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NICOTINIC ACID AND SKIN TEMPERATURE
49
Relation between intravenous function. Bx
=
renal
miconazole
therapy
and
renal
biopsy.
mg daily. Supplementary intrathecal therapy was given in a dose of 20 mg on six occasions. These changes and the subsequent relationship between the serum creatinine and miconazole therapy are shown in the figure. Repeated CSF examinations showed normal biochemistry, slight pleocytosis, but no evidence of active cryptococcal infection. The timing of the serum creatinine changes in relation to the dose of miconazole suggests that this patient’s acute renal failure was a consequence of therapy with this drug. The association of renal toxicity with miconazole therapy has not previously been reported, although one patient treated with a daily dose of 2100 mg was reported to show a falling creatinine clearance from 90 to 30 ml/min.4In patients with renal failure the volume of distribution of the drug is significantly lower, so plasma levels are higherthan those found in patients with normal renal function, even though the elimination half-life does not alter with chronic renal insufficiency. Rouleaux formation and red cell agglutination occurred in our patient. These changes have been reported by others in connection with miconazole and could have contributed to the development of renal failure, but the relationship observed between the improved renal function and the reduction in drug dose in this case, suggests a direct nephrotoxic mechanism. It would therefore seem wise to modify the dosage of miconazole when it is used in patients with chronic renal insufficiency.
therapy, 3,6
Renal Unit and Department of Pathology, Queen Elizabeth Hospital, Woodville, South Australia 5011
K. N. LAI M. NEWTON A. SEYMOUR D. PUGSLEY T. JONES
NEONATAL DISTALGESIC POISONING
SIR,-A 14-day-old male infant weighing 4 43 kg was brought to
hospital as an emergency. 2 h previously his 2-year-old brother had been discovered feeding him an unknown number of ’Distalgesic’ tablets. His mother, a nurse, at first thought ingestion unlikely because of the large tablet size, but one hour later the infant became pale, drowsy, and unresponsive with shallow respirations. On arrival at hospital he was pale, mottled, and limp. His pupils were markedly constricted and he was practically apnoeic with only 4. Neill HB. Miconazole carrier
solution, hyperlipidemia and hematologic problems. N Engl J Med 1977; 296: 1479. 5. Lewi PJ, Boelaert J, Daneels R, et al. Pharmacokinetic profile of intravenous miconazole in man: Comparison of normal subjects and patients with renal insufficiency. Europ J Clin Pharmacol 1976; 10: 49-54. 6. Sung JP, Grendahl JG. Side-effects of miconazole for systemic mycoses. N Engl J Med 1977; 297: 786-87.
occasional shallow gasps. Naloxone 0 .1 mg intramuscularly resulted in complete recovery after only 20-30 s. Magnesium sulphate 500 mg in solution was administered by nasogastric tube as a cathartic. At 4 h post-ingestion the plasma paracetamol was 1 1 mmol/l. Four further episodes of apnoea occurred at 6, 7, 10, and 11 h post-ingestion. Naloxone 0 1 mg was administered intravenously on three occasions and once by intramuscular injection, with immediate response every time. The therapeutic effect was more sustained after the intramuscular dose. Plasma alanine transaminase and glucose remained normal but there was a transient rise in aspartate transaminase to 49 U/1, perhaps reflecting iatrogenic muscle trauma. He was discharged home after four days and followup has shown no sequelae. We believe this to be the youngest recorded case of distalgesic poisoning. Distalgesic (paracetamol [acetaminophen] 325 mg, dextropropoxyphene 32 5 mg) is commonly encountered in nonaccidental overdosage in adults.’ The effects reflect the separate toxicities of its two constituents. Dextropropoxyphene causes recurrent respiratory depression which can be counteracted by repeated administration of naloxone, a pure narcotic antagonist. A recent report has highlighted the safety of naloxone in neonatal narcotic poisoning in doses exceeding those recommended by the manufacturer,2and Curnock has suggested its diagnostic use in any child with unexplained respiratory depression.3The paracetamol component proved innocuous in our case; plasma levels normally "toxic" in adults are well tolerated by young children.4 An infant with codeine-induced narcosis described by Dr Wilkes and colleagues (May 23, p. 1166) required mouth-to-mouth ventilation by his general practitioner until he reached hospital. Such action is laudable but should be unnecessary. The frequency of narcotic-induced respiratory depression, both in adults and children, is such that general practitioners should perhaps carry naloxone for such emergencies. Department of Child Health, University of Glasgow, Royal Hospital for Sick Children, Glasgow G3 8SJ; and Department of Paediatrics, Stobhill General Hospital, Glasgow
J. O. BEATTIE C. P. CHEN T. H. MACDONALD
NICOTINIC ACID AND SKIN TEMPERATURE
SIR,—Dr Phillips and Dr Lightman (April 4, p. 754) found that an injection of nicotinic acid caused an increase in facial temperature of almost 3°C. We measured temperature changes after giving 200 mg nicotinic acid orally to three subjects and observed the characteristic body and facial flush.5,6 Skin temperature, measured with thermistors and infrared thermometry (AGA 680, Medical Thermovision), was no different after ingestion of nicotinic acid. Our subjects were in a constant ambient temperature of25°C. Phillips and Lightman do not mention environmental conditions in their paper. This is important since the initial facial temperatures of about 33°C in fig. 1 of their paper are low (normally 34-35°C). We wonder if their experiments were done at a lower ambient temperature than ours and whether the results they obtained are dependent upon ambient temperature. If so, their evaluation ofantiprostaglandin activity in various compounds should be done under stricter ambient temperature control. Defence and Civil Institute of Environmental Medicine, P.O. Box 2000, Downsview, Ontario M3M 3B9, Canada
1.
S. D. LIVINGSTONE L. A. KUEHN
for concern. Br Med J 1980; 280: 1045-47. 2. Gober AE, Kearns GL, Yokel RA, Danziger L. Repeated naloxone administration for morphine overdose in a 1 month old infant. Pediatrics 1979; 63: 606-08. 3. Curnock DA. Respiratory depression due to unsuspected narcotic ingestion treated with naloxone Arch Dis Childh 1978; 53: 508-9 4. Rumack BH, Peterson RG Acetaminophen overdose: Incidence, diagnosis and management in 416 patients. Pediatrics 1978; 62 (suppl): 898-903. 5. Kuehn L, Livingstone S, Limmer R, Weatherson B. The effect of ethanol consumption on human heat exchange. In: Folinsee, Wagner, Borgia, Drinkwater, Gliner, Bedi, eds. Environmental Stress. New York: Academic Press, 1978: 303-13. 6. Livingstone S, Kuehn L, Limmer R, Weatherson B. The effect of alcohol on body heat loss. Aviat Space Environ Med 1980, 51: 961-64
Young RJ, Lawson AAH. Distalgesic poisoning: Cause
Relation between intravenous function. Bx
=
renal
miconazole
therapy
and
renal
biopsy.
mg daily. Supplementary intrathecal therapy was given in a dose of 20 mg on six occasions. These changes and the subsequent relationship between the serum creatinine and miconazole therapy are shown in the figure. Repeated CSF examinations showed normal biochemistry, slight pleocytosis, but no evidence of active cryptococcal infection. The timing of the serum creatinine changes in relation to the dose of miconazole suggests that this patient’s acute renal failure was a consequence of therapy with this drug. The association of renal toxicity with miconazole therapy has not previously been reported, although one patient treated with a daily dose of 2100 mg was reported to show a falling creatinine clearance from 90 to 30 ml/min.4In patients with renal failure the volume of distribution of the drug is significantly lower, so plasma levels are higherthan those found in patients with normal renal function, even though the elimination half-life does not alter with chronic renal insufficiency. Rouleaux formation and red cell agglutination occurred in our patient. These changes have been reported by others in connection with miconazole and could have contributed to the development of renal failure, but the relationship observed between the improved renal function and the reduction in drug dose in this case, suggests a direct nephrotoxic mechanism. It would therefore seem wise to modify the dosage of miconazole when it is used in patients with chronic renal insufficiency.
therapy, 3,6
Renal Unit and Department of Pathology, Queen Elizabeth Hospital, Woodville, South Australia 5011
K. N. LAI M. NEWTON A. SEYMOUR D. PUGSLEY T. JONES
NEONATAL DISTALGESIC POISONING
SIR,-A 14-day-old male infant weighing 4 43 kg was brought to
hospital as an emergency. 2 h previously his 2-year-old brother had been discovered feeding him an unknown number of ’Distalgesic’ tablets. His mother, a nurse, at first thought ingestion unlikely because of the large tablet size, but one hour later the infant became pale, drowsy, and unresponsive with shallow respirations. On arrival at hospital he was pale, mottled, and limp. His pupils were markedly constricted and he was practically apnoeic with only 4. Neill HB. Miconazole carrier
solution, hyperlipidemia and hematologic problems. N Engl J Med 1977; 296: 1479. 5. Lewi PJ, Boelaert J, Daneels R, et al. Pharmacokinetic profile of intravenous miconazole in man: Comparison of normal subjects and patients with renal insufficiency. Europ J Clin Pharmacol 1976; 10: 49-54. 6. Sung JP, Grendahl JG. Side-effects of miconazole for systemic mycoses. N Engl J Med 1977; 297: 786-87.
occasional shallow gasps. Naloxone 0 .1 mg intramuscularly resulted in complete recovery after only 20-30 s. Magnesium sulphate 500 mg in solution was administered by nasogastric tube as a cathartic. At 4 h post-ingestion the plasma paracetamol was 1 1 mmol/l. Four further episodes of apnoea occurred at 6, 7, 10, and 11 h post-ingestion. Naloxone 0 1 mg was administered intravenously on three occasions and once by intramuscular injection, with immediate response every time. The therapeutic effect was more sustained after the intramuscular dose. Plasma alanine transaminase and glucose remained normal but there was a transient rise in aspartate transaminase to 49 U/1, perhaps reflecting iatrogenic muscle trauma. He was discharged home after four days and followup has shown no sequelae. We believe this to be the youngest recorded case of distalgesic poisoning. Distalgesic (paracetamol [acetaminophen] 325 mg, dextropropoxyphene 32 5 mg) is commonly encountered in nonaccidental overdosage in adults.’ The effects reflect the separate toxicities of its two constituents. Dextropropoxyphene causes recurrent respiratory depression which can be counteracted by repeated administration of naloxone, a pure narcotic antagonist. A recent report has highlighted the safety of naloxone in neonatal narcotic poisoning in doses exceeding those recommended by the manufacturer,2and Curnock has suggested its diagnostic use in any child with unexplained respiratory depression.3The paracetamol component proved innocuous in our case; plasma levels normally "toxic" in adults are well tolerated by young children.4 An infant with codeine-induced narcosis described by Dr Wilkes and colleagues (May 23, p. 1166) required mouth-to-mouth ventilation by his general practitioner until he reached hospital. Such action is laudable but should be unnecessary. The frequency of narcotic-induced respiratory depression, both in adults and children, is such that general practitioners should perhaps carry naloxone for such emergencies. Department of Child Health, University of Glasgow, Royal Hospital for Sick Children, Glasgow G3 8SJ; and Department of Paediatrics, Stobhill General Hospital, Glasgow
J. O. BEATTIE C. P. CHEN T. H. MACDONALD
NICOTINIC ACID AND SKIN TEMPERATURE
SIR,—Dr Phillips and Dr Lightman (April 4, p. 754) found that an injection of nicotinic acid caused an increase in facial temperature of almost 3°C. We measured temperature changes after giving 200 mg nicotinic acid orally to three subjects and observed the characteristic body and facial flush.5,6 Skin temperature, measured with thermistors and infrared thermometry (AGA 680, Medical Thermovision), was no different after ingestion of nicotinic acid. Our subjects were in a constant ambient temperature of25°C. Phillips and Lightman do not mention environmental conditions in their paper. This is important since the initial facial temperatures of about 33°C in fig. 1 of their paper are low (normally 34-35°C). We wonder if their experiments were done at a lower ambient temperature than ours and whether the results they obtained are dependent upon ambient temperature. If so, their evaluation ofantiprostaglandin activity in various compounds should be done under stricter ambient temperature control. Defence and Civil Institute of Environmental Medicine, P.O. Box 2000, Downsview, Ontario M3M 3B9, Canada
1.
S. D. LIVINGSTONE L. A. KUEHN
for concern. Br Med J 1980; 280: 1045-47. 2. Gober AE, Kearns GL, Yokel RA, Danziger L. Repeated naloxone administration for morphine overdose in a 1 month old infant. Pediatrics 1979; 63: 606-08. 3. Curnock DA. Respiratory depression due to unsuspected narcotic ingestion treated with naloxone Arch Dis Childh 1978; 53: 508-9 4. Rumack BH, Peterson RG Acetaminophen overdose: Incidence, diagnosis and management in 416 patients. Pediatrics 1978; 62 (suppl): 898-903. 5. Kuehn L, Livingstone S, Limmer R, Weatherson B. The effect of ethanol consumption on human heat exchange. In: Folinsee, Wagner, Borgia, Drinkwater, Gliner, Bedi, eds. Environmental Stress. New York: Academic Press, 1978: 303-13. 6. Livingstone S, Kuehn L, Limmer R, Weatherson B. The effect of alcohol on body heat loss. Aviat Space Environ Med 1980, 51: 961-64
Young RJ, Lawson AAH. Distalgesic poisoning: Cause