Andrew Ross Davies

Critical care services and 2009 H1N1 influenza in Australia and New Zealand

BACKGROUND Planning for the treatment of infection with the 2009 pandemic influenza A (H1N1) virus through health care systems in developed countries during winter in the Northern Hemisphere is hampered by a lack of information from similar health care systems. METHODS We conducted an inception-cohort study in all Australian and New Zealand intensive care units (ICUs) during the winter of 2009 in the Southern Hemisphere. We calculated, per million inhabitants, the numbers of ICU admissions, bed-days, and days of mechanical ventilation due to infection with the 2009 H1N1 virus. We collected data on demographic and clinical characteristics of the patients and on treatments and outcomes. RESULTS From June 1 through August 31, 2009, a total of 722 patients with confirmed infection with the 2009 H1N1 virus (28.7 cases per million inhabitants; 95% confidence interval [CI], 26.5 to 30.8) were admitted to an ICU in Australia or New Zealand. Of the 722 patients, 669 (92.7%) were under 65 years of age and 66 (9.1%) were pregnant women; of the 601 adults for whom data were available, 172 (28.6%) had a body-mass index (the weight in kilograms divided by the square of the height in meters) greater than 35. Patients infected with the 2009 H1N1 virus were in the ICU for a total of 8815 bed-days (350 per million inhabitants). The median duration of treatment in the ICU was 7.0 days (interquartile range, 2.7 to 13.4); 456 of 706 patients (64.6%) with available data underwent mechanical ventilation for a median of 8 days (interquartile range, 4 to 16). The maximum daily occupancy of the ICU was 7.4 beds (95% CI, 6.3 to 8.5) per million inhabitants. As of September 7, 2009, a total of 103 of the 722 patients (14.3%; 95% CI, 11.7 to 16.9) had died, and 114 (15.8%) remained in the hospital. CONCLUSIONS The 2009 H1N1 virus had a substantial effect on ICUs during the winter in Australia and New Zealand. Our data can assist planning for the treatment of patients during the winter in the Northern Hemisphere.

Early Parenteral Nutrition in Critically Ill Patients With Short-term Relative Contraindications to Early Enteral Nutrition: A Randomized Controlled Trial

IMPORTANCE Systematic reviews suggest adult patients in intensive care units (ICUs) with relative contraindications to early enteral nutrition (EN) may benefit from parenteral nutrition (PN) provided within 24 hours of ICU admission. OBJECTIVE To determine whether providing early PN to critically ill adults with relative contraindications to early EN alters outcomes. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, single-blind clinical trial conducted between October 2006 and June 2011 in ICUs of 31 community and tertiary hospitals in Australia and New Zealand. Participants were critically ill adults with relative contraindications to early EN who were expected to remain in the ICU longer than 2 days. INTERVENTIONS Random allocation to pragmatic standard care or early PN. MAIN OUTCOMES AND MEASURES Day-60 mortality; quality of life, infections, and body composition. RESULTS A total of 1372 patients were randomized (686 to standard care, 686 to early PN). Of 682 patients receiving standard care, 199 patients (29.2%) initially commenced EN, 186 patients (27.3%) initially commenced PN, and 278 patients (40.8%) remained unfed. Time to EN or PN in patients receiving standard care was 2.8 days (95% CI, 2.3 to 3.4). Patients receiving early PN commenced PN a mean of 44 minutes after enrollment (95% CI, 36 to 55). Day-60 mortality did not differ significantly (22.8% for standard care vs 21.5% for early PN; risk difference, -1.26%; 95% CI, -6.6 to 4.1; P = .60). Early PN patients rated day-60 quality of life (RAND-36 General Health Status) statistically, but not clinically meaningfully, higher (45.5 for standard care vs 49.8 for early PN; mean difference, 4.3; 95% CI, 0.95 to 7.58; P = .01). Early PN patients required fewer days of invasive ventilation (7.73 vs 7.26 days per 10 patient × ICU days, risk difference, -0.47; 95% CI, -0.82 to -0.11; P = .01) and, based on Subjective Global Assessment, experienced less muscle wasting (0.43 vs 0.27 score increase per week; mean difference, -0.16; 95% CI, -0.28 to -0.038; P = .01) and fat loss (0.44 vs 0.31 score increase per week; mean difference, -0.13; 95% CI, -0.25 to -0.01; P = .04). CONCLUSIONS AND RELEVANCE The provision of early PN to critically ill adults with relative contraindications to early EN, compared with standard care, did not result in a difference in day-60 mortality. The early PN strategy resulted in significantly fewer days of invasive ventilation but not significantly shorter ICU or hospital stays. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN012605000704695.

Evolution of Mortality over Time in Patients Receiving Mechanical Ventilation

RATIONALE Baseline characteristics and management have changed over time in patients requiring mechanical ventilation; however, the impact of these changes on patient outcomes is unclear. OBJECTIVES To estimate whether mortality in mechanically ventilated patients has changed over time. METHODS Prospective cohort studies conducted in 1998, 2004, and 2010, including patients receiving mechanical ventilation for more than 12 hours in a 1-month period, from 927 units in 40 countries. To examine effects over time on mortality in intensive care units, we performed generalized estimating equation models. MEASUREMENTS AND MAIN RESULTS We included 18,302 patients. The reasons for initiating mechanical ventilation varied significantly among cohorts. Ventilatory management changed over time (P < 0.001), with increased use of noninvasive positive-pressure ventilation (5% in 1998 to 14% in 2010), a decrease in tidal volume (mean 8.8 ml/kg actual body weight [SD = 2.1] in 1998 to 6.9 ml/kg [SD = 1.9] in 2010), and an increase in applied positive end-expiratory pressure (mean 4.2 cm H2O [SD = 3.8] in 1998 to 7.0 cm of H2O [SD = 3.0] in 2010). Crude mortality in the intensive care unit decreased in 2010 compared with 1998 (28 versus 31%; odds ratio, 0.87; 95% confidence interval, 0.80-0.94), despite a similar complication rate. Hospital mortality decreased similarly. After adjusting for baseline and management variables, this difference remained significant (odds ratio, 0.78; 95% confidence interval, 0.67-0.92). CONCLUSIONS Patient characteristics and ventilation practices have changed over time, and outcomes of mechanically ventilated patients have improved. Clinical trials registered with www.clinicaltrials.gov (NCT01093482).

Relative hyperlactatemia and hospital mortality in critically ill patients: a retrospective multi-centre study

IntroductionHigher lactate concentrations within the normal reference range (relative hyperlactatemia) are not considered clinically significant. We tested the hypothesis that relative hyperlactatemia is independently associated with an increased risk of hospital death.MethodsThis observational study examined a prospectively obtained intensive care database of 7,155 consecutive critically ill patients admitted to the Intensive Care Units (ICUs) of four Australian university hospitals. We assessed the relationship between ICU admission lactate, maximal lactate and time-weighted lactate levels and hospital outcome in all patients and also in those patients whose lactate concentrations (admission n = 3,964, maximal n = 2,511, and time-weighted n = 4,584) were under 2 mmol.L-1 (i.e. relative hyperlactatemia).ResultsWe obtained 172,723 lactate measurements. Higher admission and time-weightedlactate concentration within the reference range was independently associated with increased hospital mortality (admission odds ratio (OR) 2.1, 95% confidence interval (CI) 1.3 to 3.5, P = 0.01; time-weighted OR 3.7, 95% CI 1.9 to 7.00, P < 0.0001). This significant association was first detectable at lactate concentrations > 0.75 mmol.L-1. Furthermore, in patients whose lactate ever exceeded 2 mmol.L-1, higher time-weighted lactate remained strongly associated with higher hospital mortality (OR 4.8, 95% CI 1.8 to 12.4, P < 0.001).ConclusionsIn critically ill patients, relative hyperlactataemia is independently associated with increased hospital mortality. Blood lactate concentrations > 0.75 mmol.L-1 can be used by clinicians to identify patients at higher risk of death. The current reference range for lactate in the critically ill may need to be re-assessed.

A randomised controlled trial of an open lung strategy with staircase recruitment, titrated PEEP and targeted low airway pressures in patients with acute respiratory distress syndrome

IntroductionTidal volume and plateau pressure minimisation are the standard components of a protective lung ventilation strategy for patients with acute respiratory distress syndrome (ARDS). Open lung strategies, including higher positive end-expiratory pressure (PEEP) and recruitment manoeuvres to date have not proven efficacious. This study examines the effectiveness and safety of a novel open lung strategy, which includes permissive hypercapnia, staircase recruitment manoeuvres (SRM) and low airway pressure with PEEP titration.MethodTwenty ARDS patients were randomised to treatment or ARDSnet control ventilation strategies. The treatment group received SRM with decremental PEEP titration and targeted plateau pressure < 30 cm H2O. Gas exchange and lung compliance were measured daily for 7 days and plasma cytokines in the first 24 hours and on days 1, 3, 5 and 7 (mean ± SE). Duration of ventilation, ICU stay and hospital stay (median and interquartile range) and hospital survival were determined.ResultsThere were significant overall differences between groups when considering plasma IL-8 and TNF-α. For plasma IL-8, the control group was 41% higher than the treatment group over the seven-day period (ratio 1.41 (1.11 to 1.79), P = 0.01), while for TNF-α the control group was 20% higher over the seven-day period (ratio 1.20 (1.01 to 1.42) P = 0.05). PaO2/FIO2 (204 ± 9 versus 165 ± 9 mmHg, P = 0.005) and static lung compliance (49.1 ± 2.9 versus 33.7 ± 2.7 mls/cm H2O, P < 0.001) were higher in the treatment group than the control group over seven days. There was no difference in duration of ventilation (180 (87 to 298) versus 341 (131 to 351) hrs, P = 0.13), duration of ICU stay (9.9 (5.6 to 14.8) versus 16.0 (8.1 to 19.3) days, P = 0.19) and duration of hospital stay (17.9 (13.7 to 34.5) versus 24.7 (20.5 to 39.8) days, P = 0.16) between the treatment and control groups.ConclusionsThis open lung strategy was associated with greater amelioration in some systemic cytokines, improved oxygenation and lung compliance over seven days. A larger trial powered to examine clinically-meaningful outcomes is warranted.Trial registrationACTRN12607000465459

Long-term quality of life in patients with acute respiratory distress syndrome requiring extracorporeal membrane oxygenation for refractory hypoxaemia

IntroductionThe purpose of the study was to assess the long term outcome and quality of life of patients with acute respiratory distress syndrome (ARDS) receiving extracorporeal membrane oxygenation (ECMO) for refractory hypoxemia.MethodsA retrospective observational study with prospective health related quality of life (HRQoL) assessment was conducted in ARDS patients who had ECMO as a rescue therapy for reversible refractory hypoxemia from January 2009 until April 2011 in a tertiary Australian centre. Survival and long-term quality of life assessment, using the Short-Form 36 (SF-36) and the EuroQol health related quality of life questionnaire (EQ5D) were assessed and compared to international data from other research groups.ResultsTwenty-one patients (mean age 36.3 years) with ARDS receiving ECMO for refractory hypoxemia were studied. Eighteen (86%) patients were retrieved from external intensive care units (ICUs) by a dedicated ECMO retrieval team. Eleven (55%) had H1N1 influenza A-associated pneumonitis. Eighteen (86%) patients survived to hospital discharge. Of the 18 survivors, ten (56%) were discharged to other hospitals and 8 (44%) were discharged directly home. Sequelae and health related quality of life were evaluated for 15 of the 18 (71%) long-term survivors (assessment at median 8 months). Mean SF-36 scores were significantly lower across all domains compared to age and sex matched Australian norms. Mean SF-36 scores were lower (minimum important difference at least 5 points) than previously described ARDS survivors in the domains of general health, mental health, vitality and social function. One patient had long-term disability as a result of ICU acquired weakness. Only 26% of survivors had returned to previous work levels at the time of follow-up.ConclusionsThis ARDS cohort had a high survival rate (86%) after use of ECMO support for reversible refractory hypoxemia. Long term survivors had similar physical health but decreased mental health, general health, vitality and social function compared to other ARDS survivors and an unexpectedly poor return to work.

Comparisons between intragastric and small intestinal delivery of enteral nutrition in the critically ill: a systematic review and meta-analysis.

INTRODUCTION The largest cohort of critically ill patients evaluating intragastric and small intestinal delivery of nutrients was recently reported. This systematic review included recent data to compare the effects of small bowel and intragastric delivery of enteral nutrients in adult critically ill patients. METHODS This is a systematic review of all randomised controlled studies published between 1990 and March 2013 that reported the effects of the route of enteral feeding in the critically ill on clinically important outcomes. RESULTS Data from 15 level-2 studies were included. Small bowel feeding was associated with a reduced risk of pneumonia (Relative Risk, RR, small intestinal vs. intragastric: 0.75 (95% confidence interval 0.60 to 0.93); P=0.01; I2=11%). The point estimate was similar when only studies using microbiological data were included. Duration of ventilation (weighted mean difference: -0.36 days (-2.02 to 1.30); P=0.65; I2=42%), length of ICU stay (WMD: 0.49 days, (-1.36 to 2.33); P=0.60; I2=81%) and mortality (RR 1.01 (0.83 to 1.24); P=0.92; I2=0%) were unaffected by the route of feeding. While data were limited, and there was substantial statistical heterogeneity, there was significantly improved nutrient intake via the small intestinal route (% goal rate received: 11% (5 to 16%); P=0.0004; I2=88%). CONCLUSIONS Use of small intestinal feeding may improve nutritional intake and reduce the incidence of ICU-acquired pneumonia. In unselected critically ill patients other clinically important outcomes were unaffected by the site of the feeding tube.

Use of a concentrated enteral nutrition solution to increase calorie delivery to critically ill patients: a randomized, double-blind, clinical trial

BACKGROUND Critically ill patients typically receive ∼60% of estimated calorie requirements. OBJECTIVES We aimed to determine whether the substitution of a 1.5-kcal/mL enteral nutrition solution for a 1.0-kcal/mL solution resulted in greater calorie delivery to critically ill patients and establish the feasibility of conducting a multicenter, double-blind, randomized trial to evaluate the effect of an increased calorie delivery on clinical outcomes. DESIGN A prospective, randomized, double-blind, parallel-group, multicenter study was conducted in 5 Australian intensive care units. One hundred twelve mechanically ventilated patients expected to receive enteral nutrition for ≥2 d were randomly assigned to receive 1.5 (n = 57) or 1.0 (n = 55) kcal/mL enteral nutrition solution at a rate of 1 mL/kg ideal body weight per hour for 10 d. Protein and fiber contents in the 2 solutions were equivalent. RESULTS The 2 groups had similar baseline characteristics (1.5 compared with 1.0 kcal/mL). The mean (±SD) age was 56.4 ± 16.8 compared with 56.5 ± 16.1 y, 74% compared with 75% were men, and the Acute Physiology and Chronic Health Evaluation II score was 23 ± 9.1 compared with 22 ± 8.9. The groups received similar volumes of enteral nutrition solution [1221 mL/d (95% CI: 1120, 1322 mL/d) compared with 1259 mL/d (95% CI: 1143, 1374 mL/d); P = 0.628], which led to a 46% increase in daily calories in the group given the 1.5-kcal/mL solution [1832 kcal/d (95% CI: 1681, 1984 kcal/d) compared with 1259 kcal/d (95% CI: 1143, 1374 kcal/d); P < 0.001]. The 1.5-kcal/mL solution was not associated with larger gastric residual volumes or diarrhea. In this feasibility study, there was a trend to a reduced 90-d mortality in patients given 1.5 kcal/mL [11 patients (20%) compared with 20 patients (37%); P = 0.057]. CONCLUSIONS The substitution of a 1.0- with a 1.5-kcal/mL enteral nutrition solution administered at the same rate resulted in a 46% greater calorie delivery without adverse effects. The results support the conduct of a large-scale trial to evaluate the effect of increased calorie delivery on clinically important outcomes in the critically ill.

Implementation of a management guideline aimed at minimizing the severity of primary graft dysfunction after lung transplant.

OBJECTIVE Primary graft dysfunction, a severe form of lung injury that occurs in the first 72 hours after lung transplant, is associated with morbidity and mortality. We sought to assess the impact of an evidence-based guideline as a protocol for respiratory and hemodynamic management. METHODS Preoperative and postoperative data for patients treated per the guideline (n = 56) were compared with those of a historical control group (n = 53). Patient data such as ratio of arterial Po(2) to inspired oxygen fraction, central venous pressure, cumulative fluid balance, vasopressor dose, and serum urea and creatinine were measured and documented at specific times. Primary outcome was severity of primary graft dysfunction within the first 72 hours. RESULTS Primary graft dysfunction grade was progressively lower in patients treated after introduction of the guideline (P = .01). Lower postoperative fluid balances (P = .01) and vasopressor doses (P = .007) were seen, with no associated renal dysfunction. There were no differences in duration of mechanical ventilation or mortality. Nonadherence to the guideline occurred in 10 cases (18%). CONCLUSIONS Implementation of an evidence-based guideline for managing respiratory and hemodynamic status is feasible and safe and was associated with reduction in severity of primary graft dysfunction. Further studies are required to determine whether such a guideline would lead to a consistent reduction in severity of primary graft dysfunction at other institutions. Creation of a protocol for postoperative care provides a template for further studies of novel therapies or management strategies for primary graft dysfunction.

Practicalities of nutrition support in the intensive care unit: The usefulness of gastric residual volume and prokinetic agents with enteral nutrition

The provision of early nutrition therapy to critically ill patients is established as the standard of care in most intensive care units around the world. Despite the known benefits, tolerance of enteral nutrition in the critically ill varies and delivery is often interrupted. Observational research has demonstrated that clinicians deliver little more than half of the enteral nutrition they plan to provide. The main clinical tool for assessing gastric tolerance is gastric residual volume; however, its usefulness in this setting is debated. There are several strategies employed to improve the tolerance and hence adequacy of enteral nutrition delivery in the critically ill. One of the most widely used strategies is that of prokinetic drug administration, most commonly metoclopramide and erythromycin. Although there are new agents being investigated, none are ready for routine application in the critically ill and the benefits are still being established. This review investigates current practice and considers the literature on assessment of enteral tolerance and optimization of enteral nutrition in the critically ill.