Graeme MacLaren

Position paper for the organization of extracorporeal membrane oxygenation programs for acute respiratory failure in adult patients

The use of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory failure (ARF) in adults is growing rapidly given recent advances in technology, even though there is controversy regarding the evidence justifying its use. Because ECMO is a complex, high-risk, and costly modality, at present it should be conducted in centers with sufficient experience, volume, and expertise to ensure it is used safely. This position paper represents the consensus opinion of an international group of physicians and associated health-care workers who have expertise in therapeutic modalities used in the treatment of patients with severe ARF, with a focus on ECMO. The aim of this paper is to provide physicians, ECMO center directors and coordinators, hospital directors, health-care organizations, and regional, national, and international policy makers a description of the optimal approach to organizing ECMO programs for ARF in adult patients. Importantly, this will help ensure that ECMO is delivered safely and proficiently, such that future observational and randomized clinical trials assessing this technique may be performed by experienced centers under homogeneous and optimal conditions. Given the need for further evidence, we encourage restraint in the widespread use of ECMO until we have a better appreciation for both the potential clinical applications and the optimal techniques for performing ECMO.

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.

Part 6: Pediatric basic life support and pediatric advanced life support. 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations

The Pediatric Task Force reviewed all questions submitted by the International Liaison Committee on Resuscitation (ILCOR) member councils in 2010, reviewed all council training materials and resuscitation guidelines and algorithms, and conferred on recent areas of interest and controversy. We identified a few areas where there were key differences in council-specific guidelines based on historical recommendations, such as the A-B-C (Airway, Breathing, Circulation) versus C-A-B (Circulation, Airway, Breathing) sequence of provision of cardiopulmonary resuscitation (CPR), initial back blows versus abdominal thrusts for foreign-body airway obstruction, an upper limit for recommended chest compression rate, and initial defibrillation dose for shockable rhythms (2 versus 4 J/kg). We produced a working list of prioritized questions and topics, which was adjusted with the advent of new research evidence. This led to a prioritized palate of 21 PICO (population, intervention, comparator, outcome) questions for ILCOR task force focus. The 2015 process was supported by information specialists who performed in-depth systematic searches, liaising with pediatric content experts so that the most appropriate terms and outcomes and the most relevant publications were identified. Relevant adult literature was considered (extrapolated) in those PICO questions that overlapped with other task forces, or when there were insufficient pediatric data. In rare circumstances (in the absence of sufficient human data), appropriate animal studies were incorporated into reviews of the literature. However, these data were considered only when higher levels of evidence were not available and the topic was deemed critical. When formulating the PICO questions, the task force felt it important to evaluate patient outcomes that extend beyond return of spontaneous circulation (ROSC) or discharge from the pediatric intensive care unit (PICU). In recognition that the measures must have meaning, not only to clinicians but also to parents and caregivers, longer-term outcomes at 30 …

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.

Mortality related to invasive infections, sepsis, and septic shock in critically ill children in Australia and New Zealand, 2002–13: a multicentre retrospective cohort study

BACKGROUND Severe infections kill more than 4·5 million children every year. Population-based data for severe infections in children requiring admission to intensive care units (ICUs) are scarce. We assessed changes in incidence and mortality of severe infections in critically ill children in Australia and New Zealand. METHODS We did a retrospective multicentre cohort study of children requiring intensive care in Australia and New Zealand between 2002 and 2013, with data from the Australian and New Zealand Paediatric Intensive Care Registry. We included children younger than 16 years with invasive infection, sepsis, or septic shock. We assessed incidence and mortality in the ICU for 2002-07 versus 2008-13. FINDINGS During the study period, 97 127 children were admitted to ICUs, 11 574 (11·9%) had severe infections, including 6688 (6·9%) with invasive infections, 2847 (2·9%) with sepsis, and 2039 (2·1%) with septic shock. Age-standardised incidence increased each year by an average of 0·56 cases per 100 000 children (95% CI 0·41-0·71) for invasive infections, 0·09 cases per 100 000 children (0·00-0·17) for sepsis, and 0·08 cases per 100 000 children (0·04-0·12) for septic shock. 260 (3·9%) of 6688 patients with invasive infection died, 159 (5·6%) of 2847 with sepsis died, and 346 (17·0%) of 2039 with septic shock died, compared with 2893 (3·0%) of all paediatric ICU admissions. Children admitted with invasive infections, sepsis, and septic shock accounted for 765 (26·4%) of 2893 paediatric deaths in ICUs. Comparing 2008-13 with 2002-07, risk-adjusted mortality decreased significantly for invasive infections (odds ratio 0·72, 95% CI 0·56-0·94; p=0·016), and for sepsis (0·66, 0·47-0·93; p=0·016), but not significantly for septic shock (0·79, 0·61-1·01; p=0·065). INTERPRETATION Severe infections remain a major cause of mortality in paediatric ICUs, representing a major public health problem. Future studies should focus on patients with the highest risk of poor outcome, and assess the effectiveness of present sepsis interventions in children. FUNDING National Medical Health and Research Council, Australian Resuscitation Outcomes Consortium, Centre of Research Excellence (1029983).

Bench to bedside review: Extracorporeal carbon dioxide removal, past present and future

Acute respiratory distress syndrome (ARDS) has a substantial mortality rate and annually affects more than 140,000 people in the USA alone. Standard management includes lung protective ventilation but this impairs carbon dioxide clearance and may lead to right heart dysfunction or increased intracranial pressure. Extracorporeal carbon dioxide removal has the potential to optimize lung protective ventilation by uncoupling oxygenation and carbon dioxide clearance. The aim of this article is to review the carbon dioxide removal strategies that are likely to be widely available in the near future. Relevant published literature was identified using PubMed and Medline searches. Queries were performed by using the search terms ECCOR, AVCO2R, VVCO2R, respiratory dialysis, and by combining carbon dioxide removal and ARDS. The only search limitation imposed was English language. Additional articles were identified from reference lists in the studies that were reviewed. Several novel strategies to achieve carbon dioxide removal were identified, some of which are already commercially available whereas others are in advanced stages of development.

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.

American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock

Objectives: The American College of Critical Care Medicine provided 2002 and 2007 guidelines for hemodynamic support of newborn and pediatric septic shock. Provide the 2014 update of the 2007 American College of Critical Care Medicine “Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock.” Design: Society of Critical Care Medicine members were identified from general solicitation at Society of Critical Care Medicine Educational and Scientific Symposia (2006–2014). The PubMed/Medline/Embase literature (2006–14) was searched by the Society of Critical Care Medicine librarian using the keywords: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation, and American College of Critical Care Medicine guidelines in the newborn and pediatric age groups. Measurements and Main Results: The 2002 and 2007 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and American Heart Association/Pediatric Advanced Life Support sanctioned recommendations. The review of new literature highlights two tertiary pediatric centers that implemented quality improvement initiatives to improve early septic shock recognition and first-hour compliance to these guidelines. Improved compliance reduced hospital mortality from 4% to 2%. Analysis of Global Sepsis Initiative data in resource rich developed and developing nations further showed improved hospital mortality with compliance to first-hour and stabilization guideline recommendations. Conclusions: The major new recommendation in the 2014 update is consideration of institution—specific use of 1) a “recognition bundle” containing a trigger tool for rapid identification of patients with septic shock, 2) a “resuscitation and stabilization bundle” to help adherence to best practice principles, and 3) a “performance bundle” to identify and overcome perceived barriers to the pursuit of best practice principles.

Part 6: Pediatric basic life support and pediatric advanced life support

The Pediatric Task Force reviewed all questions submitted by the International Liaison Committee on Resuscitation (ILCOR) member councils in 2010, reviewed all council training materials and resuscitation guidelines and algorithms, and conferred on recent areas of interest and controversy. We identified a few areas where there were key differences in council-specific guidelines based on historical recommendations, such as the A-B-C (Airway, Breathing, Circulation) versus C-A-B (Circulation, Airway, Breathing) sequence of provision of cardiopulmonary resuscitation (CPR), initial back blows versus abdominal thrusts for foreign-body airway obstruction, an upper limit for recommended chest compression rate, and initial defibrillation dose for shockable rhythms (2 versus 4 J/kg). We produced a working list of prioritized questions and topics, which was adjusted with the advent of new research evidence. This led to a prioritized palate of 21 PICO (population, intervention, comparator, outcome) questions for ILCOR task force focus. The 2015 process was supported by information specialists who performed in-depth systematic searches, liaising with pediatric content experts so that the most appropriate terms and outcomes and the most relevant publications were identified. Relevant adult literature was considered (extrapolated) in those PICO questions that overlapped with other task forces, or when there were insufficient pediatric data. In rare circumstances (in the absence of sufficient human data), appropriate animal studies were incorporated into reviews of the literature. However, these data were considered only when higher levels of evidence were not available and the topic was deemed critical. When formulating the PICO questions, the task force felt it important to evaluate patient outcomes that extend beyond return of spontaneous circulation (ROSC) or discharge from the pediatric intensive care unit (PICU). In recognition that the measures must have meaning, not only to clinicians but also to parents and caregivers, longer-term outcomes at 30 …

Clinical review: mechanical circulatory support for cardiogenic shock complicating acute myocardial infarction

Acute myocardial infarction is one of the 10 leading reasons for admission to adult critical care units. In-hospital mortality for this condition has remained static in recent years, and this is related primarily to the development of cardiogenic shock. Recent advances in reperfusion therapies have had little impact on the mortality of cardiogenic shock. This may be attributable to the underutilization of life support technology that may assist or completely supplant the patients own cardiac output until adequate myocardial recovery is established or long-term therapy can be initiated. Clinicians working in the intensive care environment are increasingly likely to be exposed to these technologies. The purpose of this review is to outline the various techniques of mechanical circulatory support and discuss the latest evidence for their use in cardiogenic shock complicating acute myocardial infarction.