Faculty Bibliography

Tangier Disease (TD), a rare autosomal disorder, is characterized by low plasma cholesterol, decreased or absent A-I apolipoprotein and normal ol elevated plasma triglycerides. ID was diagnosed antemortem by serologic and electrophoretic studies. Careful examination of the organs at autopsy showed the presence of lipid-laden macrophages, the hallmark of TD, only in the rectosigmoid mucosa, and not in other organs usually affected in ID. These findings indicate that the widespread distribution of lipid deposits may be absent in patients with ID early in life. In addition, DiGeorge syndrome (DGS) was recognised at autopsy by absence of the thymus and presence of only one parathyroid, thus explaining the multiple opportunistic infections during life

OBJECTIVES: (a) To examine the frequency, type, and severity of complications occurring in a pediatric intensive care unit; (b) to identify populations at risk; and (c) to study the impact of complications on morbidity and mortality. DESIGN: Prospective survey. SETTING: Pediatric intensive care unit (PICU) of a university-affiliated hospital. PATIENTS: 1035 consecutive admissions over an 18-month period. RESULTS: 115 complications occurred during 83 (8.0%) admissions, for 2.7 complications per 100 PICU-days; 48 (42%) complications were major, 45 (39%) moderate, and 22 (19%) minor. Sixty complications (52%) were ventilator-related, 14 were drug-related, 13 procedure-related, 24 infectious, and 22 involved invasive devices (18 vascular catheters). Human error was involved in 41 (36%) cases, 21 of which were major (18%). Treatments included reintubation < 24 h (28), intravenous antimicrobials (24), and invasive bedside procedures (14). Cardiopulmonary resuscitation was required in 6 patients. Thirteen patients with complications died (15.7%); 2 deaths were directly due to complications. Patients with complications were younger, had longer lengths of stay, and had a higher mortality. Length of stay was a positive risk factor for complication risk (odds ratio = 1.09, 95% confidence interval: 1.05 to 1.13; p = 0.0001); other patient characteristics had no predictive effect. Kaplan-Meier estimates showed that the most severe complications occurred early in the PICU stay. The best indicators of patient mortality were number of complications (odds ratio = 2.96, 95% confidence interval 1.72 to 5.08; p = 0.0001), and mortality risk derived from the Pediatric Risk of Mortality Score (odds ratio = 1.08, 95% confidence interval 1.06 to 1.10; p = 0.0001). Mortality was correlated with increasing severity of complications. CONCLUSION: Complications have a significant impact on patient care. Patients may be at increased risk earlier in their PICU course, when the number of interventions may be greatest. Complications may increase patient mortality and predict patient death better than other patient variables.

Systemic lupus erythematosus (SLE) affects approximately 0.6 children per 100,000. The disease is extremely rare in children under 5 years of age and is diagnosed predominantly in adolescent females. Children tend to present with more severe multisystem involvement than adults. Pericarditis occurs in approximately 25% of patients with SLE in all age groups. Progression to tamponade is extremely uncommon in the pediatric population. In the current report, an adolescent girl is diagnosed with SLE after presenting with signs and symptoms consistent with cardiac tamponade. A review of other pediatric patients with a similar presentation is also included.

STUDY OBJECTIVE: To examine the correlation between clinical diagnoses and autopsy findings in children who die in the pediatric intensive care unit (PICU). DESIGN: Retrospective chart review. SETTING: PICU of a university-affiliated hospital. PATIENTS: A consecutive sample of patients who died in the PICU and had autopsies performed. MEASUREMENTS AND MAIN RESULTS: Of 193 patients who died during the 7 1/2-year study period, 50 (26%) had autopsies performed. The mean age was 34.7 months (range 15 hours to 17 years), and the mean length of stay in the PICU was 12.2 days (range 2 hours to 60 days). Major admitting diagnoses included postoperative cardiac surgery (19), nonoperative cardiac disease (7), hematologic/malignant disorder (5), and acquired immunodeficiency syndrome (5). There were 5 cases (10%) where autopsy revealed a major finding that, if known prior to death, would have altered clinical management and might have resulted in cure or prolonged survival. In another 9 patients (18%) the autopsy revealed major findings that, if known prior to death, would not have altered management. Eight of these findings related to the cause of death and 2 of them involved the basic disease. There was no correlation between new findings and either patient age or length of stay in the PICU. CONCLUSIONS: Despite modern diagnostic techniques, the autopsy continues to reveal valuable and unsuspected information.

Sudden release of platelet-activating factor (PAF) into the circulation can cause hypotension, tachycardia, and circulatory collapse. To further examine this response, we performed detailed studies of cardiovascular function after PAF administration to young domestic pigs and newborn piglets. Our results indicate that circulatory dysfunction after PAF reflects severe constriction of pulmonary resistance vessels and consequent acute right ventricular failure. Although PAF-induced coronary artery constriction and contractile depression may be complicating problems, left ventricular underperfusion and dysfunction after PAF are mainly the result of systemic arterial hypotension and diminished left ventricular filling. The adverse hemodynamic effects of PAF are accompanied by substantial release of thromboxane A2 (TxA2). These effects are mimicked by the TxA2 agonist U-46619 and partially blocked by specific and nonspecific inhibitors of TxA2 synthesis (OKY-046 and indomethacin). Even more potent blockade of PAF action is exerted by the TxA2 receptor blocker, SQ 29,548. Taken together, these findings indicate that severe pulmonary vascular constriction and hemodynamic collapse soon after intravenous PAF are at least partially mediated by PAF-induced TxA2 release. Tachyphylaxis to PAF influence has been observed in studies of leukocyte and platelet function. We hypothesized that tachyphylaxis to PAF might also occur in our studies of constrictor responses in pulmonary vessels. Recently, we have examined the capacity of PAF to produce sustained pulmonary vasoconstriction in open-chested, anesthetized newborn piglets. Infusions sufficient to produce 100% increase in mean pulmonary artery pressure after 3 min showed no loss of efficacy when sustained for 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute exposure to platelet-activating factor (PAF) causes severe pulmonary vasoconstriction (PV), but its action may be markedly limited by tachyphylaxis. To determine the effects of PAF exposure per se and the effects compared with the hypoxemic state (33 +/- 1 mm Hg), PAF infusions (0.05-0.15 nmol/kg/min x 30-180 min) were administered to 15 open-chested, anesthetized, neonatal piglets before and during administration of selective receptor blockers to PAF (SRI 63,441, 5 mg/kg i.v. or WEB 2086, 10 mg/kg i.v.) or vehicle. Measurements included mean pulmonary (PAP) and systemic arterial pressures, cardiac index, right and left ventricular pressures and dimensions, and coronary blood flow. Mean PAP and pulmonary vascular resistance index rose in response to 30 min PAF infusion (14 +/- 1 to 30 +/- 1 mm Hg and 4500 +/- 700 to 16,400 +/- 1900 dynes s cm-5.kg, both p less than 0.01, n = 10). Similar changes occurred when PAF was infused for 180 min (n = 5). Other parameters were unaffected. Acute hypoxia also increased in PAP and pulmonary vascular resistance index (17 +/- 1 to 32 +/- 2 mm Hg and 6400 +/- 900 to 17,100 +/- 1800 dynes s cm-5.kg, both p less than 0.01) and did not alter other measured variables. Treatment with SRI 63,441 prevented PAF-induced increases in PAP (14 +/- 1 to 14 +/- 1 mm Hg, p less than 0.05) and pulmonary vascular resistance index (5300 +/- 900 to 5500 +/- 800 dynes s cm-5.kg, p less than 0.05) but failed to alter the response to hypoxia. SRI 63,441 and WEB 2086, administered during PAF infusion, rapidly reversed PAF action. Vehicle had no effect. We conclude that PAF can produce severe and sustained PV in vivo and that PAF receptor blockade may be useful in treatment of neonatal disease featuring PAF-mediated PV. PAF receptors may not be involved in PV induced by hypoxia.

Rationing of pediatric intensive care beds occurs when the severity of illness of patients admitted to and discharged from the PICU is inversely proportional to the number of available PICU beds. Bed rationing may also increase the proportion of patients using unique PICU therapies, thereby increasing efficiency. Consecutive PICU admissions (n = 283) were evaluated for three months for descriptive data, daily severity of illness, and daily care modalities. PICU and hospital censuses were also recorded. The mean PICU occupancy was 75% (range 37.5%-100%), the hospital occupancy was 79% (range 60%-96%) and the daily PICU efficiency was 78% (range 50%-100%). The PICU census was greater than 90% on 13% of the study days. Neither PICU nor hospital census was associated with the severity of illness of patients admitted to or discharged from the PICU. Severity of illness for patients admitted when only one bed was available or discharged when there were no available beds was not higher than at other times. Therefore, we did not find evidence of rationing of pediatric intensive care by using quantitative methods. As health care funding becomes more limited, quantitative analyses such as this study differentiating the need for more PICU beds from the need for better PICU bed utilization will be beneficial.