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Home , Apnea, Asphyxia, Hypercapnia, Hyperventilation, Hypoxemia, Hypoxia (medical)

CLINICAL REVIEW

Asphyxia Neonatorum

Raul C. Banagale, MD, and Steven M. Donn, MD Ann Arbor, Michigan

Various biochemical and structural changes affecting the newborn’s well­ being develop as a result of perinatal . ab­ normalities are frequent complications with high mortality and morbidity. Cardiac compromise may lead to dysrhythmias and cardiogenic . in the form of disseminated intravascular coagulation or mas­ sive are potentially lethal complications. Necrotizing enterocolitis, acute renal failure, and endocrine problems affecting fluid elec­ trolyte balance are likely to occur. Even the adrenal glands and pancreas are vulnerable to perinatal deprivation. The best form of management appears to be anticipation, early identification, and prevention of potential obstetrical-neonatal problems. Every effort should be made to carry out ef­ fective measures on the depressed infant at the time of delivery.

erinatal asphyxia produces a wide diversity of in­ molecules brought into the alveoli inadequately com­ Pjury in the newborn. Severe birth asphyxia, evi­ pensate for the uptake by the , causing decreases denced by Apgar scores of three or less at one minute, in alveolar oxygen (P02), arterial P02 (Pa02) develops not only in the preterm but also in the term and arterial . Correspondingly, arte­ and post-term infant. The knowledge encompassing rial pressure (PaC02) rises because the the causes, detection, diagnosis, and management of insufficient ventilation cannot expel the volume of the clinical entities resulting from perinatal oxygen carbon dioxide that is added to the alveoli by the pul­ deprivation has been further enriched by investigators monary capillary blood. Asphyxia can be total or par­ from various disciplines in recent years. However, in tial. Total asphyxia occurs when the ingress of oxygen spite of the many advances, the impact of perinatal and the egress of carbon dioxide is entirely halted. asphyxia on neonatal mortality and morbidity is still Partial asphyxia results when the respiratory ex­ evident. change has been reduced, but not totally abolished. Prevention of the problem is, of course, preferable For obvious reasons there is no detailed information to treatment. An understanding of the pathophysiology regarding the various chemical and biophysical of asphyxia is necessary to achieve this goal. changes of fetal or neonatal asphyxia in the . A useful substitute for the missing human model is the observation by Adamsons and co-workers1 and PATHOPHYSIOLOGY AND NATURAL Dawes2 of the natural history of total asphyxia at birth HISTORY in the rhesus monkey . Shortly after the onset of asphyxia, rapid gasping describes a clinical entity whereby occurs, accompanied by muscular effort and thrashing the fetus or the newborn infant sustains an impairment movements of the arms and legs. This ceases after a in respiratory . Neonatal asphyxia re­ little more than a minute, preceding the onset of pri­ flects acute , that is, a rapid decrease mary , which lasts almost 60 seconds. The in alveolar ventilation. The number of oxygen animal then develops a series of spontaneous deep gasps for 4 to 5 minutes, which gradually become weaker and terminate after approximately 8 minutes of total anoxia. Secondary or terminal apnea begins after Submitted, revised, April 5, 1984. the last gasp, and occurs if asphyxia is not re­ From the Section of Newborn Services, Department of , Uni­ versed within several minutes. When secondary apnea versity of Michigan Medical Center, Ann Arbor, Michigan. Requests for occurs, spontaneous cannot be induced by reprints should be addressed to Dr. Raul C. Banagale, Neonatal Special Care Unit, Emanuel Hospital, 2801 N. Gantenbein, Portland, OR 97227. any sensory stimuli. The longer the delay in initiating

c 1986 Appleton-Century-Crofts THE JOURNAL OF FAMILY PRACTICE, VOL. 22, NO. 6: 539-546, 1986 539 ASPHYXIA NEONATORUM

adequate ventilation, the longer it will take to initiate regular respirations. TABLE 1. CAUSES OF PERINATAL ASPHYXIA Assuming the changes in are similar to those Failure of the in the rhesus monkey, are mechanisms possible for a Prematurity newborn infant to protect himself or herself from such Intrauterine an insult? It has been postulated that circulatory ad­ anomalies and accidents justments occur in the human infant during total as­ Hypovolemia secondary to antepartum hemorrhage phyxia. A study of the effects of hypoxia on the rhesus Maternal conditions (cardiovascular problems, pul­ monary disease, toxemia, other systemic illness) monkey fetus by Behrman et al3 indicates that con­ Obstetrical factors comitant with the decrease in total cardiac output, Uterine and cervical malformation there is a redistribution of the available cardiac output Multiple gestation in an attempt to provide oxygenated blood to the more Abnormal presentation vital organs. Scholander,4 in his study of diving seals, Difficult delivery Respiratory obstructive diseases found that the following reflex circulatory adjustments Airway malformation occur when a seal dives: (1) profound , (2) Tumors decrease in oxygen consumption, (3) decrease in body Vocal cord paralysis , (4) accumulation of lactic acid in muscle, Meconium aspiration syndrome Primary disorders (5) maintenance of central , and (6) Nervous system continued oxygenation of arterial blood at the expense Respiratory muscle of peripheral blood. When the experimental seals re­ turn to the surface, the pre-dive state resumes, and Group B streptococcus and other bacteria after air starts, the lactic acid is removed Viral from the muscles by the bloodstream and is subse­ quently metabolized by the . There is, obviously, a fundamental difference be­ tween the diving mammal and the stressed human in­ fant. In the diving mammals, the circulatory changes as mepivacaine and , known to be rapidly are not overwhelmed under the condition of a normal transmitted to the fetus, may produce fetal bradycar­ dive. In the asphyxiated infant, however, the circula­ dia and . Respiratory obstructive diseases tory changes are in response to life-threatening such as airway malformations, tumors, vocal cord pathologic conditions and the protective mechanisms paralysis, and meconium aspiration syndrome may are quickly exhausted after short periods of asphyxia. also result in neonatal asphyxia. Primary disorders in­ Therefore, assuming there is some circulatory adapta­ volving the nervous system, respiratory muscles, and tion, such as a redistribution of the available cardiac neuromuscular junction (such as neonatal myasthenia output and provision of oxygenated blood to vital or­ gravis) are rare, but are also potential causes. gans such as the , , and adrenal glands, it Intrauterine and may result in se­ must be at the expense of the kidneys, , , vere perinatal asphyxia. and intestine. As a result, the newborn human is still likely to suffer many possible complications. BIOCHEMICAL CHANGES DURING ASPHYXIA Of the different biochemical events (Table 2) occurring as a result of asphyxia, the most important is the con­ ETIOLOGY version from aerobic oxidation of to anaerobic glycolysis. This conversion leads to accumulation of Table 1 lists the different causes of impairment in res­ lactic acid and the development of metabolic . piratory gas exchange. Failure of the respiratory center may also occur because of the has been associated with prematurity, intrauterine rapid elevation of PaC02. A profound drop in pH is, hypoxia, obstetrical complications, and administration therefore, the result of a mixed acidosis coincidental of drugs. Prolapse and compression of the umbilical with the hypoxia. Free fatty acids and glycerol, prod­ cord, hypovolemia (resulting from previa, ucts of neutral hydrolysis, increase in the blood in abruptio placenta, or any other form of blood loss), response to hypoxia, which may be mobilized by the and umbilical cord or placental anomalies can lead to release of epinephrine and norepinephrine. During . Other obstetrical problems that labor, maternal blood glucose is elevated secondary to may lead to severe perinatal asphyxia include uterine sympathetic stimulation, leading to a corresponding and cervical malformation, multifetal gestation, ab­ blood sugar elevation in the fetus. When the maternal normal presentation, and traumatic delivery. Adminis­ blood glucose supply is terminated at birth, tration of certain drugs including local anesthetics such glycogenojysis begins immediately to provide a con-

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TABLE 2. BIOCHEMICAL CHANGES RESULTING FROM these conditions in asphyxiated newborns have been ASPHYXIA described extensively.9 The role of asphyxia in the production of central Respiratory and nervous system hemorrhage is multifactorial. First, Increased free fatty acids and glycerol hypoxia is associated with impairment of vascular au­ Mobilization of hepatic glycogen toregulation.10 Second, asphyxia produces augmenta­ Hyperkalemia and amino acidemia Hypocalcemia tion of cerebral blood flow, which may lead to the or hyperglycemia development of intracranial hemorrhage.11 Third, con­ Hyperammonemia gestion in cerebral veins causes increased pressure Hyperuricemia (?) within the periventricular capillaries.9 Fourth, hypoxia results in a distinct to the capillary endothelial cells and the vascular border zones within the germinal timing source of glucose to the newborn’s brain. De­ matrix.12 The diagnosis of intraventricular hemorrhage pletion of carbohydrate reserves with a corresponding and possible subsequent ventricular dilation is no hypoglycemic state is not an uncommon finding in as­ longer a problem with the present advances in com­ phyxiated newborns. Animal studies5 have shown that puted tomography and ultrasonography.9,13 the triphosphate level is maintained initially Supportive treatment involves maintenance of cere­ at the expense of phosphocreatinine. Hyperglycemia bral perfusion9 through maintenance of blood pressure has also been observed following perinatal asphyxia, and prevention of , , and but the genesis of this problem is unknown. acidemia. Hyperosmolar and rapid volume Hyperuricemia has been postulated to occur in expansion should be avoided. Appropriate supportive association with perinatal hypoxia.6 Hypocalcemia has care and serial assessment of ventricular size are man­ been noted following perinatal asphyxia, possibly as a datory.9 Vidyasagar and associates14 reported the use­ result of anoxic stimulation of calcitonin, increasing fulness of monitoring in infants renal calcium loss, and diminishing calcium resorption with obstructive hydrocephalus. frequently from bone. Hypomagnesemia in association with occur and should be vigorously treated15 using hypocalcemia has also been noted. Hyperammonemia phenobarbital, the drug of choice, given intravenously following severe perinatal asphyxia has been de­ as a loading dose of 20 mg/kg in divided doses, ten scribed.7,8 Blood ammonia of 300 to minutes apart. If seizures continue, phenytoin may be 1,000 pg/dL have been observed along with the clinical given intravenously, using a loading dose of 20 mg/kg manifestations of central nervous system dysfunction, over ten minutes. Maintenance doses are started 12 , hyperextension, and extreme heart-rate hours after the loading dose and given every 12 hours. variability. Severe neurologic sequelae have been de­ Maintenance dosage for both drugs is 3 to 5 scribed in some surviving infants. mg/kg/d and is adjusted according to frequent measurement of blood concentrations. Management of progressive ventricular dilation has been approached differently9,16,17 and remains controversial. CLINICAL COURSE , an abnormal accumulation of fluid in either the extracellular space or within the cells of Perinatal asphyxia presents a wide variety of the brain, is one of the more severe complications of to the newborn infant (Figure 1). Each of the major perinatal asphyxia.18 If sufficiently severe, cerebral organ systems will be discussed. edema may lead to death by precipitating uncal and tonsillar herniation.15 Despite the importance of brain CENTRAL NERVOUS SYSTEM swelling in hypoxic newborns, its pathophysiology and pathogenesis remain uncertain.19,20 Cerebral edema Damage to the central nervous system accounts for can be classified into three types: cytotoxic (cellular), the greatest number by far of clinical problems secon­ vasogenic, and interstitial (hydrocephalic). Cytotoxic dary to perinatal compromise. Hypoxic-ischemic cerebral edema results from disturbance in the cell is the most common and clinically membrane permeability, leading to increased in­ significant occurrence following perinatal asphyxia. tracellular water in the gray and white matter, but Additionally, intracranial hemorrhage may be associ­ without enlargement of the extracellular space and ated with asphyxia. There are three major clinically without a breakdown of the blood-brain barrier. important categories of intracranial hemorrhage: (1) Hypoxia resulting from neonatal asphyxia17 is associ­ subdural hemorrhage, (2) subarachnoid hemorrhage, ated with cytotoxic cerebral edema. Vasogenic cere­ and (3) periventricular, intraventricular, intracerebral, bral edema is characterized by increased capillary and cerebellar hemorrhage. The distinctive patho­ endothelial permeability, allowing fluid from the vas­ geneses and clinical manifestations of each of cular compartment to enter the space between cells.

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CHS: Hemorrhage Edema/ "Anoxic encephalopathy"

CARDIOVASCULAR: Dysrhythmia Myocardial Dysfunction R—► L DIC

RESPIRATORY TRACT: Respiratory Distress MPH

GASTROINTESTINAL TRACT: NEC

URINARY TRACT: ATN/Renal Failure Asphyxiated Bladder Syndrome

ENDOCRINE: SIADH Adrenal Hemorrhage Pancreatic Insult? INTEGUMENT

Figure 1. Acute neonatal problems as a consequence of asphyxia, by organ system

Interstitial edema results in periventricular accumula­ that some infants with severe asphyxia are resusci­ tion of spinal fluid, such as that occurring with tated and later recover, displaying persistent obstructive hydrocephalus. neurologic deficits. On the other hand, Windle22 has The treatment of cerebral edema has been subject to shown that asphyxiation for more than seven minutes debate. Osmotically active agents (30 percent urea at a invariably produced at least transient neurological dose of 1 to 1.5 g/kg, or 20 percent mannitol at 1.5 to 2 signs and permanent . When hypoxic- g/kg) given over 30 to 60 minutes have been ischemic encephalopathy is suspected, it certainly is suggested.18 These hypertonic agents produce an os­ unwise to give a definitive statement of the individual motic gradient between the intravascular and ex- infant’s long-term prognosis during the immediate travascular compartments, reducing the extravascular postnatal period.23 Extensive discussions concerning water content. Glucocorticoid (dexamethasone) in a ethical and medico-legal issues in the management of dose of 0.5 to I mg/kg/d in two divided doses, given at severely damaged newborns have been published 12-hour intervals has been noted to be an adjunct in the elsewhere.24'25 treatment of cerebral edema. However, the exact mechanism by which steroids produce a beneficial ef­ fect in cerebral edema following asphyxia is still uncer­ CARDIOVASCULAR AND HEMATOLOGIC tain.21 Brain swelling itself, when sufficiently severe, SYSTEMS can lead to local capillary or small vessel occlusion, The relationship between the degree of asphyxia and resulting in tissue necrosis. The question of when cer­ appearance of myocardial damage in the newborn is ebral necrosis occurs is also not known. As most as­ not precisely known. However, it is possible for as­ phyxiated infants initially require respiratory support, phyxia to produce ultrastructural changes,26 which has been attempted. The vascular may lead to dysrhythmias because of alterations in compartment, if responsive to changes in carbon automaticity and conduction patterns. This rhythm dioxide tension and hyperventilation, causes a reduc­ disturbance may be sinoatrial block or supraventricu­ tion of the intracranial pressure by constricting cere­ lar or ventricular dysrhythmias. Sinusoidal bral vessels and decreasing cerebral blood flow, which rhythms in severe neonatal hypoxia were reported by leads to a decrease of blood volume within the cranial Reid et al.27 Transient tricuspid insufficiency (ischemic cavity. papillary muscle necrosis) in 14 term newborn infants The outcome of asphyxiated infants with central associated with significant perinatal asphyxia was nervous system complications is confusing in the noted by Bucciarelli and co-workers.28

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Asphyxia may result in right-to-left shunting through fibrin deposition. Deficient anabolism of alveolar cells a patent foramen ovale or , then decreases production and contributes leading to and signs of respiratory distress. to further . The treatment is largely symp­ Further discussion of the mechanisms involved is pre­ tomatic and supportive, and usually follows the com­ sented under the . mon modalities in the management of respiratory dis­ Cardiogenic shock associated with perinatal as­ tress syndrome. This condition has some resemblance phyxia in preterm infants may resemble respiratory to “ shock " in adult patients. distress syndrome.29 Primary diagnosis of cardiac fail­ Massive pulmonary hemorrhage (MPH), a condition ure is made with the recognition of cardiomegaly, of unknown pathogenesis, has been associated with , electrocardiographic changes of myo­ asphyxia and acidosis.35 Factors predisposing to the cardial , decreased myocardial contrac­ development of MPH are multiple. Hypoxia or tility, elevated central venous pressure, and severe acidemia may lead to and a . The treatment of , includ­ right-to-left shunt at the ductal and atrial levels with ing the use of inotropic agents, may result in rapid left ventricular failure. When the left ventricle fails, improvement in the clinical manifestations within 24 to the left atrial pressure and the pulmonary capillary 36 hours in transient myocardial insufficiency. pressure rise, leading to increased filtration of liquid Disseminated intravascular coagulation (DIC), also into the interstitial tissues of the lungs. This results in known as consumption coagulopathy or defibrination edema formation and rupture of the pulmonary capil­ syndrome, is not in itself a primary disease but a re­ laries and alveolar membranes. Management consists sponse to certain stimuli. There are many conditions of maintenance of an adequate airway and assisted associated with DIC,30 including , respiratory ventilation. Increased peak-inspiratory and end- distress syndrome, trauma, abruptio placenta, and tox­ expiratory have been recommended.36 emia of . Gross alteration in the clotting These maneuvers may produce a tamponade effect on process in hypoxic infants with consumption of clot­ the transudation of edema fluid and red cells from ting factors leading to hemorrhagic diathesis has been engorged capillaries and may also decrease the flow of noted.31 Marked increase in fibrinogen turnover and blood from ruptured precapillary arterioles by reduc­ fibrinolytic activity has also been observed. Hypoxia ing pulmonary blood flow and increasing intrathoracic may lead to a multiple diathesis, triggering pressure. Postural drainage and chest physiotherapy to widespread coagulation with the formation of intra­ maintain good pulmonary toilet are essential. Accurate vascular thrombi and utilization of coagulation maintenance of blood volume and correction of factors and platelets. Absolute control of DIC necessi­ hemostatic abnormalities are necessary.37 tates an effective treatment of the underlying disease state. Anticoagulation with the use of heparin remains controversial. Exchange transfusion with fresh adult GASTROINTESTINAL SYSTEM blood offers several potential advantages in treating DIC in newborns.32 Necrotizing enterocolitis (NEC), a disease of uncer­ and a “ shift to the left" in white blood tain pathogenesis and multifactorial etiology, has been cell differential counts have also been associated with associated with perinatal complications, particularly neonatal asphyxia. hypoxia.38 Poor of the gut during the perinatal period may be caused not only by asphyxia, but also by other conditions such as umbilical arterial RESPIRATORY SYSTEM catheter placement, sepsis, respiratory distress, DIC, Perinatal asphyxia results in alterations of the normal exchange transfusion, hypertonic formula feeding, pulmonary physiologic transition, causing respiratory immature systemic immunity, congenital heart defects distress in the newborn infant. Significant pulmonary (including patent ductus arteriosus), and hyperviscos­ may occur following asphyxia, trig­ ity.39,40 gering a progressive and usually self-perpetuating The onset of acute necrotizing enterocolitis usually cycle similar to that found in infants with respiratory occurs in the first week of life. The clinical picture is distress syndrome.33,34 Pulmonary vasoconstriction characterized by gastric retention, intolerance of feed­ may lead to an increase in pulmonary vascular resist­ ing (with or without of bile-stained fluid), and ance, producing a right-to-left shunting of blood. The abdominal distention usually accompanied by bloody resulting venous admixture leads to anaerobic metab­ . The course is progressive. The baby may olism and subsequent acidosis. These changes poten­ become lethargic, apneic, jaundiced, and appear to be tiate the pulmonary vasoconstriction, alveolar hypo­ in the shock-like state usually seen in sepsis. The typi­ perfusion. damage to the alveolar lining cells, and cal roentgenographic findings of an abnormal gas pat­ an increase in alveolar wall permeability with effusion tern with intramural gas ()41 or of plasma and red blood cells into the air spaces with gas in the portal vein are not always observed.

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Other radiographic findings that have been noted42 troversial. Single trial doses of these agents may be include and elongation of bowel loops, loss of given if the patient is well hydrated and normotensive, bowel wall definition, and a disorganized atonic pat­ and usually only if no is obtained after a dose tern of intestinal gas. Bowel perforation with the pro­ of 20 mL/kg of normal saline is given intravenously duction of peritonitis and pneumoperitoneum may oc­ over a 20-minute period. Dialysis, especially peri­ cur. In the absence of an acute abdomen requiring toneal, is instituted when one or more of the fol­ surgery, medical management includes discontinua­ lowing are present: (1) intractable acidosis, (2) intract­ tion of oral feeding, provision of adequate parenteral able hyperkalemia. (3) abnormal expansion of the ex­ nutrition, gastric , and appropriate cor­ tracellular fluid with hypertension and congestive rection of acid-base and electrolyte imbalance. heart failure, and (4) rapid deterioration in the general Evaluation for infection, including blood, stool, cere­ clinical condition. brospinal fluid, and urine cultures should be done, fol­ Delayed micturition, despite the presence of lowed by parenteral administration of broad-spectrum adequate urine formation and in the absence of gross antibiotics. Measurement of the abdominal girth and anatomic abnormalities, has been reported48 secon­ follow-up radiographs of the abdomen permit early di­ dary to the asphyxiated bladder syndrome. These pa­ agnosis of bowel perforation. Serial abdominal transil­ tients present with distended bladders, but with urine lumination has been found to be very useful in the easily expressed by the Crede method, aspirated by early detection of pneumoperitoneum in the newborn suprapubic tap, or drained by catheterization. with necrotizing enterocolitis.43 Some surviving in­ fants may show mechanical and functional abnor­ malities of the involved intestine secondary to stricture formation or short bowel syndrome. ENDOCRINE SYSTEM The syndrome of inappropriate antidiuretic hormone GENITOURINARY SYSTEM (SIADH) secretion has mutliple causes49 and has been reported in infants following asphyxia,50 though the The acute reversible renal failure that may follow as­ mechanism is unknown. Possibly the osmoreceptor phyxia is commonly referred to as acute tubular ne­ cells in the anterior are affected by as­ crosis (ATN).44 Oliver and co-workers45 observed that phyxia leading to inappropriate hypersecretion of the glomeruli and blood vessels appear, for the most antidiuretic hormone, resulting in water retention and part, histologically normal, whereas the tubular expansion of the volume. This se­ epithelium is irregularly damaged. The cause of renal quence in turn inhibits the secretion of aldosterone by failure was presumed to be tubular obstruction by cel­ the adrenal cortex and leads to salt loss in the urine. lular debris with the back of filtrate through The features of SIADH are (1) hyponatremia of mod­ the damaged tubular walls. The kidneys are very sen­ erate to marked degree without significant renal, ad­ sitive to oxygen deprivation.46 renal, hepatic, or cardiac disease, (2) excretion of a A new concept of acute renal failure has been pro­ hypertonic urine, (3) normal or low blood urea nitro­ posed. Reduced cortical blood flow and diminished gen, (4) urinary loss of administered sodium, (5) in­ glomerular filtration46 have been emphasized over the ability to maintain abnormal serum sodium concentra­ hypothesis of tubular blockage45 in the pathophysiol­ tions by infusions of hypertonic saline, (6) correction ogy of acute renal failure. Catecholamine release in­ of hypoatremia by fluid restriction, and (7) urine serum creases sympathetic tone, and activation of the renin- osmolality ratio of greater than one. angiotensin system further decreases cortical blood The most crucial differential diagnosis should be to flow. The decrease in cortical perfusion leads to a de­ distinguish between SIADH and adrenal insufficiency. crease in glomerular filtration and oliguria. Within 24 Infants with primary adrenal insufficiency usually hours of an ischemic episode, renal insufficiency may have hyperkalemia, dehydration, hypovolemia, and occur. This condition is almost always reversible, but hypotension. When hyponatremia is not severe, ex­ prolonged renal insufficiency can also lead to irrevers­ cessive fluid retention can be reversed with a rise in ible cortical and medullary necrosis. Renal papillary serum sodium and a decrease in urinary sodium loss by necrosis is rare in newborns and infants. simply restricting fluid intake. Supplemental sodium Infants with oliguric renal failure may be managed by mouth or intravenous isotonic saline is of no benefit successfully by employing restriction of fluid, sodium, under these circumstances, as the sodium will be and potassium.44 Correction of other predisposing fac­ rapidly and completely excreted. Steroids are of no tors should be done. Careful monitoring of serum direct benefit in SIADH. although they are sometimes creatinine, urinalysis, and serum drug concentrations used in the management when adrenal insufficiency (especially when nephrotoxic antibiotics are required) cannot be ruled out. decreases the risks of further renal damage. The use of Adrenal hemorrhage has been associated with fetal mannitol and furosemide as therapeutic agents is con­ hypoxia.51 Intrapartum asphyxia was associated with

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adrenal hemorrhage or necrosis in about 32 percent of the time of delivery to carry out adequate and effective the cases studied.52 Massive adrenal hemorrhage in the resuscitation. Anticipation of the sequelae of asphyxia newborn usually occurs within the first few days after neonatorum and aggressive treatment of problems as delivery. Shock and lethargy are the usual mode of they first arise will be the key to reducing the high presentation; and often by the time symptoms appear, morbidity associated with this unfortunate event. a mass is already palpable. Blood may leak into the tissue around the gland and also be present in the peritoneal cavity. Renal vein closely re­ sembles this problem. The blood urea may be elevated in both conditions, but gross hematuria is usually seen only in renal vein thrombosis. Intravenous pyelog­ References raphy in renal vein thrombosis shows no excretion of 1. Adamsons K Jr, Behrman R, James LS, et al: Resuscitation the affected side, while in adrenal hemorrhage the kid­ by positive pressure ventilation and Tris-hydroxymethyl- ney is displaced downward and rotated outward with aminomethane of rhesus monkeys asphyxiated at birth. J flattening of the upper calyces. Sometimes a retro­ Pediatr 1964; 65:807-818 grade pyelogram is necessary to show the characteris­ 2. Dawes GS: Foetal and Neonatal Physiology: A Comparative Study of the Changes at Birth, ed 1, Chicago, Year Book tic appearance. Ultrasound53 and computerized to­ Medical, 1969, pp 141-159 mography are now being utilized in confirming sus­ 3. Behrman RE, Lees MH, Peterson EN, et al: Distribution of pected adrenal hemorrhage. Treatment consists of the circulation in the normal and asphyxiated fetal primate. blood transfusions; occasionally antibiotics are neces­ Am J Obstet Gynecol 1970: 108:956-969 4. Scholander PF: The master switch of life. Sci Am 1963; sary. The use of intravenous corticosteroids is rarely 209:92-105 necessary, but in the presence of severe shock or in 5. Richter D: Biochemical changes in hypoxia. In James LS, bilateral hemorrhage, adrenal insufficiency should be Meyers R, Gaull G (eds): Brain Damage in the Fetus and ruled out and renal hypertension should be excluded.51 Newborn from Hypoxia or Asphyxia. Report on the 57th The pancreas may also be compromised in perinatal Ross Conference on Pediatric Research. Columbus, Ohio, Ross Laboratories, 1967, p 56 asphyxia. Hypoglycemia and, in rare cases, hy­ 6. Raivio KO: Neonatal hyperuricemia. J Pediatr 1976; 88:625- perglycemia have been observed in small for gesta­ 630 tional age (SGA) asphyxiated neonates. Pathogenesis 7. Goldberg RN, Cabal LA, Sinatra FR, et al: Hyperammonemia of hypoglycemia or hyperglycemia54 is probably more associated with perinatal asphyxia. Pediatrics 1979; 64:336-341 related to the altered glucose , decreased 8. Donn SM, Banagale RC: Neonatal hyperammonemia. glycogen, and delayed maturation of the pancreatic Pediatr Rev 1984; 5:203-208 beta cells in SGA infants rather than a direct result of 9. Volpe JJ: Intraventricular hemorrhage in premature infants. anoxic pancreatic insult. Pediatr Rev 1980; 2:145-153 10. Lou HC, Lassen NA, Friis-Hansen B: Impaired autoregula­ tion of cerebral blood flow in the distressed newborn infant. J Pediatr 1979; 94:118-121 INTEGUMENT 11. Lou HC: Perinatal hypoxic-ischemic brain damage and in­ Recently, Mogilner and colleagues55 described a case traventricular hemorrhage. Arch Neurol 1980; 37:585-587 of widespread subcutaneous fat necrosis in a newborn 12. Takashima S, Tanaka K: Microangiography and vascular permeability of the subependymal matrix in the premature who had suffered severe perinatal asphyxia. They pos­ infant. Can J Neurol Sci 1978; 5:45-50 tulated that generalized ischemia of the skin occurred 13. Donn SM, Goldstein GW, Silver TM: Real-time ultrasonog­ during the circulatory redistribution that accompanies raphy. Am J Dis Child 1981; 135:319-321 the ‘diving seal” reflex. Characteristic lesions are in­ 14. Vidyasagar D, Raju TNK, Chiang J: Clinical significance of durated, reddish-purple in color, and nodular. The le­ monitoring anterior fonatenal pressure in sick neonates and infants. Pediatrics 1978; 62:996-999 sions vary in size, but do not appear to be tender or 15. Volpe JJ: Neonatal seizures. Clin Perinatol 1977; 4:43-63 warm, and are generally located in the subcutaneous 16. Papile LA, Burstein J, Burstein R, et al: Posthemorrhagic fat adjacent to bony structures. The prognosis for reso­ hydrocephalus in low-birth- infants: Treatment by lution is usually excellent. serial lumbar punctures. J Pediatr 1980; 97:273-277 17. Hill A, Volpe JJ: Seizures, hypoxic-ischemic brain injury, and intraventricular hemorrhage in the newborn. Ann Neurol 1981; 10:109-121 CONCLUSIONS 18. Batzdorf U: The management of cerebral edema in pediatric practice. Pediatrics 1976; 58:78-87 19. Tweed WA, Pash M, Doig G: Cerebrovascular mechanisms It is obvious that anticipation or prevention of the in perinatal asphyxia: The role of vasogenic brain edema. many problems discussed is the key to management of Pediatr Res 1981; 15:44-46 perinatal asphyxia. Early identification of potential 20. Goldstein GW: Pathogenesis of brain edema and hemor­ rhage: Role of the brain capillary. Pediatrics 1979; 64:357- obstetrical problems is mandatory, and for the high- 360 risk fetus that may have gone through pregnancy and 21. Fishman RA: Steroids in the treatment of brain edema. N labor without detection, every effort should be made at Engl J Med 1982; 306:359-360

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