Pilot Mechanistic Study of Insulin Modulation of Somatotrophic Hormones, Inflammation, and Lipid Metabolism During Critical Illness in Children.

OBJECTIVES: To evaluate the mechanism of insulin modulation on somatotrophic response, inflammation, and lipid metabolism in critically ill children. DESIGN: Open-label randomized mechanistic study. SETTING: Two-center, tertiary PICU study. PATIENTS: Thirty critically ill children between 1 month and 14 years old, requiring mechanical ventilation and with evidence of two or more organ system failures. INTERVENTIONS: Randomized physiologic design of hyperinsulinemic-euglycemic clamp using continuous insulin infusion at 0.1 U/kg/hr versus conventional management. MEASUREMENTS AND MAIN RESULTS: Thirteen children underwent hyperinsulinemic-euglycemic clamp. Blood samples for somatotrophic, inflammatory, and metabolic evaluation were obtained before randomization, and 24 and 72 hours later. A growth hormone oscillation profile was obtained during the first night. There was no difference between groups at baseline. Growth hormone resistance, increased proinflammatory cytokines, and increased lipolysis with low lipoprotein levels were present in all patients. Hyperinsulinemic-euglycemic clamp did not affect growth hormone, insulin-like growth factor-1 or insulin-like growth factor binding protein-3 levels. By day 2, insulin reduced insulin-like growth factor binding protein-1 levels. Tumor necrosis factor-α and interleukin-1ß were similar in both groups, whereas interleukin-6 levels reduced over time only in children receiving hyperinsulinemic-euglycemic clamp. Hyperinsulinemic-euglycemic clamp also decreased free fatty acid levels, which was accompanied by increased low-density lipoprotein cholesterol and relative increase in high-density lipoprotein levels. Total cholesterol and triglycerides were unchanged. CONCLUSIONS: Insulin does not reverse most of the somatotrophic changes induced by the stress of critical illness. Rather, it may improve lipid metabolism and down-regulate some markers of the inflammatory response.

Influence of Acute Kidney Injury Defined by the Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease Score on the Clinical Course of PICU Patients.

OBJECTIVE: To evaluate the predictive value of the pediatric-modified Risk, Injury, Failure, Loss, End-stage renal disease criteria for disease course severity in patients with or without acute kidney injury admitted to a PICU. DESIGN: Retrospective cohort study. SETTING: A 12-bed PICU at a tertiary referral center in Southern Brazil. PATIENTS: All patients admitted to the study unit over a 1-year period. INTERVENTIONS: A database of all eligible patients was analyzed retrospectively. MEASUREMENTS AND MAIN RESULTS: Patients were classified by pediatric-modified Risk, Injury, Failure, Loss, End-stage renal disease score at admission and worst pediatric-modified Risk, Injury, Failure, Loss, End-stage renal disease score during PICU hospitalization. The outcomes of interest were length of PICU stay, duration of mechanical ventilation, duration of vasoactive drug therapy, and mortality. The Pediatric Index of Mortality 2 was used to assess overall disease severity at the time of PICU admission. Of 375 patients, 169 (45%) presented acute kidney injury at the time of admission and 37 developed acute kidney injury during PICU stay, for a total of 206 of 375 patients (55%) diagnosed with acute kidney injury during the study period. The median Pediatric Index of Mortality 2 score predicted a mortality rate of 9% among non-acute kidney injury patients versus a mortality rate of 16% among acute kidney injury patients (p = 0.006). The mortality of patients classified as pediatric-modified Risk, Injury, Failure, Loss, End-stage renal disease F was double that predicted by Pediatric Index of Mortality 2 (7 vs 3.2). Patients classified as having severe acute kidney injury (pediatric-modified Risk, Injury, Failure, Loss, End-stage renal disease I + F) exhibited higher mortality (14.1%; p = 0.001) and prolonged PICU length of stay (median, 7 d; p = 0.001) when compared with other patients. Acute kidney injury is a very frequent occurrence among patients admitted to PICUs. CONCLUSIONS: The degree of acute kidney injury severity, as assessed by the pediatric-modified Risk, Injury, Failure, Loss, End-stage renal disease criteria, is a good predictor of morbidity and mortality in this population. Pediatric Index of Mortality 2 tends to underestimate mortality in pediatric patients with severe acute kidney injury.

Mitigating Latent Threats Identified through an Embedded In Situ Simulation Program and Their Comparison to Patient Safety Incidents: A Retrospective Review.

OBJECTIVE: To assess the impact of service improvements implemented because of latent threats (LTs) detected during in situ simulation. DESIGN: Retrospective review from April 2008 to April 2015. SETTING: Paediatric Intensive Care Unit in a specialist tertiary hospital. INTERVENTION: Service improvements from LTs detection during in situ simulation. Action plans from patient safety incidents (PSIs). MAIN OUTCOME MEASURES: The quantity, category, and subsequent service improvements for LTs. The quantity, category, and subsequent action plans for PSIs. Similarities between PSIs and LTs before and after service improvements. RESULTS: 201 Simulated inter-professional team training courses with 1,144 inter-professional participants. 44 LTs were identified (1 LT per 4.6 courses). Incident severity varied: 18 (41%) with the potential to cause harm, 20 (46%) that would have caused minimal harm, and 6 (13%) that would have caused significant temporary harm. Category analysis revealed the majority of LTs were resources (36%) and education and training (27%). The remainder consisted of equipment (11%), organizational and strategic (7%), work and environment (7%), medication (7%), and systems and protocols (5%). 43 service improvements were developed: 24 (55%) resources/equipment; 9 (21%) educational; 6 (14%) organizational changes; 2 (5%) staff communications; and 2 (5%) guidelines. Four (9%) service improvements were adopted trust wide. 32 (73%) LTs did not recur after service improvements. 24 (1%) of 1,946 PSIs were similar to LTs: 7 resource incidents, 7 catastrophic blood loss, 4 hyperkalaemia arrests, 3 emergency buzzer failures, and 3 difficulties contacting staff. 34 LTs (77%) were never recorded as PSIs. CONCLUSION: An in situ simulation program can identify important LTs which traditional reporting systems miss. Subsequent improvements in workplace systems and resources can improve efficiency and remove error traps.