Calcium ion activity in the sick neonate effect of bicarbonate administration and exchange transfusion – pdf brain anoxia

1 pediat. Res. 6: (1972) acidosis hypocalccmia calcium magnesium developmental physiology nconatcs phosphorus calcium ion activity in the sick neonate: effect of bicarbonate administration and exchange transfusion INGEBORG C. RADDEI’ 22 ‘, DAVID K. PARKINSON, BERND. HOEEKEN, KWASI E. APPIAH, AND WILLIAM B. HANI.EY I’epartmcnt of pediatrics, university of toronto, and the research institute, the hospital for sick children, toronto, ontario, canada extract calcium ion activity was measured in plasma obtained by venous or arterial puncture using a calcium-selective flow-through electrode. Mean level of ionized calcium in umbilical venous plasma was 2.48 ± 0.04 meq/liter.

Within 30 hr after birth, the values decreased in sick infants to 1.35 ± 0.11 meq/liter.Brain anoxia total calcium concentra tions were in the normal adult range at birth (5.20 meq/liter), showing a subsequent decline to subnormal values (3.47 ± 0.28 meq/liter at age hr). A calcium ion activity of less than 1.4 meq/liter was associated with total calcium level at or below 3 meq/liter in 80% of patients. Symptoms and signs attributable to hypocalcemia (ionized fraction) or hypornagnesemia, or both, were found only in infants in whom plasma levels of both divalent cations were below the lower limit of normal. Administration of nahgos for acidosis caused a slight rise in ph (from 7.20 to 7.28 rneq/liter) and a decrease in plasma calcium ion activity (from 1.68 to 1.51 meq/liter). During exchange transfusion with acid-citrate-dextrose (ACD)-tham buffered blood, calcium ion activity decreased significantly from 1.90 to 1.20 ± 0.09 mecj, liter, whereas total calcium levels increased consistently (from 4.22 db 0.13 to 5.33 ± 0.15 meq/liter).Brain anoxia speculation the temporary hypocalcemia, observed in sick newborn infants, may also occur in healthy newborns. It is thought to initiate normal calcium homeostasis by stimulating parathormone secretion and by bringing into play the two feedback mechanisms for calcitonin and parathormone secretion. Introduction trode [12, 18J, these changes can be assessed directly. One of the many adaptations that the newborn infant calculations of ionized calcium levels by the applicadon of formulas among other defidencies do not take faces in the immediate neonatal period is the change imo account the possibility of rapid changes in the from high to low calcium levels in the blood [1, 3, 7, 9, internal milieu in the neonate.Brain anoxia this applies particu- 14]. With the development of a rapid and simple larly to parameters known to influence ionized calmethod for measuring calcium ion activity in small cium: ph, protein, inorganic phosphate, and other calamounts of plasma by means of a calcium-selective elec- cium complexors. 43

2 44 RADDE ET AL. The problem of calcium abnormalities in the neonatc is illustrated by the occurrence of significant hypocalcemia (plasma calcium levels 0.1), facilitates the rapid processing of the blood. Blood was sampled either from umbilical vein catheter or by venous or arterial puncture. The ph of the blood was determined immediately; the syringe was then centrifuged for 5 min at 3000 rpm and the plasma was removed anaerobically into a 1-ml tuberculin syringe.Brain anoxia calcium ion activity was determined within 30 min after the blood was drawn, or the syringe was capped with parafilm and frozen immediately. After thawing, the plasma in the syringe was briefly agitated on a vortex mixer and the syringe was centrifuged. The calcium ion activity was determined by means of a flow-through calciumselective electrode [19]. The remaining plasma was analyzed for total calcium, magnesium, and protein levels and for inorganic phosphate concentrations. A minimum of 0.7 ml blood was required for these determinations. Chemical methods total calcium and magnesium levels in plasma were determined by emission and atomic absorption flame spectrophotometry [2, 11], respectively.Brain anoxia inorganic phosphate levels were measured by an automatic adaptation of the gomori procedure [8]; total protein levels were measured by an automatic modification of the procedure of lowry et al. [10], using human serum albumin as standard. The standards for calcium ion activity measurements were prepared with 150 mm nacl by diluting the appropriate amounts of cacl stock solution. Working standards also contained 3 drops 1 M triethanolamine solution and 0.06 g trypsin per 100 ml. They were prepared fresh weekly and stored in the refrigerator when not used. Unkown samples were bracketed between two adjacent standards. Serial measurements results values obtained from 35 patients on whom serial measurements of ionized calcium were made are reported.Brain anoxia values following nahco 3 treatment, exchange transfusion, or calcium administration were excluded. Figure 1 shows the pattern of ca ion activity in these infants up to 120 hr of age. During the first 5 hr of life, calcium ion activity was greater than that

3 calcium ion activity in the sick neonate 45 found in older children and adults, except in two infants whose mothers’ calcium levels at delivery were reduced (0.65 and 1.30 meq/liter); these infants also showed relative hypocalcemia at the time of birth. Thereafter, ionized calcium levels decreased, with a minimum which was below the lower limit of normal occurring between 15 and 45 hr of life. By the end of 120 hr, calcium ion activity in plasma had risen to values similar to those found in older children (table I)- when total calcium levels were plotted in a similar fashion (fig. 2), the pattern that emerges is of levels in the normal adult range at birth and a subsequent decline to subnormal values.Brain anoxia A calcium ion activity of less than 1.4 meq/liter was associated with total calcium levels at or below 3 meq/liter in approximately 80% of patients, but did not correlate well in the remainder. The correlation coefficient between total and ionic calcium was: r = 0.76, P rotein, g/lou ml birth hr hi lir hr hr hr hr hr 111 hr-10days days 2.48 ± (2 IP 2.06 ± 0.05 (33) 1.68 ± 0.05 (23) ± 0.11 ( c -») 1.42 (14) 1.62 ± ± ± ± ± cord blood. 2 mean ± SE. 3 number in parentheses: number of observati 4 : insufficient number of observations (32) ± 0.19 ± 0.22 ± 0.28 ± 0.26 (14) ± 0.35 ± 0.20 (12) ± 0.26 ± 0.30 ± ± 0.03 ± 0.05 (26) ± 0.07 ± 0.06 ± 0.12 (8) ± ) ± 0.10 (8) ± 0.31 ± ± ± (26) ± 0.30 ± 0.47 (ID ± 0.52 ± 0.47 i 4.94 ± ± ± ± ± ± (23) 7.29 ± (18) 7.29 ± ± ± ± ± ± ± ± ± 0.20 (28) 4.28 ± 0.24 (16) ± 0 ± 0 (0) ± o (8) ± ± 0.30 ±

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4 46 RADDE ET AI meq/l AGE HOURS DAYS fig. 2. Serial total calcium levels in plasma of sick newborn infants arranged according to age. The normal range in older children and adults is indicated by the bar labeled A*. The line connects group mean values at 0, 5, 15, 25, 35, 45, 60, 80, and 100 hr of age DAYS mg meq/l * X x X «* * . Gestational age and minimal values of calcium ion activity when we correlated the gestational age of the baby (or the birth weight) with the ionized calcium values found, it became evident that premature or dysmature (small for gestational age) infants showed more severe and prolonged depression of calcium ion activity in their plasma than did full term infants. During the first 5 hr of life, however, gestational age did not correlate well with calcium ion activity, the latter being high in all instances // ; i i i ca + + meq/l fig. 3.Brain anoxia correlation between calcium ion activity and magnesium levels in newborn infants. The horizontal interrupted line indicates the lower limit of normal for magnesium values; the vertical interrupted line indicates the lower limit of normal for calcium ion activity. Crosses represent values for blood taken at the time of neuromuscular hyperirritability in the infants. 1.3 meq/liter, and the infant showed muscle twitching. Figure 3 depicts the relationship between ionized calcium and plasma magnesium levels. A positive correlation was observed which was highly significant (r = 0.86; P IS * case no. I’ig. J. Calcium ion activity (lower panel) and total calcium levels {upperpanel) in plasma taken before and after exchange transfusion.Brain anoxia shaded areas indicate the normal range for each calcium value. Pre- and postexchange (10 min) levels of calcium ion activity and total calcium concentration. In every patient, there was a significant decrease in calcium ion activity in spite of the administration of the standard dose of calcium gluconate. Levels below 1.2 meq/liter were reached in eight patients, and were associated with muscle twitching or frank convulsions in four cases. Total calcium levels, on the other hand, increased consistently, in four instances into the frankly hypercalcemic range. The highest level observed was 6.75 meq/liter. The average blood ph did not change during transfusion (table III). Plasma magnesium levels decreased significantly, but only to slightly below normal values.Brain anoxia the changes in inorganic phosphate concentration were less clear-cut, and the difference between pre- and postexchange mean values was not statistically significant. Total protein levels in plasma did not change consistently during exchange transfusion. Discussion the development of a calcium-selective electrode has given us a helpful tool for correlating symptoms of neuromuscular hyperirritability with the concentration of the physiologically active fraction of plasma calcium in the sick newborn infant. As results are available within 20 min of drawing the blood, effective treatment of the significant hypocalcemia which occurs frequently in these neonates is facilitated. Although previous reports have indicated the existence of hypocalcemia in the neonatal period [6, 17], these changes were not serially related to symptoms nor was the discrepancy between total and ionized calcium fully

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6 48 RADDE ET AL. Table III. Effect of exchange, transfusion on the plasma of sick newborn infants 1 pi I ca +t, meci/liter total oi, meq/liter mg, meq/liter PO4, mg/100 ml protein, g/100 ml before transfusion after transfusion mean difference 2 ± SK P 7.31 ± ± ± ± ± ± ± ± 0.11 NS 3 ADOI’OI,I.OS, M., BATTACLIA, F. C, BRU.NS, P. D., AND MLSCHIA, G.: total protein-bound, and ultra-filterable calcium in maternal and fetal plasma. Amer. J. Physiol., 213: 363 (1967). 7. DORMANCY, ‘I’. L., AND BEOUM, R.: the plasma calcium and plasma magnesium response to standard metabolic loads in infants. In: D. Barltrop and W. I.. Burland: mineral metabolism in paediatrics, p. 31 (blackwell scientific publications, oxford, 1969). 8.Brain anoxia GOMORI, G.: A modification of the colorimetric phosphorus determination for use with the photoelectric colorimeter. J. Lab. Clin. Med., 27: 955 (1942). 9. IIOHENAUFR, L., ROSENBERG, I’. F., AND OH, W.: calcium and phosphorus homeostasis on the first day of life. Biol. Xeonatorum, IS: 49 (1970). 10. I.OWRY, O. II., ROSEBHOUGH, X. J., FARR, A. L., AND RANDALL, R. J.: protein measurement with the folin phenol reagent. J. Biol. Chcm., 193: 265 (1951). 11. MACINTYRE, I.: flame photometry. Advan. Clin. Chcm., 4: 1 (1961). 12. MOORE, E. \\\: ionized calcium in normal serum, ultraiiltrates and whole blood determined by ion-exchange electrodes. J. Clin. Invest., 19: 318 (1970). 13. NELSON, IN. M., AND RII.GEL, K.Brain anoxia P.: A schematic approach to acid-base therapy in the newborn. Pediatrics, 13: 821 (1969). 14. PAUPE, J., COLIN, J., POLITIS, E., AND LELONC, M.: some physiological variations of blood calcium level in mothers during labor, in cord and newborn infants. Biol. Xeonalorum, 3: 357 (1961). 15. RADDE, I. C, IIOFFKEN, IS., AND PARKINSON, D. K.: effects of alterations of blood ph on calcium ion activity in rat plasma. Clin. Orthop. Related res., 7,y.- 30 (1971). 16. RADUF, I. C, HOFFKEN, B., PARKINSON, 1). K., SHF.EI’I.RS, J., AND l.Txikham, A.: practical aspects of a measurement technique for calcium ion activity in plasma. Clin. (.Hem., 17: 1002 (1971). 17. ROSENKRANZ, A.: der serumcalziumspiegel beim friihgeborenen in den ersten lebenstagen.Brain anoxia paediat. Paedol., 2: 367 (1966). 18. SACHS, C, BOURDEAU, A.-M., AND BALSAX, S.: determination clu calcium ionize dans le serum avec line electrode specilique a membrane liquidc. Ann. Biol. Clin., 2: 487 (1969). 19. Model 99-20, orion research corporation, inc., cambridge, mass. 20. The authors wisli to acknowledge the helpful ad\ice of dr. P. Swyer, M.A., M.B. (cantab.). M.R.C.P. (I.Ond.), in whose neonatal unit the clinical part of the study was carried out; the competent technical assistance of mrs. J. Sheepers, R. T., and miss A. I.Uckham, R. T., and the enthusiastic help of messrs. Peter storms, B.Sc, and D. Mc- lean. 21. Supported in part by grant no. MA-1797 from the medical research council of canada. 22.Brain anoxia requests for reprints should be addressed to: INKEISORG C. RADDE, M.D., research institute, the hospital for sick children, 555 university avenue, toronto 2, ontario, canada. 23. Accepted for publication april 15, copyright 1972 international l’ecliatric research foundation, inc. Printed in U.S.A.