Derek Best

Extracorporeal membrane oxygenation for refractory septic shock in children: one institution's experience.

Objective: To report our institutional experience of venoarterial extracorporeal membrane oxygenation (ECMO) in children with septic shock and circulatory collapse. Design: Retrospective case series. Setting: Intensive care unit of a tertiary pediatric referral center. Patients: Forty-five children with refractory septic shock who received venoarterial ECMO for hemodynamic support. Interventions: Venoarterial ECMO. Measurements and Main Results: We measured mean arterial pressure and inotropes before cannulation, ventilator settings, oxygenation, site and cause of infection, time on ECMO, complications of ECMO relating to the circuit or anticoagulation, survival to hospital discharge, and functional outcome assessment. Between July 1988 and October 2006, 441 children at our institution received extracorporeal life support for a variety of indications. Forty-five (10%) with septic shock received venoarterial ECMO specifically for hemodynamic support. Eighteen (40%) of these had suffered cardiac arrest and were receiving chest compressions immediately before cannulation. The median time spent on ECMO was 84 hrs (range, 32–135). There were mechanical problems with the ECMO circuit requiring intervention in 17 (38%) patients, such as oxygenator or pump head failure, clots in the circuit, or cannulae malposition. This caused no long-term harm in any but one of the patients, who died during a circuit change. Eleven patients (24%) had clinically apparent episodes of bleeding that required surgical intervention or blood transfusion. Twenty-one (47%) patients survived to hospital discharge. Atrioaortic cannulation through a sternotomy incision was associated with an improvement in survival to hospital discharge (73% of those with central cannulation survived vs. 44% without, p = .05). No survivors had severe disability at long-term follow-up. Conclusions: Extracorporeal membrane oxygenation can be safely used to resuscitate and support children with sepsis and refractory shock. Sepsis and multiorgan failure should not be considered a contraindication to ECMO. This study adds support to existing guidelines.

Central extracorporeal membrane oxygenation for refractory pediatric septic shock.

Objective: To demonstrate positive outcome, to achieve higher flow rates, and to reverse shock more quickly by implementing central extracorporeal membrane oxygenation (ECMO) in children with refractory septic shock. Children hospitalized with sepsis have significant mortality rates. The development of shock is the most important risk factor for death. For children with septic shock refractory to all other forms of therapy, ECMO has been recommended but estimated survival is <50% and the best method of applying the technology is unknown. In recent years, our institutional practice has been to cannulate children with refractory septic shock directly through the chest (central, atrioaortic ECMO) to achieve higher blood flow rates. Design: Retrospective case series. Setting: Intensive care unit of a tertiary referral pediatric hospital. Patients: Twenty-three children with refractory septic shock who received central ECMO primarily as circulatory support. Interventions: Central ECMO. Measurements and Main Results: The primary outcome measure was survival to hospital discharge. Pre-ECMO circulatory and ventilatory parameters, infecting organism, duration and complications of ECMO and length of hospital stay were also collected. Twenty-three patients (median: age, 6 yrs; weight, 20 kg) over a 9-yr period were included. All patients had microbiological evidence of infection, and meningococcemia was the most common diagnosis. Twenty-two (96%) patients had failure of at least three organ systems, and all patients received at least two inotropes with a mean inotrope score of 82.2 (sd, 115.6). Eight (35%) patients suffered cardiac arrest and required external cardiac massage before ECMO. Eighteen (78%) patients survived to be decannulated off ECMO, and 17 (74%) children survived to hospital discharge. Higher pre-ECMO arterial lactate levels were associated with increased mortality (11.7 mmol/L in nonsurvivors vs. 6.0 mmol/L in survivors, p = .007). Conclusions: Central ECMO seems to be associated with better survival than conventional ECMO and should be considered by clinicians as a viable strategy in children with refractory septic shock.

Hemolysis in pediatric patients receiving centrifugal-pump extracorporeal membrane oxygenation: prevalence, risk factors, and outcomes.

Objectives:To explore the prevalence and risk factors for hemolysis in children receiving extracorporeal membrane oxygenation and examine the relationship between hemolysis and adverse outcomes. Design:Retrospective, single-center study. Setting:Tertiary PICU. Patients:Two hundred seven children receiving extracorporeal membrane oxygenation. Interventions:None. Measurements and Main Results:Plasma-free hemoglobin was tested daily and hemolysis was diagnosed based on peak plasma-free hemoglobin as mild (< 0.5 g/L), moderate (0.5–1.0 g/L), or severe (> 1.0 g/L). Gender, age, weight, diagnosis, oxygenator type, cannulation site, mean venous inlet pressure, mean pump speed, mean flow, and visible clots in the extracorporeal membrane oxygenation circuit were entered into the ordered logistic regression model to identify risk factors of hemolysis. Complications and clinical outcomes were compared across four hemolysis groups. Of the 207 patients, 69 patients (33.3%; 95% CI, 27.0–40.2%) did not have hemolysis, 98 patients (47.3%; 95% CI, 40.4–54.4%) had mild hemolysis, 26 patients (12.5%; 95% CI, 8.4–17.9%) had moderate hemolysis, and 14 patients (6.8%; 95% CI, 3.7–11.1%) had severe hemolysis with a median peak plasma-free hemoglobin of 1.51 g/L (1.18–2.05 g/L). The independent risk factors for hemolysis during extracorporeal membrane oxygenation were use of Quadrox D (odds ratio, 7.25; 95% CI, 3.10–16.95; p < 0.001) or Lilliput (odds ratio, 37.32; 95% CI, 8.95–155.56; p < 0.001) oxygenators, mean venous inlet pressure (odds ratio, 0.95; 95% CI, 0.91–0.98; p = 0.002), and mean pump speed (odds ratio, 2.89; 95% CI, 1.36–6.14; p = 0.006). Patients with hemolysis were more likely to experience a longer extracorporeal membrane oxygenation run and require more blood products. After controlling for age, weight, pediatric index of mortality 2, and diagnosis, patients with severe hemolysis were more likely to die in the ICU (odds ratio, 5.93; 95% CI, 1.64–21.43; p = 0.007) and in hospital (odds ratio, 6.34; 95% CI, 1.71–23.54; p = 0.006). Conclusions:Hemolysis during extracorporeal membrane oxygenation with centrifugal pumps was common and associated with a number of adverse outcomes. Risk factors for hemolysis included oxygenator types, mean venous inlet pressure, and mean pump speed. Further studies are warranted comparing pump types while controlling both physical and nonphysical confounders.

Elective decompression of the left ventricle in pediatric patients may reduce the duration of venoarterial extracorporeal membrane oxygenation.

We aimed to determine the effect of elective left heart decompression at the time of initiation of central venoarterial extracorporeal membrane oxygenation (VA ECMO) on VA ECMO duration and clinical outcomes in children in a single tertiary ECMO referral center with a large pediatric population from a national referral center for pediatric cardiac surgery. We studied 51 episodes of VA ECMO in a historical cohort of 49 pediatric patients treated between the years 1990 and 2013 in the Paediatric Intensive Care Unit (PICU) of the Royal Childrens Hospital, Melbourne. The cases had a variety of diagnoses including congenital cardiac abnormalities, sepsis, myocarditis, and cardiomyopathy. Left heart decompression as an elective treatment or an emergency intervention for left heart distension was effectively achieved by a number of methods, including left atrial venting, blade atrial septostomy, and left ventricular cannulation. Elective left heart decompression was associated with a reduction in time on ECMO (128 h) when compared with emergency decompression (236 h) (P = 0.013). Subgroup analysis showed that ECMO duration was greatest in noncardiac patients (elective 138 h, emergency 295 h; P = 0.02) and in patients who died despite both emergency decompression and ECMO (elective 133 h, emergency 354 h; P = 0.002). As the emergency cases had a lower pH, a higher PaCO2 , and a lower oxygenation index and were treated with a higher mean airway pressure, positive end-expiratory pressure, and respiratory rate prior to receiving VA ECMO, we undertook multivariate linear regression modeling to show that only PaCO2 and the timing of left heart decompression were associated with ECMO duration. However, elective left heart decompression was not associated with a reduction in length of PICU stay, duration of mechanical ventilation, or duration of oxygen therapy. Elective left heart decompression was not associated with improved ECMO survival or survival to PICU discharge. Elective left heart decompression may reduce ECMO duration and has therefore the potential to reduce ECMO-related complications. A prospective, randomized controlled trial is indicated to study this intervention further.

Hemofiltration is not associated with increased mortality in children receiving extracorporeal membrane oxygenation.

Objectives: To investigate whether the use of continuous renal replacement therapy is independently associated with increased in-hospital mortality in children on extracorporeal membrane oxygenation. Design: Retrospective, 1:1 propensity-matched cohort study. Setting: Tertiary PICU. Patients: Eighty-six children on extracorporeal membrane oxygenation, 43 of whom also received hemofiltration. Interventions: None. Measurements and Main Results: Demographics, pre–extracorporeal membrane oxygenation hemodynamic data, fluid status, and biochemistry tests were collected, as well as duration of extracorporeal membrane oxygenation, blood product use, complications, and mortality. Forty-three children receiving extracorporeal membrane oxygenation and continuous renal replacement therapy were matched to a cohort of 43 children on extracorporeal membrane oxygenation not receiving continuous renal replacement therapy. The main indication for hemofiltration was fluid overload in 29 patients (67.4%), renal failure in nine patients (20.9%), and electrolyte abnormalities in five patients (11.6%). The median duration of hemofiltration was 108 hours (47–209 hr). Patients receiving hemofiltration had a longer duration of extracorporeal membrane oxygenation (127 hr [94–302 hr] vs 121 hr [67–182 hr]; p = 0.05) and received more platelet transfusions (0.91 mL/kg/hr [0.43–1.58 mL/kg/hr] vs 0.63 mL/kg/hr [0.30–0.79 mL/kg/hr]; p = 0.01). There were otherwise no differences in mechanical or patient-related complications between both groups. There was no difference in the proportion of patients who were successfully decannulated (81.4% vs 74.4%; p = 0.44), survived to ICU discharge (65.1% vs 55.8%; p = 0.38), or survived to hospital discharge (62.8% vs 48.8%; p = 0.19) in the controls versus the hemofiltration group. Conclusions: In-hospital mortality was similar between children on extracorporeal membrane oxygenation with and without hemofiltration although hemofiltration appeared to be associated with a slight increase in the duration of extracorporeal membrane oxygenation and more liberal platelet transfusions.

Outcomes of Second-Run Extracorporeal Life Support in Children: A Single-Institution Experience

BACKGROUND After weaning from mechanical circulatory support with extracorporeal membrane oxygenation or ventricular assist devices, patients may recurrently deteriorate and require reinstitution of support. Potential benefits of this desperate strategy are not well documented. METHODS We reviewed the hospital records of all patients in whom second-run mechanical circulatory support was instituted from May 1988 to August 2010. RESULTS Second-run support was instigated in 26 (4.6%) of 567 patients who underwent short-term mechanical circulatory support. Underlying pathologies requiring support were cardiac in 20 patients (76.9%) and noncardiac in 6 patients (23.1%).The majority of patients were younger than 1 year old (73.1%, n=19). Fifteen patients (57.7%) survived second-run support, but only 7 patients (26.9%) survived to discharge from the hospital. After a median follow-up of 42.5 months (range, 16 to 66 months), 4 patients (15.4%) were alive, but 3 of them had various degrees of developmental delay. CONCLUSIONS Selection of patients who can benefit from second-run support is a complex process with unpredictable results. Survival after second-run mechanical circulatory support in children is worse compared with single-run patients. Long-term prospects for survivors are so grim that this strategy should probably not be recommended.

Extracorporeal membrane modality conversions

We report the case of a patient with cardiovascular and respiratory failure due to severe anaphylaxis requiring multiple extracorporeal membrane oxygenation (ECMO) cannulation strategies to provide adequate oxygen delivery and ventilatory support during a period of rapid physiological change. ECMO provides partial or complete support of oxygenation-ventilation and circulation. The choice of which ECMO modality to use is governed by anatomical (vessel size, cardiovascular anatomy and previous surgeries) and physiological (respiratory and/or cardiac failure) factors. The urgency with which ECMO needs to be implemented (emergency cardiopulmonary resuscitation (eCPR), urgent, elective) and the institutional experience will also influence the type of ECMO provided. Here we describe a 12-year-old schoolgirl who, having been resuscitated with peripheral veno-venous (VV) ECMO for severe hypoxemia due to status asthmaticus in the setting of acute anaphylaxis, required escalation to peripheral veno-arterial (VA) ECMO for precipitous cardiovascular deterioration. Insufficient oxygen delivery for adequate cellular metabolic function and possible cerebral hypoxia due to significant differential hypoxia necessitated ECMO modification. After six days of central (transthoracic) VA ECMO support and 21 days of intensive care unit (ICU) care, she made a complete recovery with no neurological sequelae. The use of ECMO support warrants careful consideration of the interplay of a patient’s pathophysiology and extracorporeal circuit dynamics. Particular emphasis should be placed on the potential for mismatch between cardiovascular and respiratory support as well as the need to meet metabolic demands through adequate cerebral, coronary and systemic oxygenation. Cannulation strategies occasionally require alteration to meet and anticipate the patient’s evolving needs.

Extracorporeal membrane oxygenation via sternotomy for circulatory shock.

Extracorporeal membrane oxygenation (ECMO) has been used to treat sepsis in children at the Royal Children’s Hospital since 1988, with overall survival of 47%. Before 2000, our pediatric population requiring mechanical support for sepsis was supported with ECMO with cannulae implanted peripherally in the right common carotid artery and the right internal jugular vein. Since 2000, to improve delivered flows, we started to cannulate directly the aorta and right atrium through a sternotomy.

Delayed extracorporeal membrane oxygenation in children after cardiac surgery: two-institution experience

OBJECTIVE There are limited data on the outcomes of children receiving delayed (≥7 days) extracorporeal membrane oxygenation after cardiac surgery. The primary aim of this project is to identify the aetiology and outcomes of extracorporeal membrane oxygenation in children receiving delayed (≥7 days) extracorporeal membrane oxygenation after cardiac surgery. PATIENTS AND METHODS We conducted a retrospective review of all children ≤18 years supported with delayed extracorporeal membrane oxygenation after cardiac surgery between the period January, 2001 and March, 2012 at the Arkansas Childrens Hospital, United States of America, and Royal Childrens Hospital, Australia. The data collected in our study included patient demographic information, diagnoses, extracorporeal membrane oxygenation indication, extracorporeal membrane oxygenation support details, medical and surgical history, laboratory, microbiological, and radiographic data, information on organ dysfunction, complications, and patient outcomes. The outcome variables evaluated in this report included: survival to hospital discharge and current survival with emphasis on neurological, renal, pulmonary, and other end-organ function. RESULTS During the study period, 423 patients undergoing cardiac surgery were supported with extracorporeal membrane oxygenation at two institutions, with a survival of 232 patients (55%). Of these, 371 patients received extracorporeal membrane oxygenation <7 days after cardiac surgery, with a survival of 205 (55%) patients, and 52 patients received extracorporeal membrane oxygenation ≥7 days after cardiac surgery, with a survival of 27 (52%) patients. The median duration of extracorporeal membrane oxygenation run for the study cohort was 5 days (interquartile range: 3, 10). In all, 14 patients (25%) received extracorporeal membrane oxygenation during active cardiopulmonary resuscitation with chest compressions. There were 24 patients (44%) who received dialysis while being on extracorporeal membrane oxygenation. There were eight patients (15%) who had positive blood cultures and four patients (7%) who had positive urine cultures while being on extracorporeal membrane oxygenation. There were nine patients (16%) who had bleeding complications associated with extracorporeal membrane oxygenation runs. There were 10 patients (18%) who had cerebrovascular thromboembolic events associated with extracorporeal membrane oxygenation runs. Of these, 19 patients are still alive with significant comorbidities. CONCLUSIONS This study demonstrates that mortality outcomes are comparable among children receiving extracorporeal membrane oxygenation ≥7 days and <7 days after cardiac surgery. The proportion of patients receiving extracorporeal membrane oxygenation ≥7 days is small and the aetiology diverse.

Prevalence of dysglycemia and association with outcomes in pediatric extracorporeal membrane oxygenation.

Objectives: To evaluate the relationship between glucose derangement, insulin administration, and mortality among children on extracorporeal membrane oxygenation. Design: Retrospective cohort. Setting: Tertiary PICU. Patients: Two hundred nine children receiving extracorporeal membrane oxygenation, including 97 neonates. Interventions: None. Measurements and Main Results: Hyperglycemia and severe hyperglycemia were defined as a single blood glucose level greater than 15 mmol/L (270 mg/dL) and greater than 20 mmol/L (360 mg/dL), respectively. Hypoglycemia and severe hypoglycemia were defined as any single glucose level less than 3.3 mmol/L (60 mg/dL) and less than 2.2 mmol/L (40 mg/dL), respectively. A total of 15,912 glucose values were recorded. The median number of glucose values was 59 per patient, corresponding to a mean 0.53 ± 0.12 tests per hour. Sixty-nine patients (33.0%) without dysglycemia and who received no insulin were defined as the control group. Eighty-nine (42.6%) and 26 (12.4%) patients developed hyperglycemia and severe hyperglycemia, respectively. Sixty-three (30.1%) and 17 (8.1%) patients developed hypoglycemia and severe hypoglycemia, respectively. Sixty-one patients (29.2%) received IV insulin during extracorporeal membrane oxygenation. Both hyperglycemia and hypoglycemia were associated with increased mortality on extracorporeal membrane oxygenation (46% and 48%, respectively, vs 29% of controls; p = 0.03). However, after adjusting for severity of illness and extracorporeal membrane oxygenation complications, abnormal glucose levels were not independently related to mortality. Conclusions: Dysglycemia in children on extracorporeal membrane oxygenation was common but not independently associated with increased mortality. The optimal glucose range for this high-risk population requires further investigation.