- Email: [email protected]
Carnitine and neonatal lipid metabolism
848
E d i t o r i a l correspondence
The lateral decubitus position has been applied successfully by us at two other institutions. In 4 years 18 premature patients were treated via this maneuver at the University of Washington Hospital in Seattle. After treatment with decubitus positioning for periods ranging from 7 to 25 days, there was complete resolution of PIE in 16 and one responded initially but had a late recurrence. Lobectomy was required in one infant with treatment failure. One patient initially responded to 3 days of positioning for right-sided PIE, but 1 week later developed left-sided PIE that was successfully treated with 3 days of positioning. Several other patients have been successfully treated via the lateral decubitus position at Mt. Zion Hospital and Medical Center in San Francisco. We also observed one patient there in whom PIE was initially treated with extubation. Thereafter, without further exposure to positive airway pressure, the PIE progressed, resulting in mediastinal shift, contralateral atelectasis, and respiratory failure, demonstrating the susceptibility of certain predisposed neonatal lungs to this pathologic process. We continue to believe that the lateral decubitus position appears to be a relatively benign, noninvasive therapeutic maneuver that should be attempted before more invasive methods are used to treat serious focal pulmonary interstitial emphysema. However, caution should be exercised and the patient closely monitored when it is used.
Ronatd S. Cohen, M.D. Department o f Pediatrics Mt. Zion Hospital & Medical Center San Francisco, CA 94115 David K. Stevenson, M.D. Department o f Pediatrics Stanford University Stanford. CA 94305 Allan N. Schwartz, M.D. C. Benjamin Graham, M.D. Departments o f Pediatrics and Radiology Children's Orthopedics Hospital and Medical Center Seattle, WA 98105
WARNING." New umbilical catheter To the Editor." Recently, the length markings on the standard polyvinyl catheter (Argyle, Sherwood Medical Industries, St. Louis) were c h a n g e d Previously labeled with black marks at 5.10. and 15 cm. the catheters are identical except for additional markings at 20 and 25 cm. The new packaging is virtually identical to the older style, and although the label does state the new marking locations, this change is not emphasized. Moreover, this packaging is removed prior to vcsscl cannalation, thus decreasing the likelihood of prompt recognition of the altered catheter markings. Both catheters are frequently stocked side by side during the transition. We have encountered five cases in three intensive care nurseries in 1 month in which residents and fellows, unaware of this change, have inserted the catheters, following the guidelines of Dunn, ~ 10 cm beyond the intended location. This mistake is easily understood if one assumes the final marking outside the infant's body is at 15
The Journal o f Pediatrics November 1984
cm when it is actually at 25 cm. Although the errors were immediately detected in all cases, the potential for d a m a g e is substantial. We have notified the manufacturer of our concerns and hope this letter can serve as a timely warning to pediatricians.
Douglas Richardson, M.D. Mervin Yoder, M.D. Endla Anday, M.D. Division o f Neonatology Hospital o f the University o f Pennsylvania and Children's Hospital o f Philadelphia Philadelphia, PA 19104 REFERENCE
1.
Dunn P: Localization of the umbilical catheter by postmortem measurement. Arch Dis Child 42:69, 1966.
Carnitine and neonatal lipid metabolism To the Editor. The conclusion of Orzali et al? that low carnitine plasma concentrations do not necessarily indicate a depletion of body carnitine and therefore are not associated with impaired lipid utilization is probably correct in the patients (primarily term infants) studied. However, it may not be true in premature infants. We recently found a 50% decrease in liver carnitine content in premature infants who had received carnitine-free total parenteral nutrition for longer than 10 days. Premature infants also had much lower carnitine tissue reserves on the first day of life compared with full-term infants. This suggests that the possible metabolic consequences of carnitine-free nutrition are gestational age related. Accordingly, we could demonstrate impaired fatty acid oxidation and ketogenesis resulting from carnitine deficiency only in infants of <34 weeks gestation? The design of Orzali's study m a y not give a final answer to the question whether carnitine is a rate-limiting factor in fatty acid utilization: Glucose simultaneously infused with Intralipid will depress fatty acid oxidation, as the authors pointed out. Moreover, the time span of carnitine administration (4 hours) m a y not be long enough to restore carnitine-depleted tissues even if unphysiologically high doses (200 m g / k g L-carnitine) are given. In our opinion, the most important question yet to be answered is not whether the utilization of Intralipid can be pharmacologicall3 influcnccd by k-carnitine but whether carnitine mu~t be considered an essential nutrient in a defined group of infants at risk for carnitine deficiency.
Eberhard Schmidt-Sommerfeld, M.D. Duna Penn, M,D. Zemrum ff~r KitMerheilkuade Justus-Liebig-Universitgzt 6300 Giessen, West Germany REFERENCES
1.
Orzali A, Maetzke G , Donzelli F, Rubaltelli FF: Effect of carnitine on lipid metabolism in the neonate. II. Carnitine addition to lil~id infusion during prolonged total parenteral nutrition. J PEDIATn 104:436, 1984.
Volume 105 Number 5
Schmidt-Sommerfeld E, Penn D, Wolf H: Carnitine deficiency in premature infants receiving total parenteral nutrition: Effect of L-carnitine supplementation. J PEDIATR 102:931, 1983.
Rep To the Editor." We agree that it is not yet clear whether carnitine must be considered an essential nutrient in a "defined group of infants at risk for carnitine deficiency." However, the aim of our study was to investigate whether carnitine supplementation, during lipid infusion performed in the course of routine total parenteral nutrition (TPN), could increase the oxidation of fatty acids administered at the time of TPN. The results, showing a significant increase (P < 0.001) in short-chain and long-chain acylcarnifine plasma values, suggest that carnitine-depleted tissues have been sufficiently restored in the group of infants given L-carnitine infusions, Nevertheless, the fact that simultaneous glucose infusion, which is normally performed in the course of TPN, depresses fatty acid oxidation makes studies of carnitine supplementation during TPN probably unsuitable to clarify the necessit!r of carnitine supplementation in infants not receiving carnitine along with nutrition. For this reason we have determined the urinary level of dicarboxylic acids (which are increased in dietarydependent carnitine deficiency~) in groups of infants receiving TPN. Preliminary data show that these values are within the normal range even in the group not receiving carnitine supplementation. In addition, we have undertaken a study in preterm and full-term infants fed, for various medical implications, formulas not containing carnitine. The preliminary results of this study show that the group without L-earnitine supplementation has higher free fatty acid and triglyceride plasma levels. Thus our results up to the present support the concept that carnitine administration during the first months of life improves lipid metabolism, even if no important lipid metabolic imbalance has been demonstrated in infants nourished without exogenous carnitine. Alberto Orzali, M.D. Firrnino F. Rubaltelli, M.D. Neona~fd Intensive Care Unit Department o f Pediatrics University o f Padova Padova, Italy
E d i t o r i a l correspondence
849
administered intravenously in neonates receiving mechanical venti ~ation. Although they report only transient cardiovascular effects (heart rate changes) and no immediate effect on blood pressure, as we had found previously) the hypoventilation seen in 10 of their patients is more worrying. Hypoventilation is not an uncommon compilation; Bourgeois et a12 reported an acute syndrome after pancuronium administration. In our own series,3 13 of 17 infants required increased ventilator pressures after intravenous pancuronium administration (100 ~Lg/kg) to maintain adequate blood gases, as assessed by arterial sampling immediately before and within 30 minutes of the injection. However, in that series there were no other serious side effects, and the increased ventilator pressure necessary to treat the hypoventilation was not associated with an increase in air leaks. Even very preterm infants are capable of vigorous respiratory effort while receiving artificial ventilation, and although all such spontaneous respiratory interaction may not be beneficial,4 between each positive pressure inflation spontaneous breathing makes a considerable contribution to the tidal exchange. This is abolished by paralysis, and this may be the cause of the hypoventilation after pancuronium administration. The administration of pancuronium has been associated with a reduction in the incidence of pneumothoraces in infants "fighting the ventilator," and this must surely justify its continued use in carefully selected patients? However, "acute hypoventilation syndrome" occurs so frequently as to restrict the use of this drug to adequately staffed neonatal intensive care units. Anne Greenough, M.A., D.C.H., M.R.C.P. University o f Cambridge Clinical School Cambridge CB2 2QQ, England REFERENCES
1.
2.
3.
4.
Runkle B, Bancalari E: Acute cardiopulmonary effects of pancuronium bromide in mechanically ventilated newborn infants. J P~DIATR 104:614, 1984. Bourgeois J, Beithier JC, Cottancin G, Milan J J, Bethenod M: Dangers de la curarisation au cours de la ventilation artificielle ehez le nouveau-ne. Pediatric 37:101, 1982. Greenough A, Wood S, Morley C J, Davis JA: Pancuronium prevents pneumothoraces in ventilated premature babies who actively expire against positive pressure inflation. Lancet 1-1, 1984. Greenough A, Morley C J, Davis JA: The interaction of spontaneous respiration with artificial ventilation in preterm babies. J PF~TR 103:769. 198"~.
REFERENCE
1.
Slonim AE, Borum PR, Tanaka K, Stanley CA, Kassetberg AG, Greene HL, Burr IM: Dietary-dependent carnitine deficiency as a cause of nonketotic hypoglycemia in an infant. J PED)ATR 99:551, 1981.
Pancuronium administration and immediate hypoventilation To the Editor: Runkle and BancalarP reinforce previous experiencez-3 of the need for extreme caution and observation when pancuronium is
Kabuki makeup s)'lzdrome (Niikawa-Kuroki syndrome) in Europe To the Editor." In 1981 Kuroki et aU and Niikawa et al. 2 described a new f syndrome, the Kabuki m~akeup syndrome, with characteristic findings of facial dysmorphia, mental retardation, and postnatal dwarfism. Soon afterward, eight more Japanese patients were described. The only patient mentioned outside of Japan was a
E d i t o r i a l correspondence
The lateral decubitus position has been applied successfully by us at two other institutions. In 4 years 18 premature patients were treated via this maneuver at the University of Washington Hospital in Seattle. After treatment with decubitus positioning for periods ranging from 7 to 25 days, there was complete resolution of PIE in 16 and one responded initially but had a late recurrence. Lobectomy was required in one infant with treatment failure. One patient initially responded to 3 days of positioning for right-sided PIE, but 1 week later developed left-sided PIE that was successfully treated with 3 days of positioning. Several other patients have been successfully treated via the lateral decubitus position at Mt. Zion Hospital and Medical Center in San Francisco. We also observed one patient there in whom PIE was initially treated with extubation. Thereafter, without further exposure to positive airway pressure, the PIE progressed, resulting in mediastinal shift, contralateral atelectasis, and respiratory failure, demonstrating the susceptibility of certain predisposed neonatal lungs to this pathologic process. We continue to believe that the lateral decubitus position appears to be a relatively benign, noninvasive therapeutic maneuver that should be attempted before more invasive methods are used to treat serious focal pulmonary interstitial emphysema. However, caution should be exercised and the patient closely monitored when it is used.
Ronatd S. Cohen, M.D. Department o f Pediatrics Mt. Zion Hospital & Medical Center San Francisco, CA 94115 David K. Stevenson, M.D. Department o f Pediatrics Stanford University Stanford. CA 94305 Allan N. Schwartz, M.D. C. Benjamin Graham, M.D. Departments o f Pediatrics and Radiology Children's Orthopedics Hospital and Medical Center Seattle, WA 98105
WARNING." New umbilical catheter To the Editor." Recently, the length markings on the standard polyvinyl catheter (Argyle, Sherwood Medical Industries, St. Louis) were c h a n g e d Previously labeled with black marks at 5.10. and 15 cm. the catheters are identical except for additional markings at 20 and 25 cm. The new packaging is virtually identical to the older style, and although the label does state the new marking locations, this change is not emphasized. Moreover, this packaging is removed prior to vcsscl cannalation, thus decreasing the likelihood of prompt recognition of the altered catheter markings. Both catheters are frequently stocked side by side during the transition. We have encountered five cases in three intensive care nurseries in 1 month in which residents and fellows, unaware of this change, have inserted the catheters, following the guidelines of Dunn, ~ 10 cm beyond the intended location. This mistake is easily understood if one assumes the final marking outside the infant's body is at 15
The Journal o f Pediatrics November 1984
cm when it is actually at 25 cm. Although the errors were immediately detected in all cases, the potential for d a m a g e is substantial. We have notified the manufacturer of our concerns and hope this letter can serve as a timely warning to pediatricians.
Douglas Richardson, M.D. Mervin Yoder, M.D. Endla Anday, M.D. Division o f Neonatology Hospital o f the University o f Pennsylvania and Children's Hospital o f Philadelphia Philadelphia, PA 19104 REFERENCE
1.
Dunn P: Localization of the umbilical catheter by postmortem measurement. Arch Dis Child 42:69, 1966.
Carnitine and neonatal lipid metabolism To the Editor. The conclusion of Orzali et al? that low carnitine plasma concentrations do not necessarily indicate a depletion of body carnitine and therefore are not associated with impaired lipid utilization is probably correct in the patients (primarily term infants) studied. However, it may not be true in premature infants. We recently found a 50% decrease in liver carnitine content in premature infants who had received carnitine-free total parenteral nutrition for longer than 10 days. Premature infants also had much lower carnitine tissue reserves on the first day of life compared with full-term infants. This suggests that the possible metabolic consequences of carnitine-free nutrition are gestational age related. Accordingly, we could demonstrate impaired fatty acid oxidation and ketogenesis resulting from carnitine deficiency only in infants of <34 weeks gestation? The design of Orzali's study m a y not give a final answer to the question whether carnitine is a rate-limiting factor in fatty acid utilization: Glucose simultaneously infused with Intralipid will depress fatty acid oxidation, as the authors pointed out. Moreover, the time span of carnitine administration (4 hours) m a y not be long enough to restore carnitine-depleted tissues even if unphysiologically high doses (200 m g / k g L-carnitine) are given. In our opinion, the most important question yet to be answered is not whether the utilization of Intralipid can be pharmacologicall3 influcnccd by k-carnitine but whether carnitine mu~t be considered an essential nutrient in a defined group of infants at risk for carnitine deficiency.
Eberhard Schmidt-Sommerfeld, M.D. Duna Penn, M,D. Zemrum ff~r KitMerheilkuade Justus-Liebig-Universitgzt 6300 Giessen, West Germany REFERENCES
1.
Orzali A, Maetzke G , Donzelli F, Rubaltelli FF: Effect of carnitine on lipid metabolism in the neonate. II. Carnitine addition to lil~id infusion during prolonged total parenteral nutrition. J PEDIATn 104:436, 1984.
Volume 105 Number 5
Schmidt-Sommerfeld E, Penn D, Wolf H: Carnitine deficiency in premature infants receiving total parenteral nutrition: Effect of L-carnitine supplementation. J PEDIATR 102:931, 1983.
Rep To the Editor." We agree that it is not yet clear whether carnitine must be considered an essential nutrient in a "defined group of infants at risk for carnitine deficiency." However, the aim of our study was to investigate whether carnitine supplementation, during lipid infusion performed in the course of routine total parenteral nutrition (TPN), could increase the oxidation of fatty acids administered at the time of TPN. The results, showing a significant increase (P < 0.001) in short-chain and long-chain acylcarnifine plasma values, suggest that carnitine-depleted tissues have been sufficiently restored in the group of infants given L-carnitine infusions, Nevertheless, the fact that simultaneous glucose infusion, which is normally performed in the course of TPN, depresses fatty acid oxidation makes studies of carnitine supplementation during TPN probably unsuitable to clarify the necessit!r of carnitine supplementation in infants not receiving carnitine along with nutrition. For this reason we have determined the urinary level of dicarboxylic acids (which are increased in dietarydependent carnitine deficiency~) in groups of infants receiving TPN. Preliminary data show that these values are within the normal range even in the group not receiving carnitine supplementation. In addition, we have undertaken a study in preterm and full-term infants fed, for various medical implications, formulas not containing carnitine. The preliminary results of this study show that the group without L-earnitine supplementation has higher free fatty acid and triglyceride plasma levels. Thus our results up to the present support the concept that carnitine administration during the first months of life improves lipid metabolism, even if no important lipid metabolic imbalance has been demonstrated in infants nourished without exogenous carnitine. Alberto Orzali, M.D. Firrnino F. Rubaltelli, M.D. Neona~fd Intensive Care Unit Department o f Pediatrics University o f Padova Padova, Italy
E d i t o r i a l correspondence
849
administered intravenously in neonates receiving mechanical venti ~ation. Although they report only transient cardiovascular effects (heart rate changes) and no immediate effect on blood pressure, as we had found previously) the hypoventilation seen in 10 of their patients is more worrying. Hypoventilation is not an uncommon compilation; Bourgeois et a12 reported an acute syndrome after pancuronium administration. In our own series,3 13 of 17 infants required increased ventilator pressures after intravenous pancuronium administration (100 ~Lg/kg) to maintain adequate blood gases, as assessed by arterial sampling immediately before and within 30 minutes of the injection. However, in that series there were no other serious side effects, and the increased ventilator pressure necessary to treat the hypoventilation was not associated with an increase in air leaks. Even very preterm infants are capable of vigorous respiratory effort while receiving artificial ventilation, and although all such spontaneous respiratory interaction may not be beneficial,4 between each positive pressure inflation spontaneous breathing makes a considerable contribution to the tidal exchange. This is abolished by paralysis, and this may be the cause of the hypoventilation after pancuronium administration. The administration of pancuronium has been associated with a reduction in the incidence of pneumothoraces in infants "fighting the ventilator," and this must surely justify its continued use in carefully selected patients? However, "acute hypoventilation syndrome" occurs so frequently as to restrict the use of this drug to adequately staffed neonatal intensive care units. Anne Greenough, M.A., D.C.H., M.R.C.P. University o f Cambridge Clinical School Cambridge CB2 2QQ, England REFERENCES
1.
2.
3.
4.
Runkle B, Bancalari E: Acute cardiopulmonary effects of pancuronium bromide in mechanically ventilated newborn infants. J P~DIATR 104:614, 1984. Bourgeois J, Beithier JC, Cottancin G, Milan J J, Bethenod M: Dangers de la curarisation au cours de la ventilation artificielle ehez le nouveau-ne. Pediatric 37:101, 1982. Greenough A, Wood S, Morley C J, Davis JA: Pancuronium prevents pneumothoraces in ventilated premature babies who actively expire against positive pressure inflation. Lancet 1-1, 1984. Greenough A, Morley C J, Davis JA: The interaction of spontaneous respiration with artificial ventilation in preterm babies. J PF~TR 103:769. 198"~.
REFERENCE
1.
Slonim AE, Borum PR, Tanaka K, Stanley CA, Kassetberg AG, Greene HL, Burr IM: Dietary-dependent carnitine deficiency as a cause of nonketotic hypoglycemia in an infant. J PED)ATR 99:551, 1981.
Pancuronium administration and immediate hypoventilation To the Editor: Runkle and BancalarP reinforce previous experiencez-3 of the need for extreme caution and observation when pancuronium is
Kabuki makeup s)'lzdrome (Niikawa-Kuroki syndrome) in Europe To the Editor." In 1981 Kuroki et aU and Niikawa et al. 2 described a new f syndrome, the Kabuki m~akeup syndrome, with characteristic findings of facial dysmorphia, mental retardation, and postnatal dwarfism. Soon afterward, eight more Japanese patients were described. The only patient mentioned outside of Japan was a