Iain MacKenzie

High-frequency oscillation for acute respiratory distress syndrome.

BACKGROUND Patients with the acute respiratory distress syndrome (ARDS) require mechanical ventilation to maintain arterial oxygenation, but this treatment may produce secondary lung injury. High-frequency oscillatory ventilation (HFOV) may reduce this secondary damage. METHODS In a multicenter study, we randomly assigned adults requiring mechanical ventilation for ARDS to undergo either HFOV with a Novalung R100 ventilator (Metran) or usual ventilatory care. All the patients had a ratio of the partial pressure of arterial oxygen (PaO) to the fraction of inspired oxygen (FiO) of 200 mm Hg (26.7 kPa) or less and an expected duration of ventilation of at least 2 days. The primary outcome was all-cause mortality 30 days after randomization. RESULTS There was no significant between-group difference in the primary outcome, which occurred in 166 of 398 patients (41.7%) in the HFOV group and 163 of 397 patients (41.1%) in the conventional-ventilation group (P=0.85 by the chi-square test). After adjustment for study center, sex, score on the Acute Physiology and Chronic Health Evaluation (APACHE) II, and the initial PaO:FiO ratio, the odds ratio for survival in the conventional-ventilation group was 1.03 (95% confidence interval, 0.75 to 1.40; P=0.87 by logistic regression). CONCLUSIONS The use of HFOV had no significant effect on 30-day mortality in patients undergoing mechanical ventilation for ARDS. (Funded by the National Institute for Health Research Health Technology Assessment Programme; OSCAR Current Controlled Trials number, ISRCTN10416500.).

Diabetic status and the relation of the three domains of glycemic control to mortality in critically ill patients: an international multicenter cohort study.

IntroductionHyperglycemia, hypoglycemia, and increased glycemic variability have each beenindependently associated with increased risk of mortality in critically illpatients. The role of diabetic status on modulating the relation of these threedomains of glycemic control with mortality remains uncertain. The purpose of thisinvestigation was to determine how diabetic status affects the relation ofhyperglycemia, hypoglycemia, and increased glycemic variability with the risk ofmortality in critically ill patients.MethodsThis is a retrospective analysis of prospectively collected data involving 44,964patients admitted to 23 intensive care units (ICUs) from nine countries, betweenFebruary 2001 and May 2012. We analyzed mean blood glucose concentration (BG),coefficient of variation (CV), and minimal BG and created multivariable models toanalyze their independent association with mortality. Patients were stratifiedaccording to the diagnosis of diabetes.ResultsAmong patients without diabetes, mean BG bands between 80 and 140 mg/dl wereindependently associated with decreased risk of mortality, and mean BG bands> 140 mg/dl, with increased risk of mortality. Among patients withdiabetes, mean BG from 80 to 110 mg/dl was associated with increased risk ofmortality and mean BG from 110 to 180 mg/dl with decreased risk of mortality. Aneffect of center was noted on the relation between mean BG and mortality.Hypoglycemia, defined as minimum BG <70 mg/dl, was independently associatedwith increased risk of mortality among patients with and without diabetes andincreased glycemic variability, defined as CV > 20%, was independentlyassociated with increased risk of mortality only among patients without diabetes.Derangements of more than one domain of glycemic control had a cumulativeassociation with mortality, especially for patients without diabetes.ConclusionsAlthough hyperglycemia, hypoglycemia, and increased glycemic variability is eachindependently associated with mortality in critically ill patients, diabeticstatus modulates these relations in clinically important ways. Our findingssuggest that patients with diabetes may benefit from higher glucose target rangesthan will those without diabetes. Additionally, hypoglycemia is independentlyassociated with increased risk of mortality regardless of the patients diabeticstatus, and increased glycemic variability is independently associated withincreased risk of mortality among patients without diabetes.See related commentary by Krinsley,http://ccforum.com/content/17/2/131See related commentary by Finfer and Billot,http://ccforum.com/content/17/2/134

Clinical review: Consensus recommendations on measurement of blood glucose and reporting glycemic control in critically ill adults

The management reporting and assessment of glycemic control lacks standardization. The use of different methods to measure the blood glucose concentration and to report the performance of insulin treatment yields major disparities and complicates the interpretation and comparison of clinical trials. We convened a meeting of 16 experts plus invited observers from industry to discuss and where possible reach consensus on the most appropriate methods to measure and monitor blood glucose in critically ill patients and on how glycemic control should be assessed and reported. Where consensus could not be reached, recommendations on further research and data needed to reach consensus in the future were suggested. Recognizing their clear conflict of interest, industry observers played no role in developing the consensus or recommendations from the meeting. Consensus recommendations were agreed for the measurement and reporting of glycemic control in clinical trials and for the measurement of blood glucose in clinical practice. Recommendations covered the following areas: How should we measure and report glucose control when intermittent blood glucose measurements are used? What are the appropriate performance standards for intermittent blood glucose monitors in the ICU? Continuous or automated intermittent glucose monitoring - methods and technology: can we use the same measures for assessment of glucose control with continuous and intermittent monitoring? What is acceptable performance for continuous glucose monitoring systems? If implemented, these recommendations have the potential to minimize the discrepancies in the conduct and reporting of clinical trials and to improve glucose control in clinical practice. Furthermore, to be fit for use, glucose meters and continuous monitoring systems must match their performance to fit the needs of patients and clinicians in the intensive care setting.See related commentary by Soto-Rivera and Agus, http://ccforum.com/content/17/3/155

Blast injuries to the lung: epidemiology and management

Lung injury is frequently a component of the polytrauma sustained by military personnel surviving blast on the battlefield. This article describes a case series of the military casualties admitted to University Hospital Birminghams critical care services (role 4 facility), during the period 1 July 2008 to 15 January 2010. Of the 135 casualties admitted, 107 (79.2%) were injured by explosive devices. Plain chest films taken soon after arrival in the role 4 facility were reviewed in 96 of the 107 patients. In 55 (57.3%) films a tracheal tube was present. One or more radiological abnormalities was present in 66 (68.75%) of the films. Five patients met the consensus criteria for the definition of adult respiratory distress syndrome (ARDS). The majority of casualties with blast-related lung injury were successfully managed with conventional ventilatory support employing a lung protective strategy; only a small minority received non-conventional support at any time in the form of high-frequency oscillatory ventilation. Of those casualties who survived to be received by the role 4 facility, none subsequently died as a consequence of lung injury.

A randomised controlled trial and cost-effectiveness analysis of high-frequency oscillatory ventilation against conventional artificial ventilation for adults with acute respiratory distress syndrome. The OSCAR (OSCillation in ARDS) study.

BACKGROUND Patients with the acute respiratory distress syndrome (ARDS) require artificial ventilation but this treatment may produce secondary lung damage. High-frequency oscillatory ventilation (HFOV) may reduce this damage. OBJECTIVES To determine the clinical benefit and cost-effectiveness of HFOV in patients with ARDS compared with standard mechanical ventilation. DESIGN A parallel, randomised, unblinded clinical trial. SETTING UK intensive care units. PARTICIPANTS Mechanically ventilated patients with a partial pressure of oxygen in arterial blood/fractional concentration of inspired oxygen (P : F) ratio of 26.7 kPa (200 mmHg) or less and an expected duration of ventilation of at least 2 days at recruitment. INTERVENTIONS Treatment arm HFOV using a Novalung R100(®) ventilator (Metran Co. Ltd, Saitama, Japan) ventilator until the start of weaning. Control arm Conventional mechanical ventilation using the devices available in the participating centres. MAIN OUTCOME MEASURES The primary clinical outcome was all-cause mortality at 30 days after randomisation. The primary health economic outcome was the cost per quality-adjusted life-year (QALY) gained. RESULTS One hundred and sixty-six of 398 patients (41.7%) randomised to the HFOV group and 163 of 397 patients (41.1%) randomised to the conventional mechanical ventilation group died within 30 days of randomisation (p = 0.85), for an absolute difference of 0.6% [95% confidence interval (CI) -6.1% to 7.5%]. After adjustment for study centre, sex, Acute Physiology and Chronic Health Evaluation II score, and the initial P : F ratio, the odds ratio for survival in the conventional ventilation group was 1.03 (95% CI 0.75 to 1.40; p = 0.87 logistic regression). Survival analysis showed no difference in the probability of survival up to 12 months after randomisation. The average QALY at 1 year in the HFOV group was 0.302 compared to 0.246. This gives an incremental cost-effectiveness ratio (ICER) for the cost to society per QALY of £88,790 and an ICER for the cost to the NHS per QALY of £ 78,260. CONCLUSIONS The use of HFOV had no effect on 30-day mortality in adult patients undergoing mechanical ventilation for ARDS and no economic advantage. We suggest that further research into avoiding ventilator-induced lung injury should concentrate on ventilatory strategies other than HFOV. TRIAL REGISTRATION Current Controlled Trials ISRCTN10416500.

What the Intensive Care Doctor Needs to Know about Blast-Related Lung Injury

Explosions are currently the primary cause of military combat injuries. A minority of civilian trauma is also caused by explosions. People hurt by explosion are likely to present with complex injuries. The aim of the article is to explain the mechanism underlying these injuries and the associated physiology to help the intensive care clinician manage these casualties properly. The generic term ‘blast injury’ is applied to a collection of injuries caused by explosion. Components of blast injuries have precise definitions relating to the elements of the explosion that caused the injuries: primary blast injury is due to a shock wave, secondary blast injury is caused by fragments and debris colliding with the victim and tertiary blast injury is due to the casualty being thrown against solid objects. Primary blast injury results in damage principally in gas-containing organs, eg the lungs (blast lung) and can lead to impaired pulmonary gas transfer and hypoxaemia. Secondary blast injuries are often penetrating and can lead to haemorrhage while tertiary blast injuries are often blunt and involve substantial tissue damage. Survivors of explosions in confined spaces are more likely to exhibit primary blast injury than those injured in open spaces. The current military approach to immediate management is to apply the C ABC principle (arrest catastrophic haemorrhage first and then deal with airway, breathing and circulation) to achieve Damage Control Resuscitation. Early administration of blood products (plasma as well as red cells) is advocated for those suffering significant haemorrhage. Initial resuscitation is hypotensive to minimise risk of dislodging nascent clots. However, if evacuation is protracted (longer than one hour) then consideration should be given to improving blood flow / oxygen delivery by adopting a revised normotensive blood pressure target to reverse the deleterious consequences of the hypotensive shock state. Animal studies have shown that titrating FiO2 to a target SaO2 of 95% can improve survival and ‘buy time’ during hypotensive resuscitation. Ventilator strategies should use a lung-protective approach with permissive hypercapnia if necessary. Blast casualties are often a challenging group of patients needing expert, tailored, care. Outcome can be good especially in young, otherwise fit, casualties with more than 96% surviving to ICU discharge, although this figure may be lower with a mixed civilian group.

High-Frequency Oscillation for Acute Respiratory Distress Syndrome

*John Radcliffe Hospital and the †University of Oxford, Oxford, ‡Bristol Royal Infirmary, Bristol, §Queen Elizabeth Hospital, Birmingham, and ||Warwick Clinical Trials, University of Warwick, Warwick, and ¶Intensive Care National Audit and Research Centre, London, UK; and #Department of Critical Care Medicine, Sunnybrook Health Sciences Centre and the Department of Anesthesiology, University of Toronto, Toronto, Ontario, Canada. Copyright * 2013 by Lippincott Williams & Wilkins DOI: 10.1097/01.SA.0000435572.01496.5c

Random errors in insulin infusion concentrations

Dear Editor, We read with interest the study of Dehmel et al. [1] showing that concentrations of manually prepared solutions of drugs for infusion (amiodarone, noradrenaline and hydrocortisone) varied from the intended concentration, and by a greater degree, than the centrally prepared, machine-made solutions. We conducted a similar study, in a general intensive care unit (ICU) in a UK teaching hospital, concerning variations in concentration of nurseprepared insulin solutions. It is common practise in the UK to deliver manually prepared insulin solutions as an infusion by syringe driver. Samples were taken from 22 insulin solutions, prescribed to contain 1 unit/ml. The samples were diluted 1,000-fold and the insulin concentration determined by fluorometric assay. Intra-assay variability was determined by taking multiple aliquots from a single insulin sample, then diluting and analysing these samples by the same method. The mean insulin concentration of the 22 solutions was 0.99 units/ml, which was not significantly different from the intended concentration of 1 iu/ml (p = 0.73, two-tailed Student’s t test). The coefficient of variation was 10 % (95 % CI 7.8–14 %) with the insulin concentration ranging from 0.84 to 1.16 iu/ ml. The intra-assay coefficient of variation was 3.6 % (95 % CI 2.4–6.8 %). As the confidence intervals for the intra-assay coefficient of variation do not overlap with those for the sample measurements, we concluded that the variability in the insulin solution concentrations was significantly greater than any random errors in the assay. Our results are presented graphically in Fig. 1. We attribute the error to the difficulties in diluting a small volume of concentrated stock solution and variations in the method of performing the dilutions between ICU staff. If an empty syringe is replaced with a new syringe, filled with the same drug but at a different concentration from the previous solution, there will be a step change in the delivery rate of the drug. This is a particular concern with intensive insulin therapy. A change in the plasma concentration of insulin causes a change in the plasma level of glucose. This is an unpredictable process, because instead of a stepchange in concentration, plasma glucose oscillates around a new mean concentration before becoming stable [2]. Introducing step changes in insulin delivery when plasma glucose levels are fluctuating has the potential to cause unstable plasma glucose levels. This may occur on a daily basis, as insulin syringes are commonly changed every 24 h. Further work is required to assess whether the use of manually prepared insulin solutions is associated with greater fluctuations in plasma glucose levels when compared to centrally prepared solutions. The benefit of tight glycaemic control in critical care is the subject of much research [3]. Recently, poor outcomes in the ICU have been shown to be related to the central tendency of glucose concentration, and variability in the plasma glucose concentration nadir and glucose concentration nadir [4]. Unfortunately, maintenance of normoglycaemia in critically ill patients is not straightforward. Insulin requirements vary widely between patients and over time. Rapid changes in plasma glucose concentrations may be precipitated by critical care interventions, e.g. bolus administration of corticosteroids, interruptions in feeding or instigation of procedures with large stress responses. Plasma glucose measurements may be subject to significant error depending on the nature of the blood sample, the site of sampling, the method of glucose analysis,