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The use of hypothermia in pediatric emergencies
THE JOURNAL OF
PEDIATRICS NOVEMBER
1962
Volume
61
Number
5
The use of bypothermia in pediatric emergencies Fifteen critically ill children were treated with hypothermia and chlorpromazine. This" was employed [or persistent convulsions, perip]~eral circulatory [ailure, or increased intracranial pressure with respirator), embarrassment. All patients had [ailed to respond to conventional measures and a [atal outcome appeared likely. Hypothermia appeared valuable in the management o[ cerebral anoxia, particularly when associated with convulsions which were well controlled by hypothermia in 6 out o[ 7 patients. One patient with severe septicemic shock survived and temporary improvement was seen in others, suggesting that hypothermia may be o[ benefit in these patients. The technique employed at the Royal Children's Hospital, Melbourne, Australia, is outlined and short summaries o[ case histories are included.
David A. McCredie, M.D., B.Sc., M.R.A.C.P. "x" MELBOURNE~ AUSTRALIA
S I N C e Bigelow I demonstrated that lowering of body temperature produced a fall in oxygen consumption without accumulation of an oxygen debt, hypothermia has been
used extensively in cardiac surgery, neurosurgery, and, to a lesser extent, in the management of poor-risk surgical patients. During this same period autonomic bIock with or without hypothermia, the so-called "artificial hibernation" of Laborit and Huguenard, t has found wide use in Europe for the management of critically ill patients with nonsurgical conditions.
From the Royal Children's Hospital, Melbourne, Australia. eAddress, ll Uvadale Grove, Kew E. 4, Vi~'toria, Australia.
653
6 54
McCredie
November 1962
T a b l e I. S u m m a r y of clinical m a t e r i a l a n d results of t r e a t m e n t
Case
Age ~
9ex
Diagnosis
Indication for hypothermia
Tern- Duration perature of hypo(~ thermia
Meningitis
Result
1, D . M .
5/12
F
2, M . J .
2 days
M Subdural hematoma
Increased intra31 to 35 cranial pressure Persistent fitting
3, P . H .
10/12
M Pyrexia with convulsions
Hyperpyrexia Persistent fitting
33
4, R. Tr.
9 days
F
Meningitis (Proteus)
Persistent fitting
32 to 35
5, J.B.
3/i2
M Heat stroke
Hyperpyrexia Persistent fitting
33 to 35 24 hours Complete recovery
6, D.P.
11/12
M Heat stroke
Hyperpyrexia Persistent fitting
32
7, K . W .
2 11/12
F
Undiagnosed neurologie condition
Hyperpyrexia and 30 to 32 peripheral circulatory failure
8, M . I .
1 5/12
F
Meningitis
Peripheral circula- 32 tory failure
Peripheral circula- 29.4 (H. influenzae tory failure
(H. influenzae)
9, R . T .
-3 days
Left spastic hemiplegia Epilepsy
16 hours Complete recovery 7 days
Follow-up
Death
Complete recovery
2 days
Complete recovery
6 days
Death
2 years
2 years 2 years 8 months 11 months
24 hours Mild spas- 12 months ticity one foot ; / otherwise normal
1 7/12
M Menlngococcat septicemia
Peripheral circula- 30 to 32 36 hours Death tory faiiure
10, A.B.
4/12
M Subarachnoid hemorrhage
Increased intra30 to 32 cranial pressure
11, D.N.
8
M Undiagnosed
12, A.S.
8 days
F
13, S.C.
5 days
Complete recovery
9 months
Increased intra27 to 32 10 days cranial pressure Respiratory failure
Spastic paraplegia and aphasia
9 months
Increased intra27 to 32 cranial pressure
7' days
Death
2 ~ days M Subdural hematoma
Persistent fitting and increased intracraniaI pressure
5 days
Right hemiplegia
14, K.S.
3/12
F
Meningococcal septicemia
Peripheral circula- 30 tory failure
15, J . C .
4/12
F
Meningitis (N.
Persistent fitting and peripheral circulatory failure
Subdural hematoma
meningitidis)
30 to 32
32 to 33
__ 7 months
10 hours Death 3 days
Death
~Age in years except when specified in days. I s o l a t e d r e p o r t s of such a p p l i c a t i o n s of h y p o t h e r m i a h a v e a p p e a r e d in the E n g l i s h l i t e r a t u r e o v e r t h e last few years, b u t v e r y little has b e e n w r i t t e n o f its use in c h i l d r e n . S t e i g m a n a n d V a l l b o n a 8 suggested its a p p l i -
c a t i o n to a v a r i e t y of g r a v e m e d i c a l c o n d i tions in c h i l d h o o d a n d d e s c r i b e d a 2 ~ - y e a r old b o y w i t h s e v e r e b u l b o s p i n a l p o l i o m y e l i t i s in w h o m a n a v e r a g e b o d y t e m p e r a t u r e of 32 ~ C. was m a i n t a i n e d for 6 days. T h e sue-
Volume 61 Number 5
'cessful use of hypothermia has since been reported by Edwards 3 in a 4 89 girl with measles meningoencephalitis and by Westin and his colleagues 9 in 6 newborn babies with asphyxia pallida in whom other methods of resuscitation had failed. The present study describes the results obtained with the use of hypothermia in 15 critically ill infants and children treated in the medical wards of the Royal Children's Hospital, Melbourne, between 1957 and 1960. MATERIAL
A summary of the patients treated is included in Table I. Hypothermia was considered in the presence of persistent convulsions, peripheral circulatory failure, or increased intracranial pressure with respiratory embarrassment and was instituted only when the patient's condition was deteriorating despite conventional treatment and when a fatal outcome appeared likely. All patients were comatose. Because of the extreme nature of the illnesses treated, a controlled investigation was not possible. METHOD
Chlorpromazine was given intravenously to control shivering which may produce a considerable increase in the metabolic rate even at low temperatures. The initial dose was 0.5 to 1.0 mg. per kilogram, and a maintenance dose of 0.5 mg. per kilogram every 4 to 6 hours usually sufficed although more frequent administration was occasionally required. This depended largely on the depth of coma present. Cooling was carried out by ice bags placed around the body of the patient, particularly over the axillae and groins. These were moved at frequent intervals and were not left in any one position for more than 5 minutes at a time. Temperature was recorded continuously by a thermometer inserted 6 cm. into the rectum. With this method the body temperature fell approximately 1~ C. every 10 minutes. When the temperature had fallen to 32 ~ C., cooling was discontinued and a further drop of 1~ to 2 ~ C.
H y p o t h e r m i a in pediatric emergencies
655
Table I I Indication for hypothermia
Persistent fitting Circulatory failure Intracranial hemorrhage with evidence of increased intracranial pressure or severe brain damage
sur- Normal No. of Total patients vivors
7 6
6 1
4 1"
4
3
1
"XMinlmal sequelae only. usually occurred. The patient was then nursed naked in the cot and the rectal temperature was maintained between 30 ~ C. and 32 ~ C. in most cases. Intravenous therapy was given at the rate of approximately 1,000 ml. per square meter per day of a solution which contained 20 mEq. per liter, each of sodium, potassium, chloride , and lactate ions. The actual amount administered depended on the urinary output, and any abnormal losses of water and electrolytes were added to this total. Daily weighings, though not performed in all cases, frequently provided a useful guide to the state of hydration. The duration of hypothermia depended on the response of the patient, and in this series lasted from 16 hours to 10 days. Rewarming was performed slowly and in general the patient was allowed to regain a normal temperature over a period of several days, without external heating. As shivering may recur at this stage, chlorpromazine was continued during rewarming, but in reduced dosage. Assessment of the patient's condition was often more difficult in this state than in the isothermic state, and very close medical and nursing supervision was essential. In all cases antibiotics and other forms of treatment likely to be beneficial were continued. RESULTS
Indications for induction, degree of cooling, and results of treatment are shown in Table I. Nine of the fifteen patients survived and, of these, 5 had no apparent se-
6 56
McCredie
quelae of their illness. One, Case 8, had minimal sequelae in the form of mitd spasticity of one foot. In 2 who lived, Cases 8 and 11, survival had been considered extremely unlikely with routine measures. Table I I shows the results in the conditions for which hypothermia was most often employed. In no case was any adverse effect apparent. CASE HISTORIES
Case 1. D. M., aged 5 months had peripheral circulatory failure resulting from type b Hemophilus influenzae meningitis. Temporary improvement occurred with intravenous plasma and antibiotics but 6 hours later the baby's condition again deteriorated. Cooling was commenced when the baby was blue and pulseless, the temperature being reduced from 39.4 ~ to 29.4 ~ C. There wast no improvement and death occurred shortly after induction. Case 2. M. J., aged 2 days, had a rightsided subdural hematoma. Following tapping of the hematoma the condition did not improve, the fontanel remained tense and pulsatile, and twitching persisted. Further attempts at aspiration were unsuccessful and it was considered by the neurosurgeon that the baby would not stand surgery. Cooling was instituted and the temperature was reduced from 36.4 ~ to 32.2 ~ C. This produced immediate improvement with cessation of twitching although the fontanel remained tense. The temperature was maintained in the region of 31 to 35 ~ C. over the next 3 days and was then gradually allowed to return to normal. Surgical evacuation of the subdural hematoma was performed 3 weeks later. The child, now 2 years of age, has a marked left spastic hemipIegia and minor epileptic manifestations which are controlled by phenobarbitone. Case 3. P. H., aged 10 months, had arthrogryposis and was admitted for inguinal herniotomy. A temperature of 41.2 ~ C. was noted during operation. Postoperatively, the temperature remained high and he twitched continuously. After 4 hours he was pulseless
November 1962
and slightly cyanotic. The temperature was reduced to 33 ~ C. and maintained at this level for 16 hours. This produced an immediate improvement with cessation of twitching. Subsequently, however, the temperature rose again to 38.7 ~ C. and twitching recurred. Chlorpromazine and cool sponging were used to keep the temperature at normal levels, but no further hypothermia was induced. The baby remained in a state of deeerebrate rigidity for several days and slowly improved over the following 2 weeks. No cause for the hyperpyrexic illness was found. He is now 3 years of age and, apart from the arthrogryposis, appears to be developing satisfactorily. Case 4. R. Tr., aged 9 days, was admitted with jaundice, hepatosplenomegaly, and hemolytic anemia of unknown etiology. Two days after admission she began to convulse and was found to have meningitis due to B. Proteus. Since convulsions could not be controlled by sedation, the temperature was reduced from 37.9 ~ to 32.2 ~ C. and maintained between 32 ~ and 35 ~ C. during the following week. There was rapid control of the convulsions although the baby had a long and stormy convalescence from both meningitis and hemolytic anemia. Eventually she recovered from both and at the age of 2 years she appeared to be progressing normally. Case 5 and 6. J. B., aged 3 months, and D. P., aged 11 months, were admitted during a severe heat wave in January, 1959, with gross dehydration, convuMons, and temperatures of 41.6 ~ C. and 42.2 ~ C., respectively. Convulsions persisted despite rehydration, cool sponging, and sedation. The infants were cooled for 24 and 48 hours, respectively, with rapid improvement. Both made completely uneventful recoveries. Case 7. K. W., aged 211/12 years, was admitted with a left hemiparesis following an unexplained illness associated with coma of 3 days' duration 2 weeks previously. Investigations revealed cerebral atrophy, dilated ventricles, and a right subdural effusion which was evacuated. Three months after admission the child once more became sud-
Volume 61 Number 5
denly unconscious. She was pulseless and cyanotic with a temperature of 42 ~ C. The condition did not improve with ventricular puncture and infusions of pressor amines. She was, therefore, cooled to 30 ~ to 32 ~ C. for 6 days. Although the general condition and circulation appeared to improve she did not regain consciousness and died 11 days later. At necropsy multiple lesions were found in the cen~ al nervous system. Cerebral cortical atrophy was associated with acute and chronic cerebellar atrophy, basal arachnoiditis, hydrocephalus, and ascending degeneration of the spinal cord. The etiology remains obscure. Case 8. M. I., aged 1 ~ years, had type b H. influenzae meningitis with early peripheral circulatory failure. After temporary improvement the condition again deteriorated and 6 hours after admission she was cyanotic with poor peripheral circulation. Weak femoral pulses only were palpable. The temperature was 40.9 ~ C., semiconvulsive movements occurred, and dark brown green material oozed from the nose and throat. The temperature was reduced to 32 ~ C. and maintained at that level for 24 hours. The general condition improved slowly during this time, a n d she was allowed to regain normal temperature over the next 3 days. A right-sided hemiplegia has subsequently improved considerably, and at the age of 2 ~ years she appears perfectly normal apart from slight spasticity of the right foot. Case 9. R. T., aged 1~2 years, was a boy with fulminating meningococcal septicemia who had not responded to routine measures. He was pulseless, cyanotic, and had a very extensive purpuric rash over the body. Following cooling to 30 ~ to 32 ~ C. he survived for 36 hours, but no improvement was observed. Permission for autopsy was refused. Case 10. A. B., aged 4 months, had a subarachnoid hemorrhage of undetermined etiology. Despite lumbar puncture and ventricular tap the condition was deteriorating and fontanel pressure was increasing. He was cooled from 37.5 ~ C. to between 30 ~ to 32 ~ C. and maintained hypothermic for 5
Hypothermia in pediatric emergencies
657
days. During this time he improved steadily, with a decrease in tension of the fontanel. No cause for the hemorrhage was discovered. He is now 1 year and 2 months of age, and the development appears perfectly normal. Case 11. D. N., aged 8 years, was admitted with the sudden onset of delirium for which no adequate cause could be found. Two days after admission he became deeply comatose and stopped breathing in the middle of the night. Artificial respiration was performed by means of intubation and a breathing bag but he remained deeply comatose and apneic. Hypothermia was instituted after 2 hours of artificial respiration, and, without any other treatment, spontaneous respirations occurred when the rectal temperature had dropped to 30 ~ C. Subsequently cranial burr holes and ventricul0graphy were performed which showed moderately large ventricles but no other abnormality. In view of the persistent deep coma, tracheostomy was performed. The temperature was kept between 27 ~ and 32 ~ C. for 1 week and was then allowed to return slowly to normal. In the 9 months following this episode he has shown slow improvement but he has a complete right spastic hemiplegia and a gross nominal aphasia. It is extremely difficult to assess the mental state but the speech is still improving. Case 12. A. S., aged 8 days, had an extensive subdural hematoma. Two days after admission she appeared moribund, was slightly cyanotic, and had Cheyne-Stokes respirations. The condition did not improve following subdural tap. The temperature was reduced to between 30 ~ and 32 ~ C. Following this, craniotomy was performed and a large subdural collection of blood was found on the right side. Adequate evacuation of the blood clot could not be obtained despite removal of a large portion of the temporal lobe. Postoperatively the temperature was lowered further and maintained between 27 ~ and 30 ~ C. The baby's condition appeared slightly improved for several days but then deteriorated, and death occurred 7 days later. At autopsy considerable cere-
658
McCredie
bral necrosis was found underlying the area of hemorrhage. Case 13. S. C., aged 2 ~ days, presented with convulsions associated with an intracranial hemorrhage following a difficult breech delivery. Despite repeated lumbar punctures and sedation, convulsions continued and the fontanel tension remained high. The temperature was kept between 30 ~ and 32 ~ C. for 5 days with marked improvement in the baby's general condition and lessening of the twitching. Subdural taps revealed a large clot over the left hemisphere whicb was later evacuated. At the age of 6 months this baby has a right hemiparesis but otherwise appears to be developing normally. Case 14. K. S., aged 3 months, was admitted with fuhninating meningococcal septicemia. After initial improvement the condition again deteriorated. The temperature was reduced from 41.1 ~ to 30 ~ C. but no improvement occurred, and death occurred 10 hours later. Autopsy revealed bilateral adrenal hemorrhages. Case 15. J. L., aged 4 months, had meningococcal meningitis and early peripheral circulatory failure. Despite lumbar puncture and adequate sedation, the fontanel remained bulging and the baby twitched continuously. The abdomen was tense and bulging and copious dark brown aspirate was obtained from the stomach. With reduction of the temperature from 39.9 ~ to 33 ~ C. the peripheral circulation improved though twitching was not well controlled. However, improvement was only temporary and death occurred after 3 days. Tile urinary output remained poor in this baby. Autopsy revealed good resolution of the meningitic process but large areas of cerebral softening were present over both hemispheres. Slight inflammatory changes of the hypostatic type were present in both lungs. DISCUSSION
Most applications of hypothermia inevitably depend on the prevention or reduction of cerebral anoxia. Cerebral anoxia appeared to be an important factor in all patients of this series.
November 1962
I-typothermia appeared particularly beneficial in the control of convulsive states. Here a vicious cycle of anoxia, edema, and further convulsions may develop quickly. Cooling may then produce good results both by lowering the cerebral oxygen demand, and, as shown by Rosomoff and Gilbert7 by decreasing brain volume and cerebrospinal fluid pressure. This was most apparent in Cases 5 and 6 where the induction of hypothermia was rapidly followed by cessation of fitting and progressive clinical improvement. Several infants with an identical sequence of events had died during this heat wave despite conventional measures. That hypothermia could be harmful in convulsive states was suggested by Noelle, Brillers, and Brendel 6 who showed that the epileptiform threshold of rabbits to electrical and chemical stimulation is actually lowered by hypothermia, particularly at temperatures between 25 ~ and 30 ~ C. However, with the exception of Case 15, convulsions were well controlled and frequently ceased promptly with the induction of hypothermia. In no case was an increased convulsive tendency apparent. A similar beneficial result was reported by Malcolm and his associates 5 in the management of eclampsia. The occurrence of spontaneous respiration in Case 11 after the body temperature had been lowered to 30 ~ C. was unexpected and suggests that, even after cerebral anoxia has occurred, brain damage may be lessened with the use of hypothermia. This effect may be related to reduction of swelling of the brain subsequent to anoxia as well as to reduction of cerebral oxygen needs. Hence, it is conceivable that the brain may withstand longer periods of anoxia at normal temperatures if hypothermia is induced afterward. A similar conclusion has been reached by Williams and Spencer 1~ as a result of their experience with patients following cardiac massage. The role of hypothermia in fulminating infections is more uncertain. Wilson 11 has suggested that hypothermia may be of value in retarding the activity of the invading or-
Volume 61 Number 5
ganism, thus enabling antibiotics a n d the body's own defences to overcome the attack. W o t k y n s , Hirose, a n d E i s e m a n 12 showed t h a t h y p o t h e r m i c animals do n o t respond adversely to infections, a n d this is borne out b y the patients in this series. E a r l y d i s a p p e a r a n c e of microorganisms f r o m the cerebrospinal fluid was found in the p a tients with meningitis, a n d the a u t o p s y of Case 15 showed subsidence of the m e n i n gitic process. Similarly, p u l m o n a r y infections have not been a problem. I n this series, h y p o t h e r m i a was used in 5 cases of f u l m i n a t i n g infection in an a t t e m p t to minimize the effects of tissue a n o x i a in states of p e r i p h e r a l c i r c u l a t o r y failure, as suggested b y Blalock a n d M a s o n 2 n e a r l y 20 years ago. O n c e severe shock was established, h y p o t h e r m i a did not a p p e a r to e x e r t a favorable effect in most cases. Nevertheless, Case 8 r e s p o n d e d very satisfactorily, although considered b y several observers to be in a state of irreversible shock; and in o t h e r cases, e.g., Case 9, survival certainly a p p e a r e d to be longer t h a n would n o r m a l l y have been expected. SUMMARY
AND CONCLUSIONS
T h e use of h y p o t h e r m i a c o m b i n e d with c h l o r p r o m a z i n e is described in 15 critically ill infants a n d children. H y p o t h e r m i a a p p e a r e d to be of definite value in conditions of cerebral anoxia, p a r ticularly, if associated w i t h convulsions, which were well controlled b y this t e c h n i q u e in 6 out of 7 patients. T h e value of h y p o t h e r m i a in patients with very severe infectiofl a n d c i r c u l a t o r y failure is uncertain, b u t survival of 1 p a t i e n t out of 5 suggests t h a t f u r t h e r trials are w a r r a n t e d . W h e t h e r the m o r b i d i t y from conditions such as meningitis a n d n e o n a t a l i n t r a c r a n i a l h e m o r r h a g e m i g h t be lowered b y the selective use of h y p o t h e r m i a in less ill p a t i e n t s remains to be d e t e r m i n e d .
Hypothermia in pediatric emergencies
659
I am indebted to Drs. C. M. Anderson, H. E. Williams, and H. L. Barnett for their help in the preparation of this paper. I also wish to thank Drs. Patricia Wilson and Margaret McCIelland for their helpful advice, the Senior MedicaI Staff of the Royal Children's Hospital under whose bed cards these patients were admitted, and the nursing and resident medical staff who worked hard to ensure the success of this investigation.
REFERENCES
1. Bigelow, W. G., Lindsay, W. K., Harrison, R. C., Gordon, R. A., and Greenwood, W. F.: Oxygen transport and utilization in dogs at low body temperatures, Am. J. Physiol. 160: 125, 1950. 2. Blaloek, A., and Mason, M. F.: Comparison of effects of heat and those of cold in prevention and treatment of shock, Arch. Surg. 42: 1054, 1941. 3. Edwards, G. E.: The use of hypothermia in a case of measles meningoeneephalitis, J. Irish M. A. 42: 181, 1958. 4. Laborit, H., and Huguenard, P.: L'Hypothermie g~nbralisbe th~rapeutique, Presse mbd. 59: 606, 1951. 5. Malcolm, J. E., Vernon, F. L., Merrifield, A. J., Beatson, T. R.: Fulminating eelampsia treated by hypothermia, Lancet 1: 863, 1959.
6. Noelle, W. K., Brillers, A., and Brendel, W. B.: Effects of cold exposure on brain activity, Fed. Proc. 11: 114, 1952. 7. Rosomoff, H. L., and Gilbert, R.: Brain volume and cerebrospinal fluid pressure during hypothermia, Am. J. Physiol. 183: 19, 1955. 8. Steigman, A. J., and ValIbona, C.: Experience with chlorpromazine in pediatrics, Internat. Rec. Med. 168: 351, 1955. 9. Westin, B., Miller, J. A,, Nyberg, R., and Wedenberg, E.: Neonatal asphyxia pallida treated with hypothermia alone or with hypothermia and transfusion of oxygenated blood, Surgery 45: 868, 1959. 10. Williams, G. R., and Spencer, F. C.: The clinical use of hypothermia following cardiac arrest, Ann.' Surg. 148: 462, 1958. 11. Wilson, P.: Therapeutic applications of hypothermia, Australian & New Zealand J. Surg. 27: 229, 1958. 12. ~Wotkyns, R. S, Hirose, H., and Eiseman, B.: Prolonged hypothermia in experimental oneumococcal peritonitis, Surg. Gynec. & Obst. 107: 363, 1958
PEDIATRICS NOVEMBER
1962
Volume
61
Number
5
The use of bypothermia in pediatric emergencies Fifteen critically ill children were treated with hypothermia and chlorpromazine. This" was employed [or persistent convulsions, perip]~eral circulatory [ailure, or increased intracranial pressure with respirator), embarrassment. All patients had [ailed to respond to conventional measures and a [atal outcome appeared likely. Hypothermia appeared valuable in the management o[ cerebral anoxia, particularly when associated with convulsions which were well controlled by hypothermia in 6 out o[ 7 patients. One patient with severe septicemic shock survived and temporary improvement was seen in others, suggesting that hypothermia may be o[ benefit in these patients. The technique employed at the Royal Children's Hospital, Melbourne, Australia, is outlined and short summaries o[ case histories are included.
David A. McCredie, M.D., B.Sc., M.R.A.C.P. "x" MELBOURNE~ AUSTRALIA
S I N C e Bigelow I demonstrated that lowering of body temperature produced a fall in oxygen consumption without accumulation of an oxygen debt, hypothermia has been
used extensively in cardiac surgery, neurosurgery, and, to a lesser extent, in the management of poor-risk surgical patients. During this same period autonomic bIock with or without hypothermia, the so-called "artificial hibernation" of Laborit and Huguenard, t has found wide use in Europe for the management of critically ill patients with nonsurgical conditions.
From the Royal Children's Hospital, Melbourne, Australia. eAddress, ll Uvadale Grove, Kew E. 4, Vi~'toria, Australia.
653
6 54
McCredie
November 1962
T a b l e I. S u m m a r y of clinical m a t e r i a l a n d results of t r e a t m e n t
Case
Age ~
9ex
Diagnosis
Indication for hypothermia
Tern- Duration perature of hypo(~ thermia
Meningitis
Result
1, D . M .
5/12
F
2, M . J .
2 days
M Subdural hematoma
Increased intra31 to 35 cranial pressure Persistent fitting
3, P . H .
10/12
M Pyrexia with convulsions
Hyperpyrexia Persistent fitting
33
4, R. Tr.
9 days
F
Meningitis (Proteus)
Persistent fitting
32 to 35
5, J.B.
3/i2
M Heat stroke
Hyperpyrexia Persistent fitting
33 to 35 24 hours Complete recovery
6, D.P.
11/12
M Heat stroke
Hyperpyrexia Persistent fitting
32
7, K . W .
2 11/12
F
Undiagnosed neurologie condition
Hyperpyrexia and 30 to 32 peripheral circulatory failure
8, M . I .
1 5/12
F
Meningitis
Peripheral circula- 32 tory failure
Peripheral circula- 29.4 (H. influenzae tory failure
(H. influenzae)
9, R . T .
-3 days
Left spastic hemiplegia Epilepsy
16 hours Complete recovery 7 days
Follow-up
Death
Complete recovery
2 days
Complete recovery
6 days
Death
2 years
2 years 2 years 8 months 11 months
24 hours Mild spas- 12 months ticity one foot ; / otherwise normal
1 7/12
M Menlngococcat septicemia
Peripheral circula- 30 to 32 36 hours Death tory faiiure
10, A.B.
4/12
M Subarachnoid hemorrhage
Increased intra30 to 32 cranial pressure
11, D.N.
8
M Undiagnosed
12, A.S.
8 days
F
13, S.C.
5 days
Complete recovery
9 months
Increased intra27 to 32 10 days cranial pressure Respiratory failure
Spastic paraplegia and aphasia
9 months
Increased intra27 to 32 cranial pressure
7' days
Death
2 ~ days M Subdural hematoma
Persistent fitting and increased intracraniaI pressure
5 days
Right hemiplegia
14, K.S.
3/12
F
Meningococcal septicemia
Peripheral circula- 30 tory failure
15, J . C .
4/12
F
Meningitis (N.
Persistent fitting and peripheral circulatory failure
Subdural hematoma
meningitidis)
30 to 32
32 to 33
__ 7 months
10 hours Death 3 days
Death
~Age in years except when specified in days. I s o l a t e d r e p o r t s of such a p p l i c a t i o n s of h y p o t h e r m i a h a v e a p p e a r e d in the E n g l i s h l i t e r a t u r e o v e r t h e last few years, b u t v e r y little has b e e n w r i t t e n o f its use in c h i l d r e n . S t e i g m a n a n d V a l l b o n a 8 suggested its a p p l i -
c a t i o n to a v a r i e t y of g r a v e m e d i c a l c o n d i tions in c h i l d h o o d a n d d e s c r i b e d a 2 ~ - y e a r old b o y w i t h s e v e r e b u l b o s p i n a l p o l i o m y e l i t i s in w h o m a n a v e r a g e b o d y t e m p e r a t u r e of 32 ~ C. was m a i n t a i n e d for 6 days. T h e sue-
Volume 61 Number 5
'cessful use of hypothermia has since been reported by Edwards 3 in a 4 89 girl with measles meningoencephalitis and by Westin and his colleagues 9 in 6 newborn babies with asphyxia pallida in whom other methods of resuscitation had failed. The present study describes the results obtained with the use of hypothermia in 15 critically ill infants and children treated in the medical wards of the Royal Children's Hospital, Melbourne, between 1957 and 1960. MATERIAL
A summary of the patients treated is included in Table I. Hypothermia was considered in the presence of persistent convulsions, peripheral circulatory failure, or increased intracranial pressure with respiratory embarrassment and was instituted only when the patient's condition was deteriorating despite conventional treatment and when a fatal outcome appeared likely. All patients were comatose. Because of the extreme nature of the illnesses treated, a controlled investigation was not possible. METHOD
Chlorpromazine was given intravenously to control shivering which may produce a considerable increase in the metabolic rate even at low temperatures. The initial dose was 0.5 to 1.0 mg. per kilogram, and a maintenance dose of 0.5 mg. per kilogram every 4 to 6 hours usually sufficed although more frequent administration was occasionally required. This depended largely on the depth of coma present. Cooling was carried out by ice bags placed around the body of the patient, particularly over the axillae and groins. These were moved at frequent intervals and were not left in any one position for more than 5 minutes at a time. Temperature was recorded continuously by a thermometer inserted 6 cm. into the rectum. With this method the body temperature fell approximately 1~ C. every 10 minutes. When the temperature had fallen to 32 ~ C., cooling was discontinued and a further drop of 1~ to 2 ~ C.
H y p o t h e r m i a in pediatric emergencies
655
Table I I Indication for hypothermia
Persistent fitting Circulatory failure Intracranial hemorrhage with evidence of increased intracranial pressure or severe brain damage
sur- Normal No. of Total patients vivors
7 6
6 1
4 1"
4
3
1
"XMinlmal sequelae only. usually occurred. The patient was then nursed naked in the cot and the rectal temperature was maintained between 30 ~ C. and 32 ~ C. in most cases. Intravenous therapy was given at the rate of approximately 1,000 ml. per square meter per day of a solution which contained 20 mEq. per liter, each of sodium, potassium, chloride , and lactate ions. The actual amount administered depended on the urinary output, and any abnormal losses of water and electrolytes were added to this total. Daily weighings, though not performed in all cases, frequently provided a useful guide to the state of hydration. The duration of hypothermia depended on the response of the patient, and in this series lasted from 16 hours to 10 days. Rewarming was performed slowly and in general the patient was allowed to regain a normal temperature over a period of several days, without external heating. As shivering may recur at this stage, chlorpromazine was continued during rewarming, but in reduced dosage. Assessment of the patient's condition was often more difficult in this state than in the isothermic state, and very close medical and nursing supervision was essential. In all cases antibiotics and other forms of treatment likely to be beneficial were continued. RESULTS
Indications for induction, degree of cooling, and results of treatment are shown in Table I. Nine of the fifteen patients survived and, of these, 5 had no apparent se-
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quelae of their illness. One, Case 8, had minimal sequelae in the form of mitd spasticity of one foot. In 2 who lived, Cases 8 and 11, survival had been considered extremely unlikely with routine measures. Table I I shows the results in the conditions for which hypothermia was most often employed. In no case was any adverse effect apparent. CASE HISTORIES
Case 1. D. M., aged 5 months had peripheral circulatory failure resulting from type b Hemophilus influenzae meningitis. Temporary improvement occurred with intravenous plasma and antibiotics but 6 hours later the baby's condition again deteriorated. Cooling was commenced when the baby was blue and pulseless, the temperature being reduced from 39.4 ~ to 29.4 ~ C. There wast no improvement and death occurred shortly after induction. Case 2. M. J., aged 2 days, had a rightsided subdural hematoma. Following tapping of the hematoma the condition did not improve, the fontanel remained tense and pulsatile, and twitching persisted. Further attempts at aspiration were unsuccessful and it was considered by the neurosurgeon that the baby would not stand surgery. Cooling was instituted and the temperature was reduced from 36.4 ~ to 32.2 ~ C. This produced immediate improvement with cessation of twitching although the fontanel remained tense. The temperature was maintained in the region of 31 to 35 ~ C. over the next 3 days and was then gradually allowed to return to normal. Surgical evacuation of the subdural hematoma was performed 3 weeks later. The child, now 2 years of age, has a marked left spastic hemipIegia and minor epileptic manifestations which are controlled by phenobarbitone. Case 3. P. H., aged 10 months, had arthrogryposis and was admitted for inguinal herniotomy. A temperature of 41.2 ~ C. was noted during operation. Postoperatively, the temperature remained high and he twitched continuously. After 4 hours he was pulseless
November 1962
and slightly cyanotic. The temperature was reduced to 33 ~ C. and maintained at this level for 16 hours. This produced an immediate improvement with cessation of twitching. Subsequently, however, the temperature rose again to 38.7 ~ C. and twitching recurred. Chlorpromazine and cool sponging were used to keep the temperature at normal levels, but no further hypothermia was induced. The baby remained in a state of deeerebrate rigidity for several days and slowly improved over the following 2 weeks. No cause for the hyperpyrexic illness was found. He is now 3 years of age and, apart from the arthrogryposis, appears to be developing satisfactorily. Case 4. R. Tr., aged 9 days, was admitted with jaundice, hepatosplenomegaly, and hemolytic anemia of unknown etiology. Two days after admission she began to convulse and was found to have meningitis due to B. Proteus. Since convulsions could not be controlled by sedation, the temperature was reduced from 37.9 ~ to 32.2 ~ C. and maintained between 32 ~ and 35 ~ C. during the following week. There was rapid control of the convulsions although the baby had a long and stormy convalescence from both meningitis and hemolytic anemia. Eventually she recovered from both and at the age of 2 years she appeared to be progressing normally. Case 5 and 6. J. B., aged 3 months, and D. P., aged 11 months, were admitted during a severe heat wave in January, 1959, with gross dehydration, convuMons, and temperatures of 41.6 ~ C. and 42.2 ~ C., respectively. Convulsions persisted despite rehydration, cool sponging, and sedation. The infants were cooled for 24 and 48 hours, respectively, with rapid improvement. Both made completely uneventful recoveries. Case 7. K. W., aged 211/12 years, was admitted with a left hemiparesis following an unexplained illness associated with coma of 3 days' duration 2 weeks previously. Investigations revealed cerebral atrophy, dilated ventricles, and a right subdural effusion which was evacuated. Three months after admission the child once more became sud-
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denly unconscious. She was pulseless and cyanotic with a temperature of 42 ~ C. The condition did not improve with ventricular puncture and infusions of pressor amines. She was, therefore, cooled to 30 ~ to 32 ~ C. for 6 days. Although the general condition and circulation appeared to improve she did not regain consciousness and died 11 days later. At necropsy multiple lesions were found in the cen~ al nervous system. Cerebral cortical atrophy was associated with acute and chronic cerebellar atrophy, basal arachnoiditis, hydrocephalus, and ascending degeneration of the spinal cord. The etiology remains obscure. Case 8. M. I., aged 1 ~ years, had type b H. influenzae meningitis with early peripheral circulatory failure. After temporary improvement the condition again deteriorated and 6 hours after admission she was cyanotic with poor peripheral circulation. Weak femoral pulses only were palpable. The temperature was 40.9 ~ C., semiconvulsive movements occurred, and dark brown green material oozed from the nose and throat. The temperature was reduced to 32 ~ C. and maintained at that level for 24 hours. The general condition improved slowly during this time, a n d she was allowed to regain normal temperature over the next 3 days. A right-sided hemiplegia has subsequently improved considerably, and at the age of 2 ~ years she appears perfectly normal apart from slight spasticity of the right foot. Case 9. R. T., aged 1~2 years, was a boy with fulminating meningococcal septicemia who had not responded to routine measures. He was pulseless, cyanotic, and had a very extensive purpuric rash over the body. Following cooling to 30 ~ to 32 ~ C. he survived for 36 hours, but no improvement was observed. Permission for autopsy was refused. Case 10. A. B., aged 4 months, had a subarachnoid hemorrhage of undetermined etiology. Despite lumbar puncture and ventricular tap the condition was deteriorating and fontanel pressure was increasing. He was cooled from 37.5 ~ C. to between 30 ~ to 32 ~ C. and maintained hypothermic for 5
Hypothermia in pediatric emergencies
657
days. During this time he improved steadily, with a decrease in tension of the fontanel. No cause for the hemorrhage was discovered. He is now 1 year and 2 months of age, and the development appears perfectly normal. Case 11. D. N., aged 8 years, was admitted with the sudden onset of delirium for which no adequate cause could be found. Two days after admission he became deeply comatose and stopped breathing in the middle of the night. Artificial respiration was performed by means of intubation and a breathing bag but he remained deeply comatose and apneic. Hypothermia was instituted after 2 hours of artificial respiration, and, without any other treatment, spontaneous respirations occurred when the rectal temperature had dropped to 30 ~ C. Subsequently cranial burr holes and ventricul0graphy were performed which showed moderately large ventricles but no other abnormality. In view of the persistent deep coma, tracheostomy was performed. The temperature was kept between 27 ~ and 32 ~ C. for 1 week and was then allowed to return slowly to normal. In the 9 months following this episode he has shown slow improvement but he has a complete right spastic hemiplegia and a gross nominal aphasia. It is extremely difficult to assess the mental state but the speech is still improving. Case 12. A. S., aged 8 days, had an extensive subdural hematoma. Two days after admission she appeared moribund, was slightly cyanotic, and had Cheyne-Stokes respirations. The condition did not improve following subdural tap. The temperature was reduced to between 30 ~ and 32 ~ C. Following this, craniotomy was performed and a large subdural collection of blood was found on the right side. Adequate evacuation of the blood clot could not be obtained despite removal of a large portion of the temporal lobe. Postoperatively the temperature was lowered further and maintained between 27 ~ and 30 ~ C. The baby's condition appeared slightly improved for several days but then deteriorated, and death occurred 7 days later. At autopsy considerable cere-
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bral necrosis was found underlying the area of hemorrhage. Case 13. S. C., aged 2 ~ days, presented with convulsions associated with an intracranial hemorrhage following a difficult breech delivery. Despite repeated lumbar punctures and sedation, convulsions continued and the fontanel tension remained high. The temperature was kept between 30 ~ and 32 ~ C. for 5 days with marked improvement in the baby's general condition and lessening of the twitching. Subdural taps revealed a large clot over the left hemisphere whicb was later evacuated. At the age of 6 months this baby has a right hemiparesis but otherwise appears to be developing normally. Case 14. K. S., aged 3 months, was admitted with fuhninating meningococcal septicemia. After initial improvement the condition again deteriorated. The temperature was reduced from 41.1 ~ to 30 ~ C. but no improvement occurred, and death occurred 10 hours later. Autopsy revealed bilateral adrenal hemorrhages. Case 15. J. L., aged 4 months, had meningococcal meningitis and early peripheral circulatory failure. Despite lumbar puncture and adequate sedation, the fontanel remained bulging and the baby twitched continuously. The abdomen was tense and bulging and copious dark brown aspirate was obtained from the stomach. With reduction of the temperature from 39.9 ~ to 33 ~ C. the peripheral circulation improved though twitching was not well controlled. However, improvement was only temporary and death occurred after 3 days. Tile urinary output remained poor in this baby. Autopsy revealed good resolution of the meningitic process but large areas of cerebral softening were present over both hemispheres. Slight inflammatory changes of the hypostatic type were present in both lungs. DISCUSSION
Most applications of hypothermia inevitably depend on the prevention or reduction of cerebral anoxia. Cerebral anoxia appeared to be an important factor in all patients of this series.
November 1962
I-typothermia appeared particularly beneficial in the control of convulsive states. Here a vicious cycle of anoxia, edema, and further convulsions may develop quickly. Cooling may then produce good results both by lowering the cerebral oxygen demand, and, as shown by Rosomoff and Gilbert7 by decreasing brain volume and cerebrospinal fluid pressure. This was most apparent in Cases 5 and 6 where the induction of hypothermia was rapidly followed by cessation of fitting and progressive clinical improvement. Several infants with an identical sequence of events had died during this heat wave despite conventional measures. That hypothermia could be harmful in convulsive states was suggested by Noelle, Brillers, and Brendel 6 who showed that the epileptiform threshold of rabbits to electrical and chemical stimulation is actually lowered by hypothermia, particularly at temperatures between 25 ~ and 30 ~ C. However, with the exception of Case 15, convulsions were well controlled and frequently ceased promptly with the induction of hypothermia. In no case was an increased convulsive tendency apparent. A similar beneficial result was reported by Malcolm and his associates 5 in the management of eclampsia. The occurrence of spontaneous respiration in Case 11 after the body temperature had been lowered to 30 ~ C. was unexpected and suggests that, even after cerebral anoxia has occurred, brain damage may be lessened with the use of hypothermia. This effect may be related to reduction of swelling of the brain subsequent to anoxia as well as to reduction of cerebral oxygen needs. Hence, it is conceivable that the brain may withstand longer periods of anoxia at normal temperatures if hypothermia is induced afterward. A similar conclusion has been reached by Williams and Spencer 1~ as a result of their experience with patients following cardiac massage. The role of hypothermia in fulminating infections is more uncertain. Wilson 11 has suggested that hypothermia may be of value in retarding the activity of the invading or-
Volume 61 Number 5
ganism, thus enabling antibiotics a n d the body's own defences to overcome the attack. W o t k y n s , Hirose, a n d E i s e m a n 12 showed t h a t h y p o t h e r m i c animals do n o t respond adversely to infections, a n d this is borne out b y the patients in this series. E a r l y d i s a p p e a r a n c e of microorganisms f r o m the cerebrospinal fluid was found in the p a tients with meningitis, a n d the a u t o p s y of Case 15 showed subsidence of the m e n i n gitic process. Similarly, p u l m o n a r y infections have not been a problem. I n this series, h y p o t h e r m i a was used in 5 cases of f u l m i n a t i n g infection in an a t t e m p t to minimize the effects of tissue a n o x i a in states of p e r i p h e r a l c i r c u l a t o r y failure, as suggested b y Blalock a n d M a s o n 2 n e a r l y 20 years ago. O n c e severe shock was established, h y p o t h e r m i a did not a p p e a r to e x e r t a favorable effect in most cases. Nevertheless, Case 8 r e s p o n d e d very satisfactorily, although considered b y several observers to be in a state of irreversible shock; and in o t h e r cases, e.g., Case 9, survival certainly a p p e a r e d to be longer t h a n would n o r m a l l y have been expected. SUMMARY
AND CONCLUSIONS
T h e use of h y p o t h e r m i a c o m b i n e d with c h l o r p r o m a z i n e is described in 15 critically ill infants a n d children. H y p o t h e r m i a a p p e a r e d to be of definite value in conditions of cerebral anoxia, p a r ticularly, if associated w i t h convulsions, which were well controlled b y this t e c h n i q u e in 6 out of 7 patients. T h e value of h y p o t h e r m i a in patients with very severe infectiofl a n d c i r c u l a t o r y failure is uncertain, b u t survival of 1 p a t i e n t out of 5 suggests t h a t f u r t h e r trials are w a r r a n t e d . W h e t h e r the m o r b i d i t y from conditions such as meningitis a n d n e o n a t a l i n t r a c r a n i a l h e m o r r h a g e m i g h t be lowered b y the selective use of h y p o t h e r m i a in less ill p a t i e n t s remains to be d e t e r m i n e d .
Hypothermia in pediatric emergencies
659
I am indebted to Drs. C. M. Anderson, H. E. Williams, and H. L. Barnett for their help in the preparation of this paper. I also wish to thank Drs. Patricia Wilson and Margaret McCIelland for their helpful advice, the Senior MedicaI Staff of the Royal Children's Hospital under whose bed cards these patients were admitted, and the nursing and resident medical staff who worked hard to ensure the success of this investigation.
REFERENCES
1. Bigelow, W. G., Lindsay, W. K., Harrison, R. C., Gordon, R. A., and Greenwood, W. F.: Oxygen transport and utilization in dogs at low body temperatures, Am. J. Physiol. 160: 125, 1950. 2. Blaloek, A., and Mason, M. F.: Comparison of effects of heat and those of cold in prevention and treatment of shock, Arch. Surg. 42: 1054, 1941. 3. Edwards, G. E.: The use of hypothermia in a case of measles meningoeneephalitis, J. Irish M. A. 42: 181, 1958. 4. Laborit, H., and Huguenard, P.: L'Hypothermie g~nbralisbe th~rapeutique, Presse mbd. 59: 606, 1951. 5. Malcolm, J. E., Vernon, F. L., Merrifield, A. J., Beatson, T. R.: Fulminating eelampsia treated by hypothermia, Lancet 1: 863, 1959.
6. Noelle, W. K., Brillers, A., and Brendel, W. B.: Effects of cold exposure on brain activity, Fed. Proc. 11: 114, 1952. 7. Rosomoff, H. L., and Gilbert, R.: Brain volume and cerebrospinal fluid pressure during hypothermia, Am. J. Physiol. 183: 19, 1955. 8. Steigman, A. J., and ValIbona, C.: Experience with chlorpromazine in pediatrics, Internat. Rec. Med. 168: 351, 1955. 9. Westin, B., Miller, J. A,, Nyberg, R., and Wedenberg, E.: Neonatal asphyxia pallida treated with hypothermia alone or with hypothermia and transfusion of oxygenated blood, Surgery 45: 868, 1959. 10. Williams, G. R., and Spencer, F. C.: The clinical use of hypothermia following cardiac arrest, Ann.' Surg. 148: 462, 1958. 11. Wilson, P.: Therapeutic applications of hypothermia, Australian & New Zealand J. Surg. 27: 229, 1958. 12. ~Wotkyns, R. S, Hirose, H., and Eiseman, B.: Prolonged hypothermia in experimental oneumococcal peritonitis, Surg. Gynec. & Obst. 107: 363, 1958