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Biomedical subjects

Joseph A Carcillo

Publications and source records attributed to Joseph A Carcillo.

At least 19 recordsLinked to original sources
PubMed2006

What is the rationale for hydrocortisone treatment in children with infection-related adrenal insufficiency and septic shock?

Recent studies show that children who die from fulminant meningococcaemia have very low cortisol:adrenocorticotrophic hormone (ACTH) ratios within the first 8 h of presentation to emergency facilities compared with survivors. This observation supports the possibility that adrenal insufficiency may contribute to rapid cardiovascular collapse in these children. In recent years, the use of hydrocortisone treatment has become increasingly popular in the care of adult and paediatric patients with septic shock. In this review, the classical adrenal insufficiency literature is presented and the existing rationale for using titrated hydrocortisone treatment (2-50 mg/kg/day) to reverse catecholamine-resistant shock in children who have absolute adrenal insufficiency (defined by peak cortisol level <18 microg/dl after ACTH challenge) or pituitary, hypothalamic or adrenal axis insufficiency is provided. In addition, the concept of relative adrenal insufficiency (basal cortisol >18 microg/dl but a peak response to ACTH <9 microg/dl) is reviewed. Although there is a good rationale supporting the use of 7 days of low-dose hydrocortisone treatment (about 5 mg/kg/day) in adults with this condition and catecholamine resistant septic shock, the paediatric literature suggests that it is prudent to conduct more studies before recommending this approach in children.

Adrenal Insufficiency↗
PubMed2006

What's new in pediatric intensive care.

PURPOSE: To provide an update on new developments in the field of pediatric intensive care. RESULTS: Pediatric intensive care and acute medicine continues to grow internationally with improving intensive care unit mortality rates (2.4% in the United States) and a positive effect on child survival from the leading causes of death in the developing and developed world (sepsis and trauma, respectively). New approaches have developed for the practicing clinician in the use of hypothermia, helium, surfactant, glucose, insulin, hydrocortisone, fluid resuscitation and fluid removal, superior vena cava oxygen saturation, goal-directed, coagulation, immune modulation, and multiple-organ extracorporeal support (MOSES) therapies. Some old drugs have fallen out of favor (propofol and etomidate) while new drugs are being evaluated with favorable (calfactant) and yet to be described effects (activated protein C). New diagnostic tests (troponin and brain natriuretic peptide levels) are being used to aid in diagnosis of heart dysfunction, and a new drug class of Ca+ + sensitizers holds promise for recalcitrant heart dysfunction (levosimendan). CONCLUSION: The field is alive, successful, and progressing across the globe.

Child↗
PubMed2006

Bench-to-bedside review: thrombocytopenia-associated multiple organ failure--a newly appreciated syndrome in the critically ill.

New onset thrombocytopenia and multiple organ failure (TAMOF) presages poor outcome in critical illness. Patients who resolve thrombocytopenia by day 14 are more likely to survive than those who do not. Patients with TAMOF have a spectrum of microangiopathic disorders that includes thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC) and secondary thrombotic microanigiopathy (TMA). Activated protein C is effective in resolving fibrin-mediated thrombosis (DIC); however, daily plasma exchange is the therapy of choice for removing ADAMTS 13 inhibitors and replenishing ADAMTS 13 activity which in turn resolves platelet: von Willebrand Factor mediated thrombosis (TTP/secondary TMA).

Critical Illness↗
PubMed2005

Prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia in children with nosocomial sepsis and multiple organ failure.

Lymphopenia and lymphoid depletion occur in adults dying of sepsis. Prolactin increases Bcl-2 expression, suppresses stress-induced lymphocyte apoptosis, and improves survival from experimental sepsis. We hypothesized that prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia occur in children dying with sepsis and multiple organ failure (MOF). Fifty-eight critically ill children with and 55 without MOF admitted to a university hospital pediatric intensive care unit were enrolled in a prospective, longitudinal, observational clinical study. Prolactin levels and absolute lymphocyte count were measured on days 1, 3, 7, 14, and 21. Lymph node, thymus, and spleen autopsy specimens were examined for lymphoid depletion, with immunohistochemical staining for CD4, CD20, and CD21 and for lymphoid apoptosis. Prolonged lymphopenia (absolute lymphocyte count < 1000 for >7 days) occurred only in children with MOF (29 vs 0%, p < 0.05) and was associated independently with nosocomial infection (odds ratio (OR), 5.5, 95% confidence interval (CI), 1.7-17, p < 0.05), death (OR, 6.8, 95% CI, 1.3-34, p < 0.05), and splenic and lymph node hypocellularity (OR, 42, 95% CI, 3.7-473, p < 0.05). Lymphocyte apoptosis and ante/postmortem infection were observed only in children with lymphoid depletion. Prolonged hypoprolactinemia (>7 days) was more common in children with MOF (17 vs 2%, p < 0.05) and was associated independently with prolonged lymphopenia (OR, 8.3, 95% CI, 2.1-33, p < 0.05) and lymphoid depletion (OR, 12.2, 95% CI, 2.2-65, p < 0.05). Prolonged lymphopenia and apoptosis-associated depletion of lymphoid organs play a role in nosocomial sepsis-related death in critically ill children. Prolonged hypoprolactinemia is a previously unrecognized risk factor for this syndrome.

Adolescent↗
PubMed2005

Absolute and relative adrenal insufficiency in children with septic shock.

OBJECTIVE: Corticosteroid replacement improves outcome in adults with relative adrenal insufficiency and catecholamine-resistant septic shock. We evaluated the relationship of absolute and relative adrenal insufficiency to catecholamine-resistant septic shock in children. DESIGN: Prospective cohort study. SETTING: University hospital pediatric intensive care unit in Brazil. PATIENTS: Fifty-seven children with septic shock. Children with HIV infection, those with a history of adrenal insufficiency, and those submitted to any steroid therapy or etomidate within the week before diagnosis of septic shock were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A short corticotropin test (250 microg) was performed, and cortisol levels were measured at baseline and 30 and 60 mins posttest. Adrenal insufficiency was defined by a response < or =9 microg/dL. Absolute adrenal insufficiency was further defined by a baseline cortisol <20 microg/dL and relative adrenal insufficiency by a baseline cortisol >20 microg/dL. Absolute adrenal insufficiency was observed in 18% of children, all of whom had catecholamine-resistant shock. Relative adrenal insufficiency was observed in 26% of children, of whom 80% had catecholamine-resistant and 20% had dopamine/dobutamine-responsive shock. All children with fluid-responsive shock had a cortisol response >9 microg/dL. Children with adrenal insufficiency had an increased risk of catecholamine-resistant shock (relative risk, 1.88; 95% confidence interval, 1.26-2.79). However, mortality was independently predicted by chronic illness or multiple organ failure (p < .05), not adrenal insufficiency. CONCLUSIONS: Absolute and relative adrenal insufficiency is common in children with catecholamine-resistant shock and absent in children with fluid-responsive shock. Studies are warranted to determine whether corticosteroid therapy has a survival benefit in children with relative adrenal insufficiency and catecholamine-resistant septic shock.

Adolescent↗
PubMed2005

Extracellular hsp70 levels in children with septic shock.

OBJECTIVE: To determine whether hsp70 is elevated in the plasma of children with septic shock. DESIGN: Cohort study. SETTING: Two academic, tertiary pediatric intensive care units. PATIENTS: Ninety-four children admitted to the pediatric intensive care unit with septic shock and 24 control children undergoing elective surgical procedures. INTERVENTIONS: Venous or arterial blood sampling. MEASUREMENTS AND MAIN RESULTS: Children admitted to the pediatric intensive care unit with a diagnosis of septic shock were enrolled in the study following written informed consent. The control group consisted of healthy children undergoing elective surgical procedures. Blood samples from children in the septic shock or control groups were obtained within 24 hrs of admission to the pediatric intensive care unit or during the preoperative visit. Samples were collected, centrifuged, and stored at -70 degrees C. The hsp70 levels were measured using a commercially available enzyme-linked immunosorbent assay. Results were analyzed by Wilcoxon's rank sum test. Extracellular hsp70 levels in children with septic shock were significantly elevated compared with control patients (51.6 ng/mL vs. 8.1 ng/mL, respectively, p = .0004). CONCLUSIONS: Extracellular hsp70 levels are significantly elevated in children with septic shock compared with controls. Given the newly described cell signaling properties of hsp70, these data suggest that extracellular hsp70 may play a role in the host response during septic shock.

Adolescent↗
PubMed2005

Scope and epidemiology of pediatric sepsis.

OBJECTIVE: To summarize the scope and epidemiology of pediatric sepsis. DESIGN: Review of published literature. RESULTS: Sepsis is a leading cause of death in infants and children, with >42,000 cases of severe sepsis annually in the United States and millions worldwide. Half of the children with severe sepsis in the United States are infants, and half of infants are low- or very low-birth-weight babies. Underlying disease occurs in 49% of U.S. children with severe sepsis. National hospital costs associated with severe sepsis in the United States were $2.3 billion in 1999. Relatively simple strategies to identify and treat children with sepsis in the developing world have shown remarkable success. These strategies have included empirical antibiotics in babies at high risk of sepsis and aggressive fluid resuscitation in Dengue hemorrhagic fever. CONCLUSIONS: Sepsis is a major health problem among children in both developing and industrialized countries. However, sepsis is both preventable and treatable. Improved prevention and treatment of sepsis could have a substantial effect on survival and quality of life of all children, both those who are otherwise healthy and those who are chronically ill. The variations in the epidemiology of pediatric sepsis underscore the need for a multidisciplinary approach and consistently applied definitions.

Adolescent↗
PubMed2005

Reducing the global burden of sepsis in infants and children: a clinical practice research agenda.

OBJECTIVE: Sepsis remains a predominant cause of mortality and morbidity in children in the developing and industrialized world. This review discusses a clinical practice research agenda to reduce this global burden. DESIGN: Summary of the literature with analysis by experts. RESULTS: Many interventions have been proven effective in decreasing sepsis. Heterologous immunization with attenuated Bacillus Camille Guerin vaccine reduces all-cause mortality, and specific immunizations further reduce morbidity and mortality from many specific microbes. Antepartum antibiotics reduce the prevalence of cerebral palsy and mortality in infants. Administration of antibiotics to neonates with signs of sepsis reduces all-cause mortality five-fold and can also reduce mortality in the big four killers of children: severe pneumonia, diarrhea, malaria, or measles. Immunonutrition with zinc and vitamin A can further reduce morbidity in diarrhea and pneumonia and reduce mortality in measles. First-hour rapid intravenous fluid resuscitation achieves 100% survival in dengue shock, and time-sensitive fluid resuscitation and inotropic support reduces mortality ten-fold in meningococcal septic shock. Multiple organ failure occurs when late or inadequate resuscitation results in systemic thrombosis or when infection is not eradicated because of immunosuppression or inadequate source control. CONCLUSIONS: The global burden of sepsis can be reduced by 1) prevention with improved heterologous or specific vaccines and vitamin or mineral supplement programs; 2) early recognition and treatment with appropriate antibiotics, intravenous fluid resuscitation, and inotropic support in organized healthcare-delivery systems; and 3) development of new diagnostics and therapeutics that reduce systemic thrombosis, improve immune function, and kill resistant organisms.

Child↗
PubMed2005

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.

Child Mortality↗
PubMed2004

Procalcitonin and C-reactive protein kinetics in postoperative pediatric cardiac surgical patients.

OBJECTIVE: To determine the kinetics of procalcitonin (PCT) and C-reactive protein (CRP) concentration after pediatric cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, clinical cohort study. SETTING: A fifteen-bed tertiary-care pediatric intensive care unit. PATIENTS: Fourteen pediatric patients admitted for cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Serum PCT and CRP were measured before cardiopulmonary bypass (CPB); after CPB; and on the first, second, and third days after surgery by means of immunoluminometry and nephelometry, respectively. Reference values for systemic inflammatory response syndrome are 0.5 to 2.0 ng/mL for PCT and <5 mg/L for CRP. Baseline serum PCT and CRP concentrations were 0.24 +/- 0.13 ng/mL and 4.06 +/- 3.60 mg/L (median 25th percentile-75th percentile), respectively. PCT concentrations increased progressively from the end of CPB (0.62 +/- 0.30 ng/mL), peaked at 24 hours postoperatively (POD1) (0.77 +/- 0.49 ng/mL), and began to decrease at 48 hours or POD2 (0.35 +/- 0.21 ng/mL). CRP increased just after CPB (58.82 +/- 42.23 mg/L) and decreased after 72 hours (7.09 +/- 9.81 mg/L). CONCLUSION: An increment of both PCT and CRP was observed just after CPB. However, PCT values remained within reference values, whereas CRP concentrations increased significantly after CPB until the third day. These preliminary results suggest that PCT was more effective than CRP to monitor patients with SIRS and a favorable outcome.

Analysis of Variance↗
PubMed2004

Sepsis associated with immunosuppressive medications: an evidence-based review.

OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for sepsis associated with immunosuppressive medications that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. METHODS: The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591. CONCLUSION: Immunosuppressed patients, by definition, are susceptible to a wider spectrum of infectious agents than immunologically normal patients and, thus, require a broader spectrum antimicrobial regimen when they present with sepsis or septic shock. Special expertise managing immunosuppressed patient populations is needed to predict and establish the correct diagnosis and to choose appropriate empiric and specific agents and maximize the likelihood that patients will survive these microbial challenges.

Adrenal Cortex Hormones↗
PubMed2004

Pediatric considerations.

OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for other supportive therapies in sepsis that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and to improve outcome in severe sepsis. DESIGN AND METHODS: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. Pediatric representatives attended the various section meetings and workshops to contrast adult and pediatric management. These are published here as pediatric considerations. CONCLUSION: Pediatric considerations included a more likely need for intubation due to low functional residual capacity, more difficult intravenous access, fluid resuscitation based on weight with 40-60 mL kg or higher needed, decreased cardiac output and increased systemic vascular resistance as the most common hemodynamic profile, greater use of physical examination therapeutic endpoints, the unsettled issue of high-dose steroids for therapy of septic shock, and greater risk of hypoglycemia with aggressive glucose control.

Cardiotonic Agents↗
PubMed2003

Cytochrome P450 mediated-drug metabolism is reduced in children with sepsis-induced multiple organ failure.

OBJECTIVE: Antipyrine metabolism is a "gold standard" measure of mixed cytochrome P450 (CYP) mediated drug metabolism in humans. Cytokines (e.g., interleukin-6) and nitric oxide reduce CYP 450 activity in vitro and in vivo. Because interleukin-6 and nitric oxide production increases in children with sepsis-induced multiple organ failure, we hypothesized impaired CYP 450 mediated drug metabolism in this population. METHODS: Fifty-one consecutive children with sepsis and six critically ill children without sepsis were enrolled and given 18 mg/kg antipyrine per NG. Plasma antipyrine elimination rate, elimination half-life, and apparent oral clearance were measured and calculated. Plasma interleukin-6 and nitrite plus nitrate levels were measured and organs failing scored on days 1-3 of sepsis. RESULTS: Children with sepsis had a twofold reduction in antipyrine clearance. Children with persistent failure of three or more organs had a fourfold reduction in antipyrine clearance. Antipyrine clearance was inversely correlated to circulating interleukin-6 and nitrite plus nitrate levels and to number of organ failures. CONCLUSIONS: Interpretation CYP 450 mediated drug metabolism is decreased in children with sepsis, related in part to the degree of inflammation and organ failure. For drugs metabolized by CYP 450 enzymes there is an urgent need to reevaluate the use of standard drug dosage schedules in the sepsis population

Adolescent↗