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Possible indomethacin-aminoglycoside interaction in preterm infants
Volume 106 Number 3
Clinical and laboratory observations
511
Clinical and laboratory observations Possible indomethacin-aminoglycoside interaction in preterm infants Yehoshua Zarfin, M.D., Gideon Koren, M.D., David Maresky, M.D., Max Perlman, M.D., and Stuart MacLeod, M.D., Ph.D. T o r o n t o , Ontari O, C a n a d a
THE COMBINED USE OF AMINOGLYCOSIDES, which are eliminated almost entirely by the kidney, ~and indomethacin, which tends to impair renal function, z may promote aminoglycoside accumulation and resulting toxicity3-5 in preterm infants. We recently reported the interaction between indometh~tcin and digoxin in this age group resulting in significant elevation of digoxin serum concentrations to potentially toxic levels.6 In the present study, we prospectively assessed the effect of indomethacin on aminoglycoside serum Concentrations when both were given in clinically recommended doses. METHODS Between May and December 1983, 22 preterm infants with a patent ductus arteriosus were given a combination of aminoglycosides (for suspected gram-negative sepsis) and indomethacin (for closure of the ductus) in the neonatal intensive care unit, The Hospital for Sick Children, Toronto. Two patients were excluded from the study because, unrelated to indomethacin therapy, they developed acute renal failure, which necessitated reduction of their aminoglycoside dosage. Twenty preterm infants (10 boys) were thus included in the final analysis. Their mean (_+SD) gestational age was 29.4 _+_2.9 weeks (range 25 to 34 weeks), and birth weights ranged from 560 to 1900 gm From the Divisions of Perinatal Medicine and Clinical Pharmacology, the Research Institute, The Hospital for Sick Children; and the Departments of Pediatrics and Pharmacology, University of Toronto. Dr. Koren is a fellow of The Hospital for Sick Ch.(ldren Foundation. Submitted for publication June 7, 1984; accepted Aug. 17, 1984. Reprint requests: G. Koren, M.D., Division of Clinical Pharmacology, The Hospital for Sick Children, 555 University Ave., Toronto, Ont., Canada M5G lX8.
(mean 1150 _+ 380 gm). Ten of the neonates were given gentamicin 3.4 to 7,5 m g / k g / d a y intravenously (mean 4.5 _+ 0.9 m g / k g / d a y ) divided into two daily doses, and 10 amikacin 12 to 20 m g / k g / d a y intravenously (mean 15.1 + 2.3 mg/kg/day), divided into two daily doses. The drugs were infused over 30 minutes. Amikacin has been in common use in our unit as part of comparative studies of nephrotoxicity.7 Indomethacin therapy was started at 4 to 16 days postnatal age (mean 7.9 -+ 4.1 days), after at least 3 days of treatment with an unchanged dose of arninoglycoside. lndomethacin was administered intravenously at a dose of 0.2 mg/kg, with up to three doses at 8-hour intervals. Before indomethacin therapy was started, a screening assessment of renal function was performed, including determination of urine output (>0.5 ml/kg/hr), BUN (<20 mg/dl), creatinine (<1.2 mg/dl), and serum electrolytes. None of the neonates received diuretics during the study period, and there was no change in intravenous electrolyte administration. After at least 3 days without change in aminoglycoside dosage or dosage interval, and before indomethacin therapy was started, both trough (predose) and peak (30 minutes after dose) aminoglycoside serum concentrations were determined from a heel prick sample. This procedure was repeated during the day following indomethacin therapy, while aminoglycoside dosage remained unchanged. Twenty-four hour urine volume, fluid input, serum creatinine concentration, BUN, and serum electrolytes were assessed the day before and the day after indomethacin administration. Gentamicin and amikacin serum concentrations were determined using an immunoenzymatic assay (EMIT; Syva Diagnostics, Palo Alto, Calif.). The values for trough and peak concentrations of aminoglycosides before and after indomethacin administration, as well as the values of seru m electrolytes, creati-
5 12
Clinical and laboratory observations
The Journal of Pediatrics March 1985
Table I. Aminoglycoside concentrations re indomethacin Before indornethacin
Gentamicin concentration 0xg/ml) Trough 3.1 • 1.2 Peak 7.6 • 1.7 Amikacin concentration (ug/ml) Trough 10.1 • 2.5 Peak 20.5 • 5.8
After indomethacin
Table II. Serum electrolytes, creatinine, urine output, and urine output/fluid intake re indomethacin
P indomethacin
4.6 • 2.0 10.1 • 2.4
<0.01 <0.001
13.0 _+ 4.0 24.0 _+ 5.0
<0.05 <0.001
Results expressed as mean • SD.
nine, urine output, and fluid intake, were compared using the Student t test for paired results. The correlation between the percentage change in aminoglycoside concentrations vs the change in the ratio 24-hour urine/fluid intake was Calculated by linear regression. Data are expressed as mean _+ 1 SD, RESULTS Significant elevation in both trough and peak concentrations of the aminoglycosides was seen in association with indomethacin therapy (Table 1). These increments in aminoglyc0side levels were paralleled by significant reduction in urine output (Table II). There was good correlation between the percentage elevation in amikacin trough levels and the percentage decrease in the ratio 24-hour urine volume/24-hour fluid intake (r = 0.69, P <0.05). No significant correlation could be found, however, between the change in the ratio urine output/fluid intake and the Change in amikacin peak levels or with similar changes in trough and peak gentamicin levels. There was a slight but significant increase in mean serum creatinine concentration (p<0.005), whereas serum sodium and chloride concentrations declined (Table II). Six of the 20 infants developed hyponatremia (Na <130 mEq/L). No significant changes in potassium or BUN concentrations were detected after indomethacin [herapy. DISCUSSION The extensive use of indomethacin to induce pharmacologic closure of patent ductus arteriosus in preterm infants is associated with acute reduction in renal function. Decreases in glomerular filtration rate, urine flow rate, free water cIearance, and electrolyte excretion have been described?.6,~-~~These observations were confirmed in our study. Inasmuch as the elimination of aminoglycosides is dependent on glomerular filtration rate,~i their administration with indomethacin creates a potential hazard of arninoglycoside accumulation. High concentrations of
Serum creatinine (mg/dl) Serum Na + (mEq/L) Serum CI- (mEq/L) Serum K+ (mEq/L) Fluid intake (ml/day) 24-Hour urine output/ fluid intake (%)
0.94 _+ 0.25
indomethacin
P
1.1 _+ 0.25 <0.005
139.0 _+ 4.6 134.0_+ 5.5 103.5• 5.8 98.7 • 6.7 4.9 • 0.66 4.99 _+ 0.64 131.0 • 30.0 144.0 • 38.0 71.1 • 20.4 47.5 _+ 15.1
<0.0005 <0.005 NS NS <0.0001
Results cxpressed as mean _+ SD. NS, not significant.
aminoglycosides are associated with nephrotoxicity,57,9 and exposure to indomethacin may lead to further insult to the kidney. Our results indicate that the dosage of gentamicin or amikacin may need to be reduced at the time of commencement of indomethacin therapy. Failure to adjust aminoglycoside dosage may result in a significant elevation in both trough and peak levels. This phenomenon is adequately explained by the indomethacin-associated reduction in renal function. It is also possible that the elevation in aminoglycoside concentrations is caused in part by their diminished volume of distribution during acute renal failure. Moreo'eer, the post-indomethacin data do not reflect a new steady-state distribution of the aminoglycosides: four to five half-lives of the aminoglycoside would need to elapse to permit achievement of new steady-state levels. During that time, which might be 40 to 50 hours in infants of :this age, the indomethacin-associated renal insufficiency may be anticipated to have subsided totally or in part. It is unlikely that the sudden elevation in serum aminoglycoside trough concentration was caused by aminoglycoside-inducednephrotoxicity, because in neonates these levels (Table I) are probably not associated with deterioration of renal function.7 Moreover, elevation of aminoglycoside levels occurred regardless of the initial concentrations, including cases in which the pre-indomethacin levels were very low. It is a common practice to assess renal function before commencing indomethacin therapy and to avoid this drug in cases of impairment. Our review indicated that reductiori of aminoglyc0side dosage did not routinely take place. A similar influence of indomethacin was previously found with digoxin; the unchanged dose of the cardiac glycoside often resulted in potentially toxic levels after the administration of indomethacin.6 Based on the above results, which were documented with the routinely recommended dosages of indomethacin and
Volume 106 Number 3
aminoglycosides, it appears advisable to consider reduction of aminoglycoside dosage prior to c o m m e n c e m e n t of indom e t h a c i n therapy. F u r t h e r a d j u s t m e n t of the aminoglycoside dose should be based on careful monitoring of its serum concentration in conjunction with assessment of the alterations in renal function caused by indomethacin. We thank Ms. Linda CiiLren for secretarial assistance.
REFERENCES 1. Goodman LS; Gilman A: The pharmacological basis of therapeutics. New York, 1980, Macmillan Publishing Co., p 1168. 2. Cifuentes PF, Olley PM, Balfe JW, Radde IC, Soldin SJ: Indomethacin and renal function in premature infants with persistent patent ductus arteriosus. J PEDIATR 95:583, 1979. 3. Lane AZ, Wr!ght GE', Blair DC: Ototoxicity and nephrotoxieity of amikacin: An overview of phase II and Phase Ill experience in the United States. Am J Med 62:911, 1977. 4. Wersall J, Lundquist PG, Bjorkroth B: Ototoxicity of gentamicin. J Infect Dis 119:410, 1969.
Clinical and laboratory observations
5 13
5. Dahlgren JG, Anderson ET, Hewitt WL: Gentamicin blood levels: A guide to nephrotoxicity. Antimicrob Agents Chemother 8:58, 1975. 6. Koren G; Zarfin Y, Perlman M, MacLeod SM: Effects of indomethacin on digoxin pharmacokineties in preterm infants. Pediatr Pharmacol 4:25, 1984. 7. Rajchgot P, Prober CG, Soldin S, Pcrlman M, Good F, Harding E, Klein J, MacLeod SM: Aminoglycoside-related nephrotoxicity in the premature infant. Clin Pharmacol Ther 35:394, t984. 8. Heyman MA: Management of PDA with prostaglandin (PG) synthetase inhibitors. Proceedings of the 75th Ross Conference on pediatric research. Columbus, Ohio, 1978, p 84. 9. Halliday HL, Hirata T, Brady JP: lndomethacin therapy for large patent ductus arteriosus in low birth weight infants: Results and complications. Pediatrics 64:154, 1979. 10. Yanagi RM, Wilson A, Newfeld EA: Indomethacin treatment for symptomatic patent ductus arteriosus: A doubleblind control study. Pediatrics 67:647, 1981. 11. Sirinavin S, McCracken GH, Nelson JD: Determining gentamicin dosage in infants and children with renal failure. J PEDIATR 96:331, ! 980.
Successful management of central sleep hypoventilation in an infant using enteral doxapram Kenneth M. Weesner, M.D., and Robert J. Boyle, M.D. W i n s t o n - S a l e m , N o r t h Carolina
CENTRAL SLEEP HYPOVENT1LATION is an u n c o m m o n condition t h a t m a y lead to respiratory failure, cor pulmonale, and d e a t h if u n t r e a t e d ) T h e usual t r e a t m e n t s for this condition include tracheostomy with long-term mechanical ventilation or d i a p h r a g m a t i c pacing) ,2 W e recently observed an infant in whom central sleep hypoventilation was successfully m a n a g e d with enterally administered doxapram. CASE REPORT This 3-month-old Oriental infant was referred to North Carolina Baptist Hospital for evaluation of cardiomegaly, cyanosis, and hypotonia. He was the product of a normal term pregnancy. On physical examination he was slightly hypotonic. His blood pressure was 75 mm Hg by oscillometric technique (Dinamapp) in
From the Department of Pediatrics, Bowman Gray School of Medicine. Submitted for publication March 2, 1984; accepted Aug. 3, 1984. Reprint requests: K. M. Weesner, M.D., Department of Pediatrics, Bowman Gray Sehool of Medicine, 300 S. Hawthorne Rd. Winston-Salem, NC 27103.
both upper and lower extremities. Respirations were 40 per minute, and pulse was 140 beats per minute. His weight was 5.6 kg, and length 62 cm. His chest was clear with the exception of left basilar rales. Cardiovascular examination revealed normal pulses, no thrills, normal St and $2 sounds, and an occasional soft regurgitant murmur at the left lower sternal border. He had no hepatosplenomegaly, and the remainder of the physical examination yielded unremarkable findings. A chest radiograph on admission revealed normal lung parenchyma with diffuse cardiomegaly. An electrocardiogram revealed right ventricular hypertrophy, and a two-dimensional echocardiogram revealed a large right ventricle with a thickened anterior wall; the right atrium was also enlarged, but the left ventricle and left atrium were normal. In several views, there was an echo-dense intraeavitary mass at the right ventricular apex, which involved some of the tricuspid valve apparatus. An initial arterial blood gas study while the patient was awake in room air revealed Po2 70 torr, Pco2 49 tort, and pH 7.48; the serum bicarbonate concentration was 35 mEq/L. Other Paco2 values during the first 3 days in the hospital were as high as 92 torr while asleep. The patient received an extensive evaluation, including electroencephalogram and computed tomography of the head; both yielded normal findings. An otolaryngology evaluation revealed no suggestion of upper airway obstruction. A 12-hour
Clinical and laboratory observations
511
Clinical and laboratory observations Possible indomethacin-aminoglycoside interaction in preterm infants Yehoshua Zarfin, M.D., Gideon Koren, M.D., David Maresky, M.D., Max Perlman, M.D., and Stuart MacLeod, M.D., Ph.D. T o r o n t o , Ontari O, C a n a d a
THE COMBINED USE OF AMINOGLYCOSIDES, which are eliminated almost entirely by the kidney, ~and indomethacin, which tends to impair renal function, z may promote aminoglycoside accumulation and resulting toxicity3-5 in preterm infants. We recently reported the interaction between indometh~tcin and digoxin in this age group resulting in significant elevation of digoxin serum concentrations to potentially toxic levels.6 In the present study, we prospectively assessed the effect of indomethacin on aminoglycoside serum Concentrations when both were given in clinically recommended doses. METHODS Between May and December 1983, 22 preterm infants with a patent ductus arteriosus were given a combination of aminoglycosides (for suspected gram-negative sepsis) and indomethacin (for closure of the ductus) in the neonatal intensive care unit, The Hospital for Sick Children, Toronto. Two patients were excluded from the study because, unrelated to indomethacin therapy, they developed acute renal failure, which necessitated reduction of their aminoglycoside dosage. Twenty preterm infants (10 boys) were thus included in the final analysis. Their mean (_+SD) gestational age was 29.4 _+_2.9 weeks (range 25 to 34 weeks), and birth weights ranged from 560 to 1900 gm From the Divisions of Perinatal Medicine and Clinical Pharmacology, the Research Institute, The Hospital for Sick Children; and the Departments of Pediatrics and Pharmacology, University of Toronto. Dr. Koren is a fellow of The Hospital for Sick Ch.(ldren Foundation. Submitted for publication June 7, 1984; accepted Aug. 17, 1984. Reprint requests: G. Koren, M.D., Division of Clinical Pharmacology, The Hospital for Sick Children, 555 University Ave., Toronto, Ont., Canada M5G lX8.
(mean 1150 _+ 380 gm). Ten of the neonates were given gentamicin 3.4 to 7,5 m g / k g / d a y intravenously (mean 4.5 _+ 0.9 m g / k g / d a y ) divided into two daily doses, and 10 amikacin 12 to 20 m g / k g / d a y intravenously (mean 15.1 + 2.3 mg/kg/day), divided into two daily doses. The drugs were infused over 30 minutes. Amikacin has been in common use in our unit as part of comparative studies of nephrotoxicity.7 Indomethacin therapy was started at 4 to 16 days postnatal age (mean 7.9 -+ 4.1 days), after at least 3 days of treatment with an unchanged dose of arninoglycoside. lndomethacin was administered intravenously at a dose of 0.2 mg/kg, with up to three doses at 8-hour intervals. Before indomethacin therapy was started, a screening assessment of renal function was performed, including determination of urine output (>0.5 ml/kg/hr), BUN (<20 mg/dl), creatinine (<1.2 mg/dl), and serum electrolytes. None of the neonates received diuretics during the study period, and there was no change in intravenous electrolyte administration. After at least 3 days without change in aminoglycoside dosage or dosage interval, and before indomethacin therapy was started, both trough (predose) and peak (30 minutes after dose) aminoglycoside serum concentrations were determined from a heel prick sample. This procedure was repeated during the day following indomethacin therapy, while aminoglycoside dosage remained unchanged. Twenty-four hour urine volume, fluid input, serum creatinine concentration, BUN, and serum electrolytes were assessed the day before and the day after indomethacin administration. Gentamicin and amikacin serum concentrations were determined using an immunoenzymatic assay (EMIT; Syva Diagnostics, Palo Alto, Calif.). The values for trough and peak concentrations of aminoglycosides before and after indomethacin administration, as well as the values of seru m electrolytes, creati-
5 12
Clinical and laboratory observations
The Journal of Pediatrics March 1985
Table I. Aminoglycoside concentrations re indomethacin Before indornethacin
Gentamicin concentration 0xg/ml) Trough 3.1 • 1.2 Peak 7.6 • 1.7 Amikacin concentration (ug/ml) Trough 10.1 • 2.5 Peak 20.5 • 5.8
After indomethacin
Table II. Serum electrolytes, creatinine, urine output, and urine output/fluid intake re indomethacin
P indomethacin
4.6 • 2.0 10.1 • 2.4
<0.01 <0.001
13.0 _+ 4.0 24.0 _+ 5.0
<0.05 <0.001
Results expressed as mean • SD.
nine, urine output, and fluid intake, were compared using the Student t test for paired results. The correlation between the percentage change in aminoglycoside concentrations vs the change in the ratio 24-hour urine/fluid intake was Calculated by linear regression. Data are expressed as mean _+ 1 SD, RESULTS Significant elevation in both trough and peak concentrations of the aminoglycosides was seen in association with indomethacin therapy (Table 1). These increments in aminoglyc0side levels were paralleled by significant reduction in urine output (Table II). There was good correlation between the percentage elevation in amikacin trough levels and the percentage decrease in the ratio 24-hour urine volume/24-hour fluid intake (r = 0.69, P <0.05). No significant correlation could be found, however, between the change in the ratio urine output/fluid intake and the Change in amikacin peak levels or with similar changes in trough and peak gentamicin levels. There was a slight but significant increase in mean serum creatinine concentration (p<0.005), whereas serum sodium and chloride concentrations declined (Table II). Six of the 20 infants developed hyponatremia (Na <130 mEq/L). No significant changes in potassium or BUN concentrations were detected after indomethacin [herapy. DISCUSSION The extensive use of indomethacin to induce pharmacologic closure of patent ductus arteriosus in preterm infants is associated with acute reduction in renal function. Decreases in glomerular filtration rate, urine flow rate, free water cIearance, and electrolyte excretion have been described?.6,~-~~These observations were confirmed in our study. Inasmuch as the elimination of aminoglycosides is dependent on glomerular filtration rate,~i their administration with indomethacin creates a potential hazard of arninoglycoside accumulation. High concentrations of
Serum creatinine (mg/dl) Serum Na + (mEq/L) Serum CI- (mEq/L) Serum K+ (mEq/L) Fluid intake (ml/day) 24-Hour urine output/ fluid intake (%)
0.94 _+ 0.25
indomethacin
P
1.1 _+ 0.25 <0.005
139.0 _+ 4.6 134.0_+ 5.5 103.5• 5.8 98.7 • 6.7 4.9 • 0.66 4.99 _+ 0.64 131.0 • 30.0 144.0 • 38.0 71.1 • 20.4 47.5 _+ 15.1
<0.0005 <0.005 NS NS <0.0001
Results cxpressed as mean _+ SD. NS, not significant.
aminoglycosides are associated with nephrotoxicity,57,9 and exposure to indomethacin may lead to further insult to the kidney. Our results indicate that the dosage of gentamicin or amikacin may need to be reduced at the time of commencement of indomethacin therapy. Failure to adjust aminoglycoside dosage may result in a significant elevation in both trough and peak levels. This phenomenon is adequately explained by the indomethacin-associated reduction in renal function. It is also possible that the elevation in aminoglycoside concentrations is caused in part by their diminished volume of distribution during acute renal failure. Moreo'eer, the post-indomethacin data do not reflect a new steady-state distribution of the aminoglycosides: four to five half-lives of the aminoglycoside would need to elapse to permit achievement of new steady-state levels. During that time, which might be 40 to 50 hours in infants of :this age, the indomethacin-associated renal insufficiency may be anticipated to have subsided totally or in part. It is unlikely that the sudden elevation in serum aminoglycoside trough concentration was caused by aminoglycoside-inducednephrotoxicity, because in neonates these levels (Table I) are probably not associated with deterioration of renal function.7 Moreover, elevation of aminoglycoside levels occurred regardless of the initial concentrations, including cases in which the pre-indomethacin levels were very low. It is a common practice to assess renal function before commencing indomethacin therapy and to avoid this drug in cases of impairment. Our review indicated that reductiori of aminoglyc0side dosage did not routinely take place. A similar influence of indomethacin was previously found with digoxin; the unchanged dose of the cardiac glycoside often resulted in potentially toxic levels after the administration of indomethacin.6 Based on the above results, which were documented with the routinely recommended dosages of indomethacin and
Volume 106 Number 3
aminoglycosides, it appears advisable to consider reduction of aminoglycoside dosage prior to c o m m e n c e m e n t of indom e t h a c i n therapy. F u r t h e r a d j u s t m e n t of the aminoglycoside dose should be based on careful monitoring of its serum concentration in conjunction with assessment of the alterations in renal function caused by indomethacin. We thank Ms. Linda CiiLren for secretarial assistance.
REFERENCES 1. Goodman LS; Gilman A: The pharmacological basis of therapeutics. New York, 1980, Macmillan Publishing Co., p 1168. 2. Cifuentes PF, Olley PM, Balfe JW, Radde IC, Soldin SJ: Indomethacin and renal function in premature infants with persistent patent ductus arteriosus. J PEDIATR 95:583, 1979. 3. Lane AZ, Wr!ght GE', Blair DC: Ototoxicity and nephrotoxieity of amikacin: An overview of phase II and Phase Ill experience in the United States. Am J Med 62:911, 1977. 4. Wersall J, Lundquist PG, Bjorkroth B: Ototoxicity of gentamicin. J Infect Dis 119:410, 1969.
Clinical and laboratory observations
5 13
5. Dahlgren JG, Anderson ET, Hewitt WL: Gentamicin blood levels: A guide to nephrotoxicity. Antimicrob Agents Chemother 8:58, 1975. 6. Koren G; Zarfin Y, Perlman M, MacLeod SM: Effects of indomethacin on digoxin pharmacokineties in preterm infants. Pediatr Pharmacol 4:25, 1984. 7. Rajchgot P, Prober CG, Soldin S, Pcrlman M, Good F, Harding E, Klein J, MacLeod SM: Aminoglycoside-related nephrotoxicity in the premature infant. Clin Pharmacol Ther 35:394, t984. 8. Heyman MA: Management of PDA with prostaglandin (PG) synthetase inhibitors. Proceedings of the 75th Ross Conference on pediatric research. Columbus, Ohio, 1978, p 84. 9. Halliday HL, Hirata T, Brady JP: lndomethacin therapy for large patent ductus arteriosus in low birth weight infants: Results and complications. Pediatrics 64:154, 1979. 10. Yanagi RM, Wilson A, Newfeld EA: Indomethacin treatment for symptomatic patent ductus arteriosus: A doubleblind control study. Pediatrics 67:647, 1981. 11. Sirinavin S, McCracken GH, Nelson JD: Determining gentamicin dosage in infants and children with renal failure. J PEDIATR 96:331, ! 980.
Successful management of central sleep hypoventilation in an infant using enteral doxapram Kenneth M. Weesner, M.D., and Robert J. Boyle, M.D. W i n s t o n - S a l e m , N o r t h Carolina
CENTRAL SLEEP HYPOVENT1LATION is an u n c o m m o n condition t h a t m a y lead to respiratory failure, cor pulmonale, and d e a t h if u n t r e a t e d ) T h e usual t r e a t m e n t s for this condition include tracheostomy with long-term mechanical ventilation or d i a p h r a g m a t i c pacing) ,2 W e recently observed an infant in whom central sleep hypoventilation was successfully m a n a g e d with enterally administered doxapram. CASE REPORT This 3-month-old Oriental infant was referred to North Carolina Baptist Hospital for evaluation of cardiomegaly, cyanosis, and hypotonia. He was the product of a normal term pregnancy. On physical examination he was slightly hypotonic. His blood pressure was 75 mm Hg by oscillometric technique (Dinamapp) in
From the Department of Pediatrics, Bowman Gray School of Medicine. Submitted for publication March 2, 1984; accepted Aug. 3, 1984. Reprint requests: K. M. Weesner, M.D., Department of Pediatrics, Bowman Gray Sehool of Medicine, 300 S. Hawthorne Rd. Winston-Salem, NC 27103.
both upper and lower extremities. Respirations were 40 per minute, and pulse was 140 beats per minute. His weight was 5.6 kg, and length 62 cm. His chest was clear with the exception of left basilar rales. Cardiovascular examination revealed normal pulses, no thrills, normal St and $2 sounds, and an occasional soft regurgitant murmur at the left lower sternal border. He had no hepatosplenomegaly, and the remainder of the physical examination yielded unremarkable findings. A chest radiograph on admission revealed normal lung parenchyma with diffuse cardiomegaly. An electrocardiogram revealed right ventricular hypertrophy, and a two-dimensional echocardiogram revealed a large right ventricle with a thickened anterior wall; the right atrium was also enlarged, but the left ventricle and left atrium were normal. In several views, there was an echo-dense intraeavitary mass at the right ventricular apex, which involved some of the tricuspid valve apparatus. An initial arterial blood gas study while the patient was awake in room air revealed Po2 70 torr, Pco2 49 tort, and pH 7.48; the serum bicarbonate concentration was 35 mEq/L. Other Paco2 values during the first 3 days in the hospital were as high as 92 torr while asleep. The patient received an extensive evaluation, including electroencephalogram and computed tomography of the head; both yielded normal findings. An otolaryngology evaluation revealed no suggestion of upper airway obstruction. A 12-hour