A Near Real-Time Risk Analytics Algorithm Predicts Elevated Lactate Levels in Pediatric Cardiac Critical Care Patients.

BACKGROUND: Postoperative pediatric congenital heart patients are predisposed to develop low-cardiac output syndrome. Serum lactate (lactic acid [LA]) is a well-defined marker of inadequate systemic oxygen delivery. OBJECTIVES: We hypothesized that a near real-time risk index calculated by a noninvasive predictive analytics algorithm predicts elevated LA in pediatric patients admitted to a cardiac ICU (CICU). DERIVATION COHORT: Ten tertiary CICUs in the United States and Pakistan. VALIDATION COHORT: Retrospective observational study performed to validate a hyperlactatemia (HLA) index using T3 platform data (Etiometry, Boston, MA) from pediatric patients less than or equal to 12 years of age admitted to CICU (n = 3,496) from January 1, 2018, to December 31, 2020. Patients lacking required data for module or LA measurements were excluded. PREDICTION MODEL: Physiologic algorithm used to calculate an HLA index that incorporates physiologic data from patients in a CICU. The algorithm uses Bayes' theorem to interpret newly acquired data in a near real-time manner given its own previous assessment of the physiologic state of the patient. RESULTS: A total of 58,168 LA measurements were obtained from 3,496 patients included in a validation dataset. HLA was defined as LA level greater than 4 mmol/L. Using receiver operating characteristic analysis and a complete dataset, the HLA index predicted HLA with high sensitivity and specificity (area under the curve 0.95). As the index value increased, the likelihood of having higher LA increased (p < 0.01). In the validation dataset, the relative risk of having LA greater than 4 mmol/L when the HLA index is less than 1 is 0.07 (95% CI: 0.06-0.08), and the relative risk of having LA less than 4 mmol/L when the HLA index greater than 99 is 0.13 (95% CI, 0.12-0.14). CONCLUSIONS: These results validate the capacity of the HLA index. This novel index can provide a noninvasive prediction of elevated LA. The HLA index showed strong positive association with elevated LA levels, potentially providing bedside clinicians with an early, noninvasive warning of impaired cardiac output and oxygen delivery. Prospective studies are required to analyze the effect of this index on clinical decision-making and outcomes in pediatric population.

Complex decision making in an intensive care environment: Perceived practice versus observed reality.

RATIONALE: Advancing our understanding of how decisions are made in cognitively, socially and technologically complex hospital environments may reveal opportunities to improve healthcare delivery, medical education and the experience of patients, families and clinicians. AIMS AND OBJECTIVES: Explore factors impacting clinician decision making in the Boston Children's Hospital Cardiac Intensive Care Unit. METHODS: A convergent mixed methods design was used. Quantitative and qualitative data sources consisted of a faculty survey, direct observations of clinical rounds in a specific patient population identified by a clinical decision support system (CDSS) and semistructured interviews (SSIs). Deductive and inductive coding was used for qualitative data. Qualitative data were translated into images using social network analysis which illustrate the frequency and connectivity of the codes in each data set. RESULTS: A total of 25 observations of eight faculty-led interprofessional teams were performed between 12 February and 31 March 2021. Individual patient characteristics were noted by faculty in SSIs to be the most important factor in their decision making, yet ethnographic observations suggested faculty cognitive traits, team expertise and value-based decisions were more heavily weighted. The development of expertise was impacted by role modeling. Decisions were perceived to be influenced by the system and environment. CONCLUSIONS: Clinician perception of decision making was not congruent with the observed behaviours in a complicated and dynamic system. This study identifies important considerations in clinical curricula as well as the design and implementation of CDSS. Our method of using social network analysis to visualize components of decision making could be adopted to explore other complex environments.

Factors associated with morbidity, mortality, and hemodynamic failure after biventricular conversion in borderline hypoplastic left hearts.

OBJECTIVE: A subset of patients with borderline hypoplastic left heart may be candidates for single to biventricular conversion, but long-term morbidity and mortality persist. Prior studies have shown conflicting results regarding the association of preoperative diastolic dysfunction and outcome, and patient selection remains challenging. METHODS: Patients with borderline hypoplastic left heart undergoing biventricular conversion from 2005 to 2017 were included. Cox regression identified preoperative factors associated with a composite outcome of time to mortality, heart transplant, takedown to single ventricle circulation, or hemodynamic failure (defined as left ventricular end-diastolic pressure >20 mm Hg, mean pulmonary artery pressure >35 mm Hg, or pulmonary vascular resistance >6 international Woods units). RESULTS: Among 43 patients, 20 (46%) met the outcome, with a median time to outcome of 5.2 years. On univariate analysis, endocardial fibroelastosis, lower left ventricular end-diastolic volume/body surface area (when <50 mL/m2), lower left ventricular stroke volume/body surface area (when <32 mL/m2), and lower left:right ventricular stroke volume ratio (when <0.7) were associated with outcome; higher preoperative left ventricular end-diastolic pressure was not. Multivariable analysis demonstrated that endocardial fibroelastosis (hazard ratio, 5.1, 95% confidence interval, 1.5-22.7, P = .033) and left ventricular stroke volume/body surface area 28 mL/m2 or less (hazard ratio, 4.3, 95% confidence interval, 1.5-12.3, P = .006) were independently associated with a higher hazard of the outcome. Approximately all patients (86%) with endocardial fibroelastosis and left ventricular stroke volume/body surface area 28 mL/m2 or less met the outcome compared with 10% of those without endocardial fibroelastosis and with higher stroke volume/body surface area. CONCLUSIONS: History of endocardial fibroelastosis and smaller left ventricular stroke volume/body surface area are independent factors associated with adverse outcomes among patients with borderline hypoplastic left heart undergoing biventricular conversion. Normal preoperative left ventricular end-diastolic pressure is insufficient to reassure against diastolic dysfunction after biventricular conversion.

Associations With Extubation Failure and Predictive Value of Risk Analytics Algorithms With Extubation Readiness Tests Following Congenital Cardiac Surgery.

OBJECTIVES: Extubation failure is associated with morbidity and mortality in children following cardiac surgery. Current extubation readiness tests (ERT) do not consider the nonrespiratory support provided by mechanical ventilation (MV) for children with congenital heart disease. We aimed to identify factors associated with extubation failure in children following cardiac surgery and assess the performance of two risk analytics algorithms for patients undergoing an ERT. DESIGN: Retrospective cohort study. SETTING: CICU at a tertiary-care children's hospital. PATIENTS: Children receiving MV greater than 48 hours following cardiac surgery between January 1, 2017, and December 31, 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six hundred fifty encounters were analyzed with 49 occurrences (8%) of reintubation. Extubation failure occurred most frequently within 6 hours of extubation. On multivariable analysis, younger age (per each 3-mo decrease: odds ratio [OR], 1.06; 95% CI, 1.001-1.12), male sex (OR, 2.02; 95% CI, 1.03-3.97), Society of Thoracic Surgery-European Association for Cardiothoracic Surgery category 5 procedure (p equals to 0.005), and preoperative respiratory support (OR, 2.08; 95% CI, 1.09-3.95) were independently associated with unplanned reintubation. Our institutional ERT had low sensitivity to identify patients at risk for reintubation (23.8%; 95% CI, 9.7-47.6%). The addition of the inadequate delivery of oxygen (IDO2) index to the ERT increased the sensitivity by 19.0% (95% CI, -2.5 to 40.7%; p = 0.05), but the sensitivity remained low and the accuracy of the test dropped by 8.9% (95% CI, 4.7-13.1%; p < 0.01). CONCLUSIONS: Preoperative respiratory support, younger age, and more complex operations are associated with postoperative extubation failure. IDO2 and IVCO2 provide unique cardiorespiratory monitoring parameters during ERTs but require further investigation before being used in clinical evaluation for extubation failure.

Fluid Restriction Contributes to Poor Nutritional Adequacy in Patients With Congenital Heart Disease Receiving Renal Replacement Therapy.

OBJECTIVES: Critically ill patients receiving renal replacement therapy (RRT) in the pediatric cardiac intensive care unit (CICU) are at high risk for inadequate nutrition delivery. The objective of this study is to evaluate barriers to adequate energy and protein delivery in critically ill patients with congenital heart disease receiving RRT. METHODS: This is a single-center retrospective cohort study of patients receiving RRT in the CICU from 2011 to 2019. Energy and protein adequacy was recorded over the first 7 days of RRT. Adequacy was defined as delivery of >80% of the energy and protein targets during this time period. Patients who achieved adequacy were compared to those who did not. Multivariable logistic regression models were constructed to determine factors independently associated with energy and protein adequacy while receiving RRT. RESULTS: Sixty patients were included for analysis. Fifty-five patients (92%) achieved energy adequacy and 37 patients (62%) achieved protein adequacy. A higher weight-for-age z-score (WAZ) on admission to the CICU was the only independent predictor of inadequate energy intake (odds ratio 0.07, 95% confidence interval 0.01-0.58, P = .014); median WAZ was -1.17 versus +1.24 for those with adequate versus inadequate energy intake, respectively. Fluid restriction to <80% of maintenance fluid at the time of RRT initiation was more likely in patients with higher WAZ. Fluid restriction was the only independent predictor of inadequate protein intake (odds ratio 0.13, 95% confidence interval 0.02-0.7, P = .018); 5% versus 30% were fluid restricted in those with adequate versus inadequate protein intake, respectively. Azotemia was not associated with inadequate protein intake. Initiation of RRT did not allow for liberalization of fluid intake over the time period evaluated. CONCLUSIONS: Protein delivery was inadequate in 38% of children undergoing RRT in the CICU. Fluid restriction was associated with inadequate protein intake and higher WAZ was associated with inadequate energy intake.

Use of a Risk Analytic Algorithm to Inform Weaning From Vasoactive Medication in Patients Following Pediatric Cardiac Surgery.

OBJECTIVES: Advanced clinical decision support tools, such as real-time risk analytic algorithms, show promise in assisting clinicians in making more efficient and precise decisions. These algorithms, which calculate the likelihood of a given underlying physiology or future event, have predominantly been used to identify the risk of impending clinical decompensation. There may be broader clinical applications of these models. Using the inadequate delivery of oxygen index, a U.S. Food and Drug Administration-approved risk analytic algorithm predicting the likelihood of low cardiac output state, the primary objective was to evaluate the association of inadequate delivery of oxygen index with success or failure of weaning vasoactive support in postoperative cardiac surgery patients. DESIGN: Multicenter retrospective cohort study. SETTING: Three pediatric cardiac ICUs at tertiary academic children's hospitals. PATIENTS: Infants and children greater than 2 kg and less than 12 years following cardiac surgery, who required vasoactive infusions for greater than 6 hours in the postoperative period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Postoperative patients were identified who successfully weaned off initial vasoactive infusions (n = 2,645) versus those who failed vasoactive wean (required reinitiation of vasoactive, required mechanical circulatory support, renal replacement therapy, suffered cardiac arrest, or died) (n = 516). Inadequate delivery of oxygen index for final 6 hours of vasoactive wean was captured. Inadequate delivery of oxygen index was significantly elevated in patients with failed versus successful weans (inadequate delivery of oxygen index 11.6 [sd 19.0] vs 6.4 [sd 12.6]; p < 0.001). Mean 6-hour inadequate delivery of oxygen index greater than 50 had strongest association with failed vasoactive wean (adjusted odds ratio, 4.0; 95% CI, 2.5-6.6). In patients who failed wean, reinitiation of vasoactive support was associated with concomitant fall in inadequate delivery of oxygen index (11.1 [sd 18] vs 8.9 [sd 16]; p = 0.007). CONCLUSIONS: During the de-escalation phase of postoperative cardiac ICU management, elevation of the real-time risk analytic model, inadequate delivery of oxygen index, was associated with failure to wean off vasoactive infusions. Future studies should prospectively evaluate utility of risk analytic models as clinical decision support tools in de-escalation practices in critically ill patients.

Shock Index, Coronary Perfusion Pressure, and Rate Pressure Product As Predictors of Adverse Outcome After Pediatric Cardiac Surgery.

OBJECTIVES: To determine whether shock index, coronary perfusion pressure, or rate pressure product in the first 24 hours after congenital heart surgery are independent predictors of subsequent clinically significant adverse outcomes. DESIGN: A retrospective cohort study. SETTING: A tertiary care center. PATIENTS: All patients less than 18 years old who underwent cardiac surgery at Boston Children's Hospital between January 1, 2010, and December 31, 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Shock index (heart rate/systolic blood pressure), coronary perfusion pressure (diastolic blood pressure-right atrial pressure), and rate pressure product (heart rate × systolic blood pressure) were calculated every 5 seconds, and the median value for the first 24 hours of cardiac ICU admission for each was used as a predictor. The composite, primary outcome was the occurrence of any of the following adverse events in the first 7 days following cardiac ICU admission: cardiopulmonary resuscitation, extracorporeal cardiopulmonary resuscitation, mechanical circulatory support, unplanned surgery, heart transplant, or death. The association of each variable of interest with this outcome was tested in a multivariate logistic regression model. Of the 4,161 patients included, 296 (7%) met the outcome within the specified timeframe. In a multivariate regression model adjusted for age, surgical complexity, inotropic and respiratory support, and organ dysfunction, shock index greater than 1.83 was significantly associated with the primary outcome (odds ratio, 6.6; 95% CI, 4.4-10.0), and coronary perfusion pressure greater than 35 mm Hg was protective against the outcome (odds ratio, 0.5; 0.4-0.7). Rate pressure product was not found to be associated with the outcome. However, the predictive ability of the shock index and coronary perfusion pressure models were not superior to their component hemodynamic variables alone. CONCLUSIONS: Both shock index and coronary perfusion pressure may offer predictive value for adverse outcomes following cardiac surgery in children, although they are not superior to the primary hemodynamic variables.

Acute coronary artery obstruction following surgical repair of congenital heart disease.

OBJECTIVES: Acute coronary artery obstruction is a rare complication of congenital heart disease surgery but imposes a high burden of morbidity and mortality. Previous case series have described episodes in specific congenital heart lesions or surgical repairs but have not examined the complication in all-comers to congenital heart surgery. We hypothesize that shorter time from a clinically recognized postoperative sentinel event suggestive of coronary ischemia to diagnosis of coronary obstruction is associated with improved clinical outcomes. METHODS: This was a single-center, retrospective review of patients diagnosed with acute coronary artery obstruction by angiography following surgical repair of congenital heart disease between January 2000 and June 2016. RESULTS: In total, 34 patients were identified. The most common procedures associated with coronary artery obstruction were the Norwood procedure, arterial switch operation, and aortic valve repair/replacement. In total, 79% required mechanical circulatory support, 41% died, and 27% were listed for heart transplant. Patients who died or were listed for heart transplant had longer median sentinel-event-to-cardiac-catheterization time (28 [6-168] hours vs 10 [3-56] hours, P = .001), and longer median sentinel-event-to-intervention time (32 [11-350] hours vs 13 [5-59] hours, P = .003). Patients with hypoplastic left heart syndrome were at greater risk of death or transplant listing (odds ratio, 9.23, P = .03). CONCLUSIONS: Time from clinically relevant postoperative sentinel event to diagnosis of coronary artery obstruction by angiography was associated with transplant-listing-free survival. Clinicians should maintain a high index of suspicion for coronary obstruction and consider early catheterization and coronary angiography for patients in whom post-operative coronary compromise is suspected.

Renal replacement therapy in the pediatric cardiac intensive care unit.

OBJECTIVE: There is an increased risk of mortality in patients in whom acute kidney injury and fluid accumulation develop after cardiothoracic surgery, and the risk is especially high when renal replacement therapy is needed. However, renal replacement therapy remains an essential intervention in managing these patients. The objective of this study was to identify risk factors for mortality in surgical patients requiring renal replacement therapy in a pediatric cardiac intensive care unit. METHODS: We performed a retrospective review of patients requiring renal replacement therapy for acute kidney injury or fluid accumulation after cardiothoracic surgery between January 2009 and December 2017. Survivors and nonsurvivors were compared with respect to multiple variables, and a multivariable logistic regression analysis was performed to identify independent risk factors associated with mortality. RESULTS: The mortality rate for the cohort was 75%. Nonsurvivors were younger (nonsurvivors: 0.8 years; interquartile range, 0.1-8.2; survivors: 14.6 years; interquartile range, 4.2-19.7; P = .002) and had a lower weight-for-age z-score (nonsurvivors: -1.5; interquartile range, -3.1 to -0.4; survivors: -0.5; interquartile range, -0.9 to 0.3; P = .02) compared with survivors. There was no difference with respect to fluid accumulation. In multivariable analysis, a longer duration of stage 3 acute kidney injury before initiation of renal replacement therapy was independently associated with mortality (adjusted odds ratio, 1.39; 95% confidence interval, 1.05-1.83; P = .021). CONCLUSIONS: Mortality in patients requiring renal replacement therapy after congenital heart disease surgery is high. A longer duration of acute kidney injury before renal replacement therapy initiation is associated with increased mortality.

Inadequate oxygen delivery index dose is associated with cardiac arrest risk in neonates following cardiopulmonary bypass surgery.

AIM: To evaluate the Inadequate oxygen delivery (IDO2) index dose as a predictor of cardiac arrest (CA) in neonates following congenital heart surgery. METHODS: Retrospective cohort study in 3 US pediatric cardiac intensive units (1/2011- 8/2016). Calculated IDO2 index values were blinded to bedside clinicians and generated from data collected up to 30 days postoperatively, or until death or ECMO initiation. Control event data was collected from patients who did not experience CA or require ECMO. IDO2 dose was computed over a 120-min window up to 30 min prior to the CA and control events. A multivariate logistic regression prediction model including the IDO2 dose and presence or absence of a single ventricle (SV) was used. Model performance metrics were the odds ratio for each regression coefficient and receiver operating characteristic area under the curve (ROC AUC). RESULTS: Of 897 patients monitored during the study period, 601 met inclusion criteria: 29 patients had CA (33 events) and 572 patients were used for control events. Seventeen (59%) CA and 125 (26%) control events occurred in SV patients. Median age/weight at surgery and level of monitoring were similar in both groups. Median postoperative event time was 0.73 days [0.05-22.39] in CA patients and 0.82 days [0.08 25.11] in control patients. Odds ratio of the IDO2 dose coefficient was 1.008 (95% CI: 1.006-1.012, p = 0.0445), and 2.952 (95% CI: 2.952-3.258, p = 0.0079) in SV. The ROC AUC using both coefficients was 0.74 (95% CI: 0.73-0.75). These associations of IDO2 dose with CA risk remained robust, even when censored periods prior to arrest were 10 and 20 min. CONCLUSION: In neonates post-CPB surgery, higher IDO2 index dose over a 120-min monitoring period is associated with increased risk of cardiac arrest, even when censoring data 10, 20 or 30 min prior to the CA event.

Risk Factors for Mortality in Critically Ill Children Requiring Renal Replacement Therapy.

OBJECTIVES: There is an increased mortality risk in critically ill children who require renal replacement therapy for acute kidney injury and fluid overload. Nevertheless, renal replacement therapy is essential in managing these patients. The objective of this study was to identify risk factors for mortality in critically ill children requiring renal replacement therapy. DESIGN: Single-center, retrospective cohort analysis. SETTING: Tertiary care children's hospital. PATIENTS: All patients admitted to an ICU at Boston Children's Hospital from January 2009 to December 2017 who required any form of renal replacement therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four-hundred sixty-three patients required inpatient renal replacement therapy over the study period. Of these, there were 98 patients who had 99 unique encounters for renal replacement therapy that met eligibility criteria for analysis. The most common diagnoses were respiratory failure, stem cell transplant, and sepsis. The overall mortality was 55.6%. Nonsurvivors had a lower ICU admission weight compared with survivors (30.0 kg vs 44.0 kg; p = 0.037) and a higher degree of fluid accumulation at the time of renal replacement therapy initiation (17.1% vs 8.1%; p = 0.021). In multivariable logistic regression analysis, invasive mechanical ventilation (odds ratio, 7.22; 95% CI, 1.88-27.7), a longer duration of stage 3 acute kidney injury (odds ratio, 1.08; 95% CI, 1.02-1.15), and higher fluid balance in the 72 hours after initiating renal replacement therapy (odds ratio, 1.12; 95% CI, 1.05-1.20) were associated with an increased odds of mortality. CONCLUSIONS: Earlier renal replacement therapy initiation with respect to the development of severe acute kidney injury was associated with lower mortality in this cohort of critically ill children. Additionally, invasive mechanical ventilation at the time of renal replacement therapy initiation and a higher degree of fluid accumulation after initiating renal replacement therapy were associated with increased mortality.

RBC Exposure in Pediatric Extracorporeal Membrane Oxygenation: Epidemiology and Factors Associated With Large Blood Transfusion Volume.

OBJECTIVES: To quantify and identify factors associated with large RBC exposure in children supported with extracorporeal membrane oxygenation. DESIGN: Retrospective cohort study. SETTING: Single tertiary care children's hospital. PATIENTS: One-hundred twenty-two children supported with extracorporeal membrane oxygenation for greater than 12 hours during January 1, 2015, to December 31, 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical, laboratory, and survival data were obtained from medical records. Only data from patients' first extracorporeal membrane oxygenation run were used. The primary outcome was RBC volume exposure during extracorporeal membrane oxygenation (mL/kg/d). Patients with RBC exposure volume greater than 75th percentile were categorized as "high RBC use" patients. A "bleeding day" was identified if mediastinum or cannula sites were explored and/or Factor VIIa administration, gastrointestinal, pulmonary, or intracranial hemorrhages occurred. Median age was 0.3 years (interquartile range, 0-3 yr). Congenital heart disease (n = 56; 46%) was the most common diagnosis. Median RBC volume transfused during extracorporeal membrane oxygenation was 39 mL/kg/d (interquartile range, 21-66 mL/kg/d). High RBC use patients were more likely be supported by venoarterial extracorporeal membrane oxygenation (100 vs 76%; p = 0.006), have congenital heart disease (68 vs 39%; p = 0.02), and experience bleeding (33 vs 11% d; p < 0.001). High RBC use patients showed a trend toward higher in-hospital mortality (58 vs 37%; p = 0.07). In the multivariable analysis, younger age (-9% per year; 95% CI, -10% to -7%; p < 0.001), more blood draws per day (+8%; 95% CI, 6-11%; p < 0.001), and higher proportion of bleeding days (+22% per 10% increase; 95% CI, 16-29%; p < 0.001) were associated with larger RBC exposure (model R = 0.66). CONCLUSIONS: Bleeding during extracorporeal membrane oxygenation, frequent laboratory draws, and younger age were associated with increased RBC exposure during extracorporeal membrane oxygenation. Higher transfusion volume was associated with increased mortality.

Responsive monitoring of mitochondrial redox states in heart muscle predicts impending cardiac arrest.

Assessing the adequacy of oxygen delivery to tissues is vital, particularly in the fields of intensive care medicine and surgery. As oxygen delivery to a cell becomes deficient, changes in mitochondrial redox state precede changes in cellular function. We describe a technique for the continuous monitoring of the mitochondrial redox state on the epicardial surface using resonance Raman spectroscopy. We quantify the reduced fraction of specific electron transport chain cytochromes, a metric we name the resonance Raman reduced mitochondrial ratio (3RMR). As oxygen deficiency worsens, heme moieties within the electron transport chain become progressively more reduced, leading to an increase in 3RMR. Myocardial 3RMR increased from baseline values of 18.1 ± 5.9 to 44.0 ± 16.9% (P = 0.0039) after inferior vena cava occlusion in rodents (n = 8). To demonstrate the diagnostic power of this measurement, 3RMR was continuously measured in rodents (n = 31) ventilated with 5 to 8% inspired oxygen for 30 min. A 3RMR value exceeding 40% at 10 min predicted subsequent cardiac arrest with 95% sensitivity and 100% specificity [area under the curve (AUC), 0.98], outperforming all current measures, including contractility (AUC, 0.51) and ejection fraction (AUC, 0.39). 3RMR correlated with indices of intracellular redox state and energy production. This technique may permit the real-time identification of critical defects in organ-specific oxygen delivery.

Pediatric Cardiac Intensive Care Society 2014 Consensus Statement: Pharmacotherapies in Cardiac Critical Care Antiarrhythmics.

OBJECTIVE: Arrhythmias are a common occurrence in critically ill pediatric patients. Pharmacotherapy is a usual modality for treatment and prevention of arrhythmias in this patient population. This review will highlight particular arrhythmias in the pediatric critical care population and discuss salient points of pharmacotherapy of these arrhythmias. The mechanisms of action for the various agents, potential adverse events, place in therapy, and evidence for their use will be summarized. DATA SOURCES: The literature was searched for articles related to the topic. Expertise of the authors and a consensus of the editors were additional sources of data in the article. DATA SYNTHESIS: The author team synthesized the current pharmacology and recommendations and present them in this review. Tables were generated to summarize the state of the art evidence-based practice. CONCLUSION: Specialized knowledge as to the safe and effective use of the antiarrhythmic pharmacotherapy in the intensive care setting can lead to safe and effective rhythm management in patients with complex heart disease.

Great need, scarce resources, and choice: reflections on ethical issues following a medical mission.

Medical missions to provide cardiac surgical procedures in developing and technologically less advanced countries is a great challenge. It is also immensely gratifying, personally and professionally. Such missions typically present significant ethical dilemmas, especially making difficult choices, given limited time and resources, and the inability to help all children in need of cardiac surgery. We describe some of these issues from our perspective as visiting cardiologists.

Extracorporeal membrane oxygenation in patients undergoing superior cavopulmonary anastomosis.

OBJECTIVE: Patients who have undergone the superior cavopulmonary anastomosis (Glenn procedure) have unique cardiopulmonary-cerebral physiology that may limit the success of cardiopulmonary resuscitation and extracorporeal membrane oxygenation (ECMO). Limited data published to date suggest grim morbidity and mortality when ECMO is used. We utilized the Extracorporeal Life Support Organization registry database to more thoroughly assess outcomes in these patients. METHODS: Data from the Extracorporeal Life Support Organization registry from 1999 to 2012 for children with Glenn physiology aged 3 months to 1 year were retrospectively analyzed. Demographics and ECMO characteristics were compared between survivors and nonsurvivors. Factors associated with mortality were evaluated using multivariate logistic regression. RESULTS: Of 103 infants, 42 (41%) survived to hospital discharge. Neurologic complications (eg, seizure, hemorrhage, or embolic stroke) were documented in 23% of patients (24 of 103) and 14% of survivors (6 of 42). In univariate analysis, inotropic requirement before ECMO, duration of ECMO, mechanical complications with the ECMO circuit, renal failure, and pulmonary hemorrhage or pneumothorax were predictors of mortality. In multivariate logistic regression, inotrope requirement (odds ratio [OR], 3.6; 95% confidence interval [CI], 1.3-9.8), longer duration of ECMO support (OR, 7.2; 95% CI, 1.8-28), combined cardiopulmonary indication for ECMO (OR, 3.7; 95% CI, 1.4-9.7), and renal failure (OR, 4.2; 95% CI, 1.5-12) were associated with mortality. CONCLUSIONS: Mortality in infants with Glenn physiology supported with ECMO is lower than that previously reported, but the incidence of neurologic injury is high. These data support use of ECMO in patients with Glenn physiology with refractory cardiopulmonary failure.

Impact of empiric nesiritide or milrinone infusion on early postoperative recovery after Fontan surgery: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: We sought to determine whether empirical nesiritide or milrinone would improve the early postoperative course after Fontan surgery. We hypothesized that compared with milrinone or placebo, patients assigned to receive nesiritide would have improved early postoperative outcomes. METHODS AND RESULTS: In a single-center, randomized, double-blinded, placebo-controlled, multi-arm parallel-group clinical trial, patients undergoing primary Fontan surgery were assigned to receive nesiritide, milrinone, or placebo. A loading dose of study drug was administered on cardiopulmonary bypass followed by a continuous infusion for ≥12 hours and ≤5 days after cardiac intensive care unit admission. The primary outcome was days alive and out of the hospital within 30 days of surgery. Secondary outcomes included measures of cardiovascular function, renal function, resource use, and adverse events. Among 106 enrolled subjects, 35, 36, and 35 were randomized to the nesiritide, milrinone, and placebo groups, respectively, and all were analyzed based on intention to treat. Demographics, patient characteristics, and operative factors were similar among treatment groups. No significant treatment group differences were found for median days alive and out of the hospital within 30 days of surgery (nesiritide, 20 [minimum to maximum, 0-24]; milrinone, 18 [0-23]; placebo, 20 [0-23]; P=0.38). Treatment groups did not significantly differ in cardiac index, arrhythmias, peak lactate, inotropic scores, urine output, duration of mechanical ventilation, intensive care or chest tube drainage, or adverse events. CONCLUSIONS: Compared with placebo, empirical perioperative nesiritide or milrinone infusions are not associated with improved early clinical outcomes after Fontan surgery. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00543309.

The association of carotid artery cannulation and neurologic injury in pediatric patients supported with venoarterial extracorporeal membrane oxygenation*.

OBJECTIVES: To describe the prevalence of neurologic injury in a recent cohort of patients 18 years old or younger cannulated for venoarterial extracorporeal membrane oxygenation. To evaluate the association of carotid artery cannulation with neurologic injury when compared with other cannulation sites. To determine if age impacts the association of carotid artery cannulation with neurologic injury. DESIGN: Retrospective analysis of data from the Extracorporeal Life Support Organization registry. SETTING: Neonatal and pediatric medical/surgical and cardiac ICUs of 118 international tertiary care centers worldwide. PATIENTS: Pediatric patients 18 years old or younger cannulated for venoarterial extracorporeal membrane oxygenation and reported to the Extracorporeal Life Support Organization registry during 2007 and 2008. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two thousand nine hundred seventy-seven patients underwent venoarterial extracorporeal membrane oxygenation during the study period. Indications for extracorporeal membrane oxygenation included pulmonary (n = 1,390, 47%), cardiac (n = 1,168, 39%), extracorporeal membrane oxygenation during cardiopulmonary resuscitation (n = 418, 14%), and unknown (n = 1). Arterial cannulation sites were aorta (n = 938, 32%), femoral artery (n = 118, 4%), and carotid artery (n = 1,921, 64%). Overall, 611 patients (21%) had evidence of neurologic injury defined as seizures, infarction, and/or hemorrhage. The occurrence of neurologic injury varied significantly by cannulation site: femoral artery (n = 18, 15%), aorta (n = 160, 17%), and carotid artery (n = 433, 23%); p equals 0.001. Neonates represented the largest group of patients cannulated for venoarterial extracorporeal membrane oxygenation (n = 1,807, 61%), the majority of patients cannulated via the carotid artery (n = 1,276, 66%), and had the highest burden of neurologic injury (n = 398, 22%). Age, preextracorporeal membrane oxygenation high-frequency oscillatory ventilation use, preextracorporeal membrane oxygenation arterial pH and serum bicarbonate level, and preextracorporeal membrane oxygenation cardiac arrest were independently associated with neurologic injury in a covariate model. Carotid artery cannulation site was added to this adjusted model and found to independently increase odds of neurologic injury (odds ratio, 1.4 [95% CI, 1.01-1.69]). An interaction term containing age and cannulation site was not associated with neurologic injury (odds ratio, 1.06 [95% CI, 0.84-1.34]). CONCLUSIONS: Carotid artery cannulation for venoarterial extracorporeal membrane oxygenation in patients 18 years old or younger is associated with statistically significant increased odds of neurologic injury. These increased odds are present across all age groups.

Extracorporeal membrane oxygenation after stage 1 palliation for hypoplastic left heart syndrome.

OBJECTIVE: To report the outcomes from a large multicenter cohort of neonates requiring extracorporeal membrane oxygenation (ECMO) after stage 1 palliation for hypoplastic left heart syndrome. METHODS: Using data from the Extracorporeal Life Support Organization (2000-2009), we computed the survival to hospital discharge for neonates (age ≤30 days) supported with ECMO after stage 1 palliation for hypoplastic left heart syndrome. The factors associated with mortality were evaluated using multivariate logistic regression analysis. RESULTS: Among 738 neonates, the survival rate was 31%. The median age at cannulation was 7 days (interquartile range, 4-11). Black race (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.2-3.6), mechanical ventilation before ECMO (>15-131 hours: OR, 1.6; 95% CI, 1.1-2.4; >131 hours: OR, 1.9; 95% CI, 1.3-2.9), use of positive end expiratory pressure (>6-8 cm H(2)O: OR, 1.7; 95% CI, 1.1-2.7; >8 cm H(2)O: OR, 1.9; 95% CI, 1.2-3.1), and longer ECMO duration (per day, OR, 1.2; 95% CI, 1.1-1.3) increased mortality. ECMO support for failure to wean from cardiopulmonary bypass (OR, 1.6; 95% CI, 1.02-2.4) also decreased survival. ECMO complications, including renal failure (OR, 1.9; 95% CI, 1.2-3.1), inotrope requirement (OR, 1.5; 95% CI, 1.1-2.1), myocardial stun (OR, 3.2; 95% CI, 1.3-7.7), metabolic acidosis (OR, 2.9; 95% CI, 1.3-6.7), and neurologic injury (OR, 1.7; 95% CI, 1.1-2.6), during support also increased mortality. CONCLUSIONS: Mortality for neonates with hypoplastic left heart syndrome supported with ECMO after stage 1 palliation is high. Longer ventilation before cannulation, longer support duration, and ECMO complications increased mortality.