Changes in intracranial pressure during exchange transfusion

Volume 94 Number 1

Brief clinical and laboratory observations

ally tend to revert toward normal with repeated sampling? On the other hand, previous reports have speculated that high fetal iCa in utero may be the basis for suppression of the fetal parathyroids, w i t h consequent functional hypoparathyroidism in the neonatal period,' Thus, it might be expected that higher iCa in cord blood would be associated with greater suppression of the fetal parathyroids and greater decrease in iCa in the postnatal period. The authors are grateful to Sheila Kennedy and Pat Holtkamp for the preparation of this manuscript. REFERENCES

1. Tsang RC, Kleinman L, Sutherland JM, and Light IJ: Hypocalcemia in infants of diabetic mothers: Studies in Ca, P, and Mg metabolism and in parathormone responsivehess, J PEDIATR80:384, 1972. 2. Tsang RC, Light IJ, Sutherland JM, and Kleinman LI: Possible pathogenetic factors in neonatal hypocalcemia of prematurity, J PEDIATg82:423, 1973.

129

3. Tsang RC, Chen I, Atkinson W, Hayes W, Atherton H, and Edwards N: Neonatal hypocalcemia in birth asphyxia, J PEDImR 84:428, 1974. 4. Tsang RC, and Chen I-W: The parathyroid glandular response to neonatal hypocalcemia, J P~DIATR83:!53, 1973 (abstr). 5. Tsang RC, Chen bW, Friedman MA, and Chen I: Neonatal parathyroid function: Role of gestational and postnatal age, J PEDIATR83:728, 1973. 6. Shami Y, and Radde IC: The effect of the Ca/Mg concentration ratio on placental (Ca/Mg)-ATPase activity, Biochem Biophys Acta 255:665, 1972. 7. Whitsett JA, Kleinman LI, and Tsang RC: Properties of Ca Mg stimulated ATPase activity in human placental yillous tissue, in Norman AW, Schaefer K, Cobum JW, DeLuca HF, Fraser D, Grigoleit HG, Herrath DV, editors: Vitamin D Biochemical, chemical and clinical aspects related to calcium metabolism, Berlin, NY, 1977, Walter deGruyter, pp 341-344. 8. Remington RD, and Schork MA: editors. Statistics with apolications to the biological and health sciences, Englewood Cliffs, N. J., 1970, Prentice-Hall, Inc., pp. 253-254.

Changes in intracranial pressure during exchange transfusion Henrietta S. Bada, M.D,* Carlos Chua, M.D., James H. Salmon, M.D., and Waleed Hajjar, M.S., Springfield, lit.

EXCHANGE TRANSFUSION is utilized in the management of neonatal conditions such as hyperbilirubinemia, respiratory distress syndrome, sepsis, and disseminated intravascular coagulopathy. With the availability of noninvasive intracranial pressure monitoring, we were able to study the changes in intracranial pressure during exchange transfusion.

MATERIALS

AND METHODS

Continuous recording of ICP by the use of a noninvasive method, the fontogram, 1 was carried out during exchange transfusion in eight newborn infants. Since in five of these infants an umbilical arterial catheter was already in place for continuous blood pressure monitorFrom the Departments of Pediatrics and Surgery, Southern Illinois University School of Medicine, and the High Risk Neonatal Center, St. John's Hospital. *Reprint address: Southern Illinois University School of Medicine, Department of Pediatrics, PO Box 3926, Springfield, IL 62708.

0022-3476/79/100129 +04500.40/0 9 1979 The C. V. Mosby Co.

ing, simultaneous blood pressure recordings were also obtained, using the standard physiologic transducer. See related articles, pp. 118 and 170.

Abbreviations used ICP: intracranial pressure MAP: mean arterial pressure CBF: cerebral blood flow AGA: appropriate for gestational age All but one infant were premature, AGA, and weighed less than 2,500 gm. One term infant weighed 4,050 gm. Five infants had the exchange transfusion done because of disseminated intravascular coagulopathy. Each of the other three infants had one of the following conditions: sepsis, hyperbilirubinemia, and bupivacaine intoxication. The exchange transfusion was performed according to the described standard procedure, through an umbilical

13 0

Brief clinical and laboratory observations

The Journal of Pediatrics January 1979

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,,,,,,,,, Figure. Tracing showing the change in intracranial pressure and blood pressure during infusion and withdrawal of 10 ml of blood. In this particular patient, cerebral perfusion pressure is about 25 mm Hg, a dangerously low level. venous catheter? The total volume of blood used was equal to twice the patient's calculated blood volume, and the increment used was 5 to 15 ml, never exceeding 10% of the blood volume. Throughout the exchange transfusion procedure, the duration of each step, withdrawal or infusion, was recorded. In addition, the initial ICP and final ICP values were obtained with each step. The term "initial" describes the observation made at the initiation of a step, and the term "final" describes the observation made at the completion of the step. In five of the patients, initial mean arterial pressure and final MAP measurements were also available. Thus, for each step the set of observations included the duration of the step, the initial ICP, the final ICP and, in some patients, the initial and final MAP, The number of withdrawal steps per patient ranged from 26 to 41, and in each patient was equal to that of the infusion steps. The sets of observations made with the withdrawal steps from all patients were combined and analyzed. To determine how the final ICP and MAP values were affected by the duration of the withdrawal steps, the partial correlation coefficients were computed, controlling for the initial ICP and MAP values, the increments used, and the individual effect. The data obtained during infusion were also combined and analyzed, controlling for the same factors. The partial correlations of the final ICP and MAP and the duration of the infusion steps were also determined. The final analysis consisted in the determinatmn of the correlation between ICP and MAP at various intervals throughout the exchange transfusion procedure; i.e., at the start and completion of all the withdrawal steps and at

the start and completion of all the infusion steps. The partial correlation coefficients were computed, controlling for the individual effect. RESULTS The associated ICP and MAP changes occurring during withdrawal and infusion of blood during exchange transfusion are illustrated in the Figure. Both ICP and MAP decreased during blood withdrawal, and both increased with infusion. The mean changes in ICP and MAP measurements and mean duration of withdrawal and infusion are shown in Table I. The partial correlation coefficients obtained with the analysis of the combined withdrawal and infusion data are shown in Table II. The significant positive correlation between the final ICP or MAP and the duration of blood withdrawal implies that the final ICP and MAP measurements are higher when blood is withdrawn over a longer period of time; i.e., the decrease in ICP and MAP is less with a longer withdrawal time. On the other hand, the significant negative correlation between the final ICP or MAP and the duration of infusion indicates that final ICP and MAP values are lower when the infusion time is longer, or that the alteration of these measurements is less with a prolonged infusion time. The results of the correlation studies performed between ICP and MAP at varying intervals during the exchange transfusion are also shown in Table II. All the partial correlation coefficients were statistically significant (P <_ 0.01). These data show the direct relationship of ICP and MAP throughout the exchange transfusion procedure.

Volume 94 Number 1 DISCUSSION The decrease and increase in MAP, which corresponded to the withdrawal and infusion of blood during exchange transfusion, may result from alterations in circulating blood volume. Aranda and Sweet 3 observed similar hemodynamic changes, and felt that too rapid withdrawal may critically decrease the perfusion to vital organs. This may partially explain necrotizing enterocolitis,' respiratory arrest, :~and the mortality5 associated with exchange transfusion. Based on the studies of Ryder and associates, ~ cerebral blood flow is a major variable in controlling ICP. The changes in ICP during exchange transfusion could possibly result from the changes in CBF. The significant direct relationship between ICP and MAP in our patients suggests a direct relationship between CBF and MAP; i.e., CBF decreases or increases with alterations in circulating blood volume when blood is withdrawn or infused. These findings are consistent with the hypothesis of impaired autoregulation of CBF in the newborn infant, proposed by Lou et al. 7 Because of the passive direct dependence of CBF on MAP, rapid blood withdrawal may result in a marked decrease in MAP and concomitant reduction in CBF to a level that could impair brain metabolism. On the other hand, it appears that rapid blood infusion is potentially as detrimental. In ill infants, especially those who are premature and have respiratory distress, dilation of the cerebral vessels occurs with hypoxia and hypercarbia. Too rapid an expansion of blood volume in these infants may result in a marked increase in CBF, thereby causing rupture of the already dilated choroid capillaries and subependymal veins. During postmortem infusion of the newborn brain, Parke 8 noted that the contrast material, when injected rapidly, extravasated from the choroid plexus into the lateral ventricles. It appears that rapid infusion of a solution, whether alkali, blood, or plasma expander, in critically ill and hypoxic infants with impaired autoregulation of CBF, may constitute an important factor in the etiology of intraventricular hemorrhage. Our experience illustrates the usefulness of noninvasive monitoring of ICP in addition to BP during exchange transfusion. It is difficult to recommend an optimal withdrawal or infusion time, since other factors, such as the volume of the increment used and the infant's blood volume, may affect the degree of change in MAP and ICP. It would be more appropriate to vary each withdrawal or infusion time based on MAP and ICP measurements during exchange transfusion. Aside from exchange transfusion, it also appears clinically useful to monitor ICP as well as BP during treatment of shock, or during infusion of sodium bicarbonate to

Brief cfinical and laboratory observations

13 1

Table I. The mean duration of withdrawal and infusion steps and the associated changes in ICP and MAP during exchange transfusion

Associated changes in

Exchange transfusion steps

Duration (sec)

ICP (mm Hg)

Withdrawal Mean ___SD 33.67___24.74 Range 10.67-264.0 Infusion Mean +__SD 38.50_ 25.92 Range 11.5-132.0

I

[ MAP [ (ram Hg)

Decrease Decrease 3.12 • 1.65 3.35 _+ 2.18 0-9.0 0-11.0 Increase Increase 3.19 _ 1.43 2.99 _+ 1.95 0-8.0 0-11.0

ICP = Intracranialpressure; MAP = meanarterial pressure. Table II. Partial correlation of various sets of observations during exchange transfusion

Exchange transfusion steps

Measurements correlated

Withdraw- Duration al and final ICP MAP Initial ICP and MAP Final ICP and MAP Infusion Duration and final ICP MAP Initial ICP and MAP Final ICP and MAP

Sets of observations

Partial correlation coefficient

P values

244 158

0.3092 0.2394

_< 0.01 _< 0.01

158

0.4925

_< 0.01

158

0.3881

_< 0.01

244 158

-0.2467 -0.1207

<_ 0.01 _< 0.10

158

0.3880

_< 0.01

158

0.4683

<__0.01

ICP = Intracranialpressure; MAP = meanarterial pressure. correct metabolic acidosis, especially in those infants at risk for developing intraventricular hemorrhage. The assistance of Mr. John Schmidt, statistician, Health Science Information Systems of Southern Illinois University School of Medicine is appreciated. REFERENCES

1. Salmon JH, Hajjar W, and Bada HS: The fontogram: A noninvasive intracranial pressure monitor, Pediatrics 60:721, 1977. 2. BowanJM: Hemolytic disease of the newborn (erythroblastosis fetalis), in Gellis SS, and Kagan BM, editors: Current pediatric therapy, Philadelphia, 1971, WB Saunders Company. 3. Aranda JV, and Sweet AY: Alterations in blood pressure

13 2

Brief clinical and laboratory observations

during exchange transfusion, Arch Dis Child 52:545, 1977. 4. Touloukian RJ, Kadar A, and Spencer RP: The gastrointestinal complications of neonatal umbilical venous exchange transfusion: A clinical and experimental study, Pediatrics 51:36, 1973. 5. BoggsTR Jr, and Westphal MC Jr: Mortality of exchange transfusion, Pediairics 26:745, 1960. 6. Ryder HW, Espey FF, Kristoff FV, and Evans JP: Obser-

The Journal of Pediatrics January 1979

vations on the interrelationships of intracranial pressure and cerebral blood flow, J Neurosurg 8:46, 1951. Lou HC, Lassen NA, and Friis-Hansen B: Impaired autoregulation of cerebral blood flow in the distressed newborn infant, J PEDIATrt94:118, 1979. Parke WW: Anteroposterior angiogram of the fetal head, plate 162, in Photographic atlas of fetal anatomy, Baltimore, 1975, University Park Press, p 337.

Serum PG I in premature and term infants William M. Liebman, M.D., and I. Michael Samloff, M.D., San Francisco and Torrance, Calif.

PEPSINOGENS are precursor zymogens secreted by gastric mucosa, which are converted to active proteolytic enzymes, pepsins, by hydrochloric acid? Two immunochemically distinguishable groups of human pepsinogens, group I (Pg I) and group IV (Pg II) exist? It is known that Pg I consists of five electrophoretically distinct fractions, is present in urine and serum, and appears to originate in the mucous neck and chief cells in gastric fundic mucosa'; it is also known that Pg II consists of two electrophoretically distinct fractions, is present in serum and seminal vesicle fluid, and appears to originate in the mucous neck and chief cells in gastric fundic mucosa, pyloric gland cells of gastric antrum, and the Brunner glands in the proximal duodenum. ' ~ The predominant pepsinogen in both gastric (oxyntic gland) mucosa and in blood is Pg I? Both groups have been measured by conventional assays of proteolytic activities.~ Recently, a radioimmunoassay specific for Pg I has been developed.:' We report serum Pg I levels measured by radioimmunoassay, specific for Pg I, in term and premature infants during the first month of life.

and 33 16 male; 17 female) were term infants. Serial samples were obtained from 43 (21 premature; 22 term) infants. Serum Pg I was determined by radioimmunoassay-a competitive binding, double-antibody assay, specific for Pg I? All determinations were performed in duplicate. Statistical analysis was completed using the t test for unpaired samples. RESULTS The mean ( _ S D ) level of serum Pg I in the 30 premature infants was 25.6 _ 2.4 ng/ml, with a range of 7.5 to 50.0. The mean level of serum Pg I in the 33 term infants was 39.1 _+ 3.5 ng/ml, with a range of 22.0 to 139.50 (P < 0.025) (Table). The mean Pg I value in 38 adult control subjects was 104 _+ 30.0 ng/ml. No significant sex differences in serum Pg I values were observed at any age tested. In addition, no significant changes in serum Pg I occurred during each of the four postnatal weeks in either group. DISCUSSION

MATERIALS

AND

METHODS

Serum samples were obtained from 63 normal infants during the first four weeks of life. Thirty (15 male: 15 female) were premature infants, 31 to 36 weeks' gestation, From the Department of Pediatrics, University of California, School of Medicine, San Francisco, and Department of Medicine, University of Los Angeles, School of Medicine, Torrance. Supported by Training Grant AM 05654 and Research Grant AM 13233from the National Institutes of Health. *Reprint address: Department of Pediatrics, Universi(v ~ California, School of Medicine, San Francisco, CA 94143.

Peptic activity has been demonstrated by the sixteenth week of gestation, subsequently increasing three- to fourfold during the third trimester? Very little, if any, acid has been found in gastric juice before 32 weeks' gestation. Thus, the ability to form pepsinogen seems to develop before acid-forming capability.~ During the neonatal period, gastric acid secretion is reported to be low compared with that in adults, ranging from 5 to 20% of adult values, during the first month of life. =. ~ However, Euler et al ~' found hyposection of gastric acid for the first five hours of life, but found subsequent secretion rates to be similar to those in older children. Maximal pepsin secretion into the stomach is lower in

0022-3476/79/100132 + 02500.20/0 9 1979 The C. V. Mosby Co.