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The effects of four different radiant warmer temperature set-points used for rewarming neonates
FETAL AND NEONATAL M E D IC I N E RichardE. Behrman,
Editor
The effects offour different radiant warmer temperature set-points usedfor rewarming neonates Temperatures for rewarming neonates have been established for convection incubators. The purpose of this study was to evaluate the effects on neonates when the skin surface was rewarmed at one of four different levels with an infra-red warmer. A total of 42 normal term neonates were lirst divided into four groups according to deep rectal temperature on admission; infants in each of the respective groups were then allotted to one of the following skin surface temperature set-point groups: 35, 36, 37, or 38~ for rewarming under a servo-controlled infra-red heat source. Although rewarming at 38 ~('100.4 ~ surface temperature bears the theoretic risk of the effects of hyperthermic stress to the neonate, particularly of apnea, the 12 infants rewarmed at this temperature set-point all achieved normal rectal temperatures significantly sooner than the infants in the other three groups without evidence of ill effects. The attainment of a rectal temperature of 37~ within the 4 hr study period and the absence of hypoglycemia in the 38 ~ skin temperature group was statistically sign([icant when compared to the frequency of occurrence in the other groups.
Kathleen J. Motil, M.D., Michael G. Blackburn, M.D.,* and
Jeanette R. Pleasure, M.D., Philadelphia, Pa.
THE IMPORTANCE of minimizing heat loss and the advantages of rapid rewarming during early neonatal adaptation are well documented. 1-5Investigations have been conducted to determine the range of ambient temperatures for providing a thermoneutral environment in convection incubators6"8 which could be expected to minimize ill effects in the immediate postnatal adjustm e n t period--in particular, the occurrence of apnea. 9,10 Infra-red warmers are used more frequently for premature and sick infantsH-14because they offer greater access to the neonate. No precise data, however, are available concerning the servo-controlled skin temperature set-points for rewarming newborn infants with these infra-red heating units. The purpose of this study was to investigate the reFrom the Division of Neonatology, Department of Pediatrics, The Medical College of Pennsylvania. Supported by the Jean Crump Memorial Fund. *Reprint address:Department of Pediatrics, The Medical College of Pennsylvania, 3300 HenryA re., Philadelphia, Pa. 19129.
Vol. 85, No. 4, pp. 546-550
sponses of normal term neonates to rewarming at one of four different temperature set-points. Heat was supplied and the temperature controlled by a servo-controlled infra-red unit. MATERIALS
AND METHODS
The following protocol was reviewed and received approval of the Clinical Investigation Committee of The Medical College of Pennsylvania prior to the commencem e n t of the study. Written parental consent was obtained for each infant included in the study. Forty-two i n f a n t s with gestational ages 37-41 wk, whose birth weights were 2,743-3,631 gm,* and who were born after uncomplicated pregnancies and deliveries were selected for study. Each infant had an Apgar score of 7 or greater at 1 and 5 min, respectively. The infants were grouped according to their deep rectal temperature on admission to the study at 0.5~ intervals be*Range encompassingthe mean + 1 SD of birth weights of term infants born at The MedicalCollegeof Pennsylvaniaduring 1972.
Volume 85 Number 4
Effects o f d(fferent temperatures for rewarming neonates
547
Table I. The number and distribution of infants in each rewarming group
Servo-controlled skin temperature setting Core temperature (~
35
36
37
38
34.5-34.9 35.0-35.4 35.5-35.9 36.0-36.4
3* 3* ---
3 3 3 3
3 3 3 3
3 3 3 3
*Study prematurelyterminatedfor one infant due to complicationsas definedin TableII. (see text). tween 34.5 and 36.4~ The infants in each group were then randomly assigned by the drawing of sealed envelopes to one of four rewarming temperature setpoints at 1~ intervals from 35-38 ~ C. No infant whose initial t e m p e r a t u r e was greater t h a n 35.4~ was assigned to the 35~ rewarming group (Table I). For the purpose of this study, successful rewarming was arbitrarily defined as the attainment of a rectal temperature of 37~ within 4 hr. The study was terminated for infants who developed any of the complications listed in Table II. All infants received standard newborn care in the delivery room including oropharyngeal suctioning, cord clamping, and physical examination before transfer to the nursery. In the neonatal unit infants were weighed and placed nude in the supine position under the servocontrolled radiant heater,* which remained in the off position until all electrodes and thermistors had been applied to the infant, the monitoring equipment standardized, and the initial blood sample drawn. The first deep rectal temperature was then recorded, the infants randomly assigned to a rewarming group, and the study immediately begun. The median time after birth at which the study was begun was approximately 25 min; it ranged from 15 to 45 rain. Deep rectal temperature was displayed by means of a direct read-out temperature monitor~" with a thermistor probe inserted 6 cm into the rectum; a second thermistor probe, connected to the servo unit, was place on the skin 2 cm above the umbilicus in the midline to regulate radiant energy output and to monitor skin temperature. Respirations and heart rate were determined by means of respiratory and cardiac monitors~; the infant's spontaneous physical activity was assessed according to the criteria of Oliver and Karlberg 15 The following clinical observations were made by one
*Models JM0015 and SPC78-1, Airshields,Inc., Warminster,Pa. tModel TM47-1,Airshields,Inc.,Warminster,Pa. *Models AM71-2and HRM74-2, Airshields,Inc., Warminster,Pa.
Table II. Criteria for premature removal of infant from study Apnea: 1. After three episodes of spontaneously resolved apnea of 20-30 sec duration 2. After two episodes of apnea requiring cutaneous stimulation between 30-45 sec 3. After apnea ) 45 sec duration Tachycardia/bradycardia: Persistent tachycardia ( ) 180/rain) or bradycardia ( (100/rain) after the first 30 min of the study Metabolic acidosis: Base excess ) --10 mEq/l after 1 hr General clinical appearance: Restlessness, tremors, poor color or general appearance
of the investigators from the onset of the study at intervals of 10 rain: rectal temperature, skin temperature, heart rate, respiratory rate, and activity. Cord blood was used for determinations of hematocrit, hemoglobin, red blood cell morphology, blood glucose concentration, pH, Pco2, and base excess. At intervals of 89 hr, capillary blood samples were collected by heel stick after the foot had been warmed for 5 rain for determinations of blood glucose, pH, Pc02, and base excess. At the termination of the study a venous sample was drawn and all determinations carried out as on the initial specimen of cord blood. An additional venous sample was collected on the third day for determinations of hematocrit, hemoglobin, red blood cell morphology, total and direct serum bilirubin concentration, pH, Pc02, and base excess. Hematocrit was measured in quadruplicate in ClayAdams Microhematocrit tubes centrifuged for 10 min at 7000 rpm. Total hemoglobin content was measured in duplicate by the cyanmethemoglobin method with a Turner Model 350 Spectrophotometer. Total and direct serum bilirubin values were determined by means of an Advanced Jackson Bilirubinometer. Blood glucose concentrations were determined in duplicate with an Ames
548
Motil, Blackburn, and Pleasure
The Journal of Pediatrics October 19 7 4
37
Table III. Number and per cent of infants developing asymptomatic hypoglycemia (blood glucose < 30 rag/100 ml) in each rewarming group. Significance of trend (p = 0.02) calculated by Rank Test method of Bross 2~
hi
hi 36 LIJ
o. 3~
0
60
120 TIME { Min)
180
240
Fig. 1. Course of mean rectal temperature of the infants in each group either until all attained 37~ rectal temperature (38~ O--Q), or until the 4 hr limit of the study (37~ O--O, 36~ h--&, 35~ A--A).
100%
~ OI
J
I
I v
I
o w
~" 12 1
~
.
T 12
0 It,l
z
,,11
,I,,I
v
360C
og o ,
, 0
60
, .......... yHH~ 120 180 TIME (Min)
0
240
Fig. 2. Cumulative number of infants attaining 37~ rectal temperatures in the study period. No infant attained 37~ rectal temperatures in the 35~ set-point group. Reflectance Meter/Dextrostix System. The pH, Pco2, and base excess were determined with a Radiometer pH Meter 22 and an Astrup AMT-1 Microtonometer System. RESULTS There was a homogeneous composition of the four rewarming set-point groups of infants with respect to gestational age, birth weight, and Apgar scores. There were no significant differences between the groups in the laboratory determinations made throughout the study, with the exception of the blood glucose values. Hypoglycemia (glucose < 30mg/100 ml) did not occur in the 12 infants in the 38~ group: three of 12 and five of 12 infants in the 37 and 36~ groups, respectively, developed asymptomatic hypoglycemia (Table III). This trend was unlikely to occur merely by chance. Owing to
Rewarming temperature set-points (~ 38 37 36
Incidence of asymptomatic hypoglycemia No. 0/12 3/12 5/12
.[
% 0
25.0 41.6
the small number o f infants in the 35~ group the frequency of hypoglycemia could not be evaluated with any confidence. There were significant differences between the groups with respect to heart and respiratory rates and to spontaneous physical activity, Fig. 1 graphically displays the mean rectal temperature of the infants in each group at 20 min intervals; Fig. 2 illustrates the cumulative numbers of infants who had attained 37~ rectal temperatures at intervals within the study period. Table IV displays the n u m b e r and the per cent of infants rewarmed to 37~ rectal temperatures within 4 hr and the mean and SD of their rewarming times. With increasingly higher skin temperature set-points there was a significant decrease in the time required for rewarming. In the 38~ group the n u m b e r of infants (12/12) rewarmed to 37~ within the 4 hr limit of the study was significantly greater, and the mean rewarming time significantly shorter, compared to all other groups. Infants who did not rewarm to a rectal temperature of 37~ within the 4 hr study period and two infants who were prematurely removed from the study were subsequently rapidly rewarmed at the 38~ set-point; there were no complications. Following the study all infants were maintained in open bassinets. Continued observation revealed no evidence of temperature aberration or untoward side effects. DISCUSSION Since the evaluation of rapid rewarming was the major objective of this investigation a limit of 4 hr was arbitrarily selected on the basis of previous studies utilizing convection incubators which indicated that a minim u m of approximately 4 hr was required for rewarming moderately chilled infants. 16Moreover, in view o f these data it was felt that hypothermia (rectal temperature less than 36.5~ extending beyond 4 hr could constitute an unnecessary stress to the neonate.
Volume 85 Number 4
No significant differences in the mean hematocrit, hemoglobin, and bilirubin values or the red blood cell morphology were observed among the groups, which might lend support to the theoretical possibility of hemoconcentration or increased hemolysis due to elevated skin temperature. Most newborn infants demonstrate some degree of metabolic acidosis at birth (base deficit 5 mEq/1) which rapidly disappears within the first 89 hr. 17,18The infants in both the 38 and 37~ rewarming groups attained normal base deficit levels within 89 hr while the 36~ rewarming group required 1 hr to achieve values <-5 mEq/ 1. Metabolic acidosis persisted in the 35~ rewarming group until 1 1/2 hr of life; this may be further evidence of the metabolic stress of prolonged hypothermia. According to Cornblath and Schwartz, 19 2.3% of normal term infants will develop significant hypoglycemia (blood glucose values below 30 mg/100 ml) within the first 4 hr of life; hypoglycemia has been observed to occur even more frequently in chilled infants. The mothers of all infants in the present study received an infusion of 5% glucose during labor and delivery; there were no significant differences in the concentrations of cord blood glucose between the four rewarming set-point groups. However, the subsequent differences in the frequency of hypoglycemia among the groups were highly significant. Asymptomatic hypoglycemia was documented with increasing frequency at each of the two temperature setpoints below 38~ and appears to be inversely related to the rewarming temperature. The absence of hypoglycemia in the 38~ group does not appear to be time related since in all groups 70% o f the a s y m p t o m a t i c hypoglycemic episodes occurred during the first 30-90 min. In the present investigation there was no evidence of significant differences in respiratory and heart rates and the variations in the spontaneous physical activities of the 38, 37, and 36~ groups. On the other hand the 35~ (95.0~ rewarming group showed a trend toward a lower mean heart rate. The study of two infants in this group was prematurely terminated; one on the basis of bradycardia and another because of poor clinical condition (marked jitteriness, peripheral cyanosis, failure to raise rectal temperature above 35~ after 3 hr of rewarming). A t the time of termination the blood glucose levels of these two infants were 60 and 40 mg/100 ml, respectively. The mean initial rectal temperatures of the infants in each study group was essentially the same (35.7~ with the exception of the 35~ group, which was composed of only infants with lower rectal temperatures (Fig. 1). Previous studies have shown that term infants rewarmed in s t a n d a r d c o n v e c t i o n incubators c o n t i n u e d to have a
Effects' of different temperatures for rewarming neonates
549
Table IV, Number and per cent in each o f the four groups of infants who attained 37~ rectal temperature within the 4 hr study period and the mean and SD of the rewarming times. Significance of trend (p = < 0.001) calculated by Rank Test method o f Bross 2~
Rewarming temperature set-points (~ 38 37 36 35
Infants attaining rectal temp. of 370(2 within 4 hr No. 12/12 7/12 2/12 0/4*
I
%
Mean and SD of rewarming time (rain)
100.0 58.3 16.7 0
104.2 _+ 36.6 174.2 _+ 64.5 228.3 _+ 28.8 > 240.0
*Two of six infants in this group did not completethe study (see text). decrease in rectal temperatures during the first 50 min of rewarming (mean 1.1~ and require a m i n i m u m of 3 hr and 45 min to restore rectal temperature to the lower 9limits of normal (36.5~ and at least 8 hr were necessary to achieve 37.0~ a6 In contrast, the infants in the present study who were rewarmed under the radiant heater at 38~ skin temperature set-point continued to have a decrease in rectal temperature for only 20 min (mean, 0.27~ and required a mean of only 1 hr and 45 min to restore rectal temperatures to 37~ Fig. 2 and Table IV illustrate that the only group in which all infants achieved normal rectal temperatures within the limit of the study period was the 38~ temperature set-point group. There was no evidence of hyperthermic stress and, furthermore, they did not demonstrate the effects of hypothermia, such as hypoglycemia, prolonged metabolic acidosis, and bradycardia as seen among infants in the other groups. A n initial cold stress at birth appears to be an important stimulus to the onset of breathing. 22,23Furthermore, there is some evidence that the thermal experience of human infants after the first week of life influences cold resistance24; however, the effects of brief initial cold exposures on homeothermic responsiveness have not been studied. The infants in the present investigation had all experienced an initial postnatal cold stress and had established normal respirations for 15-45 min prior to being rewarmed. Although apnea was anticipated, particularly in the infants in the 38~ rewarming group, it did not occur in any o f the infants studied. Anecdotes relating apneic episodes to rapid rewarming in a small number of newborn infants and experimental animals in the first few minutes of life have been reported. 21Most of the reports deal with immersion of neonates in water baths at 37~
550
Motil, Blackburn, and Pleasure
A l t h o u g h our investigation e m p l o y e d skin temperature set-points as high as 38~ there is little similarity to total i m m e r s i o n since the area of the infant's skin directly exposed to the infra-red radiation was less than 50% of the total body surface area. A p n e a has also been noted to occur in infants r e w a r m e d and m a i n t a i n e d in convection incubators. A possible explanation for the absence of apnea in this investigation in t e r m infants, as well as in the study on low-birth-weight infants carried out by Y a s h i r o a n d a s s o c i a t e s , ~4 m a y b e b a s e d o n t h e differences in the temperature of the ambient air. In an incubator, the infant breathes humidified air w a r m e d to 31-33~ whereas the infant under the radiant heater breathes r o o m air (23-25~ thereby continuously stimulating thermoreceptors in the upper respiratory tract. 24 A l t h o u g h apnea did not occur in 12 infants selected at r a n d o m in the present study, all that can be safely inferred f r o m this e x p e r i e n c e is that the " t r u e " incidence of apnea could still lie s o m e w h e r e b e t w e e n 0 and 26%. 25 We m u s t emphasize that these preliminary data are not to be interpreted as suggested guidelines for rewarming newborn infants. H o w e v e r , based on our observations in this study there may be a potential benefit f r o m rapid rewarming for sick and p r e m a t u r e infants. A n investigation with a considerably larger group of r a n d o m l y selected normal t e r m infants r e w a r m e d at the 38~ temperature set-point is presently being carried out. In addition, it is hoped that our findings stimulate replication of this investigation by others to establish the benefits and safety of this m o d e of rapid r e w a r m i n g before its introduction can be accepted in the general m a n a g e m e n t of newborn infants. REFERENCES
1. Silverman, W. A., Fertig, J. W., and Berger, A. P.: The influence of the thermal environment upon the survival of newly born premature infants, Pediatrics 22: 876, 1958. 2. Jolly, H., Molyneux, P., and Newell, D. J.: A controlled study of the effect of temperature on premature babies, J. P~DiATR.60: 889, 1962. 3. Buetow, K. C., and Klein, S. W.: Effect of maintenance of/ "normal" skin temperature on survival of infants of low birth weight, Pediatrics 34: 163, 1964. 4. Day, R. L., Caliguiri, L., Kamenski, C., and Ehrlich, F.: Body temperature and survival of premature infants, Pediatrics 34: 171, 1964. 5. Motil, K. J., and Blackburn, M. G.: Temperature regulation in the neonate: A review of the pathophysiology of thermal dynamics and methods for environmental control, Clin. Pediatr. 12: 364, 1973. 6. Oliver, T. K., Jr.: Temperature regulation and heat production in the newborn, Pediatr. Clin. North Am. 12: 765, 1965.
The Journal of Pediatrics October 19 7 4
7. Scopes, .[. W., and Ahmed, I.: Range of critical temperatures in sick and premature newborn babies, Arch. Dis. Child. 41: 417, 1966. 8. Hey, E. N., and Katz, G.: The optimum thermal environment for naked babies, Arch. Dis. Child. 45: 328, 1970. 9. Daily, W. J., Klaus, M., and Meyer, H. B.: Apnea in premature infants: Monitoring, incidence, heart rate changes, and an effect of environmental temperature, Pediatrics 43: 510, 1969. 10. Perlstein, P. H., Edwards, N. K., and Sutherland, J. M.: Apnea in premature infants and incubator-air-temperature changes, N. Engl. J. Med. 282: 461, 1970. 11. Levinson, H., Linsao, L., and Swyer, P. R.: A comparison of infra-red and convection heating for newborn infants, Lancet 2: 1346, 1966. 12. Du, J. N., and Oliver, T. K., Jr.: The baby in the delivery room, J. A. M. A. 207: 1502, 1969. 13. Dabm, L. S., and James, S.: Newborn temperature and calculated heat loss in the delivery room, Pediatrics 49: 504, 1972. 14. Yashiro, K., Adams, F. H., Emmanouilides, G. C., and Mickey, M. R.: Preliminary studies on the thermal environment of low-birth-weight infants, J. I~OIAT~. 82: 991, 1973. 15. Oliver, T. K., Jr., and Karlberg, P.: The influence of environmental temperature and 15 per cent oxygen on the gaseous metabolism of newly born infants, Acta Paediatr. 140 (Suppl): 51, 1963. 16. Miller, D. L., and Oliver, T. K., Jr.: Body temperature in the immediate neonatal period: The effect of reducing thermal losses, Am. J. Obstet. Gynecol. 94: 964, 1966. 17. Gandy, G. M., Adamson, K., Jr., Cunningham,N., Silverman, W. A., and James, L. S.: Thermal environment and acid-base homeostasis in human infants during the first few hours of life, J. Clin. Invest. 43: 751, 1964. 18. Blackburn, M. G., Mancusi-Ungaro, H. R., Jr., Orzalesi, M. M., Hobbins, J. C., and Anderson, G. G.: The effects on the neonate of the induction of labor with prostaglandin F2c` and oxytocin, Am. J. Obstet. Gynecol. 116: 847,1973. 19. Cornblath, M., and Schwartz, R.: Disorders of carbohydrate metabolism in infancy, Philadelphia, 1966, W. B. Saunders Company, pp. 34-36. 20. Bross, I. D. J.: Is there an increased risk? Fed. Am. Soc. Exp. Biol. 13: 815, 1954. 21. Oliver, T. K., scientific editor, Proc. Interdisciplinary Conference on Neonatal Respiratory Adaptation: U. S. Dept. Health, Education and Welfare, P.H.S. Publication No. 1432, Bethesda, Md. 1963. 22. Westin, B., Nyberg, R., Miller, J. A., Jr., and Wedenberg, E.: Hypothermia and transfusion with oxygenated blood in the treatment of asphyxia neonatorum, Acta Pediatr. 139 (Suppl): 162, 1951. 23. Harned, H. S., Herrington, R. T., and Ferreiro, J. I.: The effects of immersion and temperature on respiration in newborn lambs, Pediatrics 45: 598, 1970. 24. Glass, L., Silverman, W. A., and Sinclair, J. C.: Effect of the thermal environment on cold resistance and growth of infants after the first week of life, Pediatrics 41: 1033, 1968. 25. Mainland, D.: Elementary medical statistics, ed. 2, Philadelphia, 1963, W. B. Saunders Company.
Editor
The effects offour different radiant warmer temperature set-points usedfor rewarming neonates Temperatures for rewarming neonates have been established for convection incubators. The purpose of this study was to evaluate the effects on neonates when the skin surface was rewarmed at one of four different levels with an infra-red warmer. A total of 42 normal term neonates were lirst divided into four groups according to deep rectal temperature on admission; infants in each of the respective groups were then allotted to one of the following skin surface temperature set-point groups: 35, 36, 37, or 38~ for rewarming under a servo-controlled infra-red heat source. Although rewarming at 38 ~('100.4 ~ surface temperature bears the theoretic risk of the effects of hyperthermic stress to the neonate, particularly of apnea, the 12 infants rewarmed at this temperature set-point all achieved normal rectal temperatures significantly sooner than the infants in the other three groups without evidence of ill effects. The attainment of a rectal temperature of 37~ within the 4 hr study period and the absence of hypoglycemia in the 38 ~ skin temperature group was statistically sign([icant when compared to the frequency of occurrence in the other groups.
Kathleen J. Motil, M.D., Michael G. Blackburn, M.D.,* and
Jeanette R. Pleasure, M.D., Philadelphia, Pa.
THE IMPORTANCE of minimizing heat loss and the advantages of rapid rewarming during early neonatal adaptation are well documented. 1-5Investigations have been conducted to determine the range of ambient temperatures for providing a thermoneutral environment in convection incubators6"8 which could be expected to minimize ill effects in the immediate postnatal adjustm e n t period--in particular, the occurrence of apnea. 9,10 Infra-red warmers are used more frequently for premature and sick infantsH-14because they offer greater access to the neonate. No precise data, however, are available concerning the servo-controlled skin temperature set-points for rewarming newborn infants with these infra-red heating units. The purpose of this study was to investigate the reFrom the Division of Neonatology, Department of Pediatrics, The Medical College of Pennsylvania. Supported by the Jean Crump Memorial Fund. *Reprint address:Department of Pediatrics, The Medical College of Pennsylvania, 3300 HenryA re., Philadelphia, Pa. 19129.
Vol. 85, No. 4, pp. 546-550
sponses of normal term neonates to rewarming at one of four different temperature set-points. Heat was supplied and the temperature controlled by a servo-controlled infra-red unit. MATERIALS
AND METHODS
The following protocol was reviewed and received approval of the Clinical Investigation Committee of The Medical College of Pennsylvania prior to the commencem e n t of the study. Written parental consent was obtained for each infant included in the study. Forty-two i n f a n t s with gestational ages 37-41 wk, whose birth weights were 2,743-3,631 gm,* and who were born after uncomplicated pregnancies and deliveries were selected for study. Each infant had an Apgar score of 7 or greater at 1 and 5 min, respectively. The infants were grouped according to their deep rectal temperature on admission to the study at 0.5~ intervals be*Range encompassingthe mean + 1 SD of birth weights of term infants born at The MedicalCollegeof Pennsylvaniaduring 1972.
Volume 85 Number 4
Effects o f d(fferent temperatures for rewarming neonates
547
Table I. The number and distribution of infants in each rewarming group
Servo-controlled skin temperature setting Core temperature (~
35
36
37
38
34.5-34.9 35.0-35.4 35.5-35.9 36.0-36.4
3* 3* ---
3 3 3 3
3 3 3 3
3 3 3 3
*Study prematurelyterminatedfor one infant due to complicationsas definedin TableII. (see text). tween 34.5 and 36.4~ The infants in each group were then randomly assigned by the drawing of sealed envelopes to one of four rewarming temperature setpoints at 1~ intervals from 35-38 ~ C. No infant whose initial t e m p e r a t u r e was greater t h a n 35.4~ was assigned to the 35~ rewarming group (Table I). For the purpose of this study, successful rewarming was arbitrarily defined as the attainment of a rectal temperature of 37~ within 4 hr. The study was terminated for infants who developed any of the complications listed in Table II. All infants received standard newborn care in the delivery room including oropharyngeal suctioning, cord clamping, and physical examination before transfer to the nursery. In the neonatal unit infants were weighed and placed nude in the supine position under the servocontrolled radiant heater,* which remained in the off position until all electrodes and thermistors had been applied to the infant, the monitoring equipment standardized, and the initial blood sample drawn. The first deep rectal temperature was then recorded, the infants randomly assigned to a rewarming group, and the study immediately begun. The median time after birth at which the study was begun was approximately 25 min; it ranged from 15 to 45 rain. Deep rectal temperature was displayed by means of a direct read-out temperature monitor~" with a thermistor probe inserted 6 cm into the rectum; a second thermistor probe, connected to the servo unit, was place on the skin 2 cm above the umbilicus in the midline to regulate radiant energy output and to monitor skin temperature. Respirations and heart rate were determined by means of respiratory and cardiac monitors~; the infant's spontaneous physical activity was assessed according to the criteria of Oliver and Karlberg 15 The following clinical observations were made by one
*Models JM0015 and SPC78-1, Airshields,Inc., Warminster,Pa. tModel TM47-1,Airshields,Inc.,Warminster,Pa. *Models AM71-2and HRM74-2, Airshields,Inc., Warminster,Pa.
Table II. Criteria for premature removal of infant from study Apnea: 1. After three episodes of spontaneously resolved apnea of 20-30 sec duration 2. After two episodes of apnea requiring cutaneous stimulation between 30-45 sec 3. After apnea ) 45 sec duration Tachycardia/bradycardia: Persistent tachycardia ( ) 180/rain) or bradycardia ( (100/rain) after the first 30 min of the study Metabolic acidosis: Base excess ) --10 mEq/l after 1 hr General clinical appearance: Restlessness, tremors, poor color or general appearance
of the investigators from the onset of the study at intervals of 10 rain: rectal temperature, skin temperature, heart rate, respiratory rate, and activity. Cord blood was used for determinations of hematocrit, hemoglobin, red blood cell morphology, blood glucose concentration, pH, Pco2, and base excess. At intervals of 89 hr, capillary blood samples were collected by heel stick after the foot had been warmed for 5 rain for determinations of blood glucose, pH, Pc02, and base excess. At the termination of the study a venous sample was drawn and all determinations carried out as on the initial specimen of cord blood. An additional venous sample was collected on the third day for determinations of hematocrit, hemoglobin, red blood cell morphology, total and direct serum bilirubin concentration, pH, Pc02, and base excess. Hematocrit was measured in quadruplicate in ClayAdams Microhematocrit tubes centrifuged for 10 min at 7000 rpm. Total hemoglobin content was measured in duplicate by the cyanmethemoglobin method with a Turner Model 350 Spectrophotometer. Total and direct serum bilirubin values were determined by means of an Advanced Jackson Bilirubinometer. Blood glucose concentrations were determined in duplicate with an Ames
548
Motil, Blackburn, and Pleasure
The Journal of Pediatrics October 19 7 4
37
Table III. Number and per cent of infants developing asymptomatic hypoglycemia (blood glucose < 30 rag/100 ml) in each rewarming group. Significance of trend (p = 0.02) calculated by Rank Test method of Bross 2~
hi
hi 36 LIJ
o. 3~
0
60
120 TIME { Min)
180
240
Fig. 1. Course of mean rectal temperature of the infants in each group either until all attained 37~ rectal temperature (38~ O--Q), or until the 4 hr limit of the study (37~ O--O, 36~ h--&, 35~ A--A).
100%
~ OI
J
I
I v
I
o w
~" 12 1
~
.
T 12
0 It,l
z
,,11
,I,,I
v
360C
og o ,
, 0
60
, .......... yHH~ 120 180 TIME (Min)
0
240
Fig. 2. Cumulative number of infants attaining 37~ rectal temperatures in the study period. No infant attained 37~ rectal temperatures in the 35~ set-point group. Reflectance Meter/Dextrostix System. The pH, Pco2, and base excess were determined with a Radiometer pH Meter 22 and an Astrup AMT-1 Microtonometer System. RESULTS There was a homogeneous composition of the four rewarming set-point groups of infants with respect to gestational age, birth weight, and Apgar scores. There were no significant differences between the groups in the laboratory determinations made throughout the study, with the exception of the blood glucose values. Hypoglycemia (glucose < 30mg/100 ml) did not occur in the 12 infants in the 38~ group: three of 12 and five of 12 infants in the 37 and 36~ groups, respectively, developed asymptomatic hypoglycemia (Table III). This trend was unlikely to occur merely by chance. Owing to
Rewarming temperature set-points (~ 38 37 36
Incidence of asymptomatic hypoglycemia No. 0/12 3/12 5/12
.[
% 0
25.0 41.6
the small number o f infants in the 35~ group the frequency of hypoglycemia could not be evaluated with any confidence. There were significant differences between the groups with respect to heart and respiratory rates and to spontaneous physical activity, Fig. 1 graphically displays the mean rectal temperature of the infants in each group at 20 min intervals; Fig. 2 illustrates the cumulative numbers of infants who had attained 37~ rectal temperatures at intervals within the study period. Table IV displays the n u m b e r and the per cent of infants rewarmed to 37~ rectal temperatures within 4 hr and the mean and SD of their rewarming times. With increasingly higher skin temperature set-points there was a significant decrease in the time required for rewarming. In the 38~ group the n u m b e r of infants (12/12) rewarmed to 37~ within the 4 hr limit of the study was significantly greater, and the mean rewarming time significantly shorter, compared to all other groups. Infants who did not rewarm to a rectal temperature of 37~ within the 4 hr study period and two infants who were prematurely removed from the study were subsequently rapidly rewarmed at the 38~ set-point; there were no complications. Following the study all infants were maintained in open bassinets. Continued observation revealed no evidence of temperature aberration or untoward side effects. DISCUSSION Since the evaluation of rapid rewarming was the major objective of this investigation a limit of 4 hr was arbitrarily selected on the basis of previous studies utilizing convection incubators which indicated that a minim u m of approximately 4 hr was required for rewarming moderately chilled infants. 16Moreover, in view o f these data it was felt that hypothermia (rectal temperature less than 36.5~ extending beyond 4 hr could constitute an unnecessary stress to the neonate.
Volume 85 Number 4
No significant differences in the mean hematocrit, hemoglobin, and bilirubin values or the red blood cell morphology were observed among the groups, which might lend support to the theoretical possibility of hemoconcentration or increased hemolysis due to elevated skin temperature. Most newborn infants demonstrate some degree of metabolic acidosis at birth (base deficit 5 mEq/1) which rapidly disappears within the first 89 hr. 17,18The infants in both the 38 and 37~ rewarming groups attained normal base deficit levels within 89 hr while the 36~ rewarming group required 1 hr to achieve values <-5 mEq/ 1. Metabolic acidosis persisted in the 35~ rewarming group until 1 1/2 hr of life; this may be further evidence of the metabolic stress of prolonged hypothermia. According to Cornblath and Schwartz, 19 2.3% of normal term infants will develop significant hypoglycemia (blood glucose values below 30 mg/100 ml) within the first 4 hr of life; hypoglycemia has been observed to occur even more frequently in chilled infants. The mothers of all infants in the present study received an infusion of 5% glucose during labor and delivery; there were no significant differences in the concentrations of cord blood glucose between the four rewarming set-point groups. However, the subsequent differences in the frequency of hypoglycemia among the groups were highly significant. Asymptomatic hypoglycemia was documented with increasing frequency at each of the two temperature setpoints below 38~ and appears to be inversely related to the rewarming temperature. The absence of hypoglycemia in the 38~ group does not appear to be time related since in all groups 70% o f the a s y m p t o m a t i c hypoglycemic episodes occurred during the first 30-90 min. In the present investigation there was no evidence of significant differences in respiratory and heart rates and the variations in the spontaneous physical activities of the 38, 37, and 36~ groups. On the other hand the 35~ (95.0~ rewarming group showed a trend toward a lower mean heart rate. The study of two infants in this group was prematurely terminated; one on the basis of bradycardia and another because of poor clinical condition (marked jitteriness, peripheral cyanosis, failure to raise rectal temperature above 35~ after 3 hr of rewarming). A t the time of termination the blood glucose levels of these two infants were 60 and 40 mg/100 ml, respectively. The mean initial rectal temperatures of the infants in each study group was essentially the same (35.7~ with the exception of the 35~ group, which was composed of only infants with lower rectal temperatures (Fig. 1). Previous studies have shown that term infants rewarmed in s t a n d a r d c o n v e c t i o n incubators c o n t i n u e d to have a
Effects' of different temperatures for rewarming neonates
549
Table IV, Number and per cent in each o f the four groups of infants who attained 37~ rectal temperature within the 4 hr study period and the mean and SD of the rewarming times. Significance of trend (p = < 0.001) calculated by Rank Test method o f Bross 2~
Rewarming temperature set-points (~ 38 37 36 35
Infants attaining rectal temp. of 370(2 within 4 hr No. 12/12 7/12 2/12 0/4*
I
%
Mean and SD of rewarming time (rain)
100.0 58.3 16.7 0
104.2 _+ 36.6 174.2 _+ 64.5 228.3 _+ 28.8 > 240.0
*Two of six infants in this group did not completethe study (see text). decrease in rectal temperatures during the first 50 min of rewarming (mean 1.1~ and require a m i n i m u m of 3 hr and 45 min to restore rectal temperature to the lower 9limits of normal (36.5~ and at least 8 hr were necessary to achieve 37.0~ a6 In contrast, the infants in the present study who were rewarmed under the radiant heater at 38~ skin temperature set-point continued to have a decrease in rectal temperature for only 20 min (mean, 0.27~ and required a mean of only 1 hr and 45 min to restore rectal temperatures to 37~ Fig. 2 and Table IV illustrate that the only group in which all infants achieved normal rectal temperatures within the limit of the study period was the 38~ temperature set-point group. There was no evidence of hyperthermic stress and, furthermore, they did not demonstrate the effects of hypothermia, such as hypoglycemia, prolonged metabolic acidosis, and bradycardia as seen among infants in the other groups. A n initial cold stress at birth appears to be an important stimulus to the onset of breathing. 22,23Furthermore, there is some evidence that the thermal experience of human infants after the first week of life influences cold resistance24; however, the effects of brief initial cold exposures on homeothermic responsiveness have not been studied. The infants in the present investigation had all experienced an initial postnatal cold stress and had established normal respirations for 15-45 min prior to being rewarmed. Although apnea was anticipated, particularly in the infants in the 38~ rewarming group, it did not occur in any o f the infants studied. Anecdotes relating apneic episodes to rapid rewarming in a small number of newborn infants and experimental animals in the first few minutes of life have been reported. 21Most of the reports deal with immersion of neonates in water baths at 37~
550
Motil, Blackburn, and Pleasure
A l t h o u g h our investigation e m p l o y e d skin temperature set-points as high as 38~ there is little similarity to total i m m e r s i o n since the area of the infant's skin directly exposed to the infra-red radiation was less than 50% of the total body surface area. A p n e a has also been noted to occur in infants r e w a r m e d and m a i n t a i n e d in convection incubators. A possible explanation for the absence of apnea in this investigation in t e r m infants, as well as in the study on low-birth-weight infants carried out by Y a s h i r o a n d a s s o c i a t e s , ~4 m a y b e b a s e d o n t h e differences in the temperature of the ambient air. In an incubator, the infant breathes humidified air w a r m e d to 31-33~ whereas the infant under the radiant heater breathes r o o m air (23-25~ thereby continuously stimulating thermoreceptors in the upper respiratory tract. 24 A l t h o u g h apnea did not occur in 12 infants selected at r a n d o m in the present study, all that can be safely inferred f r o m this e x p e r i e n c e is that the " t r u e " incidence of apnea could still lie s o m e w h e r e b e t w e e n 0 and 26%. 25 We m u s t emphasize that these preliminary data are not to be interpreted as suggested guidelines for rewarming newborn infants. H o w e v e r , based on our observations in this study there may be a potential benefit f r o m rapid rewarming for sick and p r e m a t u r e infants. A n investigation with a considerably larger group of r a n d o m l y selected normal t e r m infants r e w a r m e d at the 38~ temperature set-point is presently being carried out. In addition, it is hoped that our findings stimulate replication of this investigation by others to establish the benefits and safety of this m o d e of rapid r e w a r m i n g before its introduction can be accepted in the general m a n a g e m e n t of newborn infants. REFERENCES
1. Silverman, W. A., Fertig, J. W., and Berger, A. P.: The influence of the thermal environment upon the survival of newly born premature infants, Pediatrics 22: 876, 1958. 2. Jolly, H., Molyneux, P., and Newell, D. J.: A controlled study of the effect of temperature on premature babies, J. P~DiATR.60: 889, 1962. 3. Buetow, K. C., and Klein, S. W.: Effect of maintenance of/ "normal" skin temperature on survival of infants of low birth weight, Pediatrics 34: 163, 1964. 4. Day, R. L., Caliguiri, L., Kamenski, C., and Ehrlich, F.: Body temperature and survival of premature infants, Pediatrics 34: 171, 1964. 5. Motil, K. J., and Blackburn, M. G.: Temperature regulation in the neonate: A review of the pathophysiology of thermal dynamics and methods for environmental control, Clin. Pediatr. 12: 364, 1973. 6. Oliver, T. K., Jr.: Temperature regulation and heat production in the newborn, Pediatr. Clin. North Am. 12: 765, 1965.
The Journal of Pediatrics October 19 7 4
7. Scopes, .[. W., and Ahmed, I.: Range of critical temperatures in sick and premature newborn babies, Arch. Dis. Child. 41: 417, 1966. 8. Hey, E. N., and Katz, G.: The optimum thermal environment for naked babies, Arch. Dis. Child. 45: 328, 1970. 9. Daily, W. J., Klaus, M., and Meyer, H. B.: Apnea in premature infants: Monitoring, incidence, heart rate changes, and an effect of environmental temperature, Pediatrics 43: 510, 1969. 10. Perlstein, P. H., Edwards, N. K., and Sutherland, J. M.: Apnea in premature infants and incubator-air-temperature changes, N. Engl. J. Med. 282: 461, 1970. 11. Levinson, H., Linsao, L., and Swyer, P. R.: A comparison of infra-red and convection heating for newborn infants, Lancet 2: 1346, 1966. 12. Du, J. N., and Oliver, T. K., Jr.: The baby in the delivery room, J. A. M. A. 207: 1502, 1969. 13. Dabm, L. S., and James, S.: Newborn temperature and calculated heat loss in the delivery room, Pediatrics 49: 504, 1972. 14. Yashiro, K., Adams, F. H., Emmanouilides, G. C., and Mickey, M. R.: Preliminary studies on the thermal environment of low-birth-weight infants, J. I~OIAT~. 82: 991, 1973. 15. Oliver, T. K., Jr., and Karlberg, P.: The influence of environmental temperature and 15 per cent oxygen on the gaseous metabolism of newly born infants, Acta Paediatr. 140 (Suppl): 51, 1963. 16. Miller, D. L., and Oliver, T. K., Jr.: Body temperature in the immediate neonatal period: The effect of reducing thermal losses, Am. J. Obstet. Gynecol. 94: 964, 1966. 17. Gandy, G. M., Adamson, K., Jr., Cunningham,N., Silverman, W. A., and James, L. S.: Thermal environment and acid-base homeostasis in human infants during the first few hours of life, J. Clin. Invest. 43: 751, 1964. 18. Blackburn, M. G., Mancusi-Ungaro, H. R., Jr., Orzalesi, M. M., Hobbins, J. C., and Anderson, G. G.: The effects on the neonate of the induction of labor with prostaglandin F2c` and oxytocin, Am. J. Obstet. Gynecol. 116: 847,1973. 19. Cornblath, M., and Schwartz, R.: Disorders of carbohydrate metabolism in infancy, Philadelphia, 1966, W. B. Saunders Company, pp. 34-36. 20. Bross, I. D. J.: Is there an increased risk? Fed. Am. Soc. Exp. Biol. 13: 815, 1954. 21. Oliver, T. K., scientific editor, Proc. Interdisciplinary Conference on Neonatal Respiratory Adaptation: U. S. Dept. Health, Education and Welfare, P.H.S. Publication No. 1432, Bethesda, Md. 1963. 22. Westin, B., Nyberg, R., Miller, J. A., Jr., and Wedenberg, E.: Hypothermia and transfusion with oxygenated blood in the treatment of asphyxia neonatorum, Acta Pediatr. 139 (Suppl): 162, 1951. 23. Harned, H. S., Herrington, R. T., and Ferreiro, J. I.: The effects of immersion and temperature on respiration in newborn lambs, Pediatrics 45: 598, 1970. 24. Glass, L., Silverman, W. A., and Sinclair, J. C.: Effect of the thermal environment on cold resistance and growth of infants after the first week of life, Pediatrics 41: 1033, 1968. 25. Mainland, D.: Elementary medical statistics, ed. 2, Philadelphia, 1963, W. B. Saunders Company.