Melioidosis Causing Critical Illness: A Review of 24 Years of Experience From the Royal Darwin Hospital ICU.

OBJECTIVES: Melioidosis is increasing in incidence with newly recognized foci of melioidosis in the Americas, Africa, and elsewhere. This review describes the demographics, management, and outcomes of a large cohort of critically ill patients with melioidosis. DESIGN: Data were extracted from two prospective databases-the Menzies School of Health Research Melioidosis Database (1989-2013) and the Royal Darwin Hospital ICU Melioidosis Database (2001-2013). SETTING AND PATIENTS: The Royal Darwin Hospital ICU is the only ICU in the tropical Top End of Northern Territory of Australia, an endemic area for melioidosis. The study included all patients with melioidosis admitted to Royal Darwin Hospital ICU from 1989 to 2013. MEASUREMENTS AND MAIN RESULTS: From 1989 to 2013, 207 patients with melioidosis required admission to ICU. Mortality reduced from 92% (1989-1997) to 26% (1998-2013) (p < 0.001). The reduced mortality coincided with the introduction of an intensivist-led service, meropenem, and adjuvant granulocyte colony-stimulating factor for confirmed melioidosis sepsis in 1998. Pneumonia was the presenting illness in 155 of 207 (75%). ICU melioidosis patients (2001-2013) had an Acute Physiology and Chronic Health Evaluation II score of 23, median length of stay in the ICU of 7 days, and median ventilation hours of 130 and one third required renal replacement therapy. CONCLUSIONS: The mortality for critically ill patients with melioidosis in the Top End of the Northern Territory of Australia has substantially reduced over the past 24 years. The reduction in mortality coincided with the introduction of an intensivist-led model of care, the empiric use of meropenem, and adjunctive treatment with granulocyte colony-stimulating factor in 1998.

Sepsis-associated microvascular dysfunction measured by peripheral arterial tonometry: an observational study.

INTRODUCTION: Sepsis has a high mortality despite advances in management. Microcirculatory and endothelial dysfunction contribute to organ failure, and better tools are needed to assess microcirculatory responses to adjunctive therapies. We hypothesised that peripheral arterial tonometry (PAT), a novel user-independent measure of endothelium-dependent microvascular reactivity, would be impaired in proportion to sepsis severity and related to endothelial activation and plasma arginine concentrations. METHODS: Observational cohort study in a 350-bed teaching hospital in tropical Australia. Bedside microvascular reactivity was measured in 85 adults with sepsis and 45 controls at baseline and 2-4 days later by peripheral arterial tonometry. Microvascular reactivity was related to measures of disease severity, plasma concentrations of L-arginine (the substrate for nitric oxide synthase), and biomarkers of endothelial activation. RESULTS: Baseline reactive hyperaemia index (RH-PAT index), measuring endothelium-dependent microvascular reactivity; (mean [95% CI]) was lowest in severe sepsis (1.57 [1.43-1.70]), intermediate in sepsis without organ failure (1.85 [1.67-2.03]) and highest in controls (2.05 [1.91-2.19]); P < 0.00001. Independent predictors of baseline RH-PAT index in sepsis were APACHE II score and mean arterial pressure, but not plasma L-arginine or markers of endothelial activation. Low baseline RH-PAT index was significantly correlated with an increase in SOFA score over the first 2-4 days (r = -0.37, P = 0.02). CONCLUSIONS: Endothelium-dependent microvascular reactivity is impaired in proportion to sepsis severity and suggests decreased endothelial nitric oxide bioavailability in sepsis. Peripheral arterial tonometry may have a role as a user-independent method of monitoring responses to novel adjunctive therapies targeting endothelial dysfunction in sepsis.

Randomized, double-blind, placebo-controlled trial of granulocyte colony-stimulating factor in patients with septic shock.

OBJECTIVE: To investigate the effect of early administration of granulocyte colony-stimulating factor (G-CSF) on hospital mortality in nonneutropenic patients with septic shock, excluding patients with melioidosis. DESIGN: A randomized, placebo-controlled, double-blinded clinical trial. SETTING AND PATIENTS: Adult patients with septic shock admitted to the Royal Darwin Hospital Intensive Care Unit. INTERVENTIONS: Patients were randomized to receive G-CSF or placebo intravenously daily for 10 days, in addition to routine management of septic shock. MEASUREMENTS: Primary outcome was hospital mortality. Secondary outcomes included intensive care unit mortality, intensive care unit and hospital length of stay, ventilator hours, and time to resolution of shock. Patient comorbidities, baseline and daily physiology, and organ function were collected. RESULTS: Of 166 patients enrolled, 83 were allocated to receive G-CSF (81 included in analysis) and 83 were allocated to receive placebo. At baseline, 30% of patients had diabetes, 18% were known to have renal impairment or failure, and 38% had a history of hazardous alcohol use. The two groups had similar comorbidities at baseline and a similar severity of illness. The in-hospital mortality was 27% in the G-CSF group and 25% in the placebo group. Secondary end points were not different between groups. There was a higher rate of new organ failure in G-CSF-treated patients than placebo-treated patients (50% vs. 33%, p = .03), most of which was accounted for by new liver dysfunction (11% vs. 1%, p = .007). There was no significant difference in the proportion of patients with troponin I of >0.08 mg/L (78% vs. 66%, p = .09), and the prevalence of acute myocardial infarction (6% vs. 4%, p = .55) was not different during the study. The median peak troponin I level was higher in the G-CSF group (0.5 vs. 0.14 mg/L, p = .007), but baseline levels were not available. CONCLUSION: G-CSF does not improve outcomes in patients with septic shock, excluding melioidosis. Increased hepatic dysfunction and higher peak troponin levels in patients receiving G-CSF have not been reported in previous clinical trials and warrant further investigation.

Particulate face masks for protection against airborne pathogens - one size does not fit all: an observational study.

OBJECTIVE: To determine the proportion of hospital staff who pass fit tests with each of three commonly used particulate face masks, and factors influencing preference and fit test results. DESIGN: Observational study. SETTING AND PARTICIPANTS: 50 healthy hospital staff volunteers in an 18-bed general intensive care unit in an Australian teaching hospital. INTERVENTIONS: Participants were administered a questionnaire about mask use and their preferred mask and underwent qualitative fit-testing with each of three different particulate masks: Kimberly-Clark Tecnol FluidShield N95 particulate filter respirator (KC), 3M Flat Fold 9320 particulate respirator and 3M 8822 particulate respirator with exhalation valve. Participants who failed fittesting were trained in correct mask donning, and fittesting was repeated. MAIN OUTCOME MEASURES: Proportion of participants who passed the fit test for each mask and the effect of training. RESULTS: The proportion of participants who passed a fit test was low for all three masks tested (KC, 16%; flat fold, 28%; and valved, 34%). Rates improved after training: the first mask tested fitted in 18% of participants pre-training and 40% post-training (P = 0.02). None of the masks fitted for 28% of participants. There were no significant predictors of fit-test results. CONCLUSIONS: A large proportion of individuals failed a fit test with any given mask, and we were not able to identify any factors that predicted mask fit in individuals. Training on mask use improved the rates of adequate fit. Hospitals should carry a range of P2 masks, and should conduct systematic P2 mask training and fit-testing programs for all staff potentially exposed to airborne pathogens.

Disproportionate impact of pandemic (H1N1) 2009 influenza on Indigenous people in the Top End of Australia's Northern Territory.

OBJECTIVE: To describe the impact of pandemic (H1N1) 2009 influenza (nH1N1) on Indigenous people in the Top End of the Northern Territory at community, hospital and intensive care unit (ICU) levels. DESIGN, SETTING AND PARTICIPANTS: We analysed influenza notifications for the Top End from 1 June to 31 August 2009, as well as data on patients admitted through Top End emergency departments with an influenza-like illness. In addition, data on patients with nH1N1 who were admitted to Royal Darwin Hospital (RDH) and the RDH ICU were prospectively collected and analysed. MAIN OUTCOME MEASURES: Age-adjusted notification rates for nH1N1 cases, Top End hospital admission rates for patients with nH1N1 and RDH ICU admission rates for patients with nH1N1, stratified by Indigenous status. RESULTS: There were 918 nH1N1 notifications during the study period. The age-adjusted hospital admission rate for nH1N1 was 82 per 100 000 (95% CI, 68-95) estimated resident population (ERP) overall, with a markedly higher rate in the Indigenous population compared with the non-Indigenous population (269 per 100 000 versus 29 per 100 000 ERP; adjusted incidence rate ratio, 12 [95% CI, 7.8-18]). Independent predictors of ICU admission compared with hospitalisation were hypoxia (adjusted odds ratio [aOR], 4.5; CI, 1.5-13.1) and chest x-ray infiltrates (aOR, 4.3; CI, 1.5-12.6) on hospital admission. CONCLUSIONS: Pandemic (H1N1) 2009 influenza had a disproportionate impact on Indigenous Australians in the Top End, with hospitalisation rates higher than those reported elsewhere in Australia and overseas. These findings have implications for planning hospital and ICU capacity during an influenza pandemic in regions with large Indigenous populations. They also confirm the need to improve health and living circumstances and to prioritise vaccination in this population.

A clinical audit of the efficacy of tegaserod as a prokinetic agent in the intensive care unit.

OBJECTIVE: To formally document the effectiveness of tegaserod as a prokinetic agent in intensive care patients. METHODS: The audit was designed in consultation with the Northern Territory Drug and Therapeutics Committee. Tegaserod was added to the feeding protocol and prokinetic algorithm in the ICU, and a prospective audit was performed of patients receiving the medication between May and September 2006. RESULTS: Over the 5-month period, 40 patients received tegaserod after failing to respond to two doses of metoclopramide. Median daily volume of gastric aspirate was reduced from 1220mL in the 24 hours before tegaserod to 887.5mL in the first 24 hours after its introduction, and to 280mL in the second 24 hours (P=0.01 and P<0.001, respectively). Tegaserod was an effective prokinetic agent in 85% (34) patients. Attributable diarrhoea occurred in 13% (5) patients, but did not require intervention. CONCLUSIONS: Tegaserod is an effective alternative prokinetic agent for ICU patients with a safer side-effect profile. We believe it warrants further investigation.

Leptospirosis: an unusual presentation.

Leptospirosis is a common zoonosis that is endemic in the tropical Top End of the Northern Territory. Disease ranges from mild to very severe. We report a patient with anicteric leptospirosis who became critically ill, challenging the view that anicteric leptospirosis is less severe than the icteric form. Despite a typical but non-specific presentation and recreational high-risk activities, diagnosis of leptospirosis was delayed. The patient developed respiratory failure, resulting from pulmonary haemorrhage, and acute renal failure. This case highlights the multiple factors that should prompt health care workers to consider the diagnosis of leptospirosis in non-classical presentations.