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.

Ventilation is unstable during drowsiness before sleep onset.

Ventilation is unstable during drowsiness before sleep onset. We have studied the effects of transitory changes in cerebral state during drowsiness on breath duration and lung volume in eight healthy subjects in the absence of changes in airway resistance and fluctuations of ventilation and CO2 tension, characteristic of the onset of non-rapid eye movement sleep. A volume-cycled ventilator in the assist control mode was used to maintain CO2 tension close to that when awake. Changes in cerebral state were determined by the EEG on a breath-by-breath basis and classified as alpha or theta breaths. Breath duration and the pause in gas flow between the end of expiratory airflow and the next breath were computed for two alpha breaths which preceded a theta breath and for the theta breath itself. The group mean (SD) results for this alpha-to-theta transition was associated with a prolongation in breath duration from 5.2 (SD 1.3) to 13.0 s (SD 2.1) and expiratory pause from 0.7 (SD 0.4) to 7.5 s (SD 2.2). Because the changes in arterial CO2 tension (PaCO2) are unknown during the theta breaths, we made in two subjects a continuous record of PaCO2 in the radial artery. PaCO2 remained constant from the alpha breaths through to the expiratory period of the theta breath by which time the duration of breath was already prolonged, representing an immediate and altered ventilatory response to the prevailing PaCO2. In the eight subjects, the CO2 tension awake was 39.6 Torr (SD 2.3) and on assisted ventilation 38.0 Torr (1.4). We conclude that the ventilatory instability recorded in the present experiments is due to the apneic threshold for CO2 being at or just below that when awake.

A modified technique for insertion of dual lumen bicaval cannulae for venovenous extracorporeal membrane oxygenation.

PURPOSE: Venovenous extracorporeal membrane oxygenation is used increasingly in adults with severe acute reversible respiratory failure. Cannulation is associated with a risk of vascular damage or cardiac perforation. METHODS AND RESULTS: This report describes a modified technique of insertion for dual lumen bicaval cannulae. We have adopted the technique on 25 occasions and had no incidence of vascular damage or cardiac perforation. CONCLUSION: We suggest that the technique may mitigate the risk of guidewire looping during insertion of the dilators/cannula and thereby reduce the risk of perforation of the right ventricle.

Evaluating glycemic control algorithms by computer simulations.

BACKGROUND: Numerous guidelines and algorithms exist to achieve glycemic control. Their strengths and weaknesses are difficult to assess without head-to-head comparison in time-consuming clinical trials. We hypothesized that computer simulations may be useful. METHODS: Two open-label randomized clinical trials were replicated using computer simulations. One study compared performance of the enhanced model predictive control (eMPC) algorithm at two intensive care units in the United Kingdom and Belgium. The other study compared three glucose control algorithms-eMPC, Matias (the absolute glucose protocol), and Bath (the relative glucose change protocol)-in a single intensive care unit. Computer simulations utilized a virtual population of 56 critically ill subjects derived from routine data collected at four European surgical and medical intensive care units. RESULTS: In agreement with the first clinical study, computer simulations reproduced the main finding and discriminated between the two intensive care units in terms of the sampling interval (1.3 h vs. 1.8 h, United Kingdom vs. Belgium; P < 0.01). Other glucose control metrics were comparable between simulations and clinical results. The principal outcome of the second study was also reproduced. The eMPC demonstrated better performance compared with the Matias and Bath algorithms as assessed by the time when plasma glucose was in the target range between 4.4 and 6.1 mmol/L (65% vs. 43% vs. 42% [P < 0.001], eMPC vs. Matias vs. Bath) without increasing the risk of severe hypoglycemia. CONCLUSIONS: Computer simulations may provide resource-efficient means for preclinical evaluation of algorithms for glycemic control in the critically ill.

Intensive insulin therapy: enhanced Model Predictive Control algorithm versus standard care.

OBJECTIVE: To investigate the effectiveness of an enhanced software Model Predictive Control (eMPC) algorithm for intravenous insulin infusion, targeted at tight glucose control in critically ill patients, over 72 h, in two intensive care units with different management protocols. DESIGN: Comparison with standard care in a two center open randomized clinical trial. SETTING: Two adult intensive care units in University Hospitals. PATIENTS AND PARTICIPANTS: Thirty-four critically ill patients with hyperglycaemia (glucose >120 mg/dL) or already receiving insulin infusion. INTERVENTIONS: Patients were randomized, within each ICU, to intravenous insulin infusion advised by eMPC algorithm or the ICU's standard insulin infusion administration regimen. MEASUREMENTS AND RESULTS: Arterial glucose concentration was measured at study entry and when advised by eMPC or measured as part of standard care. Time-weighted average glucose concentrations in patients receiving eMPC advised insulin infusions were similar [104 mg/dL (5.8 mmol/L)] in both ICUs. eMPC advised glucose measurement interval was significantly different between ICUs (1.1 vs. 1.8 h, P < 0.01). The standard care insulin algorithms resulted in significantly different time-weighted average glucose concentrations between ICUs [128 vs. 99 mg/dL (7.1 vs. 5.5 mmol/L), P < 0.01]. CONCLUSIONS: In this feasibility study the eMPC algorithm provided similar, effective and safe tight glucose control over 72 h in critically ill patients in two different ICUs. Further development is required to reduce glucose sampling interval while maintaining a low risk of hypoglycaemia.

Glycaemic control in critically ill patients with cardiovascular disease.

PURPOSE OF REVIEW: The role of hyperglycaemia in the pathogenesis of myocardial damage during cardiac surgery or patients with acute coronary syndromes has been the subject of increasing interest over the past few years. Several further trials and meta-analyses investigating the role of insulin treatment, either aimed at tight control of blood glucose concentration or as part of a regimen including glucose and potassium, have been reported recently and are the subject of this review. RECENT FINDINGS: Good control of blood glucose has been demonstrated to improve outcomes for diabetic patients undergoing cardiac surgery and following acute myocardial infarction. In surgical intensive care patients, tight glucose control improved mortality--a finding that is awaiting confirmation in multicentre studies. The use of glucose-insulin-potassium regimens does not improve outcomes in patients with acute myocardial infarction who have undergone reperfusion therapy, but may be beneficial during cardiac surgery. SUMMARY: Tight control of blood glucose has been shown to be beneficial in several patient groups. The optimal target glucose concentration and glucose and insulin regimens remain to be confirmed or determined in each clinical situation.