David M. Axelrod

A continuous heparin infusion does not prevent catheter-related thrombosis in infants after cardiac surgery.

Objective: To determine whether a continuous infusion of heparin reduces the rate of catheter-related thrombosis in neonates and infants post cardiac surgery. Central venous and intracardiac catheters are used routinely in postoperative pediatric cardiac patients. Catheter-related thrombosis occurs in 8% to 45% of pediatric patients with central venous catheters. Design: Single-center, randomized, placebo-controlled, double-blinded trial. Setting: Cardiovascular intensive care unit, university-affiliated childrens hospital. Patients: Children <1 yr of age recovering from cardiac surgery. Interventions: Patients were randomized to receive either continuous heparin at 10 units/kg/hr or placebo. The primary end point was catheter-related thrombosis as assessed by serial ultrasonography. Results: Study enrollment was discontinued early based on results from an interim futility analysis. Ninety subjects were enrolled and received the study drug (heparin, 53; placebo, 37). The catheter-related thrombosis rate in the heparin group, compared with the placebo group, was 15% vs. 16% (p = .89). Subjects in the heparin group had a higher mean partial thromboplastin time (52 secs vs. 42 secs, p = .001), and this difference was greater for those aged <30 days (64 secs vs. 43 secs, p = .008). Catheters in place ≥7 days had both a greater risk of thrombus formation (odds ratio, 4.3; p = .02) and catheter malfunction (odds ratio, 11.2; p = .008). We observed no significant differences in other outcome measures or in the frequency of adverse events. Conclusions: A continuous infusion of heparin at 10 units/kg/hr was safe but did not reduce catheter-related thrombus formation. Heparin at this dose caused an increase in partial thromboplastin time values, which, unexpectedly, was more pronounced in neonates.

A Double-Blinded, Randomized, Placebo-Controlled Clinical Trial of Aminophylline to Prevent Acute Kidney Injury in Children Following Congenital Heart Surgery With Cardiopulmonary Bypass.

Objectives: Acute kidney injury occurs commonly in children following congenital cardiac surgery with cardiopulmonary bypass and has been associated with increased morbidity and mortality. Aminophylline, a methylxanthine nonselective adenosine receptor antagonist, has been effective in the management of acute kidney injury in certain populations. This study sought to determine whether postoperative administration of aminophylline attenuates acute kidney injury in children undergoing congenital cardiac surgery with cardiopulmonary bypass. Design: Single-center, double-blinded, placebo-controlled, randomized clinical trial. Setting: Tertiary center, pediatric cardiovascular ICU. Patients: A total of 144 children after congenital heart surgery with cardiopulmonary bypass. Interventions: Seventy-two patients were randomized to receive aminophylline and 72 patients received placebo. Study drug was administered every 6 hours for 72 hours. Measurements and Main Results: The primary outcome variable was the development of any acute kidney injury, defined by the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes. Secondary outcomes included the development of severe acute kidney injury, time between cardiovascular ICU admission and first successful extubation, percent fluid overload, total fluid balance, urine output, bioelectrical impedance, and serum neutrophil gelatinase–associated lipocalin. The unadjusted rate and severity of acute kidney injury were not different between groups; 43 of 72 (60%) of the treatment group and 36 of 72 (50%) of the placebo group developed acute kidney injury (p = 0.32). Stage 2/3 acute kidney injury occurred in 23 of 72 (32%) of the treatment group and 15 of 72 (21%) of the placebo group (p = 0.18). Secondary outcome measures also demonstrated no significant difference between treatment and placebo groups. Aminophylline administration was safe; no deaths occurred in either group, and rates of adverse events were similar (14% in the treatment group vs 18% in the placebo group; p = 0.30). Conclusions: In this placebo-controlled randomized clinical trial, we found no effect of aminophylline to prevent acute kidney injury in children recovering from cardiac surgery performed with cardiopulmonary bypass. Future study of preoperative aminophylline administration to prevent acute kidney injury may be warranted.

Initial experience using aminophylline to improve renal dysfunction in the pediatric cardiovascular ICU.

Objective: To determine if aminophylline administration is associated with improved creatinine clearance and greater urine output in children with acute kidney injury in the cardiovascular ICU. Design: Single-center retrospective cohort study. Setting: Pediatric cardiovascular ICU, university-affiliated children’s hospital. Patients: Children with congenital or acquired heart disease in the cardiovascular ICU who received aminophylline to treat oliguric acute kidney injury and fluid overload. Interventions: Patients received aminophylline after consultation with a pediatric nephrologist. Data were collected retrospectively over 7 days to assess if aminophylline was associated with improvement in creatinine clearance, urine output, and fluid overload. Measurements and Main Results: Thirty-one patients received 52 aminophylline courses. Over the 7-day study period, serum creatinine decreased from a mean of 1.13 ± 0.91 to 0.87 ± 0.83 mg/dL (–0.05 mg/dL/d, p < 0.001). A concomitant increase was seen in estimated glomerular filtration rate from a mean of 50.0 ± 30.0 to 70.6 ± 58.1 mL/min/1.73 m2 (+3.66 mL/min/1.73 m2/d, p < 0.001). Average daily urine output increased by 0.22 mL/kg/hr (p < 0.001), and fluid overload decreased on average by 0.42% per day in the 7-day study period (p = 0.005). Although mean furosemide dose increased slightly (0.12 mg/kg/d, p = 0.01), hydrochlorothiazide dosing did not significantly change over the study period. There were no complications related to aminophylline administration. Conclusions: Our study suggests that aminophylline therapy may be associated with significantly improved renal excretory function and may augment urine output in children who experience oliguric acute kidney injury in the cardiovascular ICU. Additionally, we did not identify any aminophylline-related side effects in this high-risk cardiac population. Future prospective studies are necessary to confirm the safety profile and to ensure that the beneficial effects are independent of other clinical interventions.

Dexmedetomidine Is Associated With Lower Incidence of Acute Kidney Injury After Congenital Heart Surgery.

Objectives: Recent data have suggested an association between the use of dexmedetomidine and a decreased incidence of acute kidney injury in adult patients after cardiopulmonary bypass. However, no study has focused on this association among pediatric populations where the incidence of acute kidney injury is particularly high and of critical significance. The primary objective of this study was to assess the relationship between the use of postoperative dexmedetomidine and the incidence of acute kidney injury in pediatric patients undergoing cardiopulmonary bypass. The secondary objective was to determine whether there was an association between dexmedetomidine use and duration of mechanical ventilation or cardiovascular ICU stay. Design: Single-center retrospective matched cohort study. Setting: A 20-bed quaternary cardiovascular ICU in a university-based pediatric hospital in California. Patients: Children less than 18 years old admitted after cardiac surgery with cardiopulmonary bypass between January 1, 2012, and May 31, 2014. Interventions: None. Measurements and Main Results: Data from a cohort of 102 patients receiving dexmedetomidine during the first postoperative day after cardiac surgery were compared to an age- and procedure-matched cohort not receiving dexmedetomidine. Cohorts had similar baseline and demographic characteristics. Patients receiving dexmedetomidine were less likely to develop acute kidney injury (24% vs 36%; odds ratio, 0.54; 95% CI, 0.29–0.99; p = 0.046). After adjusting for age, bypass time, nephrotoxin use, and vasoactive inotropic score, the use of dexmedetomidine was associated with a lower incidence of acute kidney injury with adjusted odds ratio of 0.43 (95% CI, 0.27–0.98; p = 0.048). There was no difference between the cohorts with respect to the duration of mechanical duration (1 d each; p = 0.98) or cardiovascular ICU stays (5 vs 6 d; p = 0.91). Conclusions: The use of a dexmedetomidine infusion in pediatric patients after congenital heart surgery was associated with a decreased incidence of acute kidney injury; however, it was not associated with changes in clinical outcomes. Further prospective study is necessary to validate these findings.

Acute kidney injury in the pediatric cardiac patient

In summary, AKI after pediatric congenital cardiac surgery represents an important diagnostic and therapeutic challenge in the modern day intensive care unit. AKI in the immediate postoperative period not only portends a poor short-term outcome, but also may relate to chronic kidney disease and mortality in the long term. Its association with increased morbidity, cost, and mortality demands the attention of clinicians and researchers. Future studies should employ a standard AKI definition and should focus on both the mitigation and prevention of AKI events.

Predictors of Mortality in Pediatric Patients on Venoarterial Extracorporeal Membrane Oxygenation

Objectives: Currently, there are no established echocardiographic or hemodynamic predictors of mortality after weaning venoarterial extracorporeal membrane oxygenation in children. We wished to determine which measurements predict mortality. Design: Over 3 years, we prospectively assessed six echo and six hemodynamic variables at 3–5 circuit rates while weaning extracorporeal membrane oxygenation flow. Hemodynamic measurements were heart rate, inotropic score, arteriovenous oxygen difference, pulse pressure, oxygenation index, and lactate. Echo variables included shortening/ejection fraction, outflow tract Doppler-derived stroke distance (velocity-time integral), degree of atrioventricular valve regurgitation, longitudinal strain (global longitudinal strain), and circumferential strain (global circumferential strain). Setting: Cardiovascular ICU at Lucille Packard Children’s Hospital Stanford, CA. Subjects: Patients were stratified into those who died or required heart transplant (Gr1) and those who did not (Gr2). For each patient, we compared the change for each variable between full versus minimum extracorporeal membrane oxygenation flow for each group. Interventions: None. Measurements and Main Results: We enrolled 21 patients ranging in age from 0.02 to 15 years. Five had dilated cardiomyopathy, and 16 had structural heart disease with severe ventricular dysfunction. Thirteen of 21 patients (62%) comprised Gr1, including two patients with heart transplants. Eight patients constituted Gr2. Gr1 patients had a significantly greater increase in oxygenation index (35% mean increase; p < 0.01) off extracorporeal membrane oxygenation compared to full flow, but no change in velocity-time integral or arteriovenous oxygen difference. In Gr2, velocity-time integral increased (31% mean increase; p < 0.01), with no change in arteriovenous oxygen difference or oxygenation index. Pulse pressure increased modestly with flow reduction only in Gr1 (p < 0.01). Conclusion: Failure to augment velocity-time integral or an increase in oxygenation index during the extracorporeal membrane oxygenation weaning is associated with poor outcomes in children. We propose that these measurements should be performed during extracorporeal membrane oxygenation wean, as they may discriminate who will require alternative methods of circulatory support for survival.

Pretransplant Midodrine Use: A Newly Identified Risk Marker for Complications after Kidney Transplantation

Background Midodrine is prescribed to prevent symptomatic hypotension and decrease complications associated with hypotension during dialysis. We hypothesized that midodrine use before kidney transplantation may be a novel marker for posttransplant risk. Methods We analyzed integrated national US transplant registry, pharmacy records, and Medicare claims data for 16 308 kidney transplant recipients transplanted 2006 to 2008, of whom 308 (1.9%) had filled midodrine prescriptions in the year before transplantation. Delayed graft function (DGF), graft failure, and patient death were ascertained from the registry. Posttransplant cardiovascular complications were identified using diagnosis codes on Medicare billing claims. Adjusted associations of pretransplant midodrine use with complications at 3 and 12 months posttransplant were quantified by multivariate Cox or logistic regression, including propensity for midodrine exposure. Results At 3 months, patients who used midodrine pretransplant had significantly (P < 0.05) higher rates of DGF, 32% versus 19%; hypotension, 14% versus 4%; acute myocardial infarction, 4% versus 2%; cardiac arrest, 2% versus 0.9%, graft failure, 5% versus 2%; and death, 4% versus 1% than nonusers. After multivariate adjustment including recipient and donor factors, as well as for the propensity of midodrine exposure, pretransplant midodrine use was independently associated with risks of DGF (adjusted odds ratio, 1.78; 95% confidence interval [CI], 1.36-2.32), and 3 month death-censored graft failure (adjusted hazard ratio, 2.0; 95% CI, 1.18-3.39), and death (adjusted hazard ratio, 3.49; 95% CI, 1.95-6.24). Patterns were similar at 12 months. Conclusions Although associations may in part reflect underlying conditions, the need for midodrine before kidney transplantation is a risk marker for complications including DGF, graft failure, and death.

Diminished exercise capacity and chronotropic incompetence in pediatric patients with congenital complete heart block and chronic right ventricular pacing

BACKGROUND Chronic right ventricular (RV) pacing has been associated with decreased exercise capacity and left ventricular (LV) function in adults with congenital complete atrioventricular block (CCAVB), but not in children. OBJECTIVE The purpose of this study was to evaluate the exercise capacity and LV function in pediatric patients with CCAVB receiving chronic RV pacing. METHODS We prospectively evaluated pediatric patients with isolated CCAVB receiving atrial synchronous RV pacing for at least 5 years. Supine bicycle ergometry was performed, and LV ejection fraction (EF) was evaluated by echocardiography. RESULTS Ten CCAVB subjects and 31 controls were matched for age, gender, and body surface area. CCAVB subjects had normal resting EF (63.1% ± 4.0%) and had been paced for 7.9 ± 1.4 years. Exercise testing demonstrated reduced functional capacity in CCAVB patients compared to controls with a lower VO₂peak (26.0 ± 6.6 mL/kg/min vs 39.9 ± 7.0 mL/kg/min, P <.001), anaerobic threshold (15.6 ± 3.9 mL/kg/min vs 18.8 ± 2.7 mL/kg/min, P = .007), and oxygen uptake efficiency slope (1210 ± 406 vs 1841 ± 452, P <.001). Maximum heart rate (165 ± 8 bpm vs 185 ± 9 bpm, P <.001) and systolic blood pressure (159 ± 17 mm Hg vs 185 ± 12 mm Hg, P <.019) also were reduced in CCAVB patients despite maximal effort (respiratory exchange ratio 1.2 ± 0.1). EF was augmented with exercise in controls but not in CCAVB patients (13.2% ± 9.3% vs 0.2% ± 4.8% increase, P <.001). CONCLUSION Clinically asymptomatic children with chronic RV pacing due to CCAVB have significant reductions in functional capacity accompanied by chronotropic incompetence and inability to augment EF with exercise.

Incidence, risk factors, and outcomes of acute kidney injury in adults undergoing surgery for congenital heart disease.

BACKGROUND Acute kidney injury after cardiac surgery is a frequent and serious complication among children with congenital heart disease (CHD) and adults with acquired heart disease; however, the significance of kidney injury in adults after congenital heart surgery is unknown. The primary objective of this study was to determine the incidence of acute kidney injury after surgery for adult CHD. Secondary objectives included determination of risk factors and associations with clinical outcomes. METHODS This single-centre, retrospective cohort study was performed in a quaternary cardiovascular ICU in a paediatric hospital including all consecutive patients ⩾18 years between 2010 and 2013. RESULTS Data from 118 patients with a median age of 29 years undergoing cardiac surgery were analysed. Using Kidney Disease: Improving Global Outcome creatinine criteria, 36% of patients developed kidney injury, with 5% being moderate to severe (stage 2/3). Among higher-complexity surgeries, incidence was 59%. Age ⩾35 years, preoperative left ventricular dysfunction, preoperative arrhythmia, longer bypass time, higher Risk Adjustment for Congenital Heart Surgery-1 category, and perioperative vancomycin use were significant risk factors for kidney injury development. In multivariable analysis, age ⩾35 years and vancomycin use were significant predictors. Those with kidney injury were more likely to have prolonged duration of mechanical ventilation and cardiovascular ICU stay in the univariable regression analysis. CONCLUSIONS We demonstrated that acute kidney injury is a frequent complication in adults after surgery for CHD and is associated with poor outcomes. Risk factors for development were identified but largely not modifiable. Further investigation within this cohort is necessary to better understand the problem of kidney injury.

Pediatric cardiac intensive care society 2014 consensus statement: Pharmacotherapies in cardiac critical care fluid management

Objective: In this Consensus Statement, we review the etiology and pathophysiology of fluid disturbances in critically ill children with cardiac disease. Clinical tools used to recognize pathologic fluid states are summarized, as are the mechanisms of action of many drugs aimed at optimal fluid management. Data Sources: The expertise of the authors and a review of the medical literature were used as data sources. Data Synthesis: The authors synthesized the data in the literature in order to present clinical tools used to recognize pathologic fluid states. For each drug, the physiologic rationale, mechanism of action, and pharmacokinetics are synthesized, and the evidence in the literature to support the therapy is discussed. Conclusions: Fluid management is challenging in critically ill pediatric cardiac patients. A myriad of causes may be contributory, including intrinsic myocardial dysfunction with its associated neuroendocrine response, renal dysfunction with oliguria, and systemic inflammation with resulting endothelial dysfunction. The development of fluid overload has been associated with adverse outcomes, including acute kidney injury, prolonged mechanical ventilation, increased vasoactive support, prolonged hospital length of stay, and mortality. An in-depth understanding of the many factors that influence volume status is necessary to guide optimal management.