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Perinatal Asphyxia and Renal Failure in Neonatal Patients
Vol. 118, July, Part 1 Printed in U .SA.
THE JOURNAL OF UROLOGY
Copyright © 1977 by The Williams & Wilkins Co.
PERINATAL ASPHYXIA AND RENAL FAILURE IN NEONATAL PATIENTS JOSEPH R. DRAGO, THOMAS J. ROHNER, JR., EDGAR J. SANFORD
AND
M. JEFFREY MAISELS
From the Divisions of Urology and Neonatology, The Milton S. Hershey Medical Center, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
ABSTRACT
Herein we discuss oliguria and azotemia in neonatal patients associated with perinatal complications, including difficult labor and delivery, and respiratory asphyxia. Renal failure in these patients is accompanied by proteinuria, microscopic hematuria and red blood cell casts, and it generally resolves in 7 to 10 days. Umbilical aortography can be helpful in determining the presence of normal kidneys in these patients. plastic infant feeding tubes. Oliguria was noted on day 1 and lasted as long as 1 week. Initial laboratory data included blood urea nitrogen (BUN) of 8 to 46 mg. per cent and routine urinalysis showed proteinuria and red blood cells (RBCs) in all patients, and RBC casts in 3. Of the 5 patients 4 survived. The 1 infant who died had severe cardiovascular and pulmonary instability, was premature at birth (1,310 gm.) and, at autopsy, had glomerular lesions most likely secondary to hypoxia. Two cases are described in detail.
Obstetricians and pediatricians, using improved techniques of fetal monitoring and resuscitation, have improved the salvage of critically ill newborns and created a new patient population with certain problems of urologic interest. When the urologist is asked to see a neonatal patient with oliguria and progressive renal failure he is especially concerned with ruling out congenital anomalies and obstructive causes. The most frequent causes of oliguria and renal failure in neonates include, in addition to anomalies and obstruction, hemorrhage, diarrhea and dehydration, hemolytic uremic syndrome, renal vein thrombosis, gastroenteritis, septicemia and perinatal hypoxia. 1 • 2 Herein we present our experience with 5 newborns who had respiratory asphyxia and renal failure without obstructive uropathy.
CASE REPORTS
Case 1 (table 3). B. B. M., MSHMC 103777, weighed 3,500 gm. at birth and was delivered by cesarean section. He had
TABLE
Pt. -Hosp. No.
Apgar
Birth Wt. 3,500
BBI-053680 BBF-062053 BGD-086966 BBB-087769
4,550 3,100 1,650 1,315
Mode of Delivery
Complication of Pregnancy
(gm.)
BBM-103777
1 1 Min.
Decreased fetal heart rate at 35 wks. of gestation Prolonged 2nd stage Eclampsia Eclampsia, toxemia, vaginal bleeding, clots Premature rupture of membranes at 29 wks. of gestation
Cesarean section
5 Mins. 3
Mid-forceps meconium stained Cesarean section Cesarean section Vaginal
4
5
1 2 7 2 Not recorded, cyanotic, intubated at birth
TABLE 2
Pt. -Hosp. No.
Resuscitation at Birth
Physical Examination
BBM-103777 BBI-053680 BBF-062053
Intubation, ventilation Intubation, ventilation Intubation, ventilation
BGD-086966 BBB-087769
Intubation, ventilation Intubation, ventilation
Total body edema Tachypnea, cephalhematoma Apneic at birth, cyanosis on room air Tachypnea, rales Cyanosis, decreased breath, sounds bi!., bi!. pneumothorax
Urinalysis
Age at Onset of OliguriaDuration Days
Protein
RBC/HPF
WBC/ HPF
Day 1-7 Day 1-7 Day 1-1½
Positive Positive Positive
Positive Positive Positive
None 2 None
Positive Positive None
Day 1-4 Day 1-3
Positive Positive
Positive Positive
None None
Positive None, died of cardiovascular pulmonary problems
CASTS/HPF
total body edema, which was not caused by erythroblastosis and Apgar scores of 1 and 3 at 1 and 5 minutes, respectively. Intubation and pulmonary resuscitation were required. Urinary output was 18 cc for the first 48 hours of life. Initial urinalysis revealed protein, RBCs and RBC casts. An excretory urogram (IVP), which was done by infusing 10 cc renografin 60 intravenously, revealed no nephrogram or visualization of the collecting systems. Aortography by way of an umbilical artery catheter was performed using a previously described technique. a-5 Normal kidneys were seen bilaterally with fetal lobulation and normal intrarenal vasculature with
MATERIALS AND METHODS
The study includes 5 infants whose births were associated with perinatal complications and difficult deliveries (tables 1 and 2). All had 1-minute Apgar scores of 4 or less and required intubation and pulmonary resuscitation. Urinary outputs were monitored by bladder catheterization with Nos. 5 and 8F Accepted for publication November 5, 1976. Read at annual meeting of Mid-Atlantic Section, American Urological Association, Dorado Beach, Puerto Rico, September 26-0ctober 1, 1976.
80
PERINATAL ASPHYXIA AND RENAL FAILURE IN NEONATAL PATIENTS
3. Case 1
TABLE
Day
BUN (mg./dl.)
Creatinine (mg.id!.)
l 3 5
8
1.3
12
36
Urine Sodium (mEq./1.)
Urine Output
Weight
(cc)
(gm.)
18 40 80
3,200 3,250 3,100 2,900 2,750 2,600 2,550 2,400 2,250 Stable
120
7 9
37
2.2
112
33
1.8
300
11
26
13 15
12 8
17
3
410 456 340
45
0.6
15
Day
BUN (mg./dl.)
39 2
51
3.3 4.0
0 25
4,550 4,500
3 4
64 43
4.8 3.3
29 50
4,450 4,350
5
37
6 7
19 17 9
3.0 0.9
8
0.8
112 200 300 plus
Oxygen Pressure
Oxygen(%)
64 65 70
50 100 50
56
50
IVP Umbilical artery study
95
82 78 53
,w
25 25 Air
4. Case 2
TABLE
Creatinine (mg./dl.)
Urine Output (cc)
Radiology
Weight (gm.)
Radiology
Oxygen Pressure
Oxygen(%)
83 80
21
65
Air
IVP, non-visualization
U mbilica! artery study
21
4,270 4,350 4,200 Stable
Fm. 1. A, umbilical artery aortogram shows normal renal arteries bilaterally. B, late phase aortogram reveals normal bilateral nephrograms. Lobulated appearance of cortex is prominent and no cystic changes are present.
no evidence of hydronephrosis or cystic renal disease (fig. 1). During the first 10 days the BUN increased to 37 mg. per cent with a serum creatinine of 2.2 mg. per cent. The urine output increased and was followed by body weight stabiligm. The patient was discharged from the hospiafter birth with a normal BUN, serum creatinine and pulmonary function. At the onset of oliguria urinary sodium concentration was 140 mEq. per 1. but this decreased to sodium 5 mEq. per 1. after diuresis. This pattern of excretion is similar to that seen in adults with acute tubular necrosis. Case 2 (table 4). B. B. I., MSHMC 053680, a post-mature (42week) male was delivered vaginally after a prosecond stage of labor and weighed 4,550 gm. Apgar scores were 4 and 5 at l and 5 minutes, respectively, and intubation was ;ec,,,,.,~ c1 Oliguria was prominent with less than 25 cc urine per 24 hours during the first 3 of life. Diuresis began on day 6. Initial laboratory data revealed a BUN of 39 mg. per cent, which increased to 65 mg. cent with a serum creatinine of 4.8 mg. per cent on 4. IVP 0
Fm. 2. A , umbilical artery aortogram shows normal renal vessels bilaterally. B, delayed aortogram with nepb.rograrn.s consistent with normal kidneys bilaterally.
on day 4 was non-diagnostic. Umbilical revealed normal renal vessels and architecture diuresis the BUN and serum creatinine and the patient was discharged from the DISCUSSION
The exact pathophysiology ofrenal failure in these neonates is not clearly defined but there are multiple factors that are likely responsible.1. 2 The neonatal kidney is sensitive to gen deprivation and decreased arterial oxygen is most the initiating factor producing renal ischemia. causes direct renal cellular damage first involving the although with severe anoxia the glomeruli and entire can be infarcted as in corticomedullary necrosis.'; cause further indirect renal damage by producing vascular instability with blood pooling and decreased renal
82
DRAGO AND ASSOCIATES
Pre-renal causes for renal failure include the use of positive pressure ventilation, which has been shown experimentally7 to decrease cardiac output and renal blood flow with an increase in renal vascular resistance. Favoring significant pre-renal causes of renal insufficiency in these patients is the rather rapid reversibility of the renal failure. However, the presence of RBC casts in 3 of our 5 patients and in other reported series supports some degree of actual renal damage similar to acute tubular necrosis. 8 Sodium excretion in our first patient was 140 mEq. per 1. in the oliguric phase with 5 mEq. per 1. following diuresis, which is characteristic of actual renal tubular damage. The use of umbilical artery aortography in the 2 patients with non-visualization by IVP was helpful in determining the presence of renal arteries and functional cortical renal tissue without incurring the risk of anesthesia and urologic instrumentation in these critically ill patients. Although routine use of this study is not warranted it can be a useful adjunct in evaluating the problem of anuria or oliguria in the seriously ill neonate. In any individual patient renal failure will continue to be a diagnostic problem and all possible causes must be considered. We urge awareness of the association of complicated obstetrical delivery, respiratory asphyxia, decreased urinary output, proteinuria, RBCs and/or REC casts in the urine, and progressive azotemia. The management of these patients is essentially supportive and includes close monitoring of vital signs and blood gases, and determination of urine osmolarity and electrolytes along with serum electrolytes and BUN. Recognition of the associ-
ated renal failure in these sick patients is important so that appropriate fluid and electrolyte treatment can be used to avoid fluid overload with hyponatremia and hyperkalemia in particular. With early diagnosis and careful management the prognosis of these patients is good. REFERENCES
1. Dauber, I. M., Krauss, A. N., Symchych, P. S. and Auld, P. A.
2. 3. 4. 5. 6. 7.
8.
M.: Renal failure following perinatal anoxia. J. Pediat., 88: 851, 1976. Guignard, J.-P., Torrado, A., Mazouni, S. M. and Gautier, E.: Renal function in respiratory distress syndrome. J. Pediat., 88: 845, 1976. Miller, F. J., Jr., Duggan, F. J. and Maisels, M. J.: Umbilical artery aortography in the newborn using power injection. J. Urol., 113: 558, 1975. Emmanouilides, G. C. and Hoy, R. C.: Transumbilical aortography and selective arteriography in newborn infants. Pediatrics, 39: 337, 1967. Fellows, K. E., Jr.: The uses and abuses of abdominal and peripheral arteriography in children. Radiol. Clin. N. Amer., 10: 349, 1972. Groshong, T. D., Taylor, A. A., Nolph, K. D., Esterly, J. and Maher, J. F.: Renal function following cortical necrosis in childhood. J. Pediat., 79: 267, 1971. Moore, E. S., Galvez, M. B., Paton, J. B., Fisher, D. E. and Behrman, R. E.: Effects of positive pressure ventilation on intrarenal blood flow in infant primates. Pediat. Res., 8: 792, 1974. Kwittken, J. and Reiner, L.: Acute tubular nephrosis in the newborn infant, a manifestation of anoxia. Pediatrics, 33: 380, 1964.
THE JOURNAL OF UROLOGY
Copyright © 1977 by The Williams & Wilkins Co.
PERINATAL ASPHYXIA AND RENAL FAILURE IN NEONATAL PATIENTS JOSEPH R. DRAGO, THOMAS J. ROHNER, JR., EDGAR J. SANFORD
AND
M. JEFFREY MAISELS
From the Divisions of Urology and Neonatology, The Milton S. Hershey Medical Center, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
ABSTRACT
Herein we discuss oliguria and azotemia in neonatal patients associated with perinatal complications, including difficult labor and delivery, and respiratory asphyxia. Renal failure in these patients is accompanied by proteinuria, microscopic hematuria and red blood cell casts, and it generally resolves in 7 to 10 days. Umbilical aortography can be helpful in determining the presence of normal kidneys in these patients. plastic infant feeding tubes. Oliguria was noted on day 1 and lasted as long as 1 week. Initial laboratory data included blood urea nitrogen (BUN) of 8 to 46 mg. per cent and routine urinalysis showed proteinuria and red blood cells (RBCs) in all patients, and RBC casts in 3. Of the 5 patients 4 survived. The 1 infant who died had severe cardiovascular and pulmonary instability, was premature at birth (1,310 gm.) and, at autopsy, had glomerular lesions most likely secondary to hypoxia. Two cases are described in detail.
Obstetricians and pediatricians, using improved techniques of fetal monitoring and resuscitation, have improved the salvage of critically ill newborns and created a new patient population with certain problems of urologic interest. When the urologist is asked to see a neonatal patient with oliguria and progressive renal failure he is especially concerned with ruling out congenital anomalies and obstructive causes. The most frequent causes of oliguria and renal failure in neonates include, in addition to anomalies and obstruction, hemorrhage, diarrhea and dehydration, hemolytic uremic syndrome, renal vein thrombosis, gastroenteritis, septicemia and perinatal hypoxia. 1 • 2 Herein we present our experience with 5 newborns who had respiratory asphyxia and renal failure without obstructive uropathy.
CASE REPORTS
Case 1 (table 3). B. B. M., MSHMC 103777, weighed 3,500 gm. at birth and was delivered by cesarean section. He had
TABLE
Pt. -Hosp. No.
Apgar
Birth Wt. 3,500
BBI-053680 BBF-062053 BGD-086966 BBB-087769
4,550 3,100 1,650 1,315
Mode of Delivery
Complication of Pregnancy
(gm.)
BBM-103777
1 1 Min.
Decreased fetal heart rate at 35 wks. of gestation Prolonged 2nd stage Eclampsia Eclampsia, toxemia, vaginal bleeding, clots Premature rupture of membranes at 29 wks. of gestation
Cesarean section
5 Mins. 3
Mid-forceps meconium stained Cesarean section Cesarean section Vaginal
4
5
1 2 7 2 Not recorded, cyanotic, intubated at birth
TABLE 2
Pt. -Hosp. No.
Resuscitation at Birth
Physical Examination
BBM-103777 BBI-053680 BBF-062053
Intubation, ventilation Intubation, ventilation Intubation, ventilation
BGD-086966 BBB-087769
Intubation, ventilation Intubation, ventilation
Total body edema Tachypnea, cephalhematoma Apneic at birth, cyanosis on room air Tachypnea, rales Cyanosis, decreased breath, sounds bi!., bi!. pneumothorax
Urinalysis
Age at Onset of OliguriaDuration Days
Protein
RBC/HPF
WBC/ HPF
Day 1-7 Day 1-7 Day 1-1½
Positive Positive Positive
Positive Positive Positive
None 2 None
Positive Positive None
Day 1-4 Day 1-3
Positive Positive
Positive Positive
None None
Positive None, died of cardiovascular pulmonary problems
CASTS/HPF
total body edema, which was not caused by erythroblastosis and Apgar scores of 1 and 3 at 1 and 5 minutes, respectively. Intubation and pulmonary resuscitation were required. Urinary output was 18 cc for the first 48 hours of life. Initial urinalysis revealed protein, RBCs and RBC casts. An excretory urogram (IVP), which was done by infusing 10 cc renografin 60 intravenously, revealed no nephrogram or visualization of the collecting systems. Aortography by way of an umbilical artery catheter was performed using a previously described technique. a-5 Normal kidneys were seen bilaterally with fetal lobulation and normal intrarenal vasculature with
MATERIALS AND METHODS
The study includes 5 infants whose births were associated with perinatal complications and difficult deliveries (tables 1 and 2). All had 1-minute Apgar scores of 4 or less and required intubation and pulmonary resuscitation. Urinary outputs were monitored by bladder catheterization with Nos. 5 and 8F Accepted for publication November 5, 1976. Read at annual meeting of Mid-Atlantic Section, American Urological Association, Dorado Beach, Puerto Rico, September 26-0ctober 1, 1976.
80
PERINATAL ASPHYXIA AND RENAL FAILURE IN NEONATAL PATIENTS
3. Case 1
TABLE
Day
BUN (mg./dl.)
Creatinine (mg.id!.)
l 3 5
8
1.3
12
36
Urine Sodium (mEq./1.)
Urine Output
Weight
(cc)
(gm.)
18 40 80
3,200 3,250 3,100 2,900 2,750 2,600 2,550 2,400 2,250 Stable
120
7 9
37
2.2
112
33
1.8
300
11
26
13 15
12 8
17
3
410 456 340
45
0.6
15
Day
BUN (mg./dl.)
39 2
51
3.3 4.0
0 25
4,550 4,500
3 4
64 43
4.8 3.3
29 50
4,450 4,350
5
37
6 7
19 17 9
3.0 0.9
8
0.8
112 200 300 plus
Oxygen Pressure
Oxygen(%)
64 65 70
50 100 50
56
50
IVP Umbilical artery study
95
82 78 53
,w
25 25 Air
4. Case 2
TABLE
Creatinine (mg./dl.)
Urine Output (cc)
Radiology
Weight (gm.)
Radiology
Oxygen Pressure
Oxygen(%)
83 80
21
65
Air
IVP, non-visualization
U mbilica! artery study
21
4,270 4,350 4,200 Stable
Fm. 1. A, umbilical artery aortogram shows normal renal arteries bilaterally. B, late phase aortogram reveals normal bilateral nephrograms. Lobulated appearance of cortex is prominent and no cystic changes are present.
no evidence of hydronephrosis or cystic renal disease (fig. 1). During the first 10 days the BUN increased to 37 mg. per cent with a serum creatinine of 2.2 mg. per cent. The urine output increased and was followed by body weight stabiligm. The patient was discharged from the hospiafter birth with a normal BUN, serum creatinine and pulmonary function. At the onset of oliguria urinary sodium concentration was 140 mEq. per 1. but this decreased to sodium 5 mEq. per 1. after diuresis. This pattern of excretion is similar to that seen in adults with acute tubular necrosis. Case 2 (table 4). B. B. I., MSHMC 053680, a post-mature (42week) male was delivered vaginally after a prosecond stage of labor and weighed 4,550 gm. Apgar scores were 4 and 5 at l and 5 minutes, respectively, and intubation was ;ec,,,,.,~ c1 Oliguria was prominent with less than 25 cc urine per 24 hours during the first 3 of life. Diuresis began on day 6. Initial laboratory data revealed a BUN of 39 mg. per cent, which increased to 65 mg. cent with a serum creatinine of 4.8 mg. per cent on 4. IVP 0
Fm. 2. A , umbilical artery aortogram shows normal renal vessels bilaterally. B, delayed aortogram with nepb.rograrn.s consistent with normal kidneys bilaterally.
on day 4 was non-diagnostic. Umbilical revealed normal renal vessels and architecture diuresis the BUN and serum creatinine and the patient was discharged from the DISCUSSION
The exact pathophysiology ofrenal failure in these neonates is not clearly defined but there are multiple factors that are likely responsible.1. 2 The neonatal kidney is sensitive to gen deprivation and decreased arterial oxygen is most the initiating factor producing renal ischemia. causes direct renal cellular damage first involving the although with severe anoxia the glomeruli and entire can be infarcted as in corticomedullary necrosis.'; cause further indirect renal damage by producing vascular instability with blood pooling and decreased renal
82
DRAGO AND ASSOCIATES
Pre-renal causes for renal failure include the use of positive pressure ventilation, which has been shown experimentally7 to decrease cardiac output and renal blood flow with an increase in renal vascular resistance. Favoring significant pre-renal causes of renal insufficiency in these patients is the rather rapid reversibility of the renal failure. However, the presence of RBC casts in 3 of our 5 patients and in other reported series supports some degree of actual renal damage similar to acute tubular necrosis. 8 Sodium excretion in our first patient was 140 mEq. per 1. in the oliguric phase with 5 mEq. per 1. following diuresis, which is characteristic of actual renal tubular damage. The use of umbilical artery aortography in the 2 patients with non-visualization by IVP was helpful in determining the presence of renal arteries and functional cortical renal tissue without incurring the risk of anesthesia and urologic instrumentation in these critically ill patients. Although routine use of this study is not warranted it can be a useful adjunct in evaluating the problem of anuria or oliguria in the seriously ill neonate. In any individual patient renal failure will continue to be a diagnostic problem and all possible causes must be considered. We urge awareness of the association of complicated obstetrical delivery, respiratory asphyxia, decreased urinary output, proteinuria, RBCs and/or REC casts in the urine, and progressive azotemia. The management of these patients is essentially supportive and includes close monitoring of vital signs and blood gases, and determination of urine osmolarity and electrolytes along with serum electrolytes and BUN. Recognition of the associ-
ated renal failure in these sick patients is important so that appropriate fluid and electrolyte treatment can be used to avoid fluid overload with hyponatremia and hyperkalemia in particular. With early diagnosis and careful management the prognosis of these patients is good. REFERENCES
1. Dauber, I. M., Krauss, A. N., Symchych, P. S. and Auld, P. A.
2. 3. 4. 5. 6. 7.
8.
M.: Renal failure following perinatal anoxia. J. Pediat., 88: 851, 1976. Guignard, J.-P., Torrado, A., Mazouni, S. M. and Gautier, E.: Renal function in respiratory distress syndrome. J. Pediat., 88: 845, 1976. Miller, F. J., Jr., Duggan, F. J. and Maisels, M. J.: Umbilical artery aortography in the newborn using power injection. J. Urol., 113: 558, 1975. Emmanouilides, G. C. and Hoy, R. C.: Transumbilical aortography and selective arteriography in newborn infants. Pediatrics, 39: 337, 1967. Fellows, K. E., Jr.: The uses and abuses of abdominal and peripheral arteriography in children. Radiol. Clin. N. Amer., 10: 349, 1972. Groshong, T. D., Taylor, A. A., Nolph, K. D., Esterly, J. and Maher, J. F.: Renal function following cortical necrosis in childhood. J. Pediat., 79: 267, 1971. Moore, E. S., Galvez, M. B., Paton, J. B., Fisher, D. E. and Behrman, R. E.: Effects of positive pressure ventilation on intrarenal blood flow in infant primates. Pediat. Res., 8: 792, 1974. Kwittken, J. and Reiner, L.: Acute tubular nephrosis in the newborn infant, a manifestation of anoxia. Pediatrics, 33: 380, 1964.