Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A(H1N1).

CONTEXT: Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients with severe acute respiratory distress syndrome (ARDS), but its role has remained controversial. ECMO was used to treat patients with ARDS during the 2009 influenza A(H1N1) pandemic. OBJECTIVE: To compare the hospital mortality of patients with H1N1-related ARDS referred, accepted, and transferred for ECMO with matched patients who were not referred for ECMO. DESIGN, SETTING, AND PATIENTS: A cohort study in which ECMO-referred patients were defined as all patients with H1N1-related ARDS who were referred, accepted, and transferred to 1 of the 4 adult ECMO centers in the United Kingdom during the H1N1 pandemic in winter 2009-2010. The ECMO-referred patients and the non-ECMO-referred patients were matched using data from a concurrent, longitudinal cohort study (Swine Flu Triage study) of critically ill patients with suspected or confirmed H1N1. Detailed demographic, physiological, and comorbidity data were used in 3 different matching techniques (individual matching, propensity score matching, and GenMatch matching). MAIN OUTCOME MEASURE: Survival to hospital discharge analyzed according to the intention-to-treat principle. RESULTS: Of 80 ECMO-referred patients, 69 received ECMO (86.3%) and 22 died (27.5%) prior to discharge from the hospital. From a pool of 1756 patients, there were 59 matched pairs of ECMO-referred patients and non-ECMO-referred patients identified using individual matching, 75 matched pairs identified using propensity score matching, and 75 matched pairs identified using GenMatch matching. The hospital mortality rate was 23.7% for ECMO-referred patients vs 52.5% for non-ECMO-referred patients (relative risk [RR], 0.45 [95% CI, 0.26-0.79]; P = .006) when individual matching was used; 24.0% vs 46.7%, respectively (RR, 0.51 [95% CI, 0.31-0.81]; P = .008) when propensity score matching was used; and 24.0% vs 50.7%, respectively (RR, 0.47 [95% CI, 0.31-0.72]; P = .001) when GenMatch matching was used. The results were robust to sensitivity analyses, including amending the inclusion criteria and restricting the location where the non-ECMO-referred patients were treated. CONCLUSION: For patients with H1N1-related ARDS, referral and transfer to an ECMO center was associated with lower hospital mortality compared with matched non-ECMO-referred patients.

Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial.

BACKGROUND: Severe acute respiratory failure in adults causes high mortality despite improvements in ventilation techniques and other treatments (eg, steroids, prone positioning, bronchoscopy, and inhaled nitric oxide). We aimed to delineate the safety, clinical efficacy, and cost-effectiveness of extracorporeal membrane oxygenation (ECMO) compared with conventional ventilation support. METHODS: In this UK-based multicentre trial, we used an independent central randomisation service to randomly assign 180 adults in a 1:1 ratio to receive continued conventional management or referral to consideration for treatment by ECMO. Eligible patients were aged 18-65 years and had severe (Murray score >3.0 or pH <7.20) but potentially reversible respiratory failure. Exclusion criteria were: high pressure (>30 cm H(2)O of peak inspiratory pressure) or high FiO(2) (>0.8) ventilation for more than 7 days; intracranial bleeding; any other contraindication to limited heparinisation; or any contraindication to continuation of active treatment. The primary outcome was death or severe disability at 6 months after randomisation or before discharge from hospital. Primary analysis was by intention to treat. Only researchers who did the 6-month follow-up were masked to treatment assignment. Data about resource use and economic outcomes (quality-adjusted life-years) were collected. Studies of the key cost generating events were undertaken, and we did analyses of cost-utility at 6 months after randomisation and modelled lifetime cost-utility. This study is registered, number ISRCTN47279827. FINDINGS: 766 patients were screened; 180 were enrolled and randomly allocated to consideration for treatment by ECMO (n=90 patients) or to receive conventional management (n=90). 68 (75%) patients actually received ECMO; 63% (57/90) of patients allocated to consideration for treatment by ECMO survived to 6 months without disability compared with 47% (41/87) of those allocated to conventional management (relative risk 0.69; 95% CI 0.05-0.97, p=0.03). Referral to consideration for treatment by ECMO led to a gain of 0.03 quality-adjusted life-years (QALYs) at 6-month follow-up [corrected]. A lifetime model predicted the cost per QALY of ECMO to be pound19 252 (95% CI 7622-59 200) at a discount rate of 3.5%. INTERPRETATION: We recommend transferring of adult patients with severe but potentially reversible respiratory failure, whose Murray score exceeds 3.0 or who have a pH of less than 7.20 on optimum conventional management, to a centre with an ECMO-based management protocol to significantly improve survival without severe disability. This strategy is also likely to be cost effective in settings with similar services to those in the UK. FUNDING: UK NHS Health Technology Assessment, English National Specialist Commissioning Advisory Group, Scottish Department of Health, and Welsh Department of Health.

Panton-Valentine leukocidin expressing Staphylococcus aureus pneumonia managed with extracorporeal membrane oxygenation: experience and outcome.

OBJECTIVE: Panton-Valentine leukocidin expressing Staphylococcus aureus pneumonia, an infection that affects predominantly young people, has a mortality rate of > 70% despite aggressive conventional management. Little information is available on the management of patients with Panton-Valentine leukocidin expressing S. aureus pneumonia with extracorporeal membrane oxygenation support. As a large extracorporeal membrane oxygenation center, we reviewed our experience and outcomes with Panton-Valentine Leukocidin expressing S. aureus pneumonia. DATA SOURCES: Locally held register of all extracorporeal membrane oxygenation patients at Glenfield Hospital. STUDY SELECTION: Retrospective study including all patients with sputum-positive Panton-Valentine leukocidin expressing S. aureus pneumonia managed with extracorporeal membrane oxygenation support at a single extracorporeal membrane oxygenation center. DATA SYNTHESIS: On review of our database held from September 1989 until date, there were four patients with sputum-confirmed Panton-Valentine leukocidin expressing S. aureus pneumonia managed with extracorporeal membrane oxygenation. Refractory hypoxemia and/or uncompensated hypercapnia despite optimal conventional management were the indications for extracorporeal membrane oxygenation. After varying periods on extracorporeal membrane oxygenation with appropriate antibiotic and ancillary care, all four patients were discharged home. CONCLUSIONS: Panton-Valentine leukocidin expressing S. aureus pneumonia can cause severe, necrotizing pneumonia associated with acute respiratory distress syndrome, which can be particularly challenging to manage. Extracorporeal membrane oxygenation support permits low pressure lung ventilation, avoiding barotrauma to lungs made friable by Panton-Valentine leukocidin expressing S. aureus infection. Although this is a small number of patients, the results are encouraging.

Primary benign bronchial schwannoma presenting as asthma.

Recurrent wheezing in children is frequently due to asthma and responds to bronchodilator therapy. We report a case of a 13-year old boy with a 2-year history of presumed asthma not responding to bronchodilator therapy. Bronchoscopy revealed a right main bronchus tumor, which was diagnosed as bronchial schwannoma after resection by sleeve lobectomy. We review the literature on this tumor.

Aortic root abscess without involvement of the aortic valve in a child caused by Panton-Valentine leukocidin-positive staphylococci.

Aortic root abscess without any involvement of the aortic valve is extremely rare. This report describes an 11-year-old girl with subperiosteal abscess due to a virulent organism called Panton-Valentine leukocidin-secreting staphylococci. Although her initial transthoracic echocardiogram did not show any cardiac abnormality, she subsequently experienced an aortic root abscess communicating with the left ventricle. The aortic valve was unaffected, and no other cardiac abnormality was detected at any stage. The girl made a complete recovery after surgical intervention for her aortic root abscess, which was increasing in size despite antibiotic therapy. Patients with such illnesses require close monitoring with repeated expert echocardiography and timely intervention.

Lack of influence of mild hypothermia on amplitude integrated-electroencephalography in neonates receiving extracorporeal membrane oxygenation.

OBJECTIVE: To observe amplitude integrated electroencephalography (aEEG) in neonates receiving ECMO and to determine whether mild hypothermia influenced the aEEG recording. METHODS: Twenty-six consecutive neonates enrolled in a pilot study of mild hypothermia during ECMO were studied. The first group (N=6) was maintained at 37 degrees C throughout the study period. Subsequent groups were cooled to 36 degrees C (N=4), 35 degrees C (N=5), and finally 34 degrees C (N=6) respectively for 24 h and the final group (N=5) to 34 degrees C for 48 h before being rewarmed to 37 degrees C. The aEEG was recorded continuously during the first 5 days of ECMO. The aEEG was classified as normal, moderately or severely suppressed and examined for the occurrence of seizures. To assess the effect of temperature, the aEEG was compared over 12 h during the final 6 h of cooling and during the first 6 h once infants were rewarmed. RESULTS: No change in aEEG amplitude was noted over the temperature range studied. Of the 26 traces obtained, 16 (62%) were normal throughout, 6 (23%) were intermittently moderately abnormal and 1 (14%) was severely abnormal. Three (11%) traces had periods of frequent seizure activity and these were not associated with clinical manifestations in two neonates. In one infant who suffered a cerebral haemorrhage, the aEEG became abnormal before cranial ultrasound abnormalities were apparent. CONCLUSIONS: Continuous cerebral monitoring with aEEG is feasible during ECMO and may add information to clinical examination. Mild hypothermia to 34 degrees C for up to 48 h does not influence the aEEG suggesting that cerebral monitoring with aEEG is possible during mild hypothermia.

The effect of temperature on the QTc interval in the newborn infant receiving extracorporeal membrane oxygenation (ECMO).

OBJECTIVE: To explore the changes in the QTc interval during mild hypothermia in neonates receiving extracorporeal membrane oxygenation (ECMO). DESIGN: Twenty seven neonates (median gestation 40 weeks; range 33-41 weeks) enrolled in a pilot study of mild hypothermia were studied during the first five days of ECMO. The first group (N=7) were maintained at 37 degrees C throughout the study period. Subsequent groups (N=5) were cooled to 36 degrees C, 35 degrees C and 34 degrees C respectively for twenty four hours and the final group to 34 degrees C for forty eight hours before being rewarmed to 37 degrees C. Using a 24 h digital monitor, the QT and QTc intervals were recorded continuously during the cooling and rewarming period and validated using standard 12 lead electrocardiograms. Patients were carefully assessed clinically and routine biochemistry (including magnesium and calcium) laboratory tests measured pre ECMO and at timed intervals during cooling and rewarming. RESULTS: The mean difference between the continuous digital and 12 lead ECG values for QTc was -13.3 ms. During the first 24 h of cooling, the mean (95th centile) values for the digitally measured QTc interval at 37 degrees C=431(506) milliseconds (ms); 36 degrees C=459(521) ms; 35 degrees C=445(516) ms; 34 degrees C=465(531) ms; 34 degrees C for 48 h=466(521) ms. During this period overall QTc increased by 3.12 ms (95% confidence intervals 6.17 to 0.84; p=0.04) for each degree fall in body temperature. During rewarming, there was no significant relationship between QTc and temperature change. No serious arrhythmias were during cooling. Using univariate analysis, no relationship was found between QTc and electrolytes, heart rate and blood pressure. CONCLUSIONS: QTc shows significant variability in individuals, and only a small proportion of this can be explained by rectal temperature. Mild hypothermia was not associated with serious cardiac arrhythmias.

Successful use of venovenous extracorporeal membrane oxygenation in accidental hypothermic cardiac arrest.

Cardiopulmonary bypass is usually used for rewarming and for providing cardiac support in patients with severe hypothermia and cardiovascular instability. We report the first case of accidental severe hypothermia associated with prolonged cardiac arrest that was successfully managed by venovenous extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation with lepirudin anticoagulation for Wegener's granulomatosis with heparin-induced thrombocytopenia.

Venovenous extracorporeal membrane oxygenation with lepirudin anticoagulation was successfully used for a complicated case of Wegener's granulomatosis and heparin-induced thrombocytopenia. Interestingly, a linear correlation was found between activated partial thromboplastin time and activated clotting time during lepirudin anticoagulation.

Poly-methyl pentene oxygenators have improved gas exchange capability and reduced transfusion requirements in adult extracorporeal membrane oxygenation.

The performance of poly-methyl pentene (PMP) oxygenators (Medos Hilite 7000LT) was compared with that of silicone membrane (SM) oxygenators (Medtronic 1-4500-2A) for adult extracorporeal membrane oxygenation (ECMO). Forty consecutive patients were selected retrospectively pre- and post-introduction of PMP oxygenators. They were selected according to the dates they received ECMO and were separated into two equal groups with similar backgrounds. The flow path resistance, gas and heat exchange efficiency, consumption of coagulation factors and platelets, blood transfusion requirements, and incidence of clots for each oxygenator type was assessed. Adult PMP oxygenators showed lower blood path resistance than SM oxygenators. However, lower consumption of blood products in these oxygenators was a direct result of their smaller surface area and heparin coated design, reducing contact activation of coagulation factors. These oxygenators are noticeably smaller, require lower priming volumes, and have better gas exchange capability than SM oxygenators. They showed greater stability and preservation of coagulation factors and platelets compared with SM oxygenators. They also had the advantage of a functioning integrated heat exchanger. Using a single PMP oxygenator in the first instance may be adequate for the majority of patients and would significantly reduce red blood cell consumption during ECMO.

Is open thoracotomy still a good treatment option for the management of empyema in children?

BACKGROUND: The incidence of pediatric postpneumonic empyema increases, and there is little consensus on its management. Open thoracotomy has been linked with high morbidity and prolonged hospitalization. Our aim was to review the outcome after open thoracotomy and to provide a set of data for comparison with other treatment modalities. METHODS: Forty-four children (median age, 8 years, 2 months to 16 years) undergoing surgery for postpneumonic empyema between 1993 and 2002 in our unit were studied. RESULTS: The median time from onset of symptoms to admission in a pediatric unit was 8 days (range, 2 to 63 days), the median time from pediatric admission to surgical referral was 3 days (range, 0 to 19 days), and the median time from surgical admission to thoracotomy was 1 day (range, 0 to 2 days). Eight children had a chest drain before surgical admission. Six patients, who were referred late (19 to 69 days), had lung abscesses. A limited muscle sparing thoracotomy (44 patients), formal decortication (36 patients), lung debridement (5 patients), and lobectomy (1 patient) were performed. After thoracotomy, median time to apyrexia was 1 day (range, 0 to 27 days) and drain removal was 3 days (range, 1 to 16 days). A pathogen was isolated in 21 patients. There were no deaths. Four children with abscesses remained septic and had lobectomies (2 patients) and debridements (2 patients). The median postoperative hospital stay was 5 to 53 days. One child had postpneumonic empyema develop and had decortication 3 months postoperatively. At follow-up, all children were doing well and had satisfactory radiographs. The Kaplan-Meier 5-year and 10-year survival rate, freedom from any reoperation, and freedom from hospital readmission were 100%, 87%, and 98%, respectively. CONCLUSIONS: Open thoracotomy remains an excellent option for management of stage II-III empyema in children. When open thoracotomy is performed in a timely manner there is low morbidity and it provides rapid resolution of symptoms with a short hospital stay. However, delayed referrals may result in advanced pulmonary sepsis and a protracted clinical course. The late results are encouraging. Use of thoracoscopy or fibrinolysis should be considered on the basis of their own merit, not on the assumption of probable adverse outcomes after thoracotomy.

Extracorporeal life support in pertussis.

Severe B. pertussis infection in infants is characterized by severe respiratory failure, pulmonary hypertension, leukocytosis, and death. This retrospective case analysis highlights the course and outcome of severe B. pertussis infection treated with extracorporeal membrane oxygenation (ECMO) at a single center. Over the last decade, out of a total caseload of nearly 800 infants and children, 12 infants with severe B. pertussis have been referred for ECMO therapy to our center. All infants with pertussis infection who received ECMO therapy were less than 3 months of age at presentation and unvaccinated. There was a high mortality rate (7 of 12 infants died), which was associated with an elevated neutrophil count at presentation and multiorgan dysfunction characterized by intractable pulmonary hypertension, persistent systemic hypotension, renal insufficiency, and fits. ECMO should be offered to children with pertussis infection and respiratory failure refractory to mechanical ventilation. However, further research is required to determine the optimal management for infants receiving ECMO therapy with this disease.

Extracorporeal membrane oxygenation for chickenpox pneumonia: a single institution's experience.

The experience of extracorporeal membrane oxygenation (ECMO) use for severe chickenpox pneumonia was reviewed. Case notes of all patients treated with ECMO for this disease between 1992 and 1997 were reviewed. Of 405 patients referred for ECMO during this period, the diagnosis was chickenpox pneumonia in 14 (3.5%); all 14 were treated with ECMO. The median age of patients was 32.5 years (range 5 to 61 years). The median duration of extracorporeal support was 164 hours (range 45 to 652). Ten of 14 patients (71%) required hemofiltration. Overall survival of patients supported with ECMO was 57% (8 of 14). Deaths were caused by sepsis (5 patients, source identified in 4) and multiorgan failure (1 patient). Pneumonia as a complication of chickenpox can rapidly become severe and life threatening. Extracorporeal respiratory support may be helpful in patients refractory to conventional ventilation.

Early experience with a polymethyl pentene oxygenator for adult extracorporeal life support.

Silicone oxygenators are the standard devices used for Extracorporeal Life Support (ECLS), but they have some limitations. Microporous polypropylene hollow fiber oxygenators overcome many of these problems but, unfortunately, develop plasma leak. Polymethyl-pentene (PMP) is a novel oxygenator material. We report our initial experience with the Medos Hilite 7000LT, a PMP hollow fiber oxygenator, in six adult respiratory ECLS patients with these characteristics: age, mean 32.2 (+/-13) years; weight, mean 81.2 (+/-17) kg; PaO2/FIO2, mean 62.8 [+/-33] mm Hg; Murray Score, mean 3.4 [+/-0.3]; and sepsis related organ failure assessment score, mean 9.6 [+/-2.3]. One patient was cannulated within 10 hours of multiple trauma and 1 hour after thoracolaparotomy; another patient was cannulated 12 hours after a thoracotomy. All six patients survived. Heparin was infused (7.8-32.5 u/kg/hr) to maintain activated clotting time at 162 to 238 seconds; international normalized ratio was 0.9 to 3.4. Two of the six patients required transfusions of fresh frozen plasma, receiving one and five units, respectively. Fibrinogen was 1.4 to 6 g/dl; no cryoprecipitate was needed. Platelet counts were between 65 and 306, and very little platelet transfusion (mean 2.33; +/-3.03 units per patient) was required to maintain these levels. Two patients did not require any platelet transfusion. Maximum blood flow was 5.3 L/min, sweep was 3 to 10 L/min, and resistance was 11 to 43 Paul Wood Units. There were no oxygenator failures. Mean duration of ECLS was 151.7 hours (+/-75.6). Our initial experience with PMP oxygenators in adults was satisfactory, and platelet consumption and resistance to blood flow seem to be greatly reduced with PMP.

Venovenous extracorporeal membrane oxygenation for respiratory failure in inotrope dependent neonates.

It is often stated that venovenous extracorporeal membrane oxygenation (VV ECMO) should not be used in inotrope dependent patients. It is our practice to use VV ECMO in most patients with respiratory failure even though many of these patients are receiving significant doses of inotropes. Our objective was to review the mode of ECMO in relation to precannulation doses of inotropes administered to neonates treated with ECMO for respiratory failure. Forty-three consecutive case notes were reviewed. Data were collected for basic demographic and ECMO parameters. Inotropic doses were converted to a single score for ease of comparison, with one point equivalent to 1 microg/kg/min dopamine. Forty-three neonates were studied; 37(86%) were treated with VV ECMO and 6 (14%) were treated with VA ECMO. Significant pre-ECMO inotropic support (score > 10) was present in 30 (70%) of the 43 cases. Of these patients, 26 were treated via VV ECMO with a survival rate of 84%, while 4 were treated with VA ECMO with a survival of 75%. Inotrope scores fell to nonsignificant levels (< 10) within 24 hours, regardless of ECMO mode. Mean arterial blood pressure remained above precannulation levels in both groups. VV ECMO allows safe treatment of neonatal respiratory failure in the presence of significant inotropic support. We recommend VV ECMO for neonatal respiratory failure in all cases except where double lumen cannulation is impossible or when septic shock is refractory to inotropic support (i.e., mean blood pressure < 35 mm Hg despite inotrope score of > 100).

Extracorporeal membrane oxygenation and severe acute respiratory distress secondary to Legionella: 10 year experience.

Legionella-associated respiratory failure has a high mortality, despite modern ventilation modalities. Extracorporeal membrane oxygenation (ECMO) is used to achieve gas exchange independent of pulmonary function in patients with severe respiratory failure. This was a retrospective review of the management and outcome of patients with Legionella-associated respiratory failure treated with ECMO support in a large ECMO center over the past 10 years. A retrospective review of patients with confirmed Legionella-associated severe respiratory failure managed with ECMO support at a single center. Between 2000 and 2010, 19 patients with severe respiratory failure caused by Legionella were managed with ECMO after failure to respond to conventional intensive care management. Median PaO2/FiO2 ratio was 66 and median pCO2 was 60 torr. Sixteen patients (84%) survived to hospital discharge. Extracorporeal membrane oxygenation should be considered in patients with Legionella-associated respiratory failure, who have failed conventional ventilation.

A unique case of a congenital diaphragmatic hernia in a boy with albinism.

Congenital diaphragmatic hernia and oculocutaneous albinism are both rare birth defects that can be diagnosed in the newborn period. However, they have not been previously reported to have occurred together. This report describes a unique case of a male Asian baby with oculocutaneous albinism and a right-sided congenital diaphragmatic hernia.

A comparison of radiographic signs of pulmonary inflammation during ECMO between silicon and poly-methyl pentene oxygenators.

INTRODUCTION: The inflammatory response caused by extracorporeal membrane oxygenation (ECMO) is clearly visible within the first 24 h of cannulation. The inflammatory process affects all areas of the lung, even areas previously spared by the primary disease. OBJECTIVE: To compare the change in the radiographic signs of inflammatory response to ECMO between poly-methyl pentene and silicon oxygenators. STUDY DESIGN: Retrospective review of neonates and adults pre- and post-replacement of silicon oxygenators with poly-methyl pentene devices. Data were collected from Extracorporeal Life Support Organisation (ELSO) registry forms and patient records. Results were analysed by quantitative and semi-quantitative methods. RESULTS: There was a significant reduction in the radiographic signs of inflammatory response to ECMO, and a reduction in the time taken to revert to pre-ECMO state in the neonatal poly-methyl pentene group compared to silicon. However, there was no significant reduction in the duration of ECMO runs and the percentage survival between these groups in the neonates. In adults, there was no difference in severity of radiographic signs between groups. However, the inflammatory changes were relatively delayed in the adult poly-methyl pentene group. CONCLUSION: Polymethyl pentene (Medos) oxygenators have reduced the host's response phenomenon 'white out' in neonates, and caused a delayed response in adults. This is most likely a consequence of smaller blood contact surface area combined with the effect of heparin coating of the oxygenator membrane. However, recovery was not a function of the type of gas exchange device used.

Predictors of outcome in patients with congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation.

BACKGROUND: The role of extracorporeal membrane oxygenation (ECMO) in patients with congenital diaphragmatic hernia is still evolving. The use of ECMO is invasive with potential complications during instrumentation for cannulation and heparinization. There are no reliable predictors of outcome in patients requiring ECMO. We aimed to identify (a) the factors that could predict outcome and (b) the incidence and relation of complications during ECMO to outcome. METHODS: "Pre" ECMO (age, sex, birth weight, blood gasses, and ventilator settings) and "on" ECMO variables (mode of ECMO, use of nitric oxide, surfactant, liquid ventilation, inotropes, timing of repair, and complications on ECMO) were analyzed to identify predictors of outcome. RESULTS: Fifty-two patients were included. The overall survival was 58%. Mean duration of ECMO (181 +/- 120 vs 317 +/- 156 hours, P = .001), use of nitric oxide (6 vs 10, P = .049), and renal complications (4 vs 14; P < .001) differed between survivors and nonsurvivors. The survival of patients requiring ECMO support for more than 2 weeks is significantly lower than that of patients requiring ECMO support for less than 2 weeks (18% vs 68%, P = .005). Multiple logistic regression revealed ECMO duration of 2 weeks or more and renal complications to be associated with mortality. CONCLUSION: No pre-ECMO variable could be identified as predictor of mortality. Prolonged duration of ECMO and renal complications on ECMO were independently associated with mortality.