? In contrast, stupor, coma, hypotonia, and weakness are rare in adults but universal in children. Chronic intoxication in adults has been associated with ataxia, weakness, optic neuritis, peripheral neuropathy, fluctuating ptosis, anisocoria, positive Babinski reflexes, hyperreflexia, and behavioral changes similar to those seen in acute intoxications.9 Failure to recognize these distinctions may result in dismissal of the diagnosis, because the symptoms and signs observed in an intoxicated child do not conform to the pattern expected in one of these related syndromes. Because of the social stigma associated with alcoholism, the family may not acknowledge the availability of disulfiram in the home. Incorrect identification of an ingested drug is also frequent. This compromises the accuracy of the history, and it is therefore essential to examine both the container from which the potential intoxicant was dispensed and its contents. Unless the possibility of disulfiram intoxication is specifically considered, the diagnosis will not be made, even when toxic encephalopathy is suspected. Disulfiram is not detected by routine "toxic screen" studies, so laboratory
The Journal of Pediatrics September 1984
diagnosis requires specific measurement of levels of disulfiram or its metabolites in blood, urine, or exhaled air? ~ Disulfiram determinations, available from regional commercial medical laboratories, may be misleading, because the drug is very rapidly reduced in vivo and may be undetectable in serum soon after ingestion,t~ Measurement of disulfiram metabolites is not routinely available, and would be useful only for confirmation of suspected ingestion. In addition, predictions of the severity of intoxication based on measurements of levels of disulfiram or its metabolites are not reliable. These considerations underscore the importance of a carefully obtained history. There is no specific treatment. Emetics, activated charcoal, and cathartics are most useful before the onset of symptoms, but may be of some value later because a portion of the absorbed drug may be bound by the charcoal in the intestinal lumen and excreted. Exchange transfusion, dialysis, and charcoal hemoperfusion hav,e also been suggested, 7 but rapid absorption and distribution of disulfiram into fatty tissues ~~make it unlikely that these would be of significant benefit. The similarity to Reye syndrome suggests that attention to cerebral perfusion and intracranial pressure also may be appropriate. The prognosis is poor. Of the seven reported patients, only three made apparently complete recoveries. One child died after a stormy course that resembled rapidly progressive Reye syndrome.4 Three survivors had moderate or severe brain damage (mental retardation and gait abnormalities.3, 5.~,This poor outlook is also in distinct contrast to the intoxication in adults, in whom withdrawal of the drug results in complete recovery? Increased awareness of the signs and symptoms of disulfiram intoxication in children may result in more frequent diagnosis of this condition, which may allow assessment of specific therapeutic measures. REFERENCES 1. Ritchie JM: The aliphatic alcohols. In Gilman AG, Goodman LS, Gilman A, editors: The pharmacological basis of therapeutics, ed 6. New York, 1980, Macmillan, pp 387-388. 2. Wokittel E: Vergiftung mit Antabuse bei einem 10 jahrigen Madchen (Antabuse poisoning in a 10-year-old girl), Arch Kinderheilk 161:145, 1960. 3. Buksowicz C: Zespol Mozgowy u Dzriecka w Nastepstevie Ostrego Zatrucia Antabusem (Cerebral syndrome in a child following acute' Antabuse poisoning). Neurol Neurochir I Psychiatria Pol 12:293, 1962. 4. Gyntelberg AF, Hansen JPH, Steentoft A, Thamdrup E: Disulfiram-forgiftning (Disulfiram [Antabuse] poisoning). Ugeskr Laeger 130:1235, 1968. 5. Schmoigl S: Akute Disulfiram-Vergiftung bei einem Kleinkind (Acute disulfiram poisoning in a small child). Nervenarzt 41:89, 1970. 6, Brzozowska-JakowickaM, Krasowska 1: Zatrucia Antikolem u 3-Letnieg6.Chlopca(Anticol poisoningin a 3-year-old boy). Wiad Lek 24:1957, 1971.
Volume 105 Number 3
7. Reichelderfer TE: Acute disulfiram Poisoning in a child. J Studies Alcohol 30:724, 1969. 8. Hotson JR, Langston JW: Disulfiram-inducedencephalopathy. Arch NeuroI 33:141, 1976. 9. Rainey JM Jr: Disulfiram toxicity and carbon disulfide poisoning. Am J Psychiatry 134:371, 1977.
Clinical and laboratory observations
48 9
10. Brien JF, Loomis CW: Disposition and pharmacokinetics of disulfiram and calcium carbimide. Drug Metab Rev 14:113, 1983.
Effect of low-dose dopamine therapy on catecholamine values in cerebrospinal fluid in preterm neonates I. Seri, M.D., T. Tulassay, M.D., J. Kiszel, M.D., E. Sulyok, M.D., T. Ertl, M.D., J. B6dis, M.D., and S. Csiim~ir, M.D. Budapest and Pbcs, Hungary
ALTHOUGH SOME DATA ARE AVAILABLE on the effect of dopamine on neonatal cardiovascular and renal functions, ~-6its exact mechanism of action is far from clear and no information on its effect on the central nervous system monoamine metabolism and on the dopamine-mediated endocrine system can be found. Because monoamines are intimately involved in the regulation of brain growth and functions in human neonates, 7 it seemed important to investigate whether intravenously administered dopamine crosses the blood-brain barrier in preterm sick neonates, and if itdoes, whether it causes any alterations in CNS monoamine metabolism. The importance of this question is stressed by the observations that in preterm infants given dopamine for systemic hypotension5 or oliguria,6 there is marked reduction in apneic episodes (unpublished data), and decreased urinary catecholamine excretion has been reported in premature neonates with apnea) Our study was conducted to determine the effect of low-dose dopamine infusion on the dopamine and noradrenaline levels in cerebrospinal flhid in preterm infants with perinatal infections.
METHODS Patients undergoing repeat lumbar puncture were enrolled in the study. Babies with symptoms of severe C N S lesions, postasphyxia, or hemorrhage were excluded. AI~i From the 1st Department of Gynecology and Obstetrics, Neonatal Intensive Care Unit, Semmelweis University Medical School; and Clinic of Gynecology and Obstetrics, University of Pbcs. Submitted for publication Aug. 5, 1983; accepted Feb. 17, 1984. Reprint requests." lstvhn Seri, M.D., Ist Department of Gynecology and Obstetrics, Neonatal Intensive Care Unit, Semmelweis University Medical School, H-I088 Budapest, Baross U 27, Hungary.
infants studied had perinatal infections. The reason for repeated spinal taps was to reveal CNS involvement (i.e., meningitis). In patients in whom the first lumbar puncture did not verify meningitis, but with clinical symptoms suspect of CNS involvement, repeat spinal tap was performed. Three infants were found to have meningitis at the first spinal tap, and two at the second lumbar puncture. These five infants were excluded from the study, and only neonates with repeatedly negative CSF samples were finally enrolled. Among them, l0 babies had not been given dopamine before the first lumbar puncture, but DA NA
Dopamine Noradrenaline
]
dopamine infusion (1 to 4 #g/kg/min) was later initiated for oliguria or systemic hypotension; the second CSF sample was obtained during dopamine treatment. The control group consisted of seven preterm neonates who did not receive dopamine infusion either before or after the first spinal tap. The average time between the two lumbar punctures in the treated and control groups was 18 and 17.7 hours, respectively. The CSF samples were frozen immediately and stored at - 2 5 ~ C until analyzed. DA and NA concentrations were determined by the spectrofluorimetric aluminum oxide adsorption procedure as modified by Hahn, 9 as follows. A high-pressure centrifugal filtration device, constructed from a disposable syringe, was used for solid-liquid separation, and facilitated considerably the aluminum oxide adsorption method of catecholamine determination: practically 100% recovery from the adsorbent in as little as 100 tzl eluent was achieved, and the total amount of catecholamines was transferred into the microcuvette of a fluorimeter. This resulted in a significant increase of sensitivity: the detection limit for both DA and NA was 0.1 ng/ml; the