Peter W J Harrigan

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.

Procalcitonin Algorithm in Critically Ill Adults with Undifferentiated Infection or Suspected Sepsis A Randomized Controlled Trial

RATIONALE The role of procalcitonin (PCT), a widely used sepsis biomarker, in critically ill patients with sepsis is undetermined. OBJECTIVES To investigate the effect of a low PCT cut-off on antibiotic prescription and to describe the relationships between PCT plasma concentration and sepsis severity and mortality. METHODS This was a multicenter (11 Australian intensive care units [ICUs]), prospective, single-blind, randomized controlled trial involving 400 patients with suspected bacterial infection/sepsis and expected to receive antibiotics and stay in ICU longer than 24 hours. The primary outcome was the cumulative number of antibiotics treatment days at Day 28. MEASUREMENTS AND MAIN RESULTS PCT was measured daily while in the ICU. A PCT algorithm, including 0.1 ng/ml cut-off, determined antibiotic cessation. Published guidelines and antimicrobial stewardship were used in all patients. Primary analysis included 196 (PCT) versus 198 standard care patients. Ninety-three patients in each group had septic shock. The overall median (interquartile range) number of antibiotic treatment days were 9 (6-21) versus 11 (6-22), P = 0.58; in patients with positive pulmonary culture, 11 (7-27) versus 15 (8-27), P = 0.33; and in patients with septic shock, 9 (6-22) versus 11 (6-24), P = 0.64; with an overall 90-day all-cause mortality of 35 (18%) versus 31 (16%), P = 0.54 in the PCT versus standard care, respectively. Using logistic regression, adjusted for age, ventilation status, and positive culture, the decline rate in log(PCT) over the first 72 hours independently predicted hospital and 90-day mortality (odds ratio [95% confidence interval], 2.76 [1.10-6.96], P = 0.03; 3.20 [1.30-7.89], P = 0.01, respectively). CONCLUSIONS In critically ill adults with undifferentiated infections, a PCT algorithm including 0.1 ng/ml cut-off did not achieve 25% reduction in duration of antibiotic treatment. Clinical trial registered with http://www.anzctr.org.au (ACTRN12610000809033).

Conservative versus Liberal Oxygenation Targets for Mechanically Ventilated Patients. A Pilot Multicenter Randomized Controlled Trial.

RATIONALE There are no randomized controlled trials comparing different oxygenation targets for intensive care unit (ICU) patients. OBJECTIVES To determine whether a conservative oxygenation strategy is a feasible alternative to a liberal oxygenation strategy among ICU patients requiring invasive mechanical ventilation (IMV). METHODS At four multidisciplinary ICUs, 103 adult patients deemed likely to require IMV for greater than or equal to 24 hours were randomly allocated to either a conservative oxygenation strategy with target oxygen saturation as measured by pulse oximetry (SpO2) of 88-92% (n = 52) or a liberal oxygenation strategy with target SpO2 of greater than or equal to 96% (n = 51). MEASUREMENTS AND MAIN RESULTS The mean area under the curve and 95% confidence interval (CI) for SpO2 (93.4% [92.9-93.9%] vs. 97% [96.5-97.5%]), SaO2 (93.5% [93.1-94%] vs. 96.8% [96.3-97.3%]), PaO2 (70 [68-73] mm Hg vs. 92 [89-96] mm Hg), and FiO2 (0.26 [0.25-0.28] vs. 0.36 [0.34-0.39) in the conservative versus liberal oxygenation arm were significantly different (P < 0.0001 for all). There were no significant between-group differences in any measures of new organ dysfunction, or ICU or 90-day mortality. The percentage time spent with SpO2 less than 88% in conservative versus liberal arm was 1% versus 0.3% (P = 0.03), and percentage time spent with SpO2 greater than 98% in conservative versus liberal arm was 4% versus 22% (P < 0.001). The adjusted hazard ratio for 90-day mortality in the conservative arm was 0.77 (95% CI, 0.40-1.50; P = 0.44) overall and 0.49 (95% CI, 0.20-1.17; P = 0.10) in the prespecified subgroup of patients with a baseline PaO2/FiO2 less than 300. CONCLUSIONS Our study supports the feasibility of a conservative oxygenation strategy in patients receiving IMV. Larger randomized controlled trials of this intervention appear justified. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN 12613000505707).

Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial

BACKGROUND Equipoise exists regarding the benefits of restricting caloric intake during electrolyte replacement for refeeding syndrome, with half of intensive care specialists choosing to continue normal caloric intake. We aimed to assess whether energy restriction affects the duration of critical illness, and other measures of morbidity, compared with standard care. METHODS We did a randomised, multicentre, single-blind clinical trial in 13 hospital intensive care units (ICUs) in Australia (11 sites) and New Zealand (two sites). Adult critically ill patients who developed refeeding syndrome within 72 h of commencing nutritional support in the ICU were enrolled and allocated to receive continued standard nutritional support or protocolised caloric restriction. 1:1 computer-based randomisation was done in blocks of variable size, stratified by enrolment serum phosphate concentration (>0·32 mmol/L vs ≤0·32 mmol/L) and body-mass index (BMI; >18 kg/m(2)vs ≤18 kg/m(2)). The primary outcome was the number of days alive after ICU discharge, with 60 day follow-up, in a modified intention-to-treat population of all randomly allocated patients except those mistakenly enrolled. Days alive after ICU discharge was a composite outcome based on ICU length of stay, overall survival time, and mortality. The Refeeding Syndrome Trial was registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR number 12609001043224). FINDINGS Between Dec 3, 2010, and Aug 13, 2014, we enrolled 339 adult critically ill patients: 170 were randomly allocated to continued standard nutritional support and 169 to protocolised caloric restriction. During the 60 day follow-up, the mean number of days alive after ICU discharge in 165 assessable patients in the standard care group was 39·9 (95% CI 36·4-43·7) compared with 44·8 (95% CI 40·9-49·1) in 166 assessable patients in the caloric restriction group (difference 4·9 days, 95% CI -2·3 to 13·6, p=0·19). Nevertheless, protocolised caloric restriction improved key individual components of the primary outcome: more patients were alive at day 60 (128 [78%] of 163 vs 149 [91%] of 164, p=0·002) and overall survival time was increased (48·9 [SD 1·46] days vs 53·65 [0·97] days, log-rank p=0·002). INTERPRETATION Protocolised caloric restriction is a suitable therapeutic option for critically ill adults who develop refeeding syndrome. We did not identify any safety concerns associated with the use of protocolised caloric restriction. FUNDING National Health and Medical Research Council of Australia.

Incidence of ventilator-associated pneumonia in Australasian intensive care units: use of a consensus-developed clinical surveillance checklist in a multisite prospective audit

Objectives With disagreements on diagnostic criteria for ventilator-associated pneumonia (VAP) hampering efforts to monitor incidence and implement preventative strategies, the study objectives were to develop a checklist for clinical surveillance of VAP, and conduct an audit in Australian/New Zealand intensive care units (ICUs) using the checklist. Setting Online survey software was used for checklist development. The prospective audit using the checklist was conducted in 10 ICUs in Australia and New Zealand. Participants Checklist development was conducted with members of a bi-national professional society for critical care physicians using a modified Delphi technique and survey. A 30-day audit of adult patients mechanically ventilated for >72 h. Primary and secondary outcome measures Presence of items on the screening checklist; physician diagnosis of VAP, clinical characteristics, investigations, treatments and patient outcome. Results A VAP checklist was developed with five items: decreasing gas exchange, sputum changes, chest X-ray infiltrates, inflammatory response, microbial growth. Of the 169 participants, 17% (n=29) demonstrated characteristics of VAP using the checklist. A similar proportion had an independent physician diagnosis (n=30), but in a different patient subset (only 17% of cases were identified by both methods). The VAP rate per 1000 mechanical ventilator days for the checklist and clinician diagnosis was 25.9 and 26.7, respectively. The item ‘inflammatory response’ was most associated with the first episode of physician-diagnosed VAP. Conclusions VAP rates using the checklist and physician diagnosis were similar to ranges reported internationally and in Australia. Of note, different patients were identified with VAP by the checklist and physicians. While the checklist items may assist in identifying patients at risk of developing VAP, and demonstrates synergy with the recently developed Centers for Disease Control (CDC) guidelines, decision-making processes by physicians when diagnosing VAP requires further exploration.

Conservative versus liberal oxygenation targets for mechanically ventilated patients: pilot multicentre randomised trial

There is now increasing recognition of potential harm due to hyperoxia. Conventional practice of oxygen therapy often result in hyperoxia. Nearly all patients on mechanical ventilation receive supplemental oxygen therapy. However, RCTs investigating the effects of different oxygenation level during MV are lacking

Neurosurgical Intensive Care

work, and while there are some similarities, Australian readers will need to know about our guidelines and legislation (such as s95aa of the Privacy Act), and this is not covered here. As such this chapter only provides a means to identify the possible scenarios that may also occur in Australia but for which there is currently no easy simple single guide to help negotiate the myriad guidelines and legislation. Chapters 4–13 cover specific cancer types or syndromes although there is significant overlap between chapters as some gene alterations cause diseases in different organs, such as with Lynch syndrome in which mutations of mismatch repair genes increase the risk of bowel and gynaecological malignancies. Each chapter is well laid out with good use of illustrations and text boxes. Particularly useful are the summaries at the end of the chapter that recap the main points. A detraction of this book is that it provides a guide to but not proper guidelines on these conditions. An analogy might be that it is like a brief tourist guide to a city that points out the features of interest and gives a few basic facts about them, but it is essential that the proper guidebook is read if one is to get the full picture on each of those features. Certainly, in Australia a proper discussion with the local familial cancer or clinical genetics service is essential to establish what the appropriate referral procedures should be. However, as a 238-page novel-sized book that easily slips into the briefcase or occupies a very small footprint on the desk or bookshelf, it serves a very useful purpose. Inevitably the book will need to be updated frequently in what is an incredibly fast-moving field. As a template format it would be great if a similar book could be produced that is tailored for Australian and New Zealand practitioners. Unfortunately, in these days of the Internet it may be simpler for practitioners to simply browse the Net for more immediate information on any of these conditions. In the final chapter, the authors suggest that specialized clinical geneticists or nurse counsellors will be required in all cancer clinics. I agree that it is inevitable that those with specialist genetic knowledge will become increasingly important, but this will further extend to sporadic cases as we learn more and more about how they arise and find novel ways to treat or prevent these conditions. To this end, all clinicians involved in cancer care will have to dramatically increase their understanding of cancer genetics, and this small book is not a bad place to start for those already engaged in cancer care.