Bivalirudin in pediatric patients maintained on extracorporeal life support.

OBJECTIVE: Anticoagulation with heparin is standard of care for patients maintained on extracorporeal life support. Very limited evidence exists for the use of alternative anticoagulants during extracorporeal life support. Patients with heparin-induced thrombocytopenia, heparin resistance, and evidence of significant thrombosis while on heparin may be candidates for alternative anticoagulation. The objective of this analysis is to present evidence for the use of bivalirudin during extracorporeal life support in pediatric patients. DESIGN: Case series. SETTING: University of California, Davis Medical Center. PATIENTS: Twelve critically ill, pediatric patients receiving bivalirudin for anticoagulation during extracorporeal life support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twelve patients meeting entry criteria received bivalirudin during the study period. The median patient age was 8 days (range, 1 d to 6 yr). Eight patients were neonates. Eight patients were male. Nine patients were supported with venoarterial extracorporeal life support. Median duration of extracorporeal life support was 226 hours (range, 111-913) and median time on bivalirudin was 92 hours (range, 60-230). Bivalirudin bolus doses were administered to select patients without bleeding complications. The maintenance dose that corresponded with initial target activated partial thromboplastin time ranged from 0.045 to 0.48 mg/kg/hr with a median rate of 0.16 mg/kg/hr. The median dose for days 1, 3, and 5 was 0.135, 0.175, and 0.267 mg/kg/hr, respectively. The correlation (r2) between dose adjustment and activated partial thromboplastin time response was 0.264. CONCLUSIONS: This is the largest case series describing the use of a direct thrombin inhibitor in pediatric extracorporeal life support patients. The maintenance dose range reflected considerable inter-patient variability. There was an observed increase in dose requirements with time. Bivalirudin, with close monitoring, is a potential option for pediatric patients on extracorporeal life support who have developed heparin-induced thrombocytopenia, heparin resistance, or significant thrombosis while on heparin.

Caspases inhibition decreases neurological sequelae in meningitis.

OBJECTIVE: To evaluate the effects of sustained caspase inhibition during the acute phase of meningitis-induced brain injury. Changes in neurobehavioral performance were the primary outcome variables. DESIGN: Randomized prospective animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Animals underwent a basilar cistern inoculation of group B Streptococci to induce meningitis. Sixteen hours later animals were randomized to receive Bocaspartyl (OMe)-fluoromethyketone (BAF) for 4 days or placebo in addition to antibiotic therapy. The assessment of neurobehavioral performance was started 7 days after initiation of treatment and continued for the following 3 wks. A subgroup underwent early kill, at 5 days, to evaluate caspase 3 activity in brain tissue. There was a group of Sham instrumented animals. MEASUREMENTS AND MAIN RESULTS: BAF decreased caspase 3 activation in meningitic animals. There were no significant motor deficit differences between the infected groups. Cognitive performance was significantly improved in the BAF group. CONCLUSION: These findings demonstrate that sustained systemic administration of BAF inhibits caspase 3 activation and decreases neurologic sequelae in a rat model of bacterial meningitis.

Right-sided superior vena cava draining into the left atrium: a rare anomaly of systemic venous return.

The most commonly encountered systemic thoracic venous anomaly is a persistent left superior vena cava that drains into the right atrium via the coronary sinus. A much rarer systemic venous anomaly is that of isolated anomalous drainage of a normally positioned right superior vena cava (RSVC) into the left atrium (LA). This has been reported in approximately 20 patients with the diagnosis usually being made by cardiac catheterization. We report the case of a toddler with asymptomatic hypoxemia resulting from anomalous drainage of a normal RSVC into his LA. This was diagnosed non-invasively by contrast-enhanced chest CT.

Clinical trials in pediatric traumatic brain injury: unique challenges and potential responses.

In order to optimize pediatric traumatic brain injury translational and clinical research, scientific and ethical challenges need to be recognized and addressed. Having recently conducted a multisite phase II safety/feasibility trial of magnesium sulfate as a neuroprotective agent, we supplement our own experience by a mini review of similar studies, identifying challenges and possible responses from the perspective of families, investigators, funding agencies and society.

Should age be a deciding factor in ethical decision-making?

The question of age as a factor in ethical decision-making takes two forms. The first form considers age as a factor at the societal, or policy, level, and the second as a factor in determining the capacity of the individual patient to make decisions regarding their own care. This article satisfies itself with a consideration of only the latter question. The issue of whether age is contributing factor in medical decision-making is frequently posited when one considers ethically charged instances of medical decision making at the end of life. Few would argue that the person who has the capacity for decision-making should be denied the ability to exercise that facility and so, it is when a person has lost their ability for making those choices that the question of age as a contributing factor in ethical decision making is raised. The question therefore becomes one of capacity more then age, with age as a useful, but inexact, gauge of that capacity. The inexactitude of age as a surrogate of capacity is a contributing factor to the problem posed in this series of articles. Therefore, to define the relative contribution of age to the capacity for ethical decision-making this article will focus not on the loss of that ability, but rather on the factors that define the realization of that faculty. To do this it will be necessary to define how that faculty is to be to be measured and what are the characteristics of an ethical decision that define it apart from other decisions. Since at the beginning of life, if age is the only variable (adjusting for other co-morbid states) then the issue of surrogacy is a temporary one and is unlike the adult where the presumption is that the person is unlikely to regain decision-making capacity as they slip further into their morbid state.

Nurse staffing and unplanned extubation in the pediatric intensive care unit.

OBJECTIVE: To determine the association between unplanned extubations and years of nurse experience and nurse-to-patient ratio in the pediatric intensive care unit (PICU). DESIGN: Case-control study. SETTING: University-affiliated children's hospital PICU. PATIENTS: Unplanned extubations were identified from January 1999 through December 2002. Three control patients for each of the patients experiencing an unplanned extubation were selected on three matching factors: age, intubation duration, and severity of illness as defined by the Pediatric Risk of Mortality (PRISM) III. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty-five of 1,004 intubated patients (5.5%) experienced an unplanned extubation during the 4-yr period. A conditional logistic regression analysis was used to evaluate the association between a patient's risk of an unplanned extubation and the nurse's years of PICU experience and nurse-to-patient ratio. Factors associated with unplanned extubations included the documentation of patient agitation (odds ratio, 2.99; 95% confidence interval, 1.14, 7.86) and a nurse-to-patient ratio of 1:2 (one nurse caring for two patients) relative to a nurse-to-patient ratio of 1:1 (odds ratio, 4.24; 95% confidence interval, 1.00, 19.10). Years of PICU nursing experience, patient restraints, and the method of sedation delivery (continuous infusion vs. intermittent bolus) were not associated with unplanned extubations. CONCLUSIONS: Pediatric patients are more likely to experience an unplanned extubation when being cared for by a nurse assigned to two patients compared with a nurse caring for one patient. To provide safe patient care, health care policymakers and hospital administrators should consider the nurse-to-patient ratio and its potential association with adverse events in hospitalized children.

Dexamethasone decreases neurological sequelae and caspase activity.

OBJECTIVE: To evaluate the use of dexamethasone in a model of meningitis-induced brain injury. Changes in neurobehavioral performance were the primary outcome variables. Changes in caspase activation and markers of neuronal injury were the secondary outcome variables. DESIGN: Randomized, prospective animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Animals underwent a basilar cistern injection of either placebo or a suspension of Group B Streptococcus. Sixteen hours after inoculation, animals were randomized and received either dexamethasone or placebo in addition to antibiotics. Neurobehavioral performance and biological markers of brain injury were assessed at 3 days and 9 days after randomization. In a second experiment, caspase 1 and 3 were evaluated at 6 h, 24 h, and 72 h after dexamethasone administration. MEASUREMENTS AND MAIN RESULTS: Neurobehavioral performance at 3 days and 9 days was significantly improved in the dexamethasone group. Serum C-tau and cerebral edema were decreased after 3 days of dexamethasone treatment. Dexamethasone decreased Caspase 3 activation in meningitic animals. CONCLUSION: These findings demonstrate that dexamethasone decreases acute brain injury in a rat model of bacterial meningitis as measured by preservation of neurobehavioral performance.

The association of race and ethnicity with rates of drug and alcohol testing among US trauma patients.

BACKGROUND: Racial and ethnic minority patients often receive differential medical care compared to Caucasians. The aim of this study was to evaluate the association of race and ethnicity with rates of alcohol and drug testing among adult US trauma patients. METHODS: Data for 79,246 adults admitted to 58 institutions participating in the US National Trauma Data Bank were evaluated using multivariable, hierarchical, mixed-effects analyses to determine the odds of receiving alcohol and drug testing among different racial/ethnic groups. The primary outcome variable was whether an alcohol or drug test was performed. The secondary outcome variable was the results of those tests. Participants were stratified by injury severity using the Injury Severity Score. Additional case-mix variables included: gender, age, Glasgow Coma Scale, day and time of arrival, and payment source. RESULTS: Black and Hispanic males in all injury severity groups were tested for alcohol more frequently than Caucasian males (odds ratio for Black men 1.31, 95% confidence interval 1.16-1.47; and for Hispanic men 1.45, 95% confidence interval 1.19-1.77, in the moderate injury group). Hispanic males in the moderate injury group were also tested for drugs more frequently then Caucasian males (odds ratio 1.33, 95% confidence interval 1.09-1.63). CONCLUSION: Racial and ethnic minority trauma patients in the US are tested for alcohol and drugs at higher rates after adjusting for potential confounders. Because having a positive alcohol or drug test can adversely affect a patient's medical care, differential testing that is racially or ethnically biased may place minority patients at risk of receiving disparate care.

Caspofungin in a pediatric patient with persistent candidemia.

OBJECTIVE: To describe the response of a child with persistent fungemia to caspofungin, a member of the echinocandin class of antifungals. DESIGN: Descriptive case report. SETTING: Pediatric intensive care unit at a university teaching hospital. PATIENT: A 3-yr-old female with persistent candidemia. INTERVENTION: After >5 wks of persistent candidemia, caspofungin was added to an antifungal regimen that included amphotericin B and flucytosine. MEASUREMENTS AND MAIN RESULTS: The addition of caspofungin resulted in rapid clearance of the candidemia. The child recovered without evidence of further fungal infection or overt toxicity. CONCLUSION: Caspofungin was administered safely in this pediatric patient and possibly contributed to her clinical improvement. Caspofungin may be considered in children with severe persistent fungal infections that are not responsive to standard therapy. More study in pediatric patients is necessary before recommending its general use.

Evaluation of race and ethnicity on alcohol and drug testing of adolescents admitted with trauma.

OBJECTIVES: To describe the incidence of alcohol and drug testing in adolescents admitted for traumatic injury and to analyze these results with reference to race, ethnicity, and gender differences. METHODS: Data were collected on adolescents (aged 12 through 17 years) from the National Trauma Data Bank. Testing statuses for alcohol and drugs were the two primary outcome variables. The results of these tests were the secondary outcome variables. Additional casemix variables included: race, ethnicity, gender, age, Glasgow Coma Scale score, Injury Severity Score, day and time of arrival, and payment source. Hierarchical, multivariable logistic regression models were used to assess the relationship of race, ethnicity, and gender with the primary and secondary outcome variables. RESULTS: Differences noted in the likelihood of alcohol and drug testing among the different racial, ethnic, and gender groups demonstrated an increased likelihood of Hispanic males and African American females to receive alcohol testing (odds ratio [OR]: 1.48; 95% CI = 1.06 to 2.06; and OR: 1.30; 95% CI = 1.01 to 1.67, respectively). Results of testing revealed that females of all races were less likely than males to test positive for alcohol and drugs. Drug and alcohol testing was more common during evenings, nights, and weekends, as well as in the presence of neurologic injury. CONCLUSIONS: Whereas small disparities in alcohol and drug testing were noted in some minority race-based groupings, systematic racial bias is not evident in adolescent trauma patients.

Modulation of nuclear factor-kappaB activation and decreased markers of neurological injury associated with hypothermic therapy in experimental bacterial meningitis.

OBJECTIVE: This study was designed to evaluate the use of moderate hypothermia in a model of meningitis-induced brain injury and its effect on the activation of nuclear factor-kappaB, biological markers of neuronal injury, and neurobehavioral performance. DESIGN: Randomized, prospective animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Animals underwent a basilar cistern tap receiving either sterile saline as a placebo or an equivalent volume of a group B streptococcal suspension. Sixteen hours after inoculation, animals were stratified by their clinical severity score, were randomized to either hypothermic (32-34 degrees C) or normothermic (37-39 degrees C) conditions, and received antibiotics. Hypothermic animals were kept under these temperature conditions for 6 hrs before rewarming. Two protocols were used. For the first protocol, changes in nuclear factor-kappaB activation and heat shock protein induction at 24 hrs and 48 hrs after inoculation were evaluated. In the second protocol, serum C-tau concentrations at 5 days and neurobehavioral performances at 3 wks were assessed. MEASUREMENTS AND MAIN RESULTS: Meningitis triggered a >50% increase in cerebral nuclear factor-kappaB activation. The addition of a 6-hr period of hypothermia reduced nuclear factor-kappaB activation by 32% when measured at the end of the hypothermic period. At 48 hrs, this decrease in nuclear factor-kappaB activation was no longer apparent, but there was a significant decrease in the heat shock response. Serum C-tau concentrations at 5 days postinjury, a biomarker of brain injury, were reduced by 69% in hypothermic treated animals. Furthermore, hypothermia reduced the brain water content of infected animals. However, hypothermia did not improve the animals' neurobehavioral performance. CONCLUSION: The findings from this study suggest that hypothermia produces a transitory attenuation of nuclear factor-kappaB activation in meningitic brain injury and improvement in some biomarkers of neuronal injury. The consequence of intermittent suppression of nuclear factor-kappaB activation by inducing specific periods of hypothermia requires further study.

Death of an adolescent athlete with sickle cell trait caused by exertional heat stroke.

OBJECTIVE: To report a case of fatal rhabdomyolysis secondary to exertional heat stroke and the potential influence of sickle cell trait on the outcome of this case. DESIGN: Descriptive case report. SETTING: Pediatric intensive care unit in an academic children's hospital. MAIN RESULTS: A description of the presentation and clinical course of exertional heatstroke with rhabdomyolysis in an adolescent athlete. The implications of the patient's clinical course and a possible connection to sickle cell trait are also discussed. CONCLUSION: Young athletes with sickle cell trait may be at an increased risk of heat-related illnesses and their complications. Epidemiologic studies are warranted to address this possibility.

Amrinone in pediatric refractory septic shock: An open-label pharmacodynamic study.

OBJECTIVE: To investigate the short-term hemodynamic effects of amrinone in pediatric patients with refractory septic shock. DESIGN: Open-label, clinical trial. SETTING: Pediatric intensive care unit. PATIENTS: Nine patients admitted with a diagnosis of septic shock receiving stable doses of vasopressors and inotropes. INTERVENTIONS: Pediatric patients with septic shock and a pulmonary artery catheter were treated with amrinone in a stepwise fashion at 5, 10, and 15 &mgr;g/kg/min. MEASUREMENTS AND MAIN RESULTS: Heart rate, blood pressure, cardiac index, rate pressure product, systemic vascular resistance index, pulmonary vascular resistance, oxygen delivery, and oxygen consumption were measured at baseline and 90 mins after each amrinone dose. The addition of amrinone increased cardiac index (p <.05) and oxygen delivery (p <.05) without increasing the rate pressure product. Decreases were observed in systemic vascular resistance index (p <.05) and pulmonary vascular resistance (p <.05). No significant changes were seen in heart rate, blood pressure, or oxygen consumption. CONCLUSIONS: In this short-term, dose-response study in children with refractory septic shock, amrinone improved cardiac index and oxygen delivery in pediatric patients with refractory septic shock without increasing myocardial work.