Brian C. Bridges

Renal Replacement Therapy in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation (ECMO) is a lifesaving procedure used in neonates, children, and adults with severe, reversible, cardiopulmonary failure. On the basis of single-center studies, the incidence of AKI occurs in 70%-85% of ECMO patients. Those with AKI and those who require renal replacement therapy (RRT) are at high risk for mortality, independent of potentially confounding variables. Fluid overload is common in ECMO patients, and is one of the main indications for RRT. RRT to maintain fluid balance and metabolic control is common in some but not all centers. RRT on ECMO can be performed via an in-line hemofilter or by incorporating a standard continuous renal replacement machine into the ECMO circuit. Both of these methods require specific technical considerations to provide safe and effective RRT. This review summarizes available epidemiologic data and how they apply to our understanding of AKI pathophysiology during ECMO, identifies indications for RRT while on ECMO, reviews technical elements for RRT application in the setting of ECMO, and finally identifies specific research-focused questions that need to be addressed to improve outcomes in this at-risk population.

A multicenter international survey of renal supportive therapy during ECMO: The Kidney Intervention during Extracorporeal Membrane Oxygenation (KIDMO) group

Acute kidney injury and fluid overload (FO) are associated with increased mortality in critically ill patients, including the subset supported with extracorporeal membrane oxygenation (ECMO). The indication for and method of application of renal support therapy (RST) during ECMO is largely unknown beyond single-center experiences. The current study uses a survey design to document practice variation regarding RST, including indication, method of interface with the ECMO circuit, and prescribing practices. Sixty-five international ECMO centers (31%) responded to an online electronic survey regarding RST during ECMO. Nearly a quarter of centers (23%) reported using no RST during ECMO. Among those using the therapy, the predominant mode of therapy applied was convection and included slow continuous ultrafiltration and continuous venovenous hemofiltration. The predominant indication for RST was the treatment (43%) or prevention (16%) of FO. Nephrology rather than critical care medicine is reported as the prescribing service in a majority of centers with a significant difference between US centers and non-US centers. The results of this study identify a wide variation in practice regarding RST during ECMO that will offer multiple important avenues for further research by this group and others regarding the interface of RST and ECMO.

Continuous glucose monitors prove highly accurate in critically ill children.

IntroductionHyperglycemia is associated with increased morbidity and mortality in critically ill patients and strict glycemic control has become standard care for adults. Recent studies have questioned the optimal targets for such management and reported increased rates of iatrogenic hypoglycemia in both critically ill children and adults. The ability to provide accurate, real-time continuous glucose monitoring would improve the efficacy and safety of this practice in critically ill patients. The aim of our study is to determine if a continuous, interstitial glucose monitor will correlate with blood glucose values in critically ill children.MethodsWe evaluated 50 critically ill children age 6 weeks to 16 years old with a commercially available continuous glucose monitor (CGM; Medtronic Guardian®). CGM values and standard blood glucose (BG) values were compared. During the study, no changes in patient management were made based on CGM readings alone.ResultsForty-seven patients had analyzable CGM data. A total of 1,555 CGM and routine BG measurements were compared using Clarke error grid and Bland-Altman analysis. For all readings, 97.9% were within clinically acceptable agreement. The mean absolute relative difference between CGM and BG readings was 15.3%. For the 1,555 paired CGM and BG measurements, there is a statistically significant linear relationship between CGM values and BG (P <.0001). A high degree of clinical agreement existed in three subpopulation analyses based on age, illness severity, and support measures. This included some of our smallest patients (that is, <12 months old), those who required vasopressors, and those who were treated for critical illness hyperglycemia.ConclusionsIn one of the largest studies to date, in a highly vulnerable ICU population, CGM values have a clinically acceptable correlation with the BG values now used diagnostically and therapeutically. Our data contest the theoretical concerns posed by some regarding CGM use in the ICU. The existing medical evidence may now support a role for CGM devices in the identification and management of hyperglycemia in diverse ICU settings.

Acute Kidney Injury Incidence in Noncritically Ill Hospitalized Children, Adolescents, and Young Adults: A Retrospective Observational Study

BACKGROUND Acute kidney injury (AKI) has been characterized in high-risk pediatric hospital inpatients, in whom AKI is frequent and associated with increased mortality, morbidity, and length of stay. The incidence of AKI among patients not requiring intensive care is unknown. STUDY DESIGN Retrospective cohort study. SETTING & PARTICIPANTS 13,914 noncritical admissions during 2011 and 2012 at our tertiary referral pediatric hospital were evaluated. Patients younger than 28 days or older than 21 years of age or with chronic kidney disease (CKD) were excluded. Admissions with 2 or more serum creatinine measurements were evaluated. FACTORS Demographic features, laboratory measurements, medication exposures, and length of stay. OUTCOME AKI defined as increased serum creatinine level in accordance with KDIGO (Kidney Disease: Improving Global Outcomes) criteria. Based on time of admission, time interval requirements were met in 97% of cases, but KDIGO time window criteria were not strictly enforced to allow implementation using clinically obtained data. RESULTS 2 or more creatinine measurements (one baseline before or during admission and a second during admission) in 2,374 of 13,914 (17%) patients allowed for AKI evaluation. A serum creatinine difference ≥0.3mg/dL or ≥1.5 times baseline was seen in 722 of 2,374 (30%) patients. A minimum of 5% of all noncritical inpatients without CKD in pediatric wards have an episode of AKI during routine hospital admission. LIMITATIONS Urine output, glomerular filtration rate, and time interval criteria for AKI were not applied secondary to study design and available data. The evaluated cohort was restricted to patients with 2 or more clinically obtained serum creatinine measurements, and baseline creatinine level may have been measured after the AKI episode. CONCLUSIONS AKI occurs in at least 5% of all noncritically ill hospitalized children, adolescents, and young adults without known CKD. Physicians should increase their awareness of AKI and improve surveillance strategies with serum creatinine measurements in this population so that exacerbating factors such as nephrotoxic medication exposures may be modified as indicated.

The use of an extracorporeal membrane oxygenation anticoagulation laboratory protocol is associated with decreased blood product use, decreased hemorrhagic complications, and increased circuit life.

Objectives: To determine if a comprehensive extracorporeal membrane oxygenation anticoagulation monitoring protocol results in fewer hemorrhagic complications, reduced blood product usage, and increased circuit life. Design: In September 2011, we augmented our standard extracorporeal membrane oxygenation laboratory protocol to include anti-factor Xa assays, thromboelastography, and antithrombin measurements. We performed a retrospective chart review to determine outcomes for patients placed on extracorporeal membrane oxygenation prior to and after the initiation of our anticoagulation laboratory protocol. Setting: Tertiary care, academic children’s hospital. Patients: All patients who were placed on extracorporeal membrane oxygenation at our institution from January 1, 2007, to September 30, 2013. Interventions: None. Measurements and Main Results: There were 261 extracorporeal membrane oxygenation runs before the initiation of the protocol and 105 extracorporeal membrane oxygenation runs after the initiation of the protocol. There were no major changes to our extracorporeal membrane oxygenation circuit or changes to our transfusion threshold during the study period. The indication for extracorporeal membrane oxygenation, age, and severity of illness of the patients were similar before and after protocol initiation. Median blood product usage for packed RBCs, fresh frozen plasma, platelets, and cryoprecipitate decreased significantly after protocol initiation. The occurrence of cannula site bleeding decreased from 22% to 12% (p = 0.04), and surgical site bleeding decreased from 38% to 25% (p = 0.02). Median extracorporeal membrane oxygenation circuit life increased from 3.6 to 4.3 days (p = 0.02). A trend toward increased patient survival was noted, but it did not reach statistical significance. Conclusions: We demonstrate an association between an extracorporeal membrane oxygenation anticoagulation laboratory protocol using anti-factor Xa assays, thromboelastography, and antithrombin measurements and a decrease in blood product transfusion, a decrease in hemorrhagic complications, and an increase in circuit life. To our knowledge, this is the first study to demonstrate clinical benefit associated with the use of these laboratory values for patients on extracorporeal membrane oxygenation.

The Incidence of Acute Kidney Injury and Its Effect on Neonatal and Pediatric Extracorporeal Membrane Oxygenation Outcomes: A Multicenter Report From the Kidney Intervention During Extracorporeal Membrane Oxygenation Study Group

Objective: In a population of neonatal and pediatric patients on extracorporeal membrane oxygenation; to describe the prevalence and timing of acute kidney injury utilizing a consensus acute kidney injury definition and investigate the association of acute kidney injury with outcomes (length of extracorporeal membrane oxygenation and mortality). Design: Multicenter retrospective observational cohort study. Setting: Six pediatric extracorporeal membrane oxygenation centers. Patients: Pediatric patients (age, < 18 yr) on extracorporeal membrane oxygenation at six centers during a period of January 1, 2007, to December 31, 2011. Interventions: None. Measurements and Main Results: Complete data were analyzed for 832 patients on extracorporeal membrane oxygenation. Sixty percent of patients had acute kidney injury utilizing the serum creatinine Kidney Disease Improving Global Outcomes criteria (AKISCr) and 74% had acute kidney injury using the full Kidney Disease Improving Global Outcomes criteria including renal support therapy (AKISCr + RST). Of those who developed acute kidney injury, it was present at extracorporeal membrane oxygenation initiation in a majority of cases (52% AKISCr and 65% AKISCr + RST) and present by 48 hours of extracorporeal membrane oxygenation support in 86% (AKISCr) and 93% (AKISCr + RST). When adjusted for patient age, center of support, mode of support, patient complications and preextracorporeal membrane oxygenation pH, the presence of acute kidney injury by either criteria was associated with a significantly longer duration of extracorporeal membrane oxygenation support (AKISCr, 152 vs 110 hr; AKISCr + RST, 153 vs 99 hr) and increased adjusted odds of mortality at hospital discharge (AKISCr: odds ratio, 1.77; 1.22–2.55 and AKISCr + RST: odds ratio, 2.50; 1.61–3.90). With the addition of renal support therapy to the model, acute kidney injury was associated with a longer duration of extracorporeal membrane oxygenation support (AKISCr, 149 vs 121 hr) and increased risk of mortality at hospital discharge (AKISCr: odds ratio, 1.52; 1.04–2.21). Conclusion: Acute kidney injury is present in 60–74% of neonatal-pediatric patients supported on extracorporeal membrane oxygenation and is present by 48 hours of extracorporeal membrane oxygenation support in 86–93% of cases. Acute kidney injury has a significant association with increased duration of extracorporeal membrane oxygenation support and increased adjusted odds of mortality at hospital discharge.Objective In a population of neonatal and pediatric patients on extracorporeal membrane oxygenation (ECMO); to describe the incidence and timing of acute kidney injury (AKI) utilizing a consensus AKI definition and investigate the association of AKI with outcomes (length of ECMO and mortality).

The Impact of Fluid Overload on Outcomes in Children Treated with Extracorporeal Membrane Oxygenation: A Multicenter Retrospective Cohort Study

Objective: To characterize the epidemiology of fluid overload and its association with mortality and duration of extracorporeal membrane oxygenation in children treated with extracorporeal membrane oxygenation. Design: Retrospective cohort study. Setting: Six tertiary children’s hospital ICUs. Patients: Seven hundred fifty-six children younger than 18 years old treated with extracorporeal membrane oxygenation for greater than or equal to 24 hours from January 1, 2007, to December 31, 2011. Interventions: None. Measurements and Main Results: Overall survival to extracorporeal membrane oxygenation decannulation and hospital discharge was 74.9% (n = 566) and 57.7% (n = 436), respectively. Median fluid overload at extracorporeal membrane oxygenation initiation was 8.8% (interquartile range, 0.3–19.2), and it differed between hospital survivors and non survival, though not between extracorporeal membrane oxygenation survivors and non survivors. Median peak fluid overload on extracorporeal membrane oxygenation was 30.9% (interquartile range, 15.4–54.8). During extracorporeal membrane oxygenation, 84.8% had a peak fluid overload greater than or equal to 10%; 67.2% of patients had a peak fluid overload of greater than or equal to 20% and 29% of patients had a peak fluid overload of greater than or equal to 50%. The median peak fluid overload was lower in patients who survived on extracorporeal membrane oxygenation (27.2% vs 44.4%; p < 0.0001) and survived to hospital discharge (24.8% vs 43.3%; p < 0.0001). After adjusting for acute kidney injury, pH at extracorporeal membrane oxygenation initiation, nonrenal complications, extracorporeal membrane oxygenation mode, support type, center and patient age, the degree of fluid overload at extracorporeal membrane oxygenation initiation (p = 0.05), and the peak fluid overload on extracorporeal membrane oxygenation (p < 0.0001) predicted duration of extracorporeal membrane oxygenation in survivors. Multivariable analysis showed that peak fluid overload on extracorporeal membrane oxygenation (adjusted odds ratio, 1.09; 95% CI, 1.04–1.15) predicted mortality on extracorporeal membrane oxygenation; fluid overload at extracorporeal membrane oxygenation initiation (adjusted odds ratio, 1.13; 95% CI, 1.05–1.22) and peak fluid overload (adjusted odds ratio, 1.18; 95% CI, 1.12–1.24) both predicted hospital morality. Conclusions: Fluid overload occurs commonly and is independently associated with adverse outcomes including increased mortality and increased duration of extracorporeal membrane oxygenation in a broad pediatric extracorporeal membrane oxygenation population. These results suggest that fluid overload is a potential target for intervention to improve outcomes in children on extracorporeal membrane oxygenation.

A case series of the successful use of ECMO, continuous renal replacement therapy, and plasma exchange for thrombocytopenia-associated multiple organ failure

We present three cases of pediatric patients with thrombocytopenia-associated multiple organ failure and the evidence for providing extracorporeal organ support. All three patients had severe cardiac dysfunction, respiratory failure, and acute kidney injury treated with venoarterial extracorporeal membrane oxygenation, continuous renal replacement therapy, and plasma exchange. Despite the presence of multiple organ failure and high risk of mortality, all three patients survived with minimal long-term sequelae.

Electronic health record-based predictive models for acute kidney injury screening in pediatric inpatients

BackgroundAcute kidney injury (AKI) is common in pediatric inpatients and is associated with increased morbidity, mortality, and length of stay. Its early identification can reduce severity.MethodsTo create and validate an electronic health record (EHR)-based AKI screening tool, we generated temporally distinct development and validation cohorts using retrospective data from our tertiary care children’s hospital, including children aged 28 days through 21 years with sufficient serum creatinine measurements to determine AKI status. AKI was defined as 1.5-fold or 0.3 mg/dl increase in serum creatinine. Age, medication exposures, platelet count, red blood cell distribution width, serum phosphorus, serum transaminases, hypotension (ICU only), and pH (ICU only) were included in AKI risk prediction models.ResultsFor ICU patients, 791/1,332 (59%) of the development cohort and 470/866 (54%) of the validation cohort had AKI. In external validation, the ICU prediction model had a c-statistic=0.74 (95% confidence interval 0.71–0.77). For non-ICU patients, 722/2,337 (31%) of the development cohort and 469/1,474 (32%) of the validation cohort had AKI, and the prediction model had a c-statistic=0.69 (95% confidence interval 0.66–0.72).ConclusionsAKI screening can be performed using EHR data. The AKI screening tool can be incorporated into EHR systems to identify high-risk patients without serum creatinine data, enabling targeted laboratory testing, early AKI identification, and modification of care.

Extracorporeal Cardiopulmonary Resuscitation Among Patients with Structurally Normal Hearts

Extracorporeal cardiopulmonary resuscitation (eCPR) has been well described as a rescue therapy in refractory cardiac arrest among patients with congenital heart disease. The purpose of this retrospective analysis of data from the Extracorporeal Life Support Organization was to evaluate outcomes of eCPR in patients with structurally normal hearts and to identify risk factors that may contribute to mortality. During the study period, 1,431 patients met inclusion criteria. Median age was 16 years. Overall survival to hospital discharge was 32%. Conditional logistic regression demonstrated an independent survival benefit among smaller patients, patients with a lower partial pressure of carbon dioxide (PaCO2) on cannulation, and those with a shorter duration from intubation to eCPR cannulation. A diagnosis of sepsis was independently associated with a nearly threefold increase in odds of mortality, whereas the diagnosis of myocarditis portended a more favorable outcome. Neurologic complications, pulmonary hemorrhage, disseminated intravascular coagulation, CPR, pH less than 7.20, and hyperbilirubinemia after eCPR cannulation were independently associated with an increase in odds of mortality. When utilizing eCPR in patients with structurally normal hearts, a diagnosis of sepsis is independently associated with mortality, whereas a diagnosis of myocarditis is protective. Neurologic complications and pulmonary hemorrhage while on extracorporeal membrane oxygenation (ECMO) are independently associated with mortality.