Impact of tacrolimus variability on pediatric heart transplant outcomes.

BACKGROUND: Tacrolimus is a narrow therapeutic index drug, requiring consistent levels to maximize transplant success while reducing adverse effects. Elevated tacrolimus level variability (ETLV) is associated with poor outcomes in both pediatric and adult solid organ transplant recipients. We sought to describe the prevalence of ETLV and identify associations with patient-specific factors and poor outcomes. METHODS: Tacrolimus levels were evaluated from 118 patients at our single center. As a marker of variability, standard deviations (SD) were calculated for each patient from their entire tacrolimus level data set (global SD), and 1-2 years and 1-5 years post-HT (prediction window SDs). SD ≥3 denoted ETLV. RESULTS: There was large variability in tacrolimus levels (median global SD 3.1; IQR 2.3, 4; SD ≥3, n = 64, 54%). Patients with elevated SD (≥3) vs lower SD (<3) were more likely to have poor outcomes including rejection (73% vs 46%), cardiac allograft vasculopathy (CAV, 22% vs 9%), and death (20% vs 6%). The prediction window analysis noted ETLV was associated with a 40% greater risk of CAV, re-HT, or death (p = .024) and increasing age at transplantation was associated with a 12% increase in the risk of rejection (p = <.001) and a 19% increase in the risk of a composite event (p = .021). CONCLUSION: ETLV is prevalent in the pediatric HT population with increased frequency of poor outcomes in those with SD ≥3. ETLV is an easily accessible marker with which to risk-stratify patients.

Treatment of Pediatric Septic Shock With the Surviving Sepsis Campaign Guidelines and PICU Patient Outcomes.

OBJECTIVES: The Surviving Sepsis Campaign recommends rapid recognition and treatment of severe sepsis and septic shock. Few reports have evaluated the impact of these recommendations in pediatrics. We sought to determine if outcomes in patients who received initial care compliant with the Surviving Sepsis Campaign time goals differed from those treated more slowly. DESIGN: Single center retrospective cohort study. SETTING: Emergency department and PICU at an academic children's hospital. PATIENTS: Three hundred twenty-one patients treated for septic shock in the emergency department and admitted directly to the PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The exposure was receipt of emergency department care compliant with the Surviving Sepsis Campaign recommendations (delivery of IV fluids, IV antibiotics, and vasoactive infusions within 1 hr of shock recognition). The primary outcome was development of new or progressive multiple organ dysfunction syndrome. Secondary outcomes included mortality, need for mechanical ventilation or vasoactive medications, and hospital and PICU length of stay. Of the 321 children studied, 117 received Surviving Sepsis Campaign compliant care in the emergency department and 204 did not. New or progressive multiple organ dysfunction syndrome developed in nine of the patients (7.7%) who received Surviving Sepsis Campaign compliant care and 25 (12.3%) who did not (p = 0.26). There were 17 deaths; overall mortality rate was 5%. There were no significant differences between groups in any of the secondary outcomes. Although only 36% of patients met the Surviving Sepsis Campaign guideline recommendation of bundled care within 1 hour of shock recognition, 75% of patients received the recommended interventions in less than 3 hours. CONCLUSIONS: Treatment for pediatric septic shock in compliance with the Surviving Sepsis Campaign recommendations was not associated with better outcomes compared with children whose initial therapies in the emergency department were administered more slowly. However, all patients were treated rapidly and we report low morbidity and mortality. This underscores the importance of rapid recognition and treatment of septic shock.

Infectious Etiologies and Patient Outcomes in Pediatric Septic Shock.

BACKGROUND: Septic shock remains an important cause of death and disability in children. Optimal care requires early recognition and treatment. METHODS: We evaluated a retrospective cohort of children (age <19) treated in our emergency department (ED) for septic shock during 2008-2012 to investigate the association between timing of antibiotic therapy and outcomes. The exposures were (1) receipt of empiric antibiotics in ≤1 hour and (2) receipt of appropriate antibiotics in ≤1 hour. The primary outcome was development of new or progressive multiple system organ dysfunction syndrome (NP-MODS). The secondary outcome was mortality. RESULTS: Among 321 patients admitted to intensive care, 48% (n = 153) received empiric antibiotics in ≤1 hour. These patients were more ill at presentation with significantly greater median pediatric index of mortality 2 (PIM2) scores and were more likely to receive recommended resuscitation in the ED (61% vs 14%); however, rates of NP-MODS (9% vs 12%) and hospital mortality (7% vs 4%) were similar to those treated later. Early, appropriate antibiotics were administered to 33% (n = 67) of patients with identified or suspected bacterial infection. These patients had significantly greater PIM2 scores but similar rates of NP-MODS (15% vs 15%) and hospital mortality (10% vs 6%) to those treated later. CONCLUSIONS: Critically ill children with septic shock treated in a children's hospital ED who received antibiotics in ≤1 hour were significantly more severely ill than those treated later, but they did not have increased risk of NP-MODS or death.