Interhospital Transfer of Children in Septic Shock: A Clinician Interview Qualitative Study.

OBJECTIVE:: To determine the factors that influence the decision to transfer children in septic shock from level II to level I pediatric intensive care unit (PICU) care. DESIGN:: Interviews with level II PICU physicians in Michigan and Northwest Ohio. A hypothetical scenario of a 14-year-old boy in septic shock was presented. BASELINE:: 40 mL/kg fluid resuscitation, central venous and peripheral arterial access, and high-dose vasopressor infusions were provided. ESCALATION POINT:: After 2 hours. When the patient is in catecholamine-resistant shock and oliguric, invasive mechanical ventilation is initiated. MEASUREMENTS AND MAIN RESULTS:: All 19 eligible physicians participated. At baseline, respondents would assess measures of perfusion and hemodynamics: blood pressure (BP; 15 [79%]), lactate (12 [63%]), and central venous oxygen saturation (ScvO2; 10 [53%]). Poor clinical response was signified by low BP (11 [58%]), elevated lactate (9 [47%]), low urine output (8 [42%]), and low ScvO2 (6 [32%]). At the escalation point, 13 of 18 respondents felt there was <50% probability of clinical turnaround without escalating treatment, though only 3 (16%) would call to discuss transfer. Seven (37%) respondents would give more fluid, whereas 8 (42%) would use central venous pressure to guide fluid resuscitation. Ultimately, 15 (79%) respondents would transfer for extracorporeal membrane oxygenation (ECMO) or renal replacement therapy if there was no response to escalated care. Four (21%) respondents would not transfer the patient: 1 felt appropriate care could be provided in the level II PICU, 2 felt transfer was unconventional, and 1 was unaware ECMO could be provided in refractory septic shock. CONCLUSIONS:: Level II to level I PICU transfer of children with septic shock is triggered by perceived nonresponse to locally available therapies. Few referring physicians do not transfer children in refractory septic shock. This study provides new insight into decision-making that influences the interhospital transfer of children with septic shock.

Interhospital transfer of children in respiratory failure: a clinician interview qualitative study.

PURPOSE: To investigate the decision making underlying transfer of children with respiratory failure from level II to level I pediatric intensive care unit care. METHODS: Interviews with 19 eligible level II pediatric intensive care unit physicians about a hypothetical scenario of a 2-year-old girl in respiratory failure: RESULTS: At baseline, indices critical to management were as follows: OI (53%), partial pressure of oxygen in arterial blood (Pao2)/Fio2 (32%), and inflation pressure (16%). Poor clinical response was signified by high OI, inflation pressure, and Fio2, and low Pao2/Fio2. At EP 1, 18 of 19 respondents would initiate high-frequency oscillatory ventilation, and 1 would transfer. At EP 2, 15 of 18 respondents would maintain high-frequency oscillatory ventilation, 9 of them calling to discuss transfer. All respondents would transfer if escalated therapies failed to reverse the patient's clinical deterioration. CONCLUSION: Interhospital transfer of children in respiratory failure is triggered by poor response to escalation of locally available care modalities. This finding provides new insight into decision making underlying interhospital transfer of children with respiratory failure.

Therapeutic plasma exchange may improve hemodynamics and organ failure among children with sepsis-induced multiple organ dysfunction syndrome receiving extracorporeal life support.

OBJECTIVE: To determine the effect of therapeutic plasma exchange on hemodynamics, organ failure, and survival in children with multiple organ dysfunction syndrome due to sepsis requiring extracorporeal life support. DESIGN: A retrospective analysis. SETTING: A PICU in an academic children's hospital. PATIENTS: Fourteen consecutive children with sepsis and multiple organ dysfunction syndrome who received therapeutic plasma exchange while on extracorporeal life support from 2005 to 2013. INTERVENTIONS: Median of three cycles of therapeutic plasma exchange with median of 1.0 times the estimated plasma volume per exchange. MEASUREMENTS AND MAIN RESULTS: Organ Failure Index and Vasoactive-Inotropic Score were measured before and after therapeutic plasma exchange use. PICU survival in our cohort was 71.4%. Organ Failure Index decreased in patients following therapeutic plasma exchange (mean ± SD: pre, 4.1 ± 0.7 vs post, 2.9 ± 0.9; p = 0.0004). Patients showed improved Vasoactive-Inotropic Score following therapeutic plasma exchange (median [25th-75th]: pre, 24.5 [13.0-69.8] vs post, 5.0 [1.5-7.0]; p = 0.0002). Among all patients, the change in Organ Failure Index was greater for early therapeutic plasma exchange use than late use (early, -1.7 ± 1.2 vs late, -0.9 ± 0.6; p = 0.14), similar to the change in Vasoactive-Inotropic Score (early, -67.5 [28.0-171.2] vs late, -12.0 [7.2-18.5]; p = 0.02). Among survivors, the change in Organ Failure Index was greater among early therapeutic plasma exchange use than late use (early, -2.3 ± 1.0 vs late, -0.8 ± 0.8; p = 0.03), as was the change in Vasoactive-Inotropic Score (early, -42.0 [16.0-76.3] vs late, -12.0 [5.3-29.0]; p = 0.17). The mean duration of extracorporeal life support after therapeutic plasma exchange according to timing of therapeutic plasma exchange was not statistically different among all patients or among survivors. CONCLUSIONS: The use of therapeutic plasma exchange in children on extracorporeal life support with sepsis-induced multiple organ dysfunction syndrome is associated with organ failure recovery and improved hemodynamic status. Initiating therapeutic plasma exchange early in the hospital course was associated with greater improvement in organ dysfunction and decreased requirement for vasoactive and/or inotropic agents.

Intracranial pressure/cerebral perfusion pressure-targeted management of life-threatening intracranial hypertension complicating diabetic ketoacidosis-associated cerebral edema: a case report.

Symptomatic cerebral edema from diabetic ketoacidosis occurs infrequently but carries a high rate of mortality and morbidity owing to complications from intracranial hypertension. Treatment options are limited but include hyperosmolar therapy with mannitol or hypertonic saline, tracheal intubation for airway protection, and hyperventilation via mechanical ventilation. We describe here the successful use of an intracranial pressure/cerebral perfusion pressure-targeted management strategy through ventriculostomy catheter placement with intracranial pressure monitoring and cerebrospinal fluid drainage, hyperosmolar therapy with hypertonic saline, and controlled hyperventilation to treat life-threatening complications of cerebral edema in a pediatric patient with severe diabetic ketoacidosis.

Fluid overload and fluid removal in pediatric patients on extracorporeal membrane oxygenation requiring continuous renal replacement therapy.

OBJECTIVE: In pediatric patients, fluid overload at continuous renal replacement therapy initiation is associated with increased mortality. The aim of this study was to characterize the association between fluid overload at continuous renal replacement therapy initiation, fluid removal during continuous renal replacement therapy, the kinetics of fluid removal and mortality in a large pediatric population receiving continuous renal replacement therapy while on extracorporeal membrane oxygenation. DESIGN: Retrospective chart review. SETTING: Tertiary children's hospital. PATIENTS: Extracorporeal membrane oxygenation patients requiring continuous renal replacement therapy from July 2006 to September 2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall intensive care unit survival was 34% for 53 patients that were initiated on continuous renal replacement therapy while on extracorporeal membrane oxygenation during the study period. Median fluid overload at continuous renal replacement therapy initiation was significantly lower in survivors compared to nonsurvivors (24.5% vs. 38%, p = .006). Median fluid overload at continuous renal replacement therapy discontinuation was significantly lower in survivors compared to nonsurvivors (7.1% vs. 17.5%, p = .035). After adjusting for percent fluid overload at continuous renal replacement therapy initiation, age, and severity of illness, the change in fluid overload at continuous renal replacement therapy discontinuation was not significantly associated with mortality (p = .212). Models investigating the rates of fluid removal in different periods, age, severity of illness, and fluid overload at continuous renal replacement therapy initiation found that fluid overload at continuous renal replacement therapy initiation was the most consistent predictor of survival. CONCLUSIONS: Our data demonstrate an association between fluid overload at continuous renal replacement therapy initiation and mortality in pediatric patients receiving extracorporeal membrane oxygenation. The degree of fluid overload at continuous renal replacement therapy discontinuation is also associated with mortality, but appears to reflect the effect of fluid overload at initiation. Furthermore, correction of fluid overload to ≤ 10% was not associated with improved survival. These results suggest that intervening prior to the development of significant fluid overload may be more clinically effective than attempting fluid removal after significant fluid overload has developed. Our findings suggest a role for earlier initiation of continuous renal replacement therapy in this population, and warrant further clinical studies.

Implications of different fluid overload definitions in pediatric stem cell transplant patients requiring continuous renal replacement therapy.

PURPOSE: In critically ill pediatric patients, fluid overload (FO) >10% has been identified as a threshold for possible interventions, including initiation of continuous renal replacement therapy (CRRT). However, multiple definitions have been reported, and there remains no consensus method for FO calculation. The goal of this study was to compare different methods of FO determination and to assess their relative value in predicting outcomes. METHODS: This is a retrospective single-center review of 21 pediatric stem cell transplant patients (PSCT) that required CRRT from 2004 to 2009. We compared eight definitions (4 weight-based and 4 fluid-balance based) that varied by baseline weights. Outcome measures were pediatric intensive care unit (PICU) mortality and pediatric logistic organ dysfunction (PELOD) scores. RESULTS: The number of patients identified as having >10% FO varied significantly according to the definition used, from 14 to 48% (p = 0.002). Significant intra-subject variability was observed; the median difference between individual minimum and maximum %FO scores was 11.4% (IQR 6.8, 17.1%). %FO was not significantly associated with PICU mortality, but five of eight FO definitions were predictive of higher subsequent PELOD scores. CONCLUSION: Our study is one of the first to compare different FO definitions and the impact on predicting outcomes. Our findings suggest that depending on the FO definition used, there is significant variability in the calculated %FO in PSCT patients, and this has important implications for clinical decision-making. Further studies are necessary to determine an optimal FO definition that is clinically relevant and predictive of important outcomes.

Donation after cardiocirculatory death: a call for a moratorium pending full public disclosure and fully informed consent.

Many believe that the ethical problems of donation after cardiocirculatory death (DCD) have been "worked out" and that it is unclear why DCD should be resisted. In this paper we will argue that DCD donors may not yet be dead, and therefore that organ donation during DCD may violate the dead donor rule. We first present a description of the process of DCD and the standard ethical rationale for the practice. We then present our concerns with DCD, including the following: irreversibility of absent circulation has not occurred and the many attempts to claim it has have all failed; conflicts of interest at all steps in the DCD process, including the decision to withdraw life support before DCD, are simply unavoidable; potentially harmful premortem interventions to preserve organ utility are not justifiable, even with the help of the principle of double effect; claims that DCD conforms with the intent of the law and current accepted medical standards are misleading and inaccurate; and consensus statements by respected medical groups do not change these arguments due to their low quality including being plagued by conflict of interest. Moreover, some arguments in favor of DCD, while likely true, are "straw-man arguments," such as the great benefit of organ donation. The truth is that honesty and trustworthiness require that we face these problems instead of avoiding them. We believe that DCD is not ethically allowable because it abandons the dead donor rule, has unavoidable conflicts of interests, and implements premortem interventions which can hasten death. These important points have not been, but need to be fully disclosed to the public and incorporated into fully informed consent. These are tall orders, and require open public debate. Until this debate occurs, we call for a moratorium on the practice of DCD.

Weight-based determination of fluid overload status and mortality in pediatric intensive care unit patients requiring continuous renal replacement therapy.

PURPOSE: In pediatric intensive care unit (PICU) patients, fluid overload (FO) at initiation of continuous renal replacement therapy (CRRT) has been reported to be an independent risk factor for mortality. Previous studies have calculated FO based on daily fluid balance during ICU admission, which is labor intensive and error prone. We hypothesized that a weight-based definition of FO at CRRT initiation would correlate with the fluid balance method and prove predictive of outcome. METHODS: This is a retrospective single-center review of PICU patients requiring CRRT from July 2006 through February 2010 (n = 113). We compared the degree of FO at CRRT initiation using the standard fluid balance method versus methods based on patient weight changes assessed by both univariate and multivariate analyses. RESULTS: The degree of fluid overload at CRRT initiation was significantly greater in nonsurvivors, irrespective of which method was used. The univariate odds ratio for PICU mortality per 1% increase in FO was 1.056 [95% confidence interval (CI) 1.025, 1.087] by the fluid balance method, 1.044 (95% CI 1.019, 1.069) by the weight-based method using PICU admission weight, and 1.045 (95% CI 1.022, 1.07) by the weight-based method using hospital admission weight. On multivariate analyses, all three methods approached significance in predicting PICU survival. CONCLUSIONS: Our findings suggest that weight-based definitions of FO are useful in defining FO at CRRT initiation and are associated with increased mortality in a broad PICU patient population. This study provides evidence for a more practical weight-based definition of FO that can be used at the bedside.

Predictors of depressive symptoms in parents of chronically ill children admitted to the pediatric intensive care unit.

OBJECTIVE: To identify factors in the pediatric intensive care unit (PICU) patient population that may result in increased risk of depressive symptoms in their parents. DESIGN: Six-month, prospective, observational study in a tertiary-level PICU on parents of chronically ill children admitted to PICU. Parents were assessed by background questionnaire and standardized depression scale. RESULTS: Data was compared to various markers such as child's diagnosis, admission reason, palliative care diagnosis type (ACT code), and course/length of disease. Incidence of depressive symptoms in parents was inversely correlated with duration of child's chronic illness. Parents of children admitted for planned postoperative management were more likely to report depressive symptoms compared to parents of children admitted for acute changes in health. CONCLUSION: Parents of certain chronically ill children may benefit from routine screening for depression.

Plasma exchange therapy for thrombotic microangiopathies.

Thrombotic microangiopathies (TMAs) are syndromes associated with thrombocytopenia and multiple organ failure. Plasma exchange is a proven therapy for primary TMA such as thrombotic thrombocytopenic purpura (TTP). There is growing evidence that plasma exchange therapy might also facilitate resolution of organ dysfunction and improve outcomes for secondary TMAs such as disseminated intravascular coagulation (DIC) and systemic inflammation-induced TTP. In this review, we survey the current available evidence and practice of plasma exchange therapy for TMAs.

A normal capillary refill time of ≤ 2 seconds is associated with superior vena cava oxygen saturations of ≥ 70%.

OBJECTIVE: To test the hypothesis that a normal capillary refill time (CRT) ≤ 2 seconds is associated with superior vena cava oxygen saturation (ScvO2) ≥ 70% in critically ill children. STUDY DESIGN: Two-year, prospective study in a tertiary-level pediatric intensive care unit. Whenever ScvO2 measurements were obtained, central (forehead/sternum) and peripheral (finger/toe) CRTs were concomitantly assessed. RESULTS: Central and peripheral CRTs ≤ 2 seconds were both associated with ScvO2 ≥ 70% (P < .01). Sensitivity/specificity analyses revealed that central CRT ≤ 2 seconds demonstrated a sensitivity of 84.4%, specificity of 71.4%, positive predictive value of 93.1%, and negative predictive value of 50.0% in predicting ScvO2 ≥ 70%. Peripheral CRT ≤ 2 seconds had a sensitivity of 71.9%, specificity of 85.7%, positive predictive value of 95.8%, and negative predictive value of 40.0% in predicting ScvO2 ≥ 70%. CONCLUSIONS: A normal CRT ≤ 2 seconds can be predictive of ScvO2 ≥ 70%. Our study corroborates the recommendations of the Pediatric Advanced Life Support curricula targeting a normal CRT ≤ 2 seconds as a therapeutic endpoint for goal-directed shock resuscitation. This clinical target remains particularly relevant in community hospitals when the ability to obtain central venous catheter access may be limited and ScvO2 data unavailable.

Mortality and functional morbidity after use of PALS/APLS by community physicians.

OBJECTIVES: To test the hypothesis that pediatric shock is a common cause of death and functional morbidity and that pediatric advanced life support (PALS)/advanced pediatric life support (APLS) resuscitation in the community hospital setting improves child health outcomes. METHODS: This study included all children consecutively transported to 5 regional, tertiary care children's hospitals over 4 years, and is a prospective cohort study comparing outcomes in children who did or did not receive PALS/APLS resuscitation in the community hospital. RESULTS: Shock occurred in 37% of the patients transferred to the tertiary centers. Regardless of trauma status, children with shock had an increased mortality rate compared with those without shock (all patients: 11.4% vs 2.6%), trauma patients (28.3% vs 1.2%), and nontrauma patients (10.5% vs 2.8%). Early shock reversal was associated with reduced mortality (5.06% vs 16.37%) and functional morbidity (1.56% vs 4.11%) rates. Early use of PALS/APLS-recommended interventions was associated with reduced mortality (8.69% vs 15.01%) and functional morbidity (1.24% vs 4.23%) rates. After controlling for center, severity of illness, and trauma status, early reversal of shock and use of PALS/APLS-recommended interventions remained associated with reduced morbidity and mortality rates. CONCLUSIONS: Shock is common in children who are transferred for tertiary care. Pediatric shock recognition and resuscitation in the community hospital improves survival and functional outcome regardless of diagnostic category. The development of shock/trauma systems for children with and without trauma seems prudent.

Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine.

BACKGROUND: The Institute of Medicine calls for the use of clinical guidelines and practice parameters to promote "best practices" and to improve patient outcomes. OBJECTIVE: 2007 update of the 2002 American College of Critical Care Medicine Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock. PARTICIPANTS: Society of Critical Care Medicine members with special interest in neonatal and pediatric septic shock were identified from general solicitation at the Society of Critical Care Medicine Educational and Scientific Symposia (2001-2006). METHODS: The Pubmed/MEDLINE literature database (1966-2006) was searched using the keywords and phrases: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation (ECMO), and American College of Critical Care Medicine guidelines. Best practice centers that reported best outcomes were identified and their practices examined as models of care. Using a modified Delphi method, 30 experts graded new literature. Over 30 additional experts then reviewed the updated recommendations. The document was subsequently modified until there was greater than 90% expert consensus. RESULTS: The 2002 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and AHA sanctioned recommendations. Centers that implemented the 2002 guidelines reported best practice outcomes (hospital mortality 1%-3% in previously healthy, and 7%-10% in chronically ill children). Early use of 2002 guidelines was associated with improved outcome in the community hospital emergency department (number needed to treat = 3.3) and tertiary pediatric intensive care setting (number needed to treat = 3.6); every hour that went by without guideline adherence was associated with a 1.4-fold increased mortality risk. The updated 2007 guidelines continue to recognize an increased likelihood that children with septic shock, compared with adults, require 1) proportionally larger quantities of fluid, 2) inotrope and vasodilator therapies, 3) hydrocortisone for absolute adrenal insufficiency, and 4) ECMO for refractory shock. The major new recommendation in the 2007 update is earlier use of inotrope support through peripheral access until central access is attained. CONCLUSION: The 2007 update continues to emphasize early use of age-specific therapies to attain time-sensitive goals, specifically recommending 1) first hour fluid resuscitation and inotrope therapy directed to goals of threshold heart rates, normal blood pressure, and capillary refill 70% and cardiac index 3.3-6.0 L/min/m.

Intensive plasma exchange increases a disintegrin and metalloprotease with thrombospondin motifs-13 activity and reverses organ dysfunction in children with thrombocytopenia-associated multiple organ failure.

BACKGROUND: Thrombocytopenia-associated multiple organ failure (TAMOF) is a poorly understood syndrome in critically ill children. A disintegrin and metalloprotease with thrombospondin motifs (ADAMTS-13), formerly known as von Willebrand factor (VWF) cleaving protease, is decreased in adults with VWF-mediated thrombotic microangiopathy, and intensive plasma exchange (PEx) both replenishes ADAMTS-13 and improves outcome in these patients. OBJECTIVES: To determine whether: 1) critically ill children with TAMOF syndrome have decreased ADAMTS-13 activity, 2) ADAMTS-13 activity correlates with platelet counts and VWF antigen, 3) the autopsies from patients who died with reduced ADAMTS-13 activity have VWF-rich microthrombi, and 4) intensive PEx will restore ADAMTS-13 activity and facilitate organ failure resolution. DESIGN: First study: observational. Second study: randomized control trial. SETTING: Single center university pediatric intensive care unit. PATIENTS: First study: thirty-seven consecutive children (17 males and 20 females; ages ranging from 9 days to 23 years) identified with > or = 2 organs dysfunction were enrolled. Seventy-six percent of these children had thrombocytopenia (platelet counts < 100,000/mm3). Five additional critically ill children without MOF were also enrolled. In the second study, children with severe TAMOF (platelet counts < 100,000/mm3 and > 3 organ failure) were randomized to PEx or standard therapy. Primary physicians and parents agreed to enrollment in 10 of the 20 eligible patients with ages ranging from 1 year to 18 years. Five patients received PEx and 5 patients received standard therapy. RESULTS: First study: children with TAMOF (n = 28) had decreased ADAMTS-13 activity, but similar plasminogen activator inhibitor-1 activity and prothrombin time compared to children with MOF without thrombocytopenia (n = 9, p < 0.05). All non-survivors (n = 7) had TAMOF, reduced ADAMTS-13 activity, and VWF-rich microvascular thromboses at autopsy. In the second study, PEx (n = 5, median 12 days, 4-28 days) restored ADAMTS-13 activity and organ function, compared to standard therapy (n = 5, p < 0.05). CONCLUSIONS: Children with TAMOF syndrome can have VWF-mediated thrombotic microangiopathy. Similar to adult experience, PEx can replenish ADAMTS-13 activity and reverse organ failure.

Unexpected increased mortality after implementation of a commercially sold computerized physician order entry system.

OBJECTIVE: In response to the landmark 1999 report by the Institute of Medicine and safety initiatives promoted by the Leapfrog Group, our institution implemented a commercially sold computerized physician order entry (CPOE) system in an effort to reduce medical errors and mortality. We sought to test the hypothesis that CPOE implementation results in reduced mortality among children who are transported for specialized care. METHODS: Demographic, clinical, and mortality data were collected of all children who were admitted via interfacility transport to our regional, academic, tertiary-care level children's hospital during an 18-month period. A commercially sold CPOE program that operated within the framework of a general, medical-surgical clinical application platform was rapidly implemented hospital-wide over 6 days during this period. Retrospective analyses of pre-CPOE and post-CPOE implementation time periods (13 months before and 5 months after CPOE implementation) were subsequently performed. RESULTS: Among 1942 children who were referred and admitted for specialized care during the study period, 75 died, accounting for an overall mortality rate of 3.86%. Univariate analysis revealed that mortality rate significantly increased from 2.80% (39 of 1394) before CPOE implementation to 6.57% (36 of 548) after CPOE implementation. Multivariate analysis revealed that CPOE remained independently associated with increased odds of mortality (odds ratio: 3.28; 95% confidence interval: 1.94-5.55) after adjustment for other mortality covariables. CONCLUSIONS: We have observed an unexpected increase in mortality coincident with CPOE implementation. Although CPOE technology holds great promise as a tool to reduce human error during health care delivery, our unanticipated finding suggests that when implementing CPOE systems, institutions should continue to evaluate mortality effects, in addition to medication error rates, for children who are dependent on time-sensitive therapies.

Early reversal of pediatric-neonatal septic shock by community physicians is associated with improved outcome.

OBJECTIVE: Experimental and clinical studies of septic shock support the concept that early resuscitation with fluid and inotropic therapies improves survival in a time-dependent manner. The new American College of Critical Care Medicine-Pediatric Advanced Life Support (ACCM-PALS) Guidelines for hemodynamic support of newborns and children in septic shock recommend this therapeutic approach. The objective of this study was to determine whether early septic shock reversal and use of resuscitation practice consistent with the new ACCM-PALS Guidelines by community physicians is associated with improved outcome. METHODS: A 9-year (January 1993-December 2001) retrospective cohort study was conducted of 91 infants and children who presented to local community hospitals with septic shock and required transport to Children's Hospital of Pittsburgh. Shock reversal (defined by return of normal systolic blood pressure and capillary refill time), resuscitation practice concurrence with ACCM-PALS Guidelines, and hospital mortality were measured. RESULTS: Overall, 26 (29%) patients died. Community physicians successfully achieved shock reversal in 24 (26%) patients at a median time of 75 minutes (when the transport team arrived at the patient's bedside), which was associated with 96% survival and >9-fold increased odds of survival (9.49 [1.07-83.89]). Each additional hour of persistent shock was associated with >2-fold increased odds of mortality (2.29 [1.19-4.44]). Nonsurvivors, compared with survivors, were treated with more inotropic therapies (dopamine/dobutamine [42% vs 20%] and epinephrine/norepinephrine [42% vs 6%]) but not increased fluid therapy (median volume; 32.9 mL/kg vs 20.0 mL/kg). Resuscitation practice was consistent with ACCM-PALS Guidelines in only 27 (30%) patients; however, when practice was in agreement with guideline recommendations, a lower mortality was observed (8% vs 38%). CONCLUSIONS: Early recognition and aggressive resuscitation of pediatric-neonatal septic shock by community physicians can save lives. Educational programs that promote ACCM-PALS recommended rapid, stepwise escalations in fluid as well as inotropic therapies may have value in improving outcomes in these children.

Glucose deprivation produces a prolonged increase in sensitivity to glutamate in cultured rat cortical neurons.

In this study we investigated whether the link between mitochondrial dysfunction and deregulation of Ca(2+) homeostasis preceding excitotoxic cell death is mediated by cellular deenergization. Glycolytic and/or mitochondrial ATP synthesis was inhibited with 2-deoxy-D-glucose (2DG) and oligomycin, respectively. Changes in cytoplasmic Ca(2+) concentration ([Ca(2+)](c)) and mitochondrial membrane potential were simultaneously measured in response to low (10 microM) glutamate concentrations, using the fluorescence dyes fura-2FF and rhodamine 123. 2DG, which blocks glycolysis and also inhibits mitochondrial respiration due to depletion of pyruvate, greatly increased and accelerated glutamate-induced elevation of [Ca(2+)](c) and mitochondrial depolarization. The 2DG-induced hypersensitivity to glutamate was observed even after 150-min washout of 2DG with glucose-containing medium, suggesting a permanent deterioration of mitochondrial function. Prior blockade of only glycolytic (2DG with pyruvate) or only mitochondrial (oligomycin) ATP synthesis did not affect neuronal sensitivity to glutamate. Collectively, these studies show that to maintain the sensitivity of neurons to glutamate at control levels at least one of the cellular sources of ATP production must be intact. Either glycolysis or oxidative phosphorylation can effectively support Ca(2+) homeostasis in cultured forebrain neurons.