Joseph A Carcillo

Childrens Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (222)691.08 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate significant new morbidities associated with pediatric critical care.
    09/2014;
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    ABSTRACT: Thrombocytopenia-associated multiple organ failure can lead to high mortality in critically ill children, possibly related to consequences of thrombotic microangiopathy. Plasma exchange therapy may improve thrombotic microangiopathy. The purpose of this observational cohort study is to describe whether there is an association between use of plasma exchange therapy and outcome in the Turkish thrombocytopenia-associated multiple organ failure network.
    07/2014;
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    ABSTRACT: The cortisol response during critical illness varies widely among patients. Our objective was to examine single nucleotide polymorphisms in candidate genes regulating cortisol synthesis, metabolism, and activity to determine if genetic differences were associated with variability in the cortisol response among critically ill children.
    07/2014;
  • Joseph A Carcillo
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    ABSTRACT: To review the past year's literature, and selected prior literature relevant to these most recent findings, regarding intravenous fluid choices in the management of critically ill children.
    Current opinion in critical care. 06/2014;
  • 06/2014; 15(5):486-488.
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    ABSTRACT: IMPORTANCE Functional status assessment methods are important as outcome measures for pediatric critical care studies. OBJECTIVE To investigate the relationships between the 2 functional status assessment methods appropriate for large-sample studies, the Functional Status Scale (FSS) and the Pediatric Overall Performance Category and Pediatric Cerebral Performance Category (POPC/PCPC) scales. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study with random patient selection at 7 sites and 8 children's hospitals with general/medical and cardiac/cardiovascular pediatric intensive care units (PICUs) in the Collaborative Pediatric Critical Care Research Network. Participants included all PICU patients younger than 18 years. MAIN OUTCOMES AND MEASURES Functional Status Scale and POPC/PCPC scores determined at PICU admission (baseline) and PICU discharge. We investigated the association between the baseline and PICU discharge POPC/PCPC scores and the baseline and PICU discharge FSS scores, the dispersion of FSS scores within each of the POPC/PCPC ratings, and the relationship between the FSS neurologic components (FSS-CNS) and the PCPC. RESULTS We included 5017 patients. We found a significant (P < .001) difference between FSS scores in each POPC or PCPC interval, with an FSS score increase with each worsening POPC/PCPC rating. The FSS scores for the good and mild disability POPC/PCPC ratings were similar and increased by 2 to 3 points for the POPC/PCPC change from mild to moderate disability, 5 to 6 points for moderate to severe disability, and 8 to 9 points for severe disability to vegetative state or coma. The dispersion of FSS scores within each POPC and PCPC rating was substantial and increased with worsening POPC and PCPC scores. We also found a significant (P < .001) difference between the FSS-CNS scores between each of the PCPC ratings with increases in the FSS-CNS score for each higher PCPC rating. CONCLUSIONS AND RELEVANCE The FSS and POPC/PCPC system are closely associated. Increases in FSS scores occur with each higher POPC and PCPC rating and with greater magnitudes of change as the dysfunction severity increases. However, the dispersion of the FSS scores indicated a lack of precision in the POPC/PCPC system when compared with the more objective and granular FSS. The relationship between the PCPC and the FSS-CNS paralleled the relationship between the FSS and POPC/PCPC system.
    JAMA pediatrics. 05/2014;
  • Pediatric Critical Care Medicine 05/2014; 15(4):380-2. · 2.35 Impact Factor
  • Joseph A Carcillo
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    ABSTRACT: This is a synopsis of the term newborn and infant portion of the 2007 document (Brierley et al., Crit Care Med 2009;37(2):666-88) which examined and graded new studies performed to test the utility and efficacy of the 2002 recommendations. This 2007 document examined and graded relevant new treatment and outcome studies to determine to what degree, if any, the 2002 guidelines should be modified. More than 30 clinical investigators and clinicians affiliated with the Society of Critical Care Medicine who had special interest in hemodynamic support of pediatric patients with sepsis volunteered to be members of the "update" task force. Subcommittees were formed to review and grade the literature using the evidence-based scoring system of the American College of Critical Care Medicine. The literature was accrued in part by searching PUBMED/MEDLINE using the following keywords: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, and ECMO. The search was narrowed to identify studies specifically relevant to term newborns, infants, and children. "Best Practice Outcomes" were identified and described clinical practice in these centers was used as a model. The new taskforce is presently working on updating new guidelines evaluating the literature of the past 6 years.
    Early human development 03/2014; 90S1:S45-S47. · 2.12 Impact Factor
  • Joseph A Carcillo
    Critical care medicine 12/2013; 41(12):e489. · 6.37 Impact Factor
  • Critical care medicine 10/2013; 41(10):e295. · 6.37 Impact Factor
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    ABSTRACT: Background:Sepsis continues to be a leading cause of death in infants and children. Natural killer (NK) cells serve as a bridge between innate and adaptive immunity, yet their role in pediatric sepsis has not been well characterized.Methods:We tested the hypothesis that decreased NK cell cytotoxicity is a common feature of pediatric systemic inflammatory response syndrome (SIRS)/sepsis patients by measuring, using flow cytometry, NK cell cytotoxicity and cell surface phenotype in the peripheral blood of 38 pediatric intensive care patients who demonstrated signs and symptoms of either SIRS and/or sepsis.Results:NK cell cytotoxicity was significantly reduced in PBMC of pediatric SIRS/sepsis patients as compared to healthy controls, and the percentage of CD56(dim) CD16(+) cytotoxic NK cells in peripheral blood mononuclear cells (PBMC) was lower in patients with SIRS/sepsis than in normal donors. However, on a per cell basis, CD56(dim) CD16(+) NK cells in patients mediated cytotoxicity as well as those in normal donors.Conclusion:The NK cell dysfunction in pediatric SIRS/sepsis patients reflects a quantitative rather than a qualitative difference from normal.Pediatric Research (2013); doi:10.1038/pr.2013.121.
    Pediatric Research 07/2013; · 2.67 Impact Factor
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    ABSTRACT: Early recognition and treatment of pediatric shock, regardless of cause, decreases mortality and improves outcome. In addition to the conventional parameters (eg, heart rate, systolic blood pressure, urine output, and central venous pressure), biomarkers and noninvasive methods of measuring cardiac output are available to monitor and treat shock. This article emphasizes how fluid resuscitation is the cornerstone of shock resuscitation, although the choice and amount of fluid may vary based on the cause of shock. Other emerging treatments for shock (ie, temperature control, extracorporeal membrane oxygenation/ventricular assist devices) are also discussed.
    Pediatric Clinics of North America 06/2013; 60(3):641-54. · 1.78 Impact Factor
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    ABSTRACT: OBJECTIVE:: Determine if the shortest sampling interval for laboratory variables used to estimate baseline severity of illness in pediatric critical care is equivalently sensitive across multiple sites without site-specific bias, while accounting for the vast majority of dysfunction compared with the standard 0- to 12-hour Pediatric Risk of Mortality III score. DESIGN:: Prospective random patient selection. SETTING:: General/medical and cardiac/cardiovascular PICUs in eight hospitals. PATIENTS:: Patients younger than 18 years admitted to the PICU. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: A total of 376 patients were included. Measurements for Pediatric Risk of Mortality III laboratory variables (pH, PCO2, total CO2, PaO2, glucose, potassium, blood urea nitrogen, creatinine, total WBC count, platelet count, and prothrombin time/partial thromboplastin time) were recorded from 2 hours prior to PICU admission through 12 hours of PICU care except for data in the operating room. Decreasing the observation period from the 0 to 12 hours post PICU admission resulted in progressive decreases in the Pediatric Risk of Mortality III laboratory variables measured. However, allowing the observation period to start 2 hours prior to PICU admission to 4 hours reduced this loss to only 3.4%. Similar trends existed for each of the individual laboratory Pediatric Risk of Mortality III variables. There was a nearly identical distribution of laboratory Pediatric Risk of Mortality III points within the -2- to 4-hour period compared with the standard period. We did not detect any institutional bias using the -2- to 4-hour time period compared with the baseline. CONCLUSIONS:: Prognostically important laboratory physiologic data collected within the interval from 2 hours prior to PICU to admission through 4 hours after admission account for the vast majority of dysfunction that these variables would contribute to Pediatric Risk of Mortality III scores. There was no institutional bias associated with this sampling period.
    Pediatric Critical Care Medicine 04/2013; · 2.35 Impact Factor
  • Source
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    ABSTRACT: OBJECTIVE:: Pertussis persists in the United States despite high immunization rates. This report characterizes the presentation and acute course of critical pertussis by quantifying demographic data, laboratory findings, clinical complications, and critical care therapies among children requiring admission to the PICU. DESIGN:: Prospective cohort study. SETTING:: Eight PICUs comprising the Eunice Kennedy Shriver National Institute for Child Health and Human Development Collaborative Pediatric Critical Care Research Network and 17 additional PICUs across the United States. PATIENTS:: Eligible patients had laboratory confirmation of pertussis infection, were younger than 18 years old, and died in the PICU or were admitted to the PICU for at least 24 hours between June 2008 and August 2011. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: A total of 127 patients were identified. Median age was 49 days, and 105 (83%) patients were less than 3 months old. Fifty-five (43%) patients required mechanical ventilation and 12 patients (9.4%) died during initial hospitalization. Pulmonary hypertension was found in 16 patients (12.5%) and was present in 75% of patients who died, compared with 6% of survivors (p < 0.001). Median WBC was significantly higher in those requiring mechanical ventilation (p < 0.001), those with pulmonary hypertension (p < 0.001), and nonsurvivors (p < 0.001). Age, sex, and immunization status did not differ between survivors and nonsurvivors. Fourteen patients received leukoreduction therapy (exchange transfusion [12], leukopheresis [1], or both [1]). Survival benefit was not apparent. CONCLUSIONS:: Pulmonary hypertension may be associated with mortality in pertussis critical illness. Elevated WBC is associated with the need for mechanical ventilation, pulmonary hypertension, and mortality risk. Research is indicated to elucidate how pulmonary hypertension, immune responsiveness, and elevated WBC contribute to morbidity and mortality and whether leukoreduction might be efficacious.
    Pediatric Critical Care Medicine 04/2013; · 2.35 Impact Factor
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    ABSTRACT: OBJECTIVES:: To describe serum concentrations of zinc, selenium, and prolactin in critically ill children within 72 hrs of PICU admission, and to investigate relationships between these immunomodulators and lymphopenia. DESIGN:: An analysis of baseline data collected as part of the multicenter Critical Illness Stress Induced Immune Suppression (CRISIS) Prevention Trial. SETTING:: PICUs affiliated with the Collaborative Pediatric Critical Care Research Network. PATIENTS:: All children enrolled in the CRISIS Prevention Trial that had baseline serum samples available for analysis. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: Of 293 critically ill children enrolled in the CRISIS Prevention Trial, 284 had baseline serum samples analyzed for prolactin concentration, 280 for zinc concentration, and 278 for selenium concentration within 72 hrs of PICU admission. Lymphocyte counts were available for 235 children. Zinc levels ranged from nondetectable (< 0.1 μg/mL) to 2.87 μg/mL (mean 0.46 μg/mL and median 0.44 μg/mL) and were below the normal reference range for 235 (83.9%) children. Selenium levels ranged from 26 to 145 ng/mL (mean 75.4 ng/mL and median 74.5 ng/mL) and were below the normal range for 156 (56.1%) children. Prolactin levels ranged from nondetectable (< 1 ng/mL) to 88 ng/mL (mean 12.2 ng/mL and median 10 ng/mL). Hypoprolactinemia was present in 68 (23.9%) children. Lymphopenia was more likely in children with zinc levels below normal than those with zinc levels within or above the normal range (82 of 193 [42.5%] vs. 10 of 39 [25.6%], p = 0.0498). Neither selenium nor prolactin concentrations were associated with lymphopenia (p = 1.0 and p = 0.72, respectively). CONCLUSIONS:: Serum concentrations of zinc, selenium, and prolactin are often low in critically ill children early after PICU admission. Low serum zinc levels are associated with lymphopenia, whereas low selenium and prolactin levels are not. The implications of these findings and the mechanisms by which they occur merit further study.
    Pediatric Critical Care Medicine 02/2013; · 2.35 Impact Factor
  • Source
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    ABSTRACT: OBJECTIVE:: To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. DESIGN:: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS:: The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Some recommendations were ungraded (UG). Recommendations were classified into three groups: 1) those directly targeting severe sepsis; 2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and 3) pediatric considerations. RESULTS:: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 hr of recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 hrs of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1C); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients) (1C); fluid challenge technique continued as long as hemodynamic improvement, as based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥ 65 mm Hg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO2/FIO2 ratio of ≤ 100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 hrs) for patients with early ARDS and a Pao2/Fio2 < 150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are > 180 mg/dL, targeting an upper blood glucose ≤ 180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 hrs after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 hrs of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5 to 10 mins (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). CONCLUSIONS:: Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.
    Critical care medicine 02/2013; 41(2):580-637. · 6.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. DESIGN: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. RESULTS: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO (2)/FiO (2) ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a PaO (2)/FI O (2) <150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are >180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5-10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). CONCLUSIONS: Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.
    European Journal of Intensive Care Medicine 01/2013; · 5.17 Impact Factor
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    ABSTRACT: OBJECTIVE:: To examine the clinical factors associated with increased opioid dose among mechanically ventilated children in the pediatric intensive care unit. DESIGN:: Prospective, observational study with 100% accrual of eligible patients. SETTING:: Seven pediatric intensive care units from tertiary-care children's hospitals in the Collaborative Pediatric Critical Care Research Network. PATIENTS:: Four hundred nineteen children treated with morphine or fentanyl infusions. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: Data on opioid use, concomitant therapy, demographic and explanatory variables were collected. Significant variability occurred in clinical practices, with up to 100-fold differences in baseline opioid doses, average daily or total doses, or peak infusion rates. Opioid exposure for 7 or 14 days required doubling of the daily opioid dose in 16% patients (95% confidence interval 12%-19%) and 20% patients (95% confidence interval 16%-24%), respectively. Among patients receiving opioids for longer than 3 days (n = 225), this occurred in 28% (95% confidence interval 22%-33%) and 35% (95% confidence interval 29%-41%) by 7 or 14 days, respectively. Doubling of the opioid dose was more likely to occur following opioid infusions for 7 days or longer (odds ratio 7.9, 95% confidence interval 4.3-14.3; p < 0.001) or co-therapy with midazolam (odds ratio 5.6, 95% confidence interval 2.4-12.9; p < 0.001), and it was less likely to occur if morphine was used as the primary opioid (vs. fentanyl) (odds ratio 0.48, 95% confidence interval 0.25-0.92; p = 0.03), for patients receiving higher initial doses (odds ratio 0.96, 95% confidence interval 0.95-0.98; p < 0.001), or if patients had prior pediatric intensive care unit admissions (odds ratio 0.37, 95% confidence interval 0.15-0.89; p = 0.03). CONCLUSIONS:: Mechanically ventilated children require increasing opioid doses, often associated with prolonged opioid exposure or the need for additional sedation. Efforts to reduce prolonged opioid exposure and clinical practice variation may prevent the complications of opioid therapy.
    Pediatric Critical Care Medicine 11/2012; · 2.35 Impact Factor
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    ABSTRACT: OBJECTIVE:: REsearching severe Sepsis and Organ dysfunction in children: A gLobal perspective (RESOLVE), a phase III trial of drotrecogin alfa (activated) in pediatric severe sepsis, examined biomarker changes in inflammation and coagulation. This report describes biomarker profiles in early severe sepsis and the pharmacodynamic assessment of drotrecogin alfa (activated) in RESOLVE. DESIGN:: Serial measurements of interleukin-1β, interleukin-6, interleukin-8, interleukin-10, tissue necrosis factor-α, procalcitonin, D-dimer, and thrombin-antithrombin complex were performed at baseline and daily over the first five study days. Protein C levels were performed at baseline and at the end of the 96-hr study drug infusion. Analysis of variance-based log-transformed data compared the treatment groups for each measured variable. SETTING:: One hundred four pediatric intensive care units in 18 countries. PATIENTS:: Four hundred seventy-seven children between 38 wks corrected gestational age and 17 yrs with sepsis-induced cardiovascular and respiratory dysfunction. INTERVENTIONS:: Drotrecogin alfa (activated). MEASUREMENTS AND MAIN RESULTS:: Pharmacodynamic activity of drotrecogin alfa (activated) compared with placebo was observed with reduction of D-dimer on day 1 (p < .01) and thrombin-antithrombin complex on days 1-4 (p < .05). There were no significant changes by treatment in multiple cytokines or procalcitonin. In the overall population, a median protein C difference was not observed (p > .05) with drotrecogin alfa (activated) administration compared with placebo, although a difference (median percentage change from baseline) in favor of drotrecogin alfa (activated) was observed in patients >1 yr old (p = .0449). CONCLUSIONS:: While children in the RESOLVE trial were similar to adults in that they showed a relationship between severity of coagulation and inflammation abnormalities and mortality, their pharmacodynamic response to drotrecogin alfa (activated) differed with respect to changes in protein C activity and systemic inflammation.
    Pediatric Critical Care Medicine 07/2012; · 2.35 Impact Factor
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    ABSTRACT: In this article, the authors review the current recommendations from the American Society for Apheresis regarding the use of plasmapheresis in many of the diseases that intensivists commonly encounter in critically ill patients. Recent experience indicates that therapeutic plasma exchange may be useful in a wide spectrum of illnesses characterized by microvascular thrombosis, the presence of autoantibodies, immune activation with dysregulation of immune response, and some infections.
    Critical care clinics 07/2012; 28(3):453-68, vii. · 1.72 Impact Factor

Publication Stats

9k Citations
691.08 Total Impact Points

Institutions

  • 2002–2014
    • Childrens Hospital of Pittsburgh
      Pittsburgh, Pennsylvania, United States
  • 1998–2014
    • University of Pittsburgh
      • • Department of Critical Care Medicine
      • • Department of Medicine
      Pittsburgh, Pennsylvania, United States
  • 2013
    • Cooper University Hospital
      Camden, New Jersey, United States
    • Boston Children's Hospital
      Boston, Massachusetts, United States
  • 2009–2012
    • Children's Hospital Los Angeles
      Los Angeles, California, United States
    • Phoenix Children's Hospital
      Phoenix, Arizona, United States
    • Syracuse University
      • Department of Communications and Rhetorical Studies
      Syracuse, NY, United States
  • 2005–2012
    • Baylor College of Medicine
      • Department of Pediatrics
      Houston, TX, United States
    • University of São Paulo
      • Faculty of Medicine (FM)
      San Paulo, São Paulo, Brazil
    • Penn State Hershey Medical Center and Penn State College of Medicine
      Hershey, Pennsylvania, United States
  • 2011
    • Cincinnati Children's Hospital Medical Center
      • Division of Critical Care Medicine
      Cincinnati, OH, United States
    • The Ohio State University
      • Department of Pediatrics
      Columbus, OH, United States
    • Institute for Transfusion Medicine
      Pittsburgh, Pennsylvania, United States
    • Society of Critical Care Medicine
      Pittsburgh, Pennsylvania, United States
    • Hospital of the University of Pennsylvania
      Philadelphia, Pennsylvania, United States
  • 2009–2011
    • University of Utah
      • Department of Pediatrics
      Salt Lake City, UT, United States
  • 2007–2011
    • Children's Hospital of Michigan
      Detroit, Michigan, United States
  • 2010
    • University of British Columbia - Vancouver
      • Division of Critical Care Medicine
      Vancouver, British Columbia, Canada
    • Karmanos Cancer Institute
      Detroit, Michigan, United States
    • The University of Tennessee Health Science Center
      • Department of Pediatrics
      Memphis, TN, United States
  • 2006–2009
    • University of Virginia
      • Department of Pediatrics
      Charlottesville, VA, United States
    • Texas Children's Hospital
      Houston, Texas, United States
  • 2004
    • Stony Brook University
      • Department of Pediatrics
      Stony Brook, NY, United States
  • 2003
    • Rhode Island Hospital
      Providence, Rhode Island, United States
    • National Institute of Child Health and Human Development
      Maryland, United States
  • 2000
    • Université de Montréal
      • Department of Pediatrics
      Montréal, Quebec, Canada