Neurology: NICU Handbook

Download Cooling Flowchart for HIE 

Michael J. Acarregui, MD
Peer Review Status: Internally Peer Reviewed

Background

There are four major types of intracranial hemorrhage which may affect the neonate. These include subdural hemorrhage, primary subarachnoid hemorrhage, intracerebellar hemorrhage and periventricular-intraventricular hemorrhage (PVH-IVH). In the Intensive Care Nursery PVH-IVH is the most common of the four and for the preterm infant represents the type of hemorrhage of greatest clinical significance.

The incidence of PVH-IVH varies considerably in the literature, the majority of centers reporting an incidence of 20-30% for infants with a birth weight <1500 g. Different incidence figures among centers reflects multiple factors such as the proportion of inborn and outborn births (the latter group have been shown to have a higher incidence of PVH-IVH compared to inborn infants), timing of sonography, and whether all eligible infants were evaluated.

There are several classifications to characterize the extent of PVH-IVH. A relatively simple classification which is often used is as follows:

• Grade I: hemorrhage limited to the germinal matrix (subependymal hemorrhage)
• Grade II: hemorrhage which has extended into the ventricular system but without dilation of the lateral ventricles.
• Grade III: hemorrhage extending into the ventricular system with the blood resulting in ventricular dilatation.
• Grade IV: hemorrhage which extends into the brain tissue (this grade is also referred to as PVH and associated with intraparenchymal echodensity (IPE) by some).

A problem with this grading system that needs acknowledgment is that objective determination of ventricular dilation is difficult. Determination of the extent of hemorrhage is important since most follow-up studies have found that the probability of neurologic morbidity (cognitive, motor, etc.) is high (>50% depending upon the study) for more extensive hemorrhage (grade III and IV). In contrast, it appears that the presence of a grade I or II PVH-IVH does not measurably increase the chance of neurologic morbidity. Lesions which occur in the periventricular white matter occur in 3-10% of infants with birth weight <1500 g, are frequently bilateral, are felt to be ischemic in origin, and will evolve into cystic lesions of the periventricular white matter (periventricular leukomalacia, PVL). The presence of PVL carries a high risk of neurologic morbidity (most often spastic diplegia).

Pathophysiology

As the name implies, PVH originate in the tissue abutting the lateral ventricle, e.g., germinal matrix. In most infants, PVH arise in the germinal matrix at the level of the foramen of Monroe, although in extremely preterm infants (<28 wks) PVH often arise further posteriorly in the germinal matrix. From multiple sonographic studies of the matural history of PVH-IVH, it is evident that most hemorrhages remain confined to the germinal matrix area (60-70% of PVH-IVH depending upon the study). Many hemorrhages will be clinically silent, and very few hemorrhages have a catastrophic presentation (e.g., profound alteration in neurologic state, hypotension, apnea, bulging fontanel, drop in hematocrit, etc.).

The pathogenesis of PVH-IVH remains unclear. A complex multifactorial etiology is likely. There have been a number of clinical trials to prevent the occurrence of PVH-IVH using phenobarbital, Vitamin E, indomethacin, Vitamin K, and ethamsylate, all without conclusive results. If PVH-IVH occurs, additional sonograms will be needed to monitor for extension of the hemorrhage and post-hemorrhagic complications (porencephaly, hydrocephalus). Using serial sonography, it has been shown that the occurrence of post-hemorrhagic hydrocephalus is relatively uncommon after PVH-IVH (~ 13%). However, using serial cranial sonography, it has been shown that enlargement of the lateral ventricles may precede change in head circumference. Thus, once PVH-IVH has occurred follow-up cranial ultrasound is indicated. Similarly, when post-hemorrhagic hydrocephalus (PHH) is evolving (50% of Grade III IVH will be complicated by PHH), management (if any) should be discussed with the Attending Staff.

Diagnosis

Since it is difficult to predict the presence or absence of neonatal intracranial hemorrhage by clinical criteria, the following schedule is used for routine head ultrasounds for "all" infants ≤1500 g birth weight:

• Ultrasound 1. 5-7 day
• Ultrasound 2. 28-30 day or before discharge
• If PVH-IVH is detected on ultrasound, should be obtained more frequently (weekly) to evaluate progression of ventricular dilatation or cystic change.

The timing of the above head ultrasound schedule takes into account that most PVH-IVH occurs in the first week of life. However, the presence of late PVH-IVH does occur and necessitates an ultrasound examination at a month of life.

Post hemorrhagic hydrocephalus

It has been well demonstrated that enlarging head circumference is an insensitive sign of hydrocephalus in the premature infant. Ventricular dilatation after neonatal intracranial hemorrhage probably begins soon after the hemorrhage in many infants and pre-dates the increase in the rate of head growth by days to weeks. Infants with hydrocephalus have a poor prognosis, and one important factor in their outcome may be a delay in the detection and treatment of hydrocephalus.

Recommendations:

The following is the recommended approach to the identification and care of these infants:

1. All infants <1500 grams will be screened by ultrasound for evidence of intraventricular hemorrhage. The screening ultrasound will be done on or about the seventh day of life. The daytime nursery ward clerks will be responsible for identifying which babies are seven days of age from the census book and filling out an x-ray request. Ultrasounds will be performed daily Monday through Friday. If an infant's seventh day falls on the weekend, the scan should be done on Friday or Monday, whichever day is closer to the seventh day. Abnormal ultrasounds will be presented at the daily radiology conference.
2. The house staff will be responsible for identifying and ordering ultrasounds on infants >1500 grams who might be at risk for significant hemorrhage.
3. Once a hemorrhage has been identified by screening ultrasound, the pediatric house officer then becomes responsible for ordering ultrasounds on a weekly basis until it is clear that the hemorrhage has resolved and that there has been no progression of ventricular size.
4. If there is clinical evidence of an intraventricular hemorrhage (drop in hematocrit, seizures, full fontanel, bloody CSF, unremitting acidosis, etc.) an ultrasound should be ordered by the resident on the day that it is desired. Emergency ultrasounds can be done whenever indicated.

Serial Lumbar Punctures:

Serial lumbar punctures have been used to control increased intracranial pressure when there is clinical evidence of rapidly progressive ventricular size.

There is little evidence in the literature of the efficacy of serial lumbar punctures for the prevention of hydrocephalus. However, it appears that serial lumbar punctures can be beneficial in protecting the cortical mantle in an infant with progressive hydrocephalus who is too small to be shunted. The care of each baby needs to be individualized, and there may be changes in our approach to these infants as new information becomes available. Decisions with regard to lumbar punctures should be made with the attending neonatologist. In general the following recommendations appear reasonable:

1. Minimally dilated ventricles without progression do not warrant the use of serial lumbar punctures.
2. If progressively enlarging ventricles are identified on ultrasound (with or without clinical signs of increased intracranial pressure), daily LP's may be indicated. Enough fluid should be removed to soften the fontanel, usually 10 to 15 ml. Those with significant intracranial pressure may need 20 to 30 ml removed. The taps should be continued until the ventricles stabilize or decrease in size, or until the infant is large enough to undergo a ventriculoperitoneal shunt. If taps are discontinued because the ventricles have decreased in size, a follow-up ultrasound should be obtained in about seven days to insure that ventricular size remains stable.
3. Enlarged ventricles may be secondary to cerebral atrophy. In such cases, ventricular dilatation is a passive process and not related to change in CSF dynamics. Serial lumbar punctures are not indicated in such cases.
4. In cases in which progressive ventricular enlargement and clinical signs of increased intracranial pressure cannot be controlled by periodic taps and in which the child's weight is still sufficiently low that shunting cannot be done, other modes of therapy should be considered after appropriate consultation.
5. If the decision is made to undertake serial lumbar punctures, certain precautions must be observed. The lumbar puncture must be done with meticulous technique because meningitis is a potential risk. In addition, electrolytes should be measured periodically if large volumes of fluid are removed.
6. Repeat head ultrasound exams should be done at weekly intervals whenever blood has been identified in the ventricles in order to monitor changes in ventricular size. Discontinuation of ultrasounds must be decided on an individual basis. In addition, consideration should be given to ordering a late head ultrasound exam at about 6 weeks of age in infants born at 26 weeks or less; the purpose of this late exam is to screen for periventricular leukomalacia.
7. Depending upon the severity of the initial hemorrhage and the clinical presentation, a single CT scan might provide information about cerebral cortical and white matter pathology not available by other means of investigation. If desired for prognostic reasons, the CT scan should be performed near the time of discharge.
8. At the time an infant with post hemorrhagic hydrocephalus is discharged, arrangements should be made for follow-up in the Neonatology Clinic in four weeks. In some cases a repeat ultrasound may be necessary at that time. The infant who has had a shunt procedure during the hospitalization should also be followed in the Neurosurgery Clinic.

References:

Goldstein GW, Chaplin ER, Maitland J. Transient hydrocephalus in premature infants: treatment by lumbar puncture. Lancet 1976;1:512-514.

Papile LA, Burstein J, Burstein R, Koffler H, Koops BL, Johnson JD. Posthemorrhagic hydrocephalus in low-birth-weight infants: treatment by serial lumbar punctures. J Pediatr 1980;97:273-277.

Kreusser KL, Tarby TJ, Kovnar E, Taylor DA, Hill A, Volpe JJ. Serial lumbar punctures for at least temporary amelioration of neonatal posthemorrhagic hydrocephalus. Pediatrics 1985;75:719-724.

Szymonowicz W, Yu VYH, Lewis EA. Post-haemorrhagic hydrocephalus in the preterm infant. Aust Paediatr J 1985;21:175-179.

Volpe J. Intraventricular hemorrhage and brain injury in the premature infant: neuropathology and pathogenesis. Clinics in Perinatology 1989;16(2):361-386.

Volpe J. Intraventricular hemorrhage and brain injury in the premature infant: diagnosis, prognosis and prevention. Clinics in perinatology 1989;16(2):387-411.

Michael J. Acarregui, MD
Peer Review Status: Internally Peer Reviewed

The term asphyxia infers an impairment of gas exchange resulting in a fall in PO₂ and a rise in PCO₂. Degrees of asphyxia exist, varying from total asphyxia, characterized by anoxia and extremes of hypercarbia, to the more commonly encountered situation of partial asphyxia, involving hypoxia and moderate elevations of PCO₂. Asphyxial events may occur in utero, at birth, or during postnatal life. Ischemia is often an integral component of asphyxia. Thus the term hypoxia-ischemia is often used interchangeably with asphyxia. A gold standard definition of asphyxia does not exist, and different criteria have been used to diagnose asphyxia including: fetal heart rate patterns, meconium stained amniotic fluid, Apgar scores, umbilical artery pH, need for resuscitation at birth, seizures, electroencephalographic abnormalities, and the development of a clinical neurologic syndrome. At birth there is often insufficient information to readily determine if an asphyxial insult has occurred, and if it has occurred, whether any organ system dysfunction has resulted. For example, seizures may not occur immediately after birth and a clinical neurologic syndrome may evolve over 2-3 postnatal days. This may pose potential problems since inappropriate triage of infants may occur and result in delay in management when obvious problems develop. In spite of these considerations it is critical to note that asphyxial insults in the perinatal period do not account for the majority of infants with brain injury in early childhood.

Perinatal asphyxia leads to multi-organ system dysfunction. Virtually any organ system can be affected, and care in the nursery should be oriented to determining the presence or absence of dysfunction of critical organ systems. Cardiovascular involvement may include alterations in blood volume, redistribution of cardiac output and a syndrome of transient myocardial dysfunction. Neurologic involvement is characterized by the evolution of a characteristic hypoxic-ischemic encephalopathy of which seizures may be a part. The Sarnat stages (I-III) of post-hypoxic encephalopathy represent a convenient description to characterize the extent of neurologic involvement and important features are listed in the table.

Metabolic involvement may include hypocalcemia, hyponatremia (as a result of inappropriate ADH secretion or direct renal injury), and alterations in glucose metabolism. Pulmonary involvement may include persistent pulmonary hypertension, aspiration syndromes (usually meconium) and asphyxial lung disease (rare). Direct renal injury may occur leading to acute tubular necrosis. Ischemic bowel disease may occur presumably as a result of the redistribution of cardiac output (dive reflex response). Less commonly, hematologic alterations (thrombocytopenia and DIC) and subcutaneous fat necrosis occur. Clinical care of these infants should be directed at surveillance and management of specific organ system dysfunction. Fluid management should be cautious.

Michael J. Acarregui, MD
Peer Review Status: Internally Peer Reviewed

Background

It is important to recognize the presence of seizures in the neonatal period since they are often related to a significant underlying illness. In addition, seizures may be sustained for considerable periods of time, interfering with essential supportive care. There are 4 major types of seizures in neonates:

1. Subtle seizures are relatively common in the neonatal period and are more often encountered in the preterm than full term infant. Such seizures include oral-buccal-lingual movements, certain ocular phenomena, peculiar limb movements, autonomic alterations and apnea.
2. Clonic seizures include focal and multifocal varieties which may migrate to another part of the body in a non-ordered fashion.
3. Tonic seizures include focal episodes (less common) and generalized episodes (more common). Generalized tonic seizures may mimic decerebrate and decorticate posturing.
4. Myclonic seizures may be focal, multifocal or generalized and are the least common of the four varieties during the neonatal period.

Seizure-like phenomena may not be accompanied by seizure activity on EEG and possibly represent movements or posturing generated by diencephalon-brainstem activity when released from the inhibitory effects of the cerebral cortex. Careful clinical assessment is often necessary to distinguish seizure from nonseizure activity. Non-seizure activity is usually provoked by sensory stimulation, suppressed by passive restraint, associated with normal eye movements, and not accompanied by autonomic phenomena.

Pathophysiology

A number of etiologies should be considered for neonatal seizure. These include:

1. Asphyxia/hypoxia-ischemia: There is usually an interval of time between the event and the onset of seizures, but this interval is quite variable (1-36 hr).
2. Intracranial hemorrhage: Seizures may be a manifestation of any form of intracranial hemorrhage including subarachnoid, intraventricular or intraparenchymal hemorrhage.
3. Metabolic disturbances: Seizures may accompany alterations of glucose, calcium or sodium homeostasis, as well as inborn errors of metabolism, e.g., hyperammonenia.
4. Intracranial infection: Meningitis, encephalitis.
5. Drug withdrawal: Heroin, methadone.
6. Structural defects of the central nervous system.

Diagnosis

A detailed history of prenatal and postnatal events is paramount in diagnosing neonatal seizures. At the time of the seizure, attention should be directed to identifying treatable causes, as outlined in the previous section. A short term screening EEG may be helpful in establishing diagnosis and prognosis. Other studies, including head ultrasound, CT or MRI and skull X-rays, should be considered depending upon the history obtained.

Treatment

Once a seizure has been diagnosed, treatment directed at the underlying disease needs to be initiated. Anticonvulsant therapy includes the following:

1. Phenobarbital is the drug of first choice to treat neonatal seizures. It is relatively effective, the side effects are well appreciated, and the pharmacokinetics are reasonably well understood for term and preterm infants. A loading dose of phenobarbital (20 mg/kg) will achieve a therapeutic level of approximately 20 µg/ml, which is not affected by birth weight or gestational age. The intravenous route is preferred because of the more rapid onset of action and more reproducible effects on blood levels. The maintenance dose of phenobarbital is lower in the first week of life (3.5 mg/kg/day) and increases to 5 mg/kg/day with increasing postnatal age.
2. Dilantin is often the second drug of choice to be added when seizures are not controlled by phenobarbital alone. A loading dose of 20 mg/kg intravenously will achieve therapeutic blood levels (approximately 15 µg/ml) and a maintenance dose is 5 mg/kg/day.
3. Lorazepam is useful for infants with "uncontrolled" seizures in spite of therapy with phenobarbital and dilantin. The usual dose is 0.05 - 0.1 mg/kg per dose. Due to the possibility of respiratory depression (especially with phenobarbital on board), the safest use of these drugs is when ventilatory support has been initiated.

Screening criteria

Screen term infants for eligibility if they had poor respiratory effort at birth and needed resuscitation or appear encephalopathic.

Inclusion criteria

Infants > 36 weeks and > 1800 grams with Perinatal Depression (Part A) and HIE (Part B).

Part A: Physiologic criteria for acute perinatal depression:

1) Cord gas or first postnatal blood gas at < 1 hour of age with either pH <7.0 or base deficit > 16 mmol/L.

OR

2) If cord gas or first postnatal blood gas at < 1 hour of age has either a pH of 7.01 - 7.15 or a base deficit of 10 - 15.9 mmol/L or if a blood gas is not available then the following additional criteria are required.

1. An acute perinatal event (e.g., late or variable decelerations, cord prolapse, cord rupture, uterine rupture, maternal trauma, hemorrhage, abruptio placenta, etc.) and either:

1. Apgar score of < 5 at 10 minutes or
2. ii. Need for ventilation initiated at birth and continued for at least 10 minutes

Exclusion criteria

1. Inability to initiate cooling by 6 hours after birth.
2. Known chromosomal anomaly (excluding Trisomy 21, Turners, etc).
3. Presence of major congenital anomalies.
4. Infants in extremis for whom no additional intensive therapy will be offered.

If an infant meets either criteria A1 or A2, proceed to Part B (neurological criteria and exam).

Part B - Neurological criteria: Infants meet criteria if either seizures or HIE is present.

Evidence for HIE:

Moderate/severe hypoxic-ischemic encephalopathy (HIE) will be defined as either seizures or in the absence of seizures, the presence of signs in 3 of 6 categories from the neurological exam.

Timing of the examination:

The exam should be done in the first 1 - 3 hours of life once the patient’s cardiopulmonary status has been stabilized.

Performance of the neurological examination for Whole Body Cooling:

The neurological examination should take 10 - 15 minutes to complete and be performed by the attending and/or fellow. The exam is to be recorded in the admit note and performed in the following order: Spontaneous activity, posture, autonomic system, tone (via ROM), primitive reflexes and level of consciousness (response to stimuli).

Patients who have HIE as defined by seizures will still need to have a neurological exam for cooling performed and documented.

If the infant meets physiologic criteria A1or A2 and neurologic criteria B without exclusion criteria, then whole body cooling can be initiated by ordering “Cooling per protocol”.

Reference: N Engl J Med 2005; 353:1574-84.