Ayse Akcan Arikan

Fluid overload is associated with impaired oxygenation and morbidity in critically ill children

Rationale: Fluid overload is common in the critically ill and is thought to contribute to oxygenation failure and mortality. Since increasing disease severity often requires more fluid for resuscitation, it is unclear whether fluid overload is a causative factor in morbidity or is simply an indicator of disease severity. Objective: Investigate the association between fluid overload and oxygenation while controlling for severity of illness by daily Pediatric Logistic Organ Dysfunction scores. Design and Setting: Retrospective chart review, tertiary children’s hospital. Patients and Methods: The oxygenation index, fluid overload percent, and daily Pediatric Logistic Organ Dysfunction scores were obtained in a retrospective chart review of 80 patients (mean age 58.7 ± 73.0 months) with respiratory failure. Univariate and multivariate approaches were used to assess the independent relation between fluid overload percent and duration of stay and ventilation. Interventions: None. Main Results: Higher peak fluid overload percent predicted higher peak oxygenation index, independent of age, gender, and Pediatric Logistic Organ Dysfunction (p = .009). Fluid overload percent ≥15% on any given day was also independently associated with that day’s oxygenation index, controlled for age, gender, and Pediatric Logistic Organ Dysfunction (p < .05). Peak fluid overload percent and severe fluid overload percent (≥15%) were both independently associated with longer duration of ventilation (p = .004, p = .01), and pediatric intensive care unit (p = .008, p = .01) and hospital length of stay (p = .02, p = .04), controlled for age, gender, Pediatric Logistic Organ Dysfunction, and in the case of ventilation, respiratory admission. Conclusion: This is the first study to report that positive fluid balance adversely affected the pediatric intensive care unit course in children who did not receive renal replacement therapy. While timely administration of fluids is lifesaving, positive fluid balance after hemodynamic stabilization may impact organ function and negatively influence important outcomes in critically ill patients.

Vancomycin-associated acute kidney injury in pediatric cardiac intensive care patients.

OBJECTIVE Acute kidney injury (AKI) is a significant source of morbidity among critically ill pediatric patients, including those that have undergone cardiac surgery. Vancomycin may contribute to AKI in pediatric patients admitted to a cardiac intensive care unit. DESIGN AND SETTING Patients admitted to the cardiac intensive care unit at Texas Childrens Hospital and received vancomycin over a 4-year period were included in a case-control study. Patients were excluded if they underwent renal replacement therapy during vancomycin therapy. Patient demographic and disease state variables, vancomycin therapy variables, and use of other nephrotoxic medications were collected. The overall incidence of AKI was calculated based on doubling of serum creatinine during or within 72 hours of vancomycin therapy (vancomycin-associated AKI [vAKI]). Patients who developed vAKI were matched with three patients who did not develop vAKI, and conditional logistic regression was used to determine independent risk factors for vAKI. RESULTS A total of 418 patients met study criteria (males 57.8%) and infants (31 days to 2 years) were the most populous age group (48.6%). Vancomycin-associated AKI occurred in 30 patients (7.2%), which resulted in a total of 120 patients (30 cases; 90 controls). No significant differences were noted in vancomycin dosing between groups. Vancomycin-associated AKI patients were less likely to have undergone cardiac surgery (P < .05), more likely to have undergone extracorporeal membrane oxygenation (P < .05), and had greater exposure to nephrotoxic medications (P < .05). A conditional logistic regression model identified extracorporeal membrane oxygenation as associated with vAKI (odds ratio 14.4, 95% confidence interval 1.02-203, P = .048) and patients with prior cardiovascular surgery (odds ratio 0.10, 95% confidence interval 0.02-0.51, P < .01) or an elevated baseline serum creatinine (odds ratio 0.009, 95% confidence interval 0.0002-0.29, P < .01) as less likely to develop vAKI. CONCLUSIONS Vancomycin-associated AKI occurs infrequently in the pediatric cardiac intensive care population and is strongly associated with patient critical illness.

Resuscitation Bundle in Pediatric Shock Decreases Acute Kidney Injury and Improves Outcomes

OBJECTIVE To investigate the impact of an early emergency department (ED) protocol-driven resuscitation (septic shock protocol [SSP]) on the incidence of acute kidney injury (AKI). STUDY DESIGN This was a retrospective pediatric cohort with clinical sepsis admitted to the pediatric intensive care unit (PICU) from the ED before (2009, PRE) and after (2010, POST) implementation of the SSP. AKI was defined by pRIFLE (pediatric version of the Risk of renal dysfunction; Injury to kidney; Failure of kidney function; Loss of kidney function, End-stage renal disease creatinine criteria). RESULTS A total of 202 patients (PRE, n = 98; POST, n = 104) were included (53% male, mean age 7.7 ± 5.6 years, mean Pediatric Logistic Organ Dysfunction [PELOD] 8.9 ± 12.7, mean Pediatric Risk of Mortality score 5.3 ± 13.9). There were no differences in demographics or illness severity between the PRE and POST groups. POST was associated with decreased AKI (54% vs 29%, P < .001), renal-replacement therapy (4 vs 0, P = .04), PICU, and hospital lengths of stay (LOS) (1.9 ± 2.3 vs 4.5 ± 7.6, P < .01; 6.3 ± 5.1 vs 15.3 ± 16.9, P < .001, respectively), and mortality (10% vs 3%, P = .037). The SSP was independently associated with decreased AKI when we controlled for age, sex, and PELOD (OR 0.27, CI 0.13-0.56). In multivariate analyses, the SSP was independently associated with shorter PICU and hospital LOS when we controlled for AKI and PELOD (P = .02, P < .001, respectively). CONCLUSION A protocol-driven implementation of a resuscitation bundle in the pediatric ED decreased AKI and need for renal-replacement therapy, as well as PICU and hospital LOS and mortality.

Interleukin-6 treatment reverses apoptosis and blunts susceptibility to intraperitoneal bacterial challenge following hemorrhagic shock*

Background:Resuscitation from hemorrhagic shock (HS) predisposes to subsequent infections. Susceptibility to infection following sepsis has been attributed to apoptosis. Interleukin (IL)-6 has been shown to have antiapoptotic properties and to decrease postresuscitation inflammation in rodent and porcine models of HS. Objective:The objective was to determine if HS increases host susceptibility to infection, if IL-6 administration at resuscitation reduces this susceptibility, and if changes in susceptibility to infection are accompanied by parallel changes in apoptosis. Subjects and Interventions:Mice were randomized into three groups—HS, sham, and no-surgery control—and each group was further randomized to receive either IL-6 (3 &mgr;g/kg; HS/IL-6) or placebo (HS/P) at the start of resuscitation. In the HS-infection protocol, each mouse was challenged intraperitoneally the next day with a sublethal dose of Staphylococcus aureus (4 × 107 colony-forming units); 24 hrs later, the peritoneal cavity was lavaged and the major organs were harvested for culture. In the HS-apoptosis protocol, the livers were harvested the next day and analyzed by means of the terminal deoxynucleotidyl transferase dUTP-biotin nick-end-labeling (TUNEL) assay. Results:HS/P mice had a six- to eight-fold increase in total bacterial counts in comparison with sham and control mice that was attributable to a seven- to nine-fold increase in liver burden. IL-6 treatment reduced total and liver bacterial counts in HS/IL-6 mice by 62% and 69%, respectively, to levels statistically indistinguishable from IL-6-treated sham and control mice. The number of TUNEL-positive liver cells in the HS/P group was increased eight-fold vs. that in the sham group (p = .002); IL-6 resuscitation completely reversed the HS-induced increase in TUNEL-positive cells in the HS/IL-6 group (p = .002). Conclusions:IL-6 treatment at resuscitation eliminated the HS-mediated increase in total and liver bacterial burden and protected the liver from HS-induced apoptosis. Reduced liver apoptosis may explain the ability of IL-6 to blunt the HS-induced increase in susceptibility to bacterial challenge.

IL-6-Mediated Activation of Stat3α Prevents Trauma/Hemorrhagic Shock-Induced Liver Inflammation

Trauma complicated by hemorrhagic shock (T/HS) is the leading cause of morbidity and mortality in the United States for individuals under the age of 44 years. Initial survivors are susceptible to developing multiple organ failure (MOF), which is thought to be caused, at least in part, by excessive or maladaptive activation of inflammatory pathways. We previously demonstrated in rodents that T/HS results in liver injury that can be prevented by IL-6 administration at the start of resuscitation; however, the contribution of the severity of HS to the extent of liver injury, whether or not resuscitation is required, and the mechanism(s) for the IL-6 protective effect have not been reported. In the experiments described here, we demonstrated that the extent of liver inflammation induced by T/HS depends on the duration of hypotension and requires resuscitation. We established that IL-6 administration at the start of resuscitation is capable of completely reversing liver inflammation and is associated with increased Stat3 activation. Global assessment of the livers showed that the main effect of IL-6 was to normalize the T/HS-induced inflammation transcriptome. Pharmacological inhibition of Stat3 activity within the liver blocked the ability of IL-6 to prevent liver inflammation and to normalize the T/HS-induced liver inflammation transcriptome. Genetic deletion of a Stat3β, a naturally occurring, dominant-negative isoform of the Stat3, attenuated T/HS-induced liver inflammation, confirming a role for Stat3, especially Stat3α, in preventing T/HS-mediated liver inflammation. Thus, T/HS-induced liver inflammation depends on the duration of hypotension and requires resuscitation; IL-6 administration at the start of resuscitation reverses T/HS-induced liver inflammation, through activation of Stat3α, which normalized the T/HS-induced liver inflammation transcriptome.

Regional citrate anticoagulation for continuous renal replacement therapy in pediatric patients with liver failure

Pediatric liver failure patients frequently develop multiple organ failure and require continuous renal replacement therapy (CRRT) as part of supportive therapy in the pediatric intensive care unit. While many centers employ no anticoagulation for fear of bleeding complications, balanced coagulation disturbance predisposes these patients to clotting as well as bleeding, making maintenance of longer circuit life to deliver adequate dialysis clearance challenging. Regional citrate anticoagulation (RCA) is an attractive option as it avoids systemic anticoagulation, but since citrate metabolism is impaired in liver failure, concerns about toxicity has limited its use. Pediatric data on RCA with liver failure is very scarce. We aimed to establish safety and efficacy of RCA in pediatric liver failure patients on CRRT. Retrospective review of pediatric patients with liver failure receiving CRRT over 30 months. Demographic data and CRRT related data were collected by chart review. Citrate accumulation (CA) was defined as total calcium (mg/dl) /ionized calcium (mmol/L) ratio >2.5 for > 48 hours. Efficacy was assessed by filter life. Safety was assessed by frequency of adverse events ((AEs) defined as bleeding, hemodynamic instability, arrhythmias). Fifty-one patients (median age 3.5 (IQR 0.75–14.2) years) received 861 CRRT days; 70% experienced at least one episode of CA, only 37% were recorded as such in the medical record. AE rate was 93/1000 CRRT days and did not differ between CA days and others. Median filter life was 66 hours (IQR 29–74); 63% filters lasted longer than 48 hrs. Though common, CA was not associated with increased AEs on in pediatric liver failure patients on CRRT receiving RCA. Filter life was adequate. RCA appears an effective anticoagulation for CRRT in pediatric liver failure. Application of a structured definition would increase recognition of CA to allow timely intervention.

Clinical Consequences of Cardiomyopathy in Children with Biliary Atresia Requiring Liver Transplantation

Cirrhotic cardiomyopathy (CCM), a comorbidity of end‐stage cirrhotic liver disease, remains uncharacterized in children, largely because of a lack of an established pediatric definition. The aim of this retrospective cohort analysis is to derive objective two‐dimensional echocardiographic (2DE) criteria to define CCM associated with biliary atresia (BA), or BA‐CCM, and correlate presence of BA‐CCM with liver transplant (LT) outcomes in this population. Using receiver operating characteristic (ROC) curve analysis, optimal cut‐off values for left ventricular (LV) geometrical parameters that were highly sensitive and specific for the primary outcomes: A composite of serious adverse events (CSAE) and peritransplant death were determined. These results were used to propose a working definition for BA‐CCM: (1) LV mass index (LVMI) ≥95 g/m2.7 or (2) relative wall thickness of LV ≥0.42. Applying these criteria, BA‐CCM was found in 34 of 69 (49%) patients with BA listed for LT and was associated with increased multiorgan dysfunction, mechanical and vasopressor support, and longer intensive care unit (ICU) and hospital stays. BA‐CCM was present in all 4 waitlist deaths, 7 posttransplant deaths, and 20 patients with a CSAE (P < 0.01). On multivariable regression analysis, BA‐CCM remained independently associated with both death and a CSAE (P < 0.01). Utilizing ROC analysis, LVMI was found to be a stronger predictor for adverse outcomes compared with current well‐established markers, including Pediatric End‐Stage Liver Disease (PELD) score. Conclusion: BA‐CCM is highly sensitive and specific for morbidity and mortality in children with BA listed for LT. 2DE screening for BA‐CCM may provide pertinent clinical information for prioritization and optimal peritransplant management of these children.

The Safety and Efficacy of Regional Citrate Anticoagulation in Albumin-Assisted Liver Dialysis for Extracorporeal Liver Support in Pediatric Patients

Aims: To establish the safety and efficacy of regional citrate anticoagulation (RCA) for pediatric liver failure (LF) patients receiving extracorporeal liver support (ELS) with albumin-assisted dialysis. Methods: Retrospective review of pediatric LF patients receiving ELS from April 2014 to December 2016 at a tertiary children’s hospital pediatric intensive care unit. Demographic and ELS data collected by chart review. Citrate accumulation (CA) was defined as total calcium (mmol/L): ionized calcium (mmol/L) > 2.5 (tCa:iCa). Efficacy was assessed by treatment duration. Safety was assessed by adverse events: bleeding, hemodynamic instability, arrhythmias, unplanned treatment discontinuation. Results: Fifteen patients (median age 3 [interquartile range (IQR) 0.7–8.0]) received 108 ELS treatments (median 5 [IQR 4–7.5]). Sixty-eight episodes of CA were identified. Of those, 6 coincided with intervention and 1 coincided with ELS discontinuation. There were no deaths attributed to ELS or RCA. Conclusion: RCA provides safe and effective anticoagulation for pediatric LF patients requiring ELS.

937: RECOGNITION OF FLUID OVERLOAD IN PEDIATRIC CRITICALLY ILL PATIENTS

Crit Care Med 2015 • Volume 43 • Number 12 (Suppl.) rated patient care as excellent or superior (4 or 5 on 5-level Likert scale), only 67% of participants rated overall communication as excellent or superior. Conclusions: Up to one-third of of SICU patients and their family members did not understand complex provider team structures. Further, satisfaction with provider-patient communication was significantly lower than satisfaction with overall patient care. Based on these results, an ICU Provider Identification tool is being developed to improve patient-provider communication, and its effect on overall patient satisfaction.

142: OUTCOMES OF PEDIATRIC CARDIAC PATIENTS WITH ACUTE KIDNEY INJURY AT RAPID RESPONSE EVENTS

Crit Care Med 2015 • Volume 43 • Number 12 (Suppl.) aVR, aVL, and aVF). We used the sum of the average QRS amplitudes for all the 6 limb leads as the overall QRS amplitude. V lead was not included because it is more sensitive to the posture of a patient. A linear regression between QRS amplitude and BNP level was calculated for each patient, and the percentage of patients with positive/negative correlation was reported. Results: The study consisted of 45 patients with more than 1 BNP lab test while admitted to the ICU from March 2013 to March 2015. Among the 45 patients, 51.1% (23/45) had a negative correlation between QRS amplitude and BNP level, while the other 48.9% (22/45) had a positive correlation. Conclusions: While the intrapatient changes of QRS amplitude alone cannot predict changes of BNP level, there may be other confounding variables such as body weight, treatment for establishing the relationship between serial QRS amplitudes and BNP levels. This will be the focus of a future study.