Clinical events in association with timing of intraventricular hemorrhage in preterm infants

Clinical events in association with timing of intraventricular hemorrhage in preterm infants

Clinical events in association with timing of intraventricular hemorrhage in preterm infants Masahisa Funato, MD, Hiroshi Tamai, MD, Kazuko Noma, MD, ...

1MB Sizes 0 Downloads 42 Views

Clinical events in association with timing of intraventricular hemorrhage in preterm infants Masahisa Funato, MD, Hiroshi Tamai, MD, Kazuko Noma, MD, Takako Kurita, MD, Yoshitaka Kajimoto, MD, Yasushi Yoshioka, MD, a n d Seiichi Shimada, MD From the Department of Pediatrics, Yodogawa Christian Hospital, Osaka, Japan To ascertain whether any routine practices or clinical manipulations in a neonatal intensive care unit could induce intraventricular hemorrhage (IVH) in preterm infants, we performed ultrasonic monitoring of the germinal layer continuously for 48 hours in 33 extremely premature infants with respiratory distress. Intraventricular hemorrhage d e v e l o p e d in 46 of these infants. In four infants t h e timing of the germinal layer hemorrhage was confirmed with ultrasonic monitoring. Three of the four c a s e s w e r e apparently associated with clinical e v e n t s occurring at the moment of IVH: manual ventilation for improvement of hyperc a p n i a associated with primary pulmonary hypertension of the newborn; correction of hyperkalemia, which was causing an arrhythmia, with administration of c a l c i u m g l u c o n a t e and sodium b i c a r b o n a t e ; and administration of surfactant-TA to improve respiratory failure c a u s e d by pulmonary hemorrhage. In t h e s e t h r e e infants it a p p e a r e d that one of the basic factors inducing IVH might be an increase in b l o o d pressure with or without hypercapnia, causing cerebral reperfusion after ischemic d a m a g e of the germinal layer. (J PEDIATR1992;124: 614-9) Many pathogenic factors have been proposed as having a relationship to intraventricular hemorrhage in preterm infantsl5; an increase in blood pressure has been noted as one such factor. 6 An increase of BP may occur as a result of routine clinical care or manipulations such as tracheal suctioning, measuring of rectal temperature, or a heel puncture.S, 7, 8 However, specific clinical IVH-inducing factors have not been determined because the precise timing of the IVH has not been demonstrated. We have devised a system for continuous monitoring by cranial ultrasonography to determine the timing of IVH

Supported in part by a grant for the Maternal and Child Health Research Program 1986-1988 from the Ministry of Health and Welfare of Japan. Submitted for publication April 10, 1990;accepted April 21, 1992. Reprint requests: Masahisa Funato, MD, Department of Pediatrics, Yodogawa Christian Hospital, 9-26 Awaji 2-Chome, Higashi Yodogawa-ku, Osaka 533, Japan. 9/23/38806

614

and to attempt to ascertain the clinical factors that might induce it. 9 We report three instances in which we successfully determined the timing of IVH and demonstrated the correlations of IVH with clinical events. METHODS Thirty-three extremely premature infants weighing less than 1500 gm who required respiratory support because of respiratory distress were monitored by ultrasonography, BP GLH IVH PPHN S-TA

Blood pressure Germinal layer hemorrhage Intraventricular hemorrhage Primary pulmonary hypertension of the newborn Surfactant-TA

with parental permission. The ethics committee of our hospital approved the study. The mean ( + SD) birth weight was 844 _+ 174 gm, and gestational age 26.3 _+ 2.2 weeks. The Aloka SSD 630 scanner (Aloka Co., Ltd., Tokyo,

Volume 121 Number 4

Timing o f I V H in preterm infants

6 15

Fig. t. Timing of GLH in patient 1. At 0129 no GLH was found on ultrasonographic monitoring. At 0130 the slow occurrence of a right-sided GLH was recorded by ultrasonography, appearing as a cystlike hypoechodensity formation (arrow).. At 0142 a right-sided grade II IVH was confirmed on parasagittal section of sonogram.

Japan) with a 7.5 MHz linear or convex probe on a VHS video set was used for monitoring IVH. The probe was placed lightly on the anterior fontanelle to visualize the coronal section of the brain, and a fixation plate (Atom Medical Corp., Tokyo, Japan) was used for a ventilation tube. With this method, continuous monitoring of the germinal layer was performed during the first 48 hours after birth. When the videotape was changed every 8 hours, the ultrasonogram was scanned by one of the authors to determine whether there were any indications that an IVH might have oecurred during that interval. Heart rate, respiratory rate, and peripheral arterial BP were continuously monitored by Lifescope 2 (Nihon Kohden Corp., Tokyo, Japan) and were recorded every 3 minutes. Arterial blood was sampled through the peripheral

arterial route for appropriate gas analysis. The gas was analyzed with an ABL-2 analyzer (Radiometer A / S , Copenhagen, Denmark). Transcutaneous oxygen tension was also monitored by a model OM-630S monitor (F. HoffmannLaRoche Ltd., Basel, Switzerland). In the nursery the exact time of every manipulation and every form of treatment used on each infant was recorded. Hourly variation in mean BP of 14 of the 17 infants without IVH, who had no serious complications and had survived, was used as the normal standard to compare with the variations of each infant in whom the timing of IVH was confirmed. The mean BP was calculated from the following formula: Mean BP = (S - D ) / 3 + D, where S is systolic BP and D is diastolic BP. Grading of respiratory distress syndrome was done on the

6 16

Funato et al.

The Journal of Pediatrics October 1992

Hr. of life 12 0 6

BP

I

18

I

I

24

30 I

36 I

42 I

48

54 I

60 I

66

72hr

I

(mmHg)

50- - 40

--

Systolic ~ - - A - - - j ~ X - I ~ ~ _

] f'///2M//'/'///Z/////~,~//~

302010.

0

-t

t

S-TA S-TA

pH

P02 PC02 (mmHg) (mmHg) 7.5" 200" 80

pH

9 7.4"

9I

0 ~

--O~

50.

7.2-

O.

7.1

02

0

O f

P02

Fig. 2. Serial changes of arterial BP and blood gas values for first 3 days in patient 1. Blood pressure was very low on admission; transient increase in BP occurred at about 3 to 7 hours of life after administration of S-TA. Just before GLH, hypercapnia caused by PPHN (Pco2 = 78.9 mm Hg) was recognized. At moment of GLH, to improve hypercapnia, one of us gave manual ventilation. Persistent increase in BP, compared with level of BP on admission, is seen. Pco2, Partial pressure of carbon dioxide; Po2, partial pressure of oxygen.

basis of radiographs of the chest, according to Bomsel's classification. 1~ G r a d i n g of I V H was performed on the basis of u l t r a s o n o g r a p h y or computed t o m o g r a p h y findings according to the m e t h o d of Papile et al. 11 RESULTS I n t r a v e n t r i c u l a r h e m o r r h a g e developed in 16 of the 33 infants (grade I hemorrhage, six infants; g r a d e II, five; grade III, one; grade IV, four). In four of these infants the precise timing of I V H was determined by ultrasonic monitoring or scanning ( t h e videotape was reviewed by a radiologist for confirmation of the m o m e n t of I V H ) . In one of the four infants, we did not notice any clinical events at the time of I V H except for a persistent increase in BP compared with hypotension at the time of admission. However, clinical events were associated with the timing of I V H in three of the infants. In other cases the timing of I V H was not det e r m i n e d on the video recording because of technical difficulties in fixing the probe on the patient's head when the infant was moving, or because of our failure to change to a new videotape every 8 hours. T h e following is a s u m m a r y of the three cases in which clinical events were recognized as significant to the timing of IVH. Patient 1, a boy, weighed 1277 gm at birth and was born at 28 weeks of gestational age. He had severe asphyxia (Apgar scores of 1 at 1 minute and at 5 minutes), type IV respiratory distress syn-

drome, and primary pulmonary hypertension of the newborn. The infant was born after an emergency cesarean section for abruptio placentae. Surfactant-TA, 120mg/kg, was administered intratracheally at about 1 hour and again at 6 hours of age. At 11:40 PM on the first day of life, no IVH was found by ultrasonography. At 1:30 AMon the following day (at about 36 hours of life) a right-sided germinal layer hemorrhage slowly developed (Fig. 1). The hemorrhage started from the upper part of the germinal layer on the body of the caudate nucleus and slowly progressed, forming a small focal hypoechodensity (cystlike) in the germinal layer within 5 minutes. At 1:45 AM the IVH (grade II) was confirmed in the right lateral ventricle on sagittal sections of the brain. Daily changes in~rterial BP and blood gas values in this patient for the first 3 days are shown in Fig. 2. Blood pressure was very low (27/18 mm Hg) at the time of admission. Albumin, 1 gm/kg per 2-hour period, and fresh whole blood, 15 ml/kg per 3-hours period, were transfused within 24 hours of life. Tolazoline, 2 mg/kg per 10 minutes and then 2 mg/kg per hour, and dopamine, 10 ~g/kg per minute, were given continuously through an intravenous catheter from about 2 hours of life; this was followed by a transient increase in BP at about 3 to 7 hours of life after the administration of S-TA. After 18 hours of life, a gradual, persistent increase in BP (40 to 50/25 to 30 mm Hg) was noticed. Just before the GLH, marked hypercapnia (arterial carbon dioxide pressure: 78.9 mm Hg), possibly related to PPHN, was recognized in association with respiratory acidosis (pH = 7.239). At the moment of GLH, manual ventilation was being given by one of us (K.N.) to improve hypercapnia. Patient 2, a boy, weighed 1122 gm at birth and was born at 27

Volume 121 Number 4

weeks of gestational age; Apgar scores were 0 at 1 minute and at 5 minutes, and 5 at 10 minutes. Because of severe fetal distress, an emergency cesarean section was performed. At birth the infant was in shock, with severe perinatal asphyxia and umbilical cord bleeding. After a quick resuscitation with endotracheal intubation, tracheal instillation of catecholamine, and intravenous administration of sodium bicarbonate, 20 ml of type O fresh whole blood was transfused in the operating room. At 9:00 AM (~19 hours of age) the infant suddenly went into shock, and ultrasonographic scanning was performed by one of us (H.T.) with another sector-type echo (Aloka Color Doppler SSD 870 [video not recorded]). In the coronal scan, no GLH was seen (9:05 AM). The neonatologist then changed the view and scanned the sagittal sections. Soon after starting the scanning on the right side, he recognized a growing GLH (9:06 AM). The hemorrhage was seen in the body of the caudate nucleus, forming a focal hypoechodensity (cystlike) in the germinal layer. At 9:09 AM the hypoechodensity was observed to change to hyperechodensity, suggestive of a right-sided grade II IVH. The BP was in the normal range (53/33 mm Hg) on admission. The blood pH was 7.26, and base excess was -13.6. A clonic seizure occurred at the time of admission, possibly as a result of a perinatal hypoxic-ischemic insult. The seizure subsided within about 6 hours after intravenous administration of phenobarbital (30 mg/kg per dose initially, followed by 5 mg/kg per day). At about 19 hours of life, the BP suddenly dropped (25/20 mm Hg) and the infant went into shock associated with a cardiac arrhythmia caused by hyperkalemia (serum potassium concentration 8.0 mEq/L); 3 ml of 8.5% calcium gluconate and 3 ml of 7% sodium bicarbonate was administered intravenously during a 3-minute period. Thereupon the level of BP was rapidly restored (up to 51/27 mm Hg). A few minutes after the restoration to a higher level of BP, the GLH developed. No acidosis was present, but hypoxemia (arterial oxygen pressure = 28.8 mm Hg) and hypocapnia (arterial carbon dioxide pressure = 19.2 mm Hg) were recognized during the episode. At the moment of the IVH, no other manipulations were being performed except for ultrasonographic scanning of the brain. Patient 3, a boy, weighed 613 gm at birth and was born by breech delivery at 23 weeks of gestational age. Apgar scores were 3 at 1 minute and 8 at 5 minutes. While the infant was in the delivery room, S-TA, 120 mg/kg, was prophylactically administered. At 7:25 AM (at about 25 hours of life), the infant suddenly had a pulmonary hemorrhage, but no IVH was seen on ultrasonographic monitoring. At 7:43 AM, before S-TA was administered, no IVH was found on ultrasonographic scanning. The scanning was discontinued while S-TA was given intratracheally. At 7:50 AM, when the ultrasound probe was again placed on the fontanelle, a bilateral GLH with focal hyperechodensities was seen on the coronal section of the body of the caudate nucleus. On sagittal section, grade II to III IVH was confirmed bilaterally. The BP was relatively low (28 to 36/15 to 18 mm Hg) during the first few hours of life. Dopamine, 5 ~g/kg per minute, was given continuously from about 4 hours of age. At 16 hours of age, glucose-insulin therapy was started because of hyperkalemia (serum potassium concentration 6.2 mEq/L). The BP gradually increased (34 to 44/20 to 27 mm Hg) until about 25 hours of age, when the

Timing of I V H in preterm infants

617

infant had a pulmonary hemorrhage. At that time the BP decreased to 31/25 mm Hg. The BP was restored (up to 49/23 mm Hg) after the surfactant was administered. However, during this episode the GLH occurred. Metabolic acidosis was noted (pH = 7.14), but no remarkable hypoxemia or hypercapnia was noted in arterial blood. In Fig. 3, hourly variations in m e a n BP in these three infants are plotted on the s t a n d a r d curve ( m e a n _+ SD) t h a t was developed from the record of 14 infants without I V H in this series. Clinical events occurred at the time of IVH: m a n u a l ventilation for i m p r o v e m e n t of hypercapnia associated with P P H N in patient 1; correction of hyperkalemia, which was causing an a r r h y t h m i a , with administration of calcium gluconate and sodium b i c a r b o n a t e in patient 2; and administration of S - T A to improve respiratory failure induced by p u l m o n a r y h e m o r r h a g e in patient 3. T h e increased level of m e a n BP was not always abnormally high in these infants. However, c o m p a r e d with the standard curve, a persistent or rapid increase of BP after antecedent hypotension was noticed at the time of I V H in these infants. DISCUSSION Several methods other t h a n u l t r a s o n o g r a p h y have been used in an effort to detect the t i m i n g of a n IVH, but the m o m e n t of I V H has not been demonstrated.12-15 W e devised a method of continuous m o n i t o r i n g with cranial ultrasonography to ascertain the timing of I V H a n d the clinical factors t h a t m a y induce I V H . T h e m e t h o d and the safety of continuous ultrasonographic monitoring for 48 hours have been discussed previously. 9 M a n y factors have been proposed as having a relationship to the pathogenesis of IVH. In addition to impaired autoregulation, 2 intravascular, vascular, and extravascular factors m a y be i m p o r t a n t pathogenic factors. 3' 4 Intravascular factors that m a y be i m p o r t a n t in high-risk p r e m a t u r e infants include fluctuating cerebral blood flow, 16, 17 increase in cerebral blood flow, 6, 18-22 increase in cerebral venous pressure, 23-25 decrease in cerebral blood flow followed by reperfusion, 18,26-3~ and platelet and coagulation disturbances.31, 32 A n increase of BP as a result of a routine clinical manipulation or t r e a t m e n t m a y affect cerebral blood flow and induce IVH. 5, 7, 8 A t the time of the IVH, an increase of BP was noted in all of our patients in comparison with the BP level before IVH. M a n u a l ventilation was being performed at the mom e n t of I V H in patient 1, calcium gluconate and sodium bicarbonate were being administered at the time of I V H in patient 2, and S - T A was being administered when I V H occurred in patient 3. In these patients we did not d e m o n s t r a t e any I V H occurring during routine clinical manipulations such as tracheal suctioning, which m i g h t induce a quick and transient increase in BP a n d possible IVH. This finding is compatible with the results of Bada et al., 33 who concluded

6 18

Funato et al.

The Journal of Pediatrics October 1992

mmHg 50

Patient 1

(1,277g, 28wks)

Mean_+S.D. (N=14, IVHO)

40

3oi 2O Manual Ventilation

10 I

Patient 2

I

(1,122g, 27wks)

mmHg

50 40 30 20 10

HC !

Patient 3

|

(613g, 23wks)

mmHg

50 40

6

3O 20 10 I

I

24

48

I

7 2 hrs of life

Fig. 3. Serial changes in mean BP in the three patients, compared with 14 cases without IVH. In patient 1 a persistent increase in mean BP was seen at the time of GLH, after hypotension in the early stage. In patient 2 a rapid restoration of mean BP was observed at the time of GLH, after sudden hypotension caused by cardiac arrhythmia. In patient 3 an increase in mean BP was noted at the time of GLH, after a hypotensive state; when pulmonary hemorrhage occurred mean BP decreased slightly. Corrected mean BP was not always extraordinarily high compared with that of control subjects (n = 14, IVH 0); in patients 1 and 3, the increased mean BP was within the standard deviation. that standard manipulation is not associated with an increased risk of grades II through IV IVHs. However, other episodes of I V H might have occurred during routine procedures when ultrasonography'vcas not being performed. In our patients the increase in BP (reperfusion) followed ischemic injury (caused by hypoperfusion) after asphyxia. This phenomenon has been demonstrated to be one of the important factors inducing I V H in a study using the newborn beagle puppy.IS In a clinical situation Fujimura et al. 28

emphasized the importance of initial hypotension as a factor inducing IVH. Miall-Allen et al. 29 and Tamai and Funato 3~ also recognized the importance of antecedent systemic hypotension as a pathogenic factor for I V H in highrisk premature infants. The principal consequence of the decrease in cerebral blood flow caused by hypotension is ischemic injury of the vessels of the germinal layer, which can then rupture subsequently on reperfusion or hyperperfusion after an increase in BP. 3, 4 The increase in BP in our patients

Volume 121 Number 4

was not always a b n o r m a l l y high; the level was actually normotensive for extremely p r e m a t u r e infants. This suggests t h a t even gradual or rapid recovery to n o r m a l BP m a y be dangerous to the injured germinal layer vessels, especially in the i n f a n t with impaired autoregulation induced by perinatal asphyxia. F u r t h e r clinical s t u d y i s necessary to confirm this hypothesis. We thank Dr. Sachio Takashima, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, for his critical review of the manuscript. We also thank Dr. Yuuichi Inoue, Radiological Department of Osaka City University Medical School, for his review of the video to confirm the moment of intraventricular hemorrhage. REFERENCES

1. Hambleton G, Wiggleworth JS. Origin of intraventricular haemorrhage in the preterm infants. Arch Dis Child 1976; 51:651-9. 2. Lou HC, Lassen NA, Friis-Hansen B. Impaired autoregulation of cerebral blood flow in the distressed newborn infants. J PEDIATR 1979;94:118-21. 3. Volpe JJ. Neurology of the newborn. 2nd ed. Philadelphia: WB Saunders, 1987:311-61. 4. Volpe JJ. Intraventricular hemorrhage and brain injury in the premature infant--neuropathology and pathogenesis. Clin Perinatol 1989;16:361-86. 5. Friis-Hansen B, Lou HC, Lassen NA; Winberley MB. The pathogenesis of cerebral hypoxic lesions and intraventricular hemorrhage in the newborn preterm infant. In: Stren L, Salle B, Friis-Hansen B, eds. Intensive care in the newborn; vol 3. New York: Masson, 1981:253-62. 6. Omar SY, Greisen G, Ibrahim MM, Youssef AM, FriisHansen B. Blood pressure responses to care procedures in ventilated preterm infants. Acta Paediatr Scand 1985;74:920-4. 7. Perlman JM, Volpe JJ. Suctioning in the preterm infant: effects on cerebral blood tt0w velocity, intracranial pressure, and arterial blood pressure. Pediatrics 1983;72:329-34. 8. Goddard J, Lewis RM, Armstrong DL, Zeller RS. Moderate, rapidly induced hypertension as a cause of intraventricular hemorrhage in the newborn beagle model. J PEDIATR 1980;96: 1057-60. 9. Funato M, Tamai H, Kodaka R, Taki H, Yoshioka Y, Shimada S. The moment of intraventricular hemorrhage. Brain Dev 1988;10:325-7. 10. Bomsel F. Radiologic study of hyaline membrane disease. Journal de Radiologie, d'Electrogie et de Medeeine Nucleaire 1970;51:259-68. 11. Papile L-A, Burstein J, Burstein R. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1500 gin. J PEDIATR 1978; 92:529-34. 12. Tsiantos A, Victorin L, Relier JP, et al. Intracranial hemorrhage in the prematurely born infant--timing of clots and evaluation of clinical signs and symptoms. J PEDIATR 1974; 85:854-9. 13. Emerson P, Fujimura M, Howat P, et al. Timing of intraventricular haemorrhage. Arch Dis Child 1977;52:183-7. 14. Dolfin T, Skidmore MB, Fong KW, Hoskins EM, Shennan AT. Incidence, severity, and timing of subependyrrial and in-

Timing o f I V H in preterm infants

6 19

traventricular hemorrhage in preterm infants born in a perinatal unit as detected by serial real-time ultrasound. Pediatrics 1983;71:541-6. 15. Ment LR, Duncan CC, Ehrenkranz RA, et al. Intraventricular hemorrhage in the preterm neonate: timing and cerebral blood flow changes. J PEDIATR 1984;104:419-25. 16. Perlman JM, MeMenamin JB, Volpe JJ. Fluctuating cerebral blood-flow velocity in respiratory distress syndrome. N Engl J Med 1983;309:204-9. 17. Perlman JM, Thach BB. Respiratory origin of fluctuations in arterial blood pressure in premature infants with respiratory distress syndrome. Pediatrics 1988;81:399-403. 18. Goddard-Finegold J, Armstrong D, Zeller RS. Intraventricular hemorrhage following volume expansion after hypovolemic hypotension in the newborn beagle. J PEDIATR 1982; 100:796-9. 19. Hill A, Perlman JM, Volpe JJ. Relationship of pneumothorax to occurrence of intraveutricular hemorrhage in the premature newborn. Pediatrics 1982;69:144-9. 20. Lou HC, Lassen NA, Friis-Hansen B. Is arterial hypertension crucial for the development of cerebral hemorrhage in premature infants? Lancet 1979;1:1215-7. 21. Greisen G, Trojaborg W. Cerebral blood flow, Paco2 changes, visual evoked potentials in mechanically ventilated, preterm infants. Acta Paediatr Scand 1987;76:394-400. 22. Younkin DP, Reivich M, Jaggi JL, Obrist WD, Delivoria-Papadopoulos M. The effect of hematocrit and systolic blood pressure on cerebral blood flow in the newborn infants. J Cereb Blood Flow Metab 1987;7:295-9. 23. Reynolds ML, Evans CAN, Reynolds EOR, Saunders NR, Durbin GM, Wiggleworth JS. Intracranial hemorrhage in the preterm sheep fetus. Early Hum Dev 1979;3:163-85. 24. Cowan F, Thoresen M. The effects of intermittent positive pressure ventilation on cerebral arterial and venous blood velocities in the newborn infant. Acta Paediatr Scand 1987;76: 239-47. 25. Perlman JM, Volpe JJ. Are venous circulatory abnormalities important in the pathogenesis of hemorrhagic and/or ischemic cerebral injury? Pediatrics 1987;80:705-11. 26. Takashima S, Mito T, Ando Y. Pathogenesis of periventricular white matter hemorrhage in preterm infants. Brain Dev 1986;8:25-30. 27. Ment LR, Stewart WB, Duncan CC. Beagle puppy model of intraventricular hemorrhage: effect of superoxide dismutase on cerebral blood flow and prostaglandins. J Neurosurg 1985;62: 563-9. 28. Fujimura M, Salisbury DM, Robinson RD, et al. Clinical events relating to intraventricular hemorrhage in the newborn. Arch Dis Child 1979;54:409-14. 29. MiaI1-Allen VM, De Vries LS, Whitelaw AGL. Mean arterial pressure and neonatal cerebral lesions. Arch Dis Child 1987;62:1068-9. 30. Tamai H, Funato M. Hypotension and intraventricular hemorrhage. Acta Neonatologica Japonica [Japan] 1989;25:805810. 31. Andrew M, Castle V, Saigal S, Carter C, Kelton JG. Clinical impact of neonata ! thrombocytopenia. J PEDIATR 1987;110: 457-64. 32. Beverley DW, Chance GW, Inwood M J, Schaus M, O'Keefe B. Intraventricular haemorrhage and haemostasis defects. Arch Dis Child 1984;59:444-8. 33. Bada HS, Korones SB, Perry EH, et al. Frequent handling in the neonatal intensive care unit and intraventricular hemorrhage. J PEDIATR 1990;117:126-31.