Acta Pzdiatr Scand 65: 43%444, 1976
ADRENOCORTICOTROPHIN AND GLUCOCORTICOID RESPONSE TO EXCHANGE TRANSFUSION R. D. G. MILNER, AGNES CSER, MARGARET GOODE and J. G. RATCLIFFE From the Department of Child Heulth, University of Manchester, England, and Radioimmunoassay Unit, Stobhill General Hospital, Glasgow, Scotland
ABSTRACT. Milner, R. D. G., Cser, A., Goode, M. and Ratcliffe, J. G. (Department of Child Health, University of Manchester, St. Mary’s Hospital, Manchester, England, and Radioimmunoassay Unit, Stobhill General Hospital, Glasgow, Scotland). Adrenocorticotrophin and glucocorticoid response to exchange transfusion. Acta Paediatr Scand, 6 5 439, 1976.Plasma adrenocorticotrophin (ACTH) and glucocorticoid concentrations were measured during and for 3 hours after exchange transfusion in four groups of infants. Transfusions with ACD blood via the umbilical artery were performed on 10 infants of 3 5 4 0 weeks gestation and 11 infants of 27 to 33 weeks gestation. Ten transfusions via the umbilical vein were performed with ACD blood and 9 with heparin blood on infants of 32 to 41 weeks gestation. In all four types of transfusion there was a significant washing out of ACTH and glucocorticoids from the baby. An associated rise of plasma ACTH and glucocorticoid levels indicated increased secretion in the larger infants transfused with ACD blood via the umbilical artery. Equivocal results were obtained in the other groups. After all types of transfusion plasma glucocorticoid levels remained relatively constant for one hour and then doubled in the second and third hour. The results suggest that ( a )exchange transfusion via the umbilical artery is more stressful than that via the umbilical vein, (b) the glucocorticoid response of premature infants to exchange transfusion is similar to that of mature infants, (c) an unspecified stimulus, which is not solely hypoglycaemia nor the metabolic reaction to a citrate load, results in a rise in plasma glucocorticoid levels 2-3 hours after all types of transfusion. KEY WORDS: Exchange transfusion, glucocorticoids, ACTH
Exchange transfusion involves the insertion of a catheter into the portal venous system or aorta of a conscious newborn infant, the acute removal of an appreciable fraction of the circulating blood and replacement with blood of a different metabolic composition. This study was based on the hypothesis that these procedures may be stressful to the baby. Measurements have therefore been made of changes in plasma adrenocorticotrophin (ACTH) and glucocorticoids during and after different types of exchange transfusion, to compare the degree
to which these procedures stimulate the hypothalamic-pituitary-adrenal axis in the newborn.
PATIENTS AND METHODS Forty exchange transfusions were performed on 32 infants. The transfusions were performed via the umbilical artery (UA) or vein (UV) using blood preserved with acid citrate and dextrose (ACD) or heparin by a technique described previously (7). The transfusions were divided into 4 groups: those performed on mature infants with ACD blood via the umbilical artery (ACD-UA), via the umbilical vein using ACD or heparin blood (ACD-UV and heparin-UV) and those performed on small infants via the Acra Pzdiatr Scand 65
440 R . D . G . Milner et al. Table 1. Clinical details of infants and exchange transfusions No. of patients and sex M
F
Mean gestational age (weeks)
2 5 5
6 4 3
37 (35-40) 36 (32-41) 37 (35-40)
3.02 (2.12-3.84) 2.53 (1.70-3.14) 2.78 (2.12-3.66)
76 (5-520) 52 (2-95) 59 (9-137)
2.2 (1.7-2.6) 2.2 (1.6-3.0) 2.2 (1.9-2.4)
2
5
29 (27-33)
1.25 (0.98-1.56)
66 (26-1 12)
2.3 (2.0-3.0)
Clinical group and number of transfusions ACD"-UAb (10) ACD"-UV' (10) Heparind-UV' (9) Small babies ACD"-UAb ( 1 1)
Mean birthweight
(ks)
Postnatal age (hours)
Volume transfused/ blood vol. of patient
Blood preserved with acid citrate and dextrose. Umbilical artery. Umbilical vein. Blood preserved with heparin. umbilical artery using ACD blood (small babies ACD-UA) (Table 1). The indication for exchange transfusion in the first three groups was usually haemolytic disease due to rhesus or ABO blood group incompatibility whereas transfusions in the small babies were because of hyperbilirubinaemia due to prematurity and/or bruising. The changes in plasma glucose, free fatty acids, insulin and growth hormone occurring in these transfusions have been reported elsewhere (1, 2, 3). Blood samples were collected and stored as described previously. Plasma ACTH was measured by radioimmunoassay after extraction by porous glass (11) using an antiserum directed at the N-terminal 1-24 portion of the ACTH molecule. Natural human ACTH prepared by Dr P. J. Lowry was employed for iodination and standardization. The detection limit of the assay varied between 20 and 50 pg/ml depending on the plasma volume extracted. In the calculation of mean values, undetectable ACTH levels were ascribed values half the limit of detection in that assay. Plasma glucocorticoids were measured by competitive protein binding assay (8) using 1.5% human pregnancy
serum as the binding reagent, tritiated cortisol (Radiochemical Centre, Amersham) as the labelled steroid and cortisol (Steraloids, London) for standardization. Two plasma samples containing a low and a high total glucocorticoid concentration were selected from 13 posttransfusion series and subjected to Sephadex LH-20 column chromatography to determine the relative contributions of corticosterone, cortisone and cortisol to the total plasma glucocorticoid concentration (9).
RESULTS During transfusion
The mean concentrations of ACTH and glucocorticoids in the different groups of donor blood were similar, as were the levels in the infants' arterial or venous blood before transfusion began (Table 2). In each group the mean
Table 2. Mean ( +S.E.) ACTH and glucocorticoid concentrations during exchange transfusion with ACD or heparin blood via the umbilical artery (UA) or vein (UV) Donor
0 ml
100 ml
200 ml
300 ml
400 ml
ACD-UA Glucocorticoids (nglml) ACTH W m l )
77k 15 (10) 30f 5(1O)
lO5f 13 (10) 47+ 8 (ZO)
114+ I4 (10) 64516 (10)
128f 17 (10) 64f15 (10)
154f25 (10) 6 8 f 1 6 (9)
128520 (10) 60f12 (9)
ACD-UV Glucocorticoids (ng/ml) ACTH (pglml)
6 3 5 9 (10) 20+ 4 (8)
124f18 (10) 6 0 f 2 1 (8)
109f 16 (10) 4 2 f 9 (8)
101f16 (9) 33+ 7 (8)
93+ 16 (10) 42+ 9 (8)
89+ 14 (10) 48513 (7)
Heparin UV Glucocorticoids (nglml) ACTH (pg/ml)
8 8 f 1 9 (9) 2 5 f 7 (5)
102f26 (9) 117f26 (9) 47518 (6) 35f 8 (6)
153530 ( 9 ) 37f10 (6)
135+31 ( 9 ) 102f20 (7) 4 7 f 1 8 (6) 38f18 (6)
ACD-UA Small babies Glucocorticoids (ng/ml)
Donor
0 ml
50 ml
100 ml
150 ml
200 ml
7 4 f 1 5 (11)
144523 (11)
176+22 (11)
158f23 (11)
145+22 (11)
132+22 (11)
Acta Padiatr Scand 65
ACTH and glucocorticoid response to exchange transfusion
1
OJ d
0
I00
200
PLASMA ACTH ( pg / m l )
Fig. I. Scatterdiagram of plasma glucocorticoid concen-
tration during ACD-UA transfusions as a function of the immediately preceding plasma ACTH concentration. Linear correlation coefficient 0.65 (p
ADRENOCORTICOTROPHIN AND GLUCOCORTICOID RESPONSE TO EXCHANGE TRANSFUSION R. D. G. MILNER, AGNES CSER, MARGARET GOODE and J. G. RATCLIFFE From the Department of Child Heulth, University of Manchester, England, and Radioimmunoassay Unit, Stobhill General Hospital, Glasgow, Scotland
ABSTRACT. Milner, R. D. G., Cser, A., Goode, M. and Ratcliffe, J. G. (Department of Child Health, University of Manchester, St. Mary’s Hospital, Manchester, England, and Radioimmunoassay Unit, Stobhill General Hospital, Glasgow, Scotland). Adrenocorticotrophin and glucocorticoid response to exchange transfusion. Acta Paediatr Scand, 6 5 439, 1976.Plasma adrenocorticotrophin (ACTH) and glucocorticoid concentrations were measured during and for 3 hours after exchange transfusion in four groups of infants. Transfusions with ACD blood via the umbilical artery were performed on 10 infants of 3 5 4 0 weeks gestation and 11 infants of 27 to 33 weeks gestation. Ten transfusions via the umbilical vein were performed with ACD blood and 9 with heparin blood on infants of 32 to 41 weeks gestation. In all four types of transfusion there was a significant washing out of ACTH and glucocorticoids from the baby. An associated rise of plasma ACTH and glucocorticoid levels indicated increased secretion in the larger infants transfused with ACD blood via the umbilical artery. Equivocal results were obtained in the other groups. After all types of transfusion plasma glucocorticoid levels remained relatively constant for one hour and then doubled in the second and third hour. The results suggest that ( a )exchange transfusion via the umbilical artery is more stressful than that via the umbilical vein, (b) the glucocorticoid response of premature infants to exchange transfusion is similar to that of mature infants, (c) an unspecified stimulus, which is not solely hypoglycaemia nor the metabolic reaction to a citrate load, results in a rise in plasma glucocorticoid levels 2-3 hours after all types of transfusion. KEY WORDS: Exchange transfusion, glucocorticoids, ACTH
Exchange transfusion involves the insertion of a catheter into the portal venous system or aorta of a conscious newborn infant, the acute removal of an appreciable fraction of the circulating blood and replacement with blood of a different metabolic composition. This study was based on the hypothesis that these procedures may be stressful to the baby. Measurements have therefore been made of changes in plasma adrenocorticotrophin (ACTH) and glucocorticoids during and after different types of exchange transfusion, to compare the degree
to which these procedures stimulate the hypothalamic-pituitary-adrenal axis in the newborn.
PATIENTS AND METHODS Forty exchange transfusions were performed on 32 infants. The transfusions were performed via the umbilical artery (UA) or vein (UV) using blood preserved with acid citrate and dextrose (ACD) or heparin by a technique described previously (7). The transfusions were divided into 4 groups: those performed on mature infants with ACD blood via the umbilical artery (ACD-UA), via the umbilical vein using ACD or heparin blood (ACD-UV and heparin-UV) and those performed on small infants via the Acra Pzdiatr Scand 65
440 R . D . G . Milner et al. Table 1. Clinical details of infants and exchange transfusions No. of patients and sex M
F
Mean gestational age (weeks)
2 5 5
6 4 3
37 (35-40) 36 (32-41) 37 (35-40)
3.02 (2.12-3.84) 2.53 (1.70-3.14) 2.78 (2.12-3.66)
76 (5-520) 52 (2-95) 59 (9-137)
2.2 (1.7-2.6) 2.2 (1.6-3.0) 2.2 (1.9-2.4)
2
5
29 (27-33)
1.25 (0.98-1.56)
66 (26-1 12)
2.3 (2.0-3.0)
Clinical group and number of transfusions ACD"-UAb (10) ACD"-UV' (10) Heparind-UV' (9) Small babies ACD"-UAb ( 1 1)
Mean birthweight
(ks)
Postnatal age (hours)
Volume transfused/ blood vol. of patient
Blood preserved with acid citrate and dextrose. Umbilical artery. Umbilical vein. Blood preserved with heparin. umbilical artery using ACD blood (small babies ACD-UA) (Table 1). The indication for exchange transfusion in the first three groups was usually haemolytic disease due to rhesus or ABO blood group incompatibility whereas transfusions in the small babies were because of hyperbilirubinaemia due to prematurity and/or bruising. The changes in plasma glucose, free fatty acids, insulin and growth hormone occurring in these transfusions have been reported elsewhere (1, 2, 3). Blood samples were collected and stored as described previously. Plasma ACTH was measured by radioimmunoassay after extraction by porous glass (11) using an antiserum directed at the N-terminal 1-24 portion of the ACTH molecule. Natural human ACTH prepared by Dr P. J. Lowry was employed for iodination and standardization. The detection limit of the assay varied between 20 and 50 pg/ml depending on the plasma volume extracted. In the calculation of mean values, undetectable ACTH levels were ascribed values half the limit of detection in that assay. Plasma glucocorticoids were measured by competitive protein binding assay (8) using 1.5% human pregnancy
serum as the binding reagent, tritiated cortisol (Radiochemical Centre, Amersham) as the labelled steroid and cortisol (Steraloids, London) for standardization. Two plasma samples containing a low and a high total glucocorticoid concentration were selected from 13 posttransfusion series and subjected to Sephadex LH-20 column chromatography to determine the relative contributions of corticosterone, cortisone and cortisol to the total plasma glucocorticoid concentration (9).
RESULTS During transfusion
The mean concentrations of ACTH and glucocorticoids in the different groups of donor blood were similar, as were the levels in the infants' arterial or venous blood before transfusion began (Table 2). In each group the mean
Table 2. Mean ( +S.E.) ACTH and glucocorticoid concentrations during exchange transfusion with ACD or heparin blood via the umbilical artery (UA) or vein (UV) Donor
0 ml
100 ml
200 ml
300 ml
400 ml
ACD-UA Glucocorticoids (nglml) ACTH W m l )
77k 15 (10) 30f 5(1O)
lO5f 13 (10) 47+ 8 (ZO)
114+ I4 (10) 64516 (10)
128f 17 (10) 64f15 (10)
154f25 (10) 6 8 f 1 6 (9)
128520 (10) 60f12 (9)
ACD-UV Glucocorticoids (ng/ml) ACTH (pglml)
6 3 5 9 (10) 20+ 4 (8)
124f18 (10) 6 0 f 2 1 (8)
109f 16 (10) 4 2 f 9 (8)
101f16 (9) 33+ 7 (8)
93+ 16 (10) 42+ 9 (8)
89+ 14 (10) 48513 (7)
Heparin UV Glucocorticoids (nglml) ACTH (pg/ml)
8 8 f 1 9 (9) 2 5 f 7 (5)
102f26 (9) 117f26 (9) 47518 (6) 35f 8 (6)
153530 ( 9 ) 37f10 (6)
135+31 ( 9 ) 102f20 (7) 4 7 f 1 8 (6) 38f18 (6)
ACD-UA Small babies Glucocorticoids (ng/ml)
Donor
0 ml
50 ml
100 ml
150 ml
200 ml
7 4 f 1 5 (11)
144523 (11)
176+22 (11)
158f23 (11)
145+22 (11)
132+22 (11)
Acta Padiatr Scand 65
ACTH and glucocorticoid response to exchange transfusion
1
OJ d
0
I00
200
PLASMA ACTH ( pg / m l )
Fig. I. Scatterdiagram of plasma glucocorticoid concen-
tration during ACD-UA transfusions as a function of the immediately preceding plasma ACTH concentration. Linear correlation coefficient 0.65 (p
