Alain Vuylsteke

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.

Safety and Efficacy of Recombinant Activated Factor VII A Randomized Placebo-Controlled Trial in the Setting of Bleeding After Cardiac Surgery

Background— Blood loss is a common complication of cardiac surgery. Evidence suggests that recombinant activated factor VII (rFVIIa) can decrease intractable bleeding in patients after cardiac surgery. Our objective was to investigate the safety and possible benefits of rFVIIa in patients who bleed after cardiac surgery. Methods and Results— In this phase II dose-escalation study, patients who had undergone cardiac surgery and were bleeding were randomized to receive placebo (n=68), 40 &mgr;g/kg rFVIIa (n=35), or 80 &mgr;g/kg rFVIIa (n=69). The primary end points were the number of patients suffering critical serious adverse events. Secondary end points included rates of reoperation, amount of blood loss, and transfusion of allogeneic blood. There were more critical serious adverse events in the rFVIIa groups. These differences did not reach statistical significance (placebo, 7%; 40 &mgr;g/kg, 14%; P=0.25; 80 &mgr;g/kg, 12%; P=0.43). After randomization, significantly fewer patients in the rFVIIa group underwent a reoperation as a result of bleeding (P=0.03) or required allogeneic transfusions (P=0.01). Conclusions— On the basis of this preliminary evidence, rFVIIa may be beneficial for treating bleeding after cardiac surgery, but caution should be applied and further clinical trials are required because there is an increase in the number of critical serious adverse events, including stroke, in those patients randomized to receive rFVIIa.

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.

Successful Extracorporeal Membrane Oxygenation Support After Pulmonary Thromboendarterectomy

BACKGROUND Pulmonary thromboendarterectomy (PTE) is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension. However, some patients develop severe cardiorespiratory compromise soon after separating from cardiopulmonary bypass, either from early reperfusion pulmonary edema or right ventricular failure secondary to residual pulmonary hypertension. Since 2005 we have used venoarterial extracorporeal membrane oxygenation (ECMO) support in this group that has no other therapeutic option. We review our experience of early ECMO support in the severely compromised patients post-PTE. METHODS We conducted a retrospective review of all patients undergoing PTE from a single national referral center between August 2005 and August 2007. RESULTS One hundred twenty-seven consecutive patients underwent PTE surgery. Seven patients (5.5%) had extreme cardiorespiratory compromise in the immediate postoperative period and required venoarterial ECMO support. Their mean age was 51.3 years with 3 males. When compared with patients not requiring ECMO, these patients had significantly poorer hemodynamic indices before the operation with mean pulmonary artery pressure of 62 mm Hg versus 51 mm Hg (p = 0.02) and pulmonary vascular resistance of 907 dynes/sec/cm(-5) versus 724 dynes/s(-1)/cm(-5) (p < 0.02). Mean duration of support was 119 hours (49 to 359 hours). Five patients were successfully weaned from ECMO support (73%) and 4 left the hospital alive, giving a salvage rate of 57%. For those who did not require ECMO support, hospital mortality was 4.2%. CONCLUSIONS Early venoarterial ECMO support has a role as rescue therapy post-PTE in patients with severe compromise who would probably otherwise die.

Circulatory arrest versus cerebral perfusion during pulmonary endarterectomy surgery (PEACOG): a randomised controlled trial

BACKGROUND For some surgical procedures to be done, a patients blood circulation needs to be stopped. In such situations, the maintenance of blood flow to the brain is perceived beneficial even in the presence of deep hypothermia. We aimed to assess the benefits of the maintenance of antegrade cerebral perfusion (ACP) compared with deep hypothermic circulatory arrest (DHCA). METHODS Patients aged 18-80 years undergoing pulmonary endarterectomy surgery in a UK centre (Papworth Hospital, Cambridge) were randomly assigned with a computer generated sequence to receive either DHCA for periods of up to 20 min at 20°C or ACP (1:1 ratio). The primary endpoint was change in cognitive function at 12 weeks after surgery, as assessed by the trail-making A and B tests, the Rey auditory verbal learning test, and the grooved pegboard test. Patients and assessors were masked to treatment allocation. Primary analysis was by intention to treat. The trial is registered with Current Controlled Trials, number ISRCTN84972261. FINDINGS We enrolled 74 of 196 screened patients (35 to receive DHCA and 39 to receive ACP). Nine patients crossed over from ACP to DHCA to allow complete endarterectomy. At 12 weeks, the mean difference between the two groups in Z scores (the change in cognitive function score from baseline divided by the baseline SD) for the three main cognitive tests was 0·14 (95% CI -0·14 to 0·42; p=0·33) for the trail-making A and B tests, -0·06 (-0·38 to 0·25; p=0·69) for the Rey auditory verbal learning test, and 0·01 (-0·26 to 0·29; p=0·92) for the grooved pegboard test. All patients showed improvement in cognitive function at 12 weeks. We recorded no significant difference in adverse events between the two groups. At 12 weeks, two patients had died (one in each group) [corrected]. INTERPRETATION Cognitive function is not impaired by either ACP or DHCA. We recommend circulatory arrest as the optimum modality for patients undergoing pulmonary endarterectomy surgery. FUNDING J P Moulton Charitable Foundation.

Comparison of clevidipine with sodium nitroprusside in the control of blood pressure after coronary artery surgery

Background and objective: We set out to compare the efficacy of clevidipine and sodium nitroprusside infusions in the control of blood pressure and the haemodynamic changes they produce in hypertensive patients after operation for elective coronary bypass grafting. Methods: Thirty patients were randomly allocated to receive either clevidipine or sodium nitroprusside after their mean arterial pressure (MAP) had reached >90 mmHg for at least 10 min in the postoperative period. The MAP was continuously measured and related to time. Thus, the efficacy of the drugs in controlling arterial pressure could be inversely related to the total area under the MAP-time curve outside a target MAP range of 70-80 mmHg normalized per hour (AUCMAP mmHg min h−1). Haemodynamic variables and the number of dose-rate adjustments required to maintain MAP were also studied. Results: There was no statistically significant difference in the efficacy (AUCMAP mmHg min h−1) of clevidipine (106 ± 25 mmHg min h−1) compared with sodium nitroprusside (101 ± 28 mmHg min h−1). Nor was any significant difference found in the total number of dose adjustments required to control MAP within the target range. The heart rate in patients receiving clevidipine increased less than in those given sodium nitroprusside. Stroke volume, central venous pressure and pulmonary artery pressure were significantly reduced upon administration of sodium nitroprusside but not of clevidipine. Conclusions: There was no significant difference between clevidipine and sodium nitroprusside in their efficacy in controlling MAP. The haemodynamic changes, including tachycardia, were less pronounced with clevidipine than with sodium nitroprusside.

The Papworth Bleeding Risk Score: a stratification scheme for identifying cardiac surgery patients at risk of excessive early postoperative bleeding

OBJECTIVE We have developed a risk stratification score to identify cardiac surgical patients at higher risk of severe postoperative bleeding to aid a decision of whether to use a specific intervention preoperatively. METHODS We prospectively created a database of 11592 consecutive patients, who underwent cardiac surgery with cardiopulmonary bypass. An adverse outcome was formally defined as a mean blood loss exceeding 2 ml kg(-1)h(-1) measured between arrival in the intensive care unit (ICU) and the earliest of the elapse of 3h; the start of transfusion of any one of fresh-frozen plasma, platelets or cryoprecipitate; return to theatre or death. Univariate and multivariate associations of severe postoperative bleeding with patient characteristics, clinical features and procedure details were analysed on a development set. The final risk stratification scheme was then evaluated on a test set. RESULTS Severe postoperative bleeding was associated with urgent or emergency surgery, surgery that was not coronary artery bypass grafting or single valve surgery, presence of aortic valve disease, low body mass index and older age. A risk stratification score was constructed from the above variables to define preoperative categories that demonstrated high, medium and low risk of severe postoperative bleeding. Patients deemed to be at high, medium and low risk by our preoperative scoring had a 21% (95% confidence interval: 18-24%), 8% (7-10%) and 3% (2-4%) rate of severe postoperative bleeding, respectively, within the test set. CONCLUSION We have developed a simple risk stratification score that can separate, preoperatively, patients into risk groups with markedly different rates of severe postoperative bleeding.

Significant blood resistance to nitric oxide transfer in the lung

Lung diffusing capacity for nitric oxide (DLNO) is used to measure alveolar membrane conductance (DMNO), but disagreement remains as to whether DMNO=DLNO, and whether blood conductance (thetaNO)=infinity. Our previous in vitro and in vivo studies suggested that thetaNO<infinity. We now show in a membrane oxygenator model perfused with whole blood that addition of a cell-free bovine hemoglobin (Hb) glutamer-200 solution increased diffusing capacity of the circuit (D) for NO (DNO) by 39%, D for carbon monoxide (DCO) by 24%, and the ratio of DNO to DCO by 12% (all P<0.001). In three anesthetized dogs, DLNO and DLCO were measured by a rebreathing technique before and after three successive equal volume-exchange transfusions with bovine Hb glutamer-200 (10 ml/kg each, total exchange 30 ml/kg). At baseline, DLNO/DLCO=4.5. After exchange transfusion, DLNO rose 57+/-16% (mean+/-SD, P=0.02) and DLNO/DLCO=7.1, whereas DLCO remained unchanged. Thus, in vitro and in vivo data directly demonstrate a finite thetaNO. We conclude that the erythrocyte and/or its immediate environment imposes considerable resistance to alveolar-capillary NO uptake. DLNO is sensitive to dynamic hematological factors and is not a pure index of conductance of the alveolar tissue membrane. With successive exchange transfusion, the estimated in vivo thetaNO [5.1 ml NO.(ml blood.min.Torr)(-1)] approached 4.5 ml NO.(ml blood.min.Torr)(-1), which was derived from in vitro measurements by Carlsen and Comroe (J Gen Physiol 42: 83-107, 1958). Therefore, we suggest use of thetaNO=4.5 ml NO.(min.Torr.ml blood)(-1) for calculation of DM(NO) and pulmonary capillary blood volume from DLNO and DLCO.

Electronic patient record use during ward rounds: a qualitative study of interaction between medical staff.

IntroductionElectronic patient records are becoming more common in critical care. As their design and implementation are optimized for single users rather than for groups, we aimed to understand the differences in interaction between members of a multidisciplinary team during ward rounds using an electronic, as opposed to paper, patient medical record.MethodsA qualitative study of morning ward rounds of an intensive care unit that triangulates data from video-based interaction analysis, observation, and interviews.ResultsOur analysis demonstrates several difficulties the ward round team faced when interacting with each other using the electronic record compared with the paper one. The physical setup of the technology may impede the consultants ability to lead the ward round and may prevent other clinical staff from contributing to discussions.ConclusionsWe discuss technical and social solutions for minimizing the impact of introducing an electronic patient record, emphasizing the need to balance both. We note that awareness of the effects of technology can enable ward-round teams to adapt their formations and information sources to facilitate multidisciplinary communication during the ward round.

A randomized controlled trial of cell salvage in routine cardiac surgery.

BACKGROUND: Previous trials have indicated that cell salvage may reduce allogeneic blood transfusion during cardiac surgery, but these studies have limitations, including inconsistent use of other blood transfusion-sparing strategies. We designed a randomized controlled trial to determine whether routine cell salvage for elective uncomplicated cardiac surgery reduces blood transfusion and is cost effective in the setting of a rigorous transfusion protocol and routine administration of antifibrinolytics. METHODS: Two-hundred-thirteen patients presenting for first-time coronary artery bypass grafting and/or cardiac valve surgery were prospectively randomized to control or cell salvage groups. The latter group had blood aspirate during surgery and mediastinal drainage the first 6 h after surgery processed in a cell saver device and autotransfused. All patients received tranexamic acid and were subjected to an algorithm for red blood cell and hemostatic blood factor transfusion. RESULTS: There was no difference between the two groups in the proportion of patients exposed to allogeneic blood (32% in both groups, relative risk 1.0 P = 0.89). At current blood products and cell saver prices, the use of cell salvage increased the costs per patient by a minimum of