Neuroimaging, physical, and developmental findings after inflicted and noninflicted traumatic brain injury in young children.

OBJECTIVE: To characterize neuroimaging, physical, neurobehavioral, and developmental findings in children with inflicted and noninflicted traumatic brain injury (TBI) and to identify characteristic features of inflicted TBI. METHODS AND PATIENTS: Forty children, 0 to 6 years of age, hospitalized for TBI who had no documented history of previous brain injury were enrolled in a prospective longitudinal study. TBI was categorized as either inflicted (n = 20) or noninflicted (n = 20) based on the assessment of hospital and county protective services. Glasgow Coma Scale scores and neonatal history were comparable in both groups. OUTCOME MEASURES: Acute computed tomography/magnetic resonance imaging studies and physical findings were evaluated. Glasgow Outcome Scale scores, cognitive development, and motor functioning were assessed an average of 1.3 months after TBI. chi2 analyses assessed differences in the distribution of findings in the inflicted and noninflicted TBI groups. RESULTS: Signs of preexisting brain injury, including cerebral atrophy, subdural hygroma, and ex vacuo ventriculomegaly, were present in 45% of children with inflicted TBI and in none of the children with noninflicted TBI. Subdural hematomas and seizures occurred significantly more often in children with inflicted TBI. Intraparenchymal hemorrhage, edema, skull fractures, and cephalohematomas were similar in both groups. Retinal hemorrhage was only identified in the inflicted TBI group. Glasgow Outcome Scale scores indicated a significantly less favorable outcome after inflicted than noninflicted TBI. Mental deficiency was present in 45% of the inflicted and 5% of the noninflicted TBI groups. CONCLUSIONS: Characteristic features of inflicted TBI included acute computed tomography/magnetic resonance imaging findings of preexisting brain injury, extraaxial hemorrhages, seizures, retinal hemorrhages, and significantly impaired cognitive function without prolonged impairment of consciousness.

Management of malignant air leak in a child with a neonatal high-frequency oscillatory ventilator.

A 10-year-old, 36-kg child with a malignant air leak who failed conventional mechanical ventilation and high-frequency jet ventilation was successfully treated with a neonatal high-frequency oscillatory ventilator for 31 days. Since the air leak resolved with minimal hemodynamic compromise, this technique may have application in the management of respiratory failure and air leak in the older and larger child for prolonged periods of time.

Neurologic complications of heart transplantation in children.

Neurologic complications can add significant morbidity to otherwise successful orthotopic heart transplantations in children. Complications have been reported to occur in up to 50% of children undergoing heart transplantation. The purpose of this study was to identify the prevalence and outcome of neurologic complications of heart transplantation in children. We reviewed all children who received orthotopic heart transplantation at Texas Children's Hospital from November 1984 to November 1990. Twenty-two patients (ages, 3 weeks to 17 years; mean, 8.5 years) underwent heart transplantation using cardiopulmonary bypass with moderate hypothermia. For analysis, we compared results during the first 3 years of our experience, 1984 through 1987 (group 1), to 1987 through 1990 (group 2). Survival was 45% (5 of 11 patients) for group 1 and 73% (8 of 11 patients) for group 2. A neurologic complication was defined as a change in the neurologic examination and/or status. Neurologic complications included seizures (6 of 22 patients), strokes (3 of 22 patients), unresponsiveness (3 of 22 patients), and change in mental status (2 of 22 patients). Early (within 2 weeks after operation) neurologic complications occurred in 45% (10 of 22 patients), were persistent (sequelae lasting more than 4 months) in 27% (6 of 22 patients), and resulted in death in 9% (2 of 22 patients). Late (after 2 weeks after operation) neurologic complications occurred in 23% (5 of 22 patients), were persistent in 9% (2 of 22 patients), and have occurred in only two survivors. Neurologic factors were not responsible for the cause of death in group 2. No neurologic complications (early or late) were seen in 1 of 11 patients in group 1 as compared with 7 of 11 patients in group 2 (p < 0.015). Serious neurologic morbidity decreased between the two groups after preoperative cyclosporine was avoided and postoperative hypertension was controlled. All survivors are functioning at age-appropriate levels. Although neurologic complications may be frequent, long-term neurologic disability in survivors is rare.

Comparison of intravenous midazolam with pentobarbital for sedation for head computed tomography imaging.

OBJECTIVE: To compare the efficacy of intravenous (IV) midazolam with that of IV pentobarbital when used for sedation for head computed tomography (CT) imaging in emergency department (ED) pediatric patients. METHODS: Prospective, randomized clinical trial in an urban children's hospital. During a two-and-a-half-year period, 55 patients were enrolled: 34 males and 21 females. Measurements included induction time, recovery time, efficacy, side effects, complications, and failure with each drug. Success of sedation was graded as good (GS), adequate (AS), poor (PS), or unsuccessful (US). RESULTS: Sedation for CT was used for patients with the following problems: head trauma (21/55), central nervous system pathology (17/55), ventriculoperitoneal shunt evaluation (6/55), periorbital cellulitis (6/55), and retropharyngeal abscess (5/55). Twenty-nine (53%) patients received pentobarbital (mean +/- SD dose 3.75 +/- 1. 10 mg/kg) and 26 (47%) patients received midazolam (mean +/- SD dose 0.2 +/- 0.03 mg/kg). In the pentobarbital group, 28 (97%) patients were scanned and successfully sedated. Pentobarbital's mean induction time was 6 minutes and duration of sedation averaged 86 minutes. In the midazolam group, only five (19%) patients were successfully scanned with midazolam alone. Of the 21 (81%) patients given midazolam who were unsuccessfully sedated, 12 (61%) were subsequently sedated with the addition of pentobarbital for completion of CT imaging. Mild oxygen desaturation, O(2) sat >90% yet <94%, was seen in only four patients. All four patients responded to blow-by oxygen and required no other intervention. CONCLUSION: Intravenous pentobarbital is more effective than IV midazolam for sedation of children requiring CT imaging.

Cerebrovascular regulation and neonatal brain injury.

Neuropathology occurring as a result of hemodynamic injury occurs in up to 25% of preterm newborns of less than 1,500 gm birth weight and in a much smaller, but nonetheless meaningful, proportion of more mature infants. Abnormalities in cerebrovascular regulation have been proposed as major contributing factors to both ischemic and hemorrhagic injuries in the newborn brain. In this review we explore several factors that play a role in cerebrovascular regulation in the immature brain and relate them to what is known about vascular regulation in the mature brain and to the types of pathology that occur in the newborn brain. One goal in this "decade of the brain" should be to increase our basic and clinical knowledge about the cerebrovasculature of the newborn in order to enhance our ability to predict and prevent perinatal brain injury.

Neuropathology of two fatal cases of measles in the 1988-1989 Houston epidemic.

The clinical course and autopsy findings of 2 patients with measles encephalitis that occurred during the 1988-1989 Houston epidemic are reported. A previously healthy 25-month-old boy had serologically-proved measles, hemophagocytic syndrome, and acute disseminated demyelinating encephalitis. A 19-year-old male with acute lymphocytic leukemia had proved measles pneumonia and acute hemorrhagic leukoencephalitis. These patients represent a broad spectrum of measles-induced immunopathic complications of the central nervous system.

Postpericardiotomy syndrome in pediatric heart transplant recipients. Immunologic characteristics.

Clinical features of postpericardiotomy syndrome (PPS) occur in pediatric heart transplant recipients despite immunosuppression, which raises questions about the mechanism of PPS. We studied the clinical and immunologic characteristics of 15 pediatric heart transplant patients, ages 1.1 to 17.8 years (mean, 7.5 years); 7 had clinical evidence of PPS (PPS+), and 8 were without clinical features of PPS (PPS-). Indicators of PPS included fever, irritability, pericardial friction rub, leukocytosis without other cause, and pericardial effusion. The onset of PPS was from 9 to 26 postoperative days (mean, 16 days). Immunosuppressive regimens were comparable up to the day of PPS diagnosis in PPS+ patients, and up to day 16 in PPS- patients (average onset of PPS in PPS+ patients). No differences were found between groups with respect to weight-adjusted dosages of cyclosporin A, azathioprine, or corticosteroids. Mean cyclosporin A levels in PPS+ and PPS- patients were 142 +/- 88 ng/mL (mean +/- standard deviation) and 265 +/- 122 ng/mL (p = 0.045), respectively. Echocardiographic data on 3 PPS+ patients within 1 day of PPS diagnosis revealed pericardial effusions ranging from 5 to 24 mm. No data were available on the remaining 4 PPS+ patients. Minimal pericardial effusions (< 10 mm) were seen in 4 PPS- patients during a comparable time period. One PPS- patient required pericardiocentesis. Endomyocardial biopsy rejection grade did not differ between groups. Means pretransplant soluble interleukin-2 receptor levels did not differ between PPS+ and PPS- patients (758 +/- 410 vs 653 +/- 270 IU/mL); nor did the PPS+ pretransplant levels differ from levels obtained 1 or 2 months postoperatively (700 +/- 437 and 751 +/- 367 IU/mL, respectively). Although pretransplant percentages of the standard T-cell (CD2, CD3, CD4, CD8) and B-cell (DR and CD19) markers differed from post-transplant values, the changes could be explained by the immunosuppressive regimen and did not differ between PPS+ and PPS- patients. In the PPS+ patients, however, there were significant increases in the proportion of activated helper T cells (CD4+/25+) and cytotoxic T cells (Leu-7+/CD8+) following heart transplantation in comparison with pretransplant levels. We speculate that these changes in activation marker in PPS+ patients suggest a possible role for cell-mediated immunity in the pathogenesis of PPS in this group of patients.

Brain blood flow responses to indomethacin during hemorrhagic hypotension in newborn piglets.

Indomethacin has been shown to reduce cerebral blood flow and cerebral blood flow velocities in newborn infants and animals of various species. To answer the question of whether there may be a compromise of cerebral perfusion in hypotensive infants who have been treated with indomethacin, cerebral blood flow and cerebral vascular resistance were determined in 10 control and 16 indomethacin-treated 1-day-old piglets during (1) steady state conditions; (2) 10 min after the administration of saline or a 0.2-mg/kg dose of indomethacin; (3) 1 h after saline or indomethacin administration, and (4) 10 min after induction of moderate hemorrhagic hypotension. Mean arterial blood pressures increased immediately after the infusion of indomethacin in the experimental group. Cerebral blood flows did not change throughout the study despite hemorrhagic hypotension in controls; cerebral blood flows were significantly decreased 10 min after indomethacin infusion in the experimental animals. However, total and regional cerebral blood flows were not further decreased in the presence of moderate hypotension. Cerebral vascular resistance increased 10 min after indomethacin infusion but returned to steady state 1 h following the indomethacin dose. These results suggest that indomethacin lowers baseline cerebral blood flow, but does not impair cerebrovascular regulatory responses during acute, moderate hemorrhagic hypotension in the newborn piglet.

Use of the Natural Death Act in pediatric patients.

OBJECTIVE: To review the use of Natural Death Act declarations (living will procedures) in pediatric patients. The implementation of such declarations for children is now possible in six states, including Texas, by specific statutory provisions. DESIGN: Retrospective study. SETTING: Pediatric ICU in a university hospital. PATIENTS: Records of patients who had a Texas Natural Death Act declaration, either discussed and signed or discussed only, were studied. Patients who had another vehicle of limiting care (e.g., a do-not-resuscitate order) were excluded from the study. MEASUREMENTS AND MAIN RESULTS: Reviewed characteristics included age, primary diagnosis, and concurrent complications. Also examined were who raised the issue of limiting care (parent or physician), the initial reaction of the other party, what support was withdrawn, what support was added, the final outcome (including the time from implementing limited care to death), and the description of witnesses. Discussions were held with parents of 17 patients, and 13 Natural Death Act declarations were actually implemented. In all but three instances, the patient died within 4 hrs from the time support was withdrawn. The main supports that were withdrawn were ventilators and catecholamines. In half of the cases, morphine sulfate was added for anticipated pain relief and sedation. All decisions were reached by close consultation between the family and the physicians, with the physicians raising the issue in 11 of the 17 cases and the family raising the issue in six cases. In 15 of the 17 patients, consultation with the Bioethics Committee was not necessary. The majority of difficulties involved resolving issues that beset patients with HIV infections, and finding appropriate witnesses as prescribed by the statute. CONCLUSIONS: We conclude that the Natural Death Act works well in situations involving dying children and their parents.

Barbiturates and hyperventilation during intracranial hypertension.

OBJECTIVE: The purpose of this study was to determine the effect of hyperventilation alone and hyperventilation plus barbiturate therapy on intracranial pressure, global and regional cerebral blood flow rates, cerebrovascular resistance, and cerebral perfusion pressure in adult dogs with and without intracranial hypertension induced by epidural balloon. DESIGN: Prospective, randomized, controlled study. SETTING: An animal laboratory of a university hospital. Four sequential global and regional cerebral blood flow determinations were made in each animal during monitoring of heart rate and systemic arterial pressure, during respiratory control and arterial blood gas monitoring, intracranial pressure monitoring, and with or without inflation of an epidural balloon catheter. SUBJECTS: Acute mongrel dogs obtained from the Baylor Center for Comparative Medicine. Five groups of animals were studied. In group 1, the response to hyperventilation was assessed in dogs without increased intracranial pressure. In group 2, the response to hyperventilation was assessed in animals with acute intracranial hypertension. In group 3, the response to hyperventilation plus barbiturate therapy was assessed in dogs without increased intracranial pressure. In group 4, the response to hyperventilation plus barbiturate therapy was assessed in dogs with acute increased intracranial pressure. In group 5, a group of dogs with increased intracranial pressure was treated with neither hyperventilation nor barbiturates. INTERVENTIONS: Hyperventilation, hyperventilation plus barbiturate therapy, or no interventions were studied in these experimental paradigms. MEASUREMENTS AND MAIN RESULTS: The main outcome measures were changes in intracranial pressure and/or changes in regional or total cerebral blood flow. A significant decrease in intracranial pressure and cerebral blood flow rate was produced by hyperventilation alone in groups with intracranial hypertension. Combined hyperventilation and barbiturate therapy resulted in a significant further decrease in cerebral blood flow rate in animals with normal and increased intracranial pressure, but no greater decrease in intracranial pressure was seen compared with treatment with hyperventilation alone. Cerebral perfusion pressures remained normal despite significant decreases in cerebral blood flow rates. CONCLUSIONS: These studies suggest that barbiturate administration in this model of intracranial hypertension was no more effective in reducing increased intracranial pressure than hyperventilation alone.

Severe laryngotracheobronchitis complicating measles.

OBJECTIVE: To determine the incidence of severe measles-related laryngotracheobronchitis in patients hospitalized during a recent measles epidemic and to evaluate factors associated with severity of airway injury and its management. DESIGN: Clinical description of patient series. SETTING: Children's hospital and county general hospital, Houston, Tex. PATIENTS: One hundred twenty-four children (aged 1 month to 19 years) admitted with a diagnosis of measles. INTERVENTIONS: None. MEASUREMENTS/RESULTS: Twenty-seven patients had significant laryngotracheobronchitis, including 10 who had not received appropriate immunization. Six patients required endotracheal intubation for relief of upper airway obstruction. The median age of patients requiring intubation was 12 months (range, 4 to 24 months). Two patients died of complications of superinfection. Two patients survived but required prolonged intubation. Two patients underwent early diagnostic laryngoscopy and bronchoscopy and required shorter artificial airway maintenance. CONCLUSIONS: Severe laryngotracheobronchitis frequently occurs in patients younger than 2 years hospitalized with measles and may be related to bacterial or viral super-infection. Early diagnostic laryngoscopy and bronchoscopy for injury assessment and possible endotracheal tube exchange are recommended and, in some severe cases, tracheostomy should be considered to shorten artificial airway maintenance and decrease the incidence of airway complications.

Cytochrome oxidase is decreased in piglet hippocampus following hypoxia-ischemia.

We assessed cytochrome oxidase (CytOx) staining in sham-operated control piglets and in piglets subjected to 30 minutes of cerebral hypoxia-ischemia (H-I) plus 4 hours of reperfusion (REP). The 1-day-old piglets were sedated, anesthetized, and ventilated. Cerebral blood flows (CBFs) were quantitated using microspheres. H-I was induced by a combination of phlebotomy and cervical tourniquet; the brain was reperfused for four hours after 30 minutes of H-I. CBF was reduced during ischemia in experimental animals from 42 + 13 to 12 + 5 ml/min/100g. CytOx staining of hippocampal sections from 3 control and 3 experimental animals was compared. The staining of the stratum pyramidale neurons of the same portion of the CA1 sector in a single high power field was assessed in a blinded fashion in 4 corresponding sections from each animal, and graded from 0 = no staining to 3 = heavy staining. The results were compared using one-way analysis of variance. Cells with grade 3 staining were significantly more numerous in controls compared to H-I/REP animals (p = 0.03). There were significantly more cells with no CytOx staining in the experimental animals (p = 0.01). These findings suggest that CytOx staining in newborn piglet CA1 is a reliable method of assessing cell dysfunction after H-I.

Acute neuroradiologic findings in young children with inflicted or noninflicted traumatic brain injury.

Acute CT/MRI findings were examined in a prospective, longitudinal study of 60 children 0-6 years of age hospitalized for moderate to severe traumatic brain injury (TBI). TBI was categorized as either inflicted (n = 31) or noninflicted (n = 29). Glasgow Coma Scale scores and perinatal history were comparable in both groups. Acute CT/MRI studies were visually inspected by a radiologist blind to group membership. Compared with the noninflicted TBI group, the inflicted TBI group had significantly elevated rates of subdural interhemispheric and convexity hemorrhages as well as signs of pre-existing brain abnormality, including cerebral atrophy, subdural hygroma, and ex vacuo ventriculomegaly. Intraparenchymal hemorrhage, shear injury, and skull fractures were more frequent after non-inflicted TBI. Subarachnoid hemorrhage and infarct/edema occurred with comparable frequency in both groups. Characteristic acute neuroimaging findings of inflicted TBI included multiple extraaxial hemorrhages in addition to the mild atrophy, subdural hygromas, and ventriculomegaly that suggest prior brain abnormality.

Correlation of near infrared spectroscopy cerebral blood flow estimations and microsphere quantitations in newborn piglets.

We compared cerebral blood flow (CBF) estimated using transmission mode near infrared spectroscopy (NIRS) and a modification of the Fick principle with CBF quantitations by radioactive microspheres (MSs) in newborn piglets. Thirteen piglets were studied during steady state, ischemia, and during two reflow periods. NIRS and MS flows were not significantly different during any measurement period. NIRS flows were compared to total brain blood flows and to regional brain blood flows quantitated with MSs and correlated best with temporal cortical flows. Linear regression analysis of the NIRS flows plotted against MS-quantitated temporal cortical flows showed r = 0.71. Thus, CBFs obtained with NIRS were not significantly different from, showed the same directional changes, and correlated acceptably with flows quantitated by MSs.