Rapid clearance of a structural isomer of bilirubin during phototherapy.

During phototherapy for neonatal jaundice, bilirubin is converted into a variety of photoproducts. Determination of the relative importance of these photoproducts to the elimination of bilirubin requires knowledge of their rates of excretion. We have measured the rate at which the structural isomer of bilirubin, lumirubin, disappeared from the serum of nine jaundiced premature infants after the cessation of phototherapy. In all patients studied, the decline in serum lumirubin could be approximated by a first-order rate equation with a half-life of 80 to 158 min. This rate of disappearance is much faster than that previously determined for the other major bilirubin photoproducts. In samples of bile aspirated from the duodenum of infants undergoing phototherapy, lumirubin was the principal bilirubin photoproduct found. These results indicate that formation and excretion of lumirubin is an important route for bilirubin elimination during phototherapy.

Bilirubin photoisomerization in premature neonates under low- and high-dose phototherapy.

Photoisomerization of native bilirubin to more polar configurational isomers (Z,E-bilirubin) and structural isomers (lumirubin) was studied in 20 premature infants with physiologic jaundice to determine the effect of low-dose (6 microW/cm2/nm) v high-dose (12 microW/cm2/nm) phototherapy. Patients were assigned prospectively to receive either low- or high-dose treatment. Study groups were comparable with regard to birth weight, gestational age, and total bilirubin prior to the initiation of phototherapy. Treatment was administered with white light produced by a commercially available halogen-tungsten lamp. Dose was measured periodically during the study to ensure a uniform distribution of irradiance and constant exposure. Sera for photoisomers were obtained before initiation of treatment and at two, four, and eight hours. Photoisomers expressed as a percent of total bilirubin were determined using high-pressure liquid chromatography. Serum proportion of both configurational and structural isomers increased with the duration of phototherapy in both treatment groups. There was no significant difference between the percent of configurational isomers in low- and high-dose phototherapy groups. However, high-dose treatment produced a significantly higher proportion of the structural isomer lumirubin after four hours (0.7% low dose v 1.3% high dose, P less than .05). These data confirm that phototherapy results in both configurational and structural isomerization of bilirubin in vivo. Furthermore, the previously described "dose" effect of phototherapy may be attributed to the production of the structural isomer, lumirubin.

Residents on the transport team. Balancing service and education.

OBJECTIVES: To describe an educational program for pediatric house staff who participate in interhospital transport and to present an evaluation of the educational program. DESIGN: Educational program evaluation that used multiple confidential surveys of participating pediatric house staff. SETTING: The interhospital transport team of a large, urban pediatric hospital. PARTICIPANTS: Twenty-six pediatric second-year residents who participated in required rotations with the transport service. INTERVENTION: The institution of an educational program designed specifically for the clinical transport rotation. RESULTS: Before their service with the transport team, residents have doubts about their clinical skills, fund of knowledge, and ability to practice independently in a mobile environment. These doubts decrease as the residents participate in the educational program during their transport clinical service. All residents perceive service on the transport rotation to be of educational benefit with regard to communications or cognitive skills. Alternatively, transport service provides little opportunity for residents to improve technical skills. Among the various skills that residents could obtain during transport service, improvement in clinical judgement was most commonly cited by residents who performed more than 10 transports. Among the specific curricular components in the educational program, interactive teaching methods were judged to be more valuable than written materials. CONCLUSIONS: Serving as a physician on interhospital transports can be an important educational opportunity for pediatric house staff when that experience is concentrated in a designated rotation and combined with a focused educational program. Contrary to expectations, there was little opportunity for residents to develop technical skills on transport. Therefore, educators should focus on the development of communications and cognitive skills. Interhospital transport programs that debate the use of residents as members of the service should consider the potential educational benefit of the clinical service to house staff.

Modern fluid and electrolyte management of the critically ill premature infant.

In this article, the authors introduce the concept of a transitional physiology which governs fluid and electrolyte balance in the immediate postnatal period. The important impact of the extrauterine environment on fluid balance is also discussed. Finally, the pathophysiology of diuresis in RDS, and fluid shifts in the VLBW infant with therapeutic recommendations are presented.

Neuromuscular relaxants in the neonate.

Neuromuscular blockade frequently is employed to facilitate mechanical ventilation and other therapeutic interventions in adults and children. In recent years it has been suggested that the use of neuromuscular blockade in the management of premature infants who are ventilated for respiratory distress will reduce the incidence of barotrauma and intracranial hemorrhage. Subsequently, neuromuscular blocking agents have become some of the most commonly used medications in the intensive care nursery. A discussion of these drugs is included in this article to improve the understanding of their pharmacology, the indications and consequence of their use, and their potential side effects. Additionally, the recent introduction of new, shorter-acting agents warrants a review of current practice.

Controversies in fluid and electrolyte therapy for the premature infant.

This article reviews the concept of maintenance therapy and describes the pertinent physiologic changes associated with premature infants transition to extra-uterine life. These discussions provide the background for the major controversies surrounding this therapy.

Water and electrolyte metabolism of the micropremie.

There are five problem schemas presented in this article that indicate potential contradictions in therapeutic goals: (1) shock and edema presenting upon premature birth; (2) the hyperosmolar state, problematic in patients less than 750 g birth weight; (3) the respiratory distress syndrome and respiratory failure, often complicated by patent ductus arteriosus; (4) bronchopulmonary dysplasia, resulting from prematurity and mechanical ventilation; and (5) late onset of hyponatremia, sometimes accompanied by growth failure in the recovering premature. These five problems considered together comprise a developmental continuum of illness and recovery, where appropriate fluid management has recently been demonstrated to benefit outcomes greatly. Clinicians over the past decade have encountered all of the fluid and electrolyte nightmares. Although there are many different formulations for treating each of these scenarios, recommending one approach for all patients is likely to be incorrect much of the time.

Recognition and management of the ill child.

Children account for 30% of visits to emergency departments, and approximately 5% of these children have serious illness requiring immediate intervention. Over the past decades, as medical knowledge and application have eradicated many illness and rendered others curable, trauma has emerged as the leading cause of morbidity and mortality after the first year of life. However, all children remain vulnerable to infection and its consequences in the first year and beyond the first year. Additionally, over this time span, there are more children with chronic complicated health problems who survive yet remain dependent on sophisticated medical care. Intuitively, prompt recognition of the very ill child and the execution of the immediate and necessary interventions may be life saving. The ability to accomplish this requires a knowledge of the common culprits resulting in serious illness, an understanding of how they manifest in the physical examination, and an array of technical skills utilizing appropriate specially sized equipment. Furthermore, an understanding of child development and the ability to interpret the physical examination of the children of different ages is essential. This article will attempt to simplify this seemingly overwhelming task by considering a common thread in all critical illness.

The potential benefits of the pediatric nonheartbeating organ donor.

OBJECTIVE: To examine the population of the pediatric intensive care unit in a large children's hospital to determine the potential importance of pediatric nonheartbeating organ donors (NHBDs). STUDY DESIGN: We analyzed retrospectively the 6307 admissions to the pediatric intensive care unit at the Children's Hospital of Philadelphia from January 1992 to July 1996 to identify all deaths. The hospital records of the children who had died were then reviewed to determine the mode of death, organ donation rate of heartbeating donors, and the number of potential NHBDs. Criteria for the NHBD included the decision to forgo life-sustaining therapy, death occurring within 2 hours of withdrawal of life support, and the absence of sepsis, HIV, hepatitis, or extracranial malignancy. RESULTS: Of 319 deaths, 102 (32.0%) died with resuscitation, 84 (26.3%) were brain-dead, 111 (34.8%) had withdrawal of life support, and 22 (6.9%) were on do-not-resuscitate orders. Of the 84 brain-dead children, 74 (88.1%) were medically suitable heartbeating donors, and 43 (58.1%) donated organs. Of the 111 patients who had life support withdrawn, 31 (27.9%) qualified for NHBDs. CONCLUSIONS: The routine use of the NHBD has the potential to increase organ donation at our institution by 42%. We discuss the ethical issues relating to NHBDs required to properly include these patients as potential organ donors.

Nasal mask positive pressure ventilation in paediatric patients with type II respiratory failure.

We report our experience with nasal mask ventilation in children and adolescents with type II respiratory failure admitted to the paediatric intensive care unit (PICU) over an 18-month period. Seven patients were treated with nasal mask ventilation during part of their PICU stay. All showed significant improvement in arterial pH, PaCO2, and PaO2/FiO2 from presentation to discharge, although at discharge PaCO2 and PaO2/FiO2 fell outside of the normal range. Complications occurred in four patients. When compared to 11 patients with type II respiratory failure not treated with nasal mask ventilation, the nasal mask ventilation group had a similar PICU length of stay and incidence of complications. We conclude that nasal mask ventilation may be useful in maintaining near normal alveolar ventilation in selected children with type II respiratory failure and that a prospective study of this technique is indicated.

Adult respiratory distress syndrome in children: associated disease, clinical course, and predictors of death.

The adult respiratory distress syndrome is a common cause of respiratory failure; however, its incidence, risk factors, course, and mortality rate for children remain incompletely understood. A 24-month surveillance of pediatric intensive care admissions identified 60 children with adult respiratory distress syndrome constituting 2.7% of such admissions, 8% of total days spent in a pediatric intensive care unit, and 33% of deaths. The mortality rate was 62% (confidence interval, 48.2% to 73.9%). Adult respiratory distress syndrome occurred in approximately 12% of children admitted for sepsis, viral pneumonia, smoke inhalation, or drowning. A low incidence (< 3%) was observed in children admitted with pulmonary contusion or multiple trauma. Ongoing changes in measures of pulmonary gas exchange varied with the magnitude of alveolar injury; no differences were associated with the underlying acute disease or lung injury mechanism. Efficiency of oxygenation differed among outcome groups by the second day after onset of adult respiratory distress syndrome. An alveolar-arterial oxygen tension difference > 420 was the best early predictor of death (sensitivity 80%, specificity 87%, positive predictive value 87%, negative predictive value 80%, and odds ratio 26.7). We conclude that adult respiratory distress syndrome behaves clinically as a single disease regardless of the underlying cause; its course and outcome are dependent on the magnitude of alveolar injury. We speculate that strategies for minimizing secondary lung injury may benefit all patients with adult respiratory distress syndrome.

The impact of adverse patient occurrences on hospital costs in the pediatric intensive care unit.

OBJECTIVES: To study the influence of adverse patient occurrences defined as airway complication (AC), vascular complication (VC), and infectious complication (IC) on intensive care unit (ICU) costs and length of stay (LOS). DESIGN: Retrospective, cohort study SETTING: An urban, tertiary care children's hospital in Philadelphia, PA. PATIENTS: All children admitted to a multidisciplinary pediatric ICU during the fiscal year 1994. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Demographic data, diagnoses, Pediatric Risk of Mortality scores, LOS, and deaths were recorded. Hospital charges were converted into costs by using cost-to-charge ratios. There were 23 AC, 35 VC, and 40 IC events. Multiple regression in models adjusting for age, Pediatric Risk of Mortality score, mortality, chronic disease, and diagnosis by using AC, VC, and IC indicator variables was performed on the dependent variables of LOS and total costs. IC was associated with an increase in total costs of $50,361.89 (p < .001), an increased LOS of 15.6 days (p < .001), and no significant increase in daily costs. There were no significant increases in costs or LOS seen with the AC and VC variables. In a matched analysis, the total costs attributable to IC averaged $32,040 per patient. CONCLUSIONS: The occurrence of complications in the pediatric ICU is associated with meaningful increases in LOS and hospital costs. ICs are more important predictors of costs than ACs or VCs. Continuing efforts should be made to minimize adverse occurrences to improve patient care and reduce costs.

Hospital costs of pediatric intensive care.

OBJECTIVE: To characterize hospital costs of pediatric intensive care and to determine which demographic and disease characteristics are associated with cost. DESIGN: Prospective cohort study. SETTING: A 20-bed pediatric intensive care unit (PICU) in an urban university-affiliated teaching children's hospital. PATIENTS: All children (n = 1,376) admitted to the multidisciplinary PICU during the fiscal year 1994. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics, diagnoses, organ failure, Pediatric Risk of Mortality score, length of stay (LOS), and outcome were recorded. All hospital charges were obtained. The actual hospital costs were calculated by two separate methods. First, we converted the itemized patient charges into costs, using corresponding cost-to-charge ratios for each charge. In addition, we examined all direct and indirect expenses for the PICU. Univariate and multivariate regression analyses were used to determine the correlates to cost. The study population was similar to that of other studies of pediatric intensive care. The PICU was 86% efficient. The total cost for PICU care was $16,983,323. Average cost per admission was $12,342 +/- $22,313, and average cost per patient day was $2,264 +/- $868. The cost because of the PICU location (room cost) was 52.1% of all costs, and cost of laboratory studies was 18.3%. Respiratory therapy, pharmacy services, and radiology each accounted for between 6% and 8%. Total cost was most closely related to LOS, but severity of illness (Pediatric Risk of Mortality), diagnosis, and organ failure were also significant. Severity of illness was the most important factor in determining the variation in daily costs. Increased severity of illness was associated with higher laboratory and diagnostic study costs. We found little difference in the PICU room cost when calculated by adding direct and indirect expenses, compared with that obtained by using the cost-to-charge ratio. CONCLUSIONS: The maintenance of the specialty location and its personnel is the most costly component of pediatric intensive care. The strongest correlate with total cost for pediatric intensive care is LOS, but if costs are normalized for LOS, severity of illness best explains cost variation among patients. These data may serve as the basis for additional studies of resource allocation and consumption in the future.

Renal adaptation to extrauterine life in patients with respiratory distress syndrome.

A spontaneous diuresis that precedes the improvement of pulmonary function has been described in patients with respiratory distress syndrome (RDS). The developmental changes in renal physiology responsible for this spontaneous diuresis are not completely understood. To describe the mechanisms responsible for the spontaneous diuresis, serial renal function studies were performed during the first five days of life in nine premature neonates with RDS. Diuresis was defined as a urine output that was at least 80% of fluid intake; prediuretic, diuretic, and postdiuretic periods were observed in all study infants. Oxygenation did not improve until the postdiuretic period. Renal function studies disclosed a significant increase in free water clearance during the diuresis with the production of dilute urine and a reciprocal rise in serum sodium concentration and plasma osmolality. The glomerular filtration rate increased at the onset of diuresis and remained elevated after the diuresis ended; however, the proportion of filtrate excreted was significantly elevated during the diuresis compared with prediuretic and postdiuretic values. These data suggest that the diuresis in patients with RDS is a water diuresis secondary to an endogenous water load.

Effect of spectral distribution on isomerization of bilirubin in vivo.

The purpose of our study was to compare the effects of narrow-spectrum blue light and broad-spectrum white light on the production of bilirubin photo-isomers in human infants with jaundice. Twelve preterm infants were studied under both white and blue light. Irradiance at 450 nm was controlled at 12 microW/cm2/nm for both light sources. Each light condition (white or blue) was administered for 12 hours. Bilirubin isomers (4Z,15E-bilirubin and lumirubin) were measured before therapy and after 12 hours of each sequential light condition. The percentage of 4Z,15E-bilirubin was greater under blue light than under white light (P less than 0.01) phototherapy. There was no significant difference in percentage lumirubin under white or blue light therapy. Our data indicate that blue light is more effective than white light in producing 4Z,15E-bilirubin in vivo. Our study demonstrates that when irradiance in the bilirubin absorbance spectrum is constant, the color of light (spectral distribution) will determine the relative concentrations of photo-isomers produced.

Routine use of fentanyl infusions for pain and stress reduction in infants with respiratory distress syndrome.

OBJECTIVE: To determine whether fentanyl infusions given to premature infants with respiratory distress syndrome reduce stress and improve long- and short-term outcome. METHODS: Twenty premature infants undergoing mechanical ventilation for respiratory distress syndrome were randomly assigned, in a double-blind fashion, to receive fentanyl by continuous infusion or a volume-matched placebo infusion. A behavioral state score was used to assess the infants' behavior. Cortisol and 11-deoxycortisol levels were measured as physiologic markers of stress. Urinary 3-methyl histidine/creatinine molar ratio was determined and the fractional excretion of urea was measured to assess catabolic state. Ventilatory indexes were recorded for each infant. RESULTS: Infants receiving fentanyl showed significantly lower behavioral state scores (p < 0.04) and lower heart rates (p < 0.001) than those receiving placebo. 11-Deoxycortisol levels were lower in the fentanyl group on days 3, 4, and 5 of the study (p < 0.003). 3-Methyl histidine/creatinine ratios and fractional excretion of urea were not significantly different between the two groups. On the third day of the study, infants receiving fentanyl required a higher ventilator rate (p < 0.01), higher peak inspiratory pressures (p < 0.001), and higher positive end-expiratory pressure (p < 0.0001) than those receiving placebo. There was no difference in long-term outcome with respect to the incidence of bronchopulmonary dysplasia, intraventricular hemorrhage, or sepsis or with respect to the duration of ventilator use. CONCLUSIONS: Although there was a reduction in stress markers in the infants receiving fentanyl, we were unable to demonstrate an improvement in catabolic state or long-term outcome. In addition, the infants receiving fentanyl required higher ventilatory support in the early phase of respiratory distress syndrome than did those receiving placebo.

Randomized trial of prophylactic phototherapy in the infant with very low birth weight.

Twenty-two preterm infants (birth weight 850 +/- 220 gm) were randomly assigned to receive phototherapy either soon after birth or after the serum bilirubin concentration reached 5 mg/dl. Infants receiving prophylactic phototherapy were placed under lights at a significantly earlier age and lower serum bilirubin concentration than infants in the routine group (P less than 0.001). There was no significant difference between groups in peak serum bilirubin concentration, age at which it peaked, rate of rise in serum bilirubin concentration, or serum bilirubin concentration at any time during the study. Infants assigned to the prophylactic phototherapy group were under lights for a significantly longer time than those in the routine group (P less than 0.05). There was a significant rise in both configurational and structural photo-isomers (P less than 0.005) independent of serum bilirubin concentration after phototherapy in all patients. These data suggest that the clinical course of hyperbilirubinemia is not altered in infants with very low birth weight receiving prophylactic phototherapy compared with infants with phototherapy begun at a bilirubin concentration of 5 mg/dl.

Toxic shock syndrome with Staphylococcus aureus exit-site infection in a patient on peritoneal dialysis.

Toxic shock syndrome (TSS) associated with exit-site infection but without peritonitis has not been described. We report a case of TSS with an isolated Staphylococcus aureus exit-site infection in a boy on chronic peritoneal dialysis. The exit site had minimal erythema and no purulence. This report re-emphasizes the fact that mildly appearing cutaneous infections in patients with chronic renal failure may have significant consequences. Particular attention should be given to patients who present with constitutional symptoms that may be of short duration. The importance of culturing all sites in such cases is highlighted. The prevalence of TSS with exit-site infections is unknown, but TSS should be considered in patients presenting with similar features.

Neonatal Staphylococcus epidermidis meningitis with unremarkable CSF examination results.

We identified 10 infants (mean +/- SD birth weight, 1000 +/- 500 g; gestation, 29 +/- 3 weeks; postnatal age, 24 +/- 19 days) who had Staphylococcus epidermidis meningitis despite unremarkable cerebrospinal fluid (CSF) blood cell counts and glucose and protein levels. Staphylococcus epidermidis meningitis was diagnosed if all the following criteria were satisfied: (1) a CSF culture positive for S epidermidis within 48 hours, (2) a blood culture positive for S epidermidis with antibiotic sensitivities identical to those of the CSF isolate, and (3) clinical symptomatology. Lumbar puncture yielded white blood cell counts lower than 10 x 10(6)/L in 8 infants. Two subjects had CSF white blood cell counts of 11 x 10(6)/L and 14 x 10(6)/L. Cerebrospinal fluid glucose (2.8 +/- 0.9 mmol/L) and protein (1.15 +/- 0.32 g/L) concentrations were also unremarkable. Infants were treated with parenteral antibiotics for 19 +/- 5 days. There was no mortality or short-term morbidity. Staphylococcus epidermidis is a recognized cause of nosocomial meningitis in low-birth-weight infants and frequently occurs without CSF abnormalities.

Nonoliguric hyperkalemia in the premature infant weighing less than 1000 grams.

Eighteen very low birth weight premature infants born before 28 weeks gestation and weighing less than 1000 gm were evaluated prospectively for disturbances in serum electrolyte concentrations and for renal glomerular and tubular functions. Clinically symptomatic hyperkalemia resulting in significant electrocardiographic dysrhythmias developed in eight of these infants; 10 babies remained normokalemic. Peak serum potassium concentration ranged from 6.9 to 9.2 mEq/L in the hyperkalemic group; all potassium values in the normokalemic group were less than 6.6 mEq/L. Indices of renal glomerular function and urine output were similar in both groups; no infant had oliguria. Serum creatinine concentrations were the same in both groups (1.04 +/- 0.16 SD mg/dl in normokalemic vs 1.19 +/- 0.24 mg/dl in hyperkalemic infants, beta less than 0.2 at alpha = 0.05), and glomerular filtration rates did not differ significantly (6.29 +/- 1.78 ml/min/1.73 m2 in normokalemic vs 5.70 +/- 1.94 ml/min/1.73 m2 in hyperkalemic infants, beta less than 0.2 at alpha = 0.05). In contrast, indicators of tubular function revealed a significantly larger fractional excretion of sodium in hyperkalemic infants: 13.9 +/- 5.4% versus 5.6 +/- 0.9% in normokalemic control subjects (p less than 0.001). Hyperkalemic infants also had a tendency toward lower urine concentrations of potassium, although there was no significant difference in their net potassium excretion in comparison with that in the normokalemic group. We speculate that hyperkalemia in the tiny baby is in part the result of immature distal tubule function with a compromise in ability to regulate potassium balance.