Antimicrobial prescription patterns and ventilator associated pneumonia: findings from a 10-site prospective audit.

OBJECTIVE: To examine anti-microbial prescribing practices associated with ventilator-associated pneumonia from data gathered during an audit of practice and outcomes in intensive care units (ICUs) in a previously published study. RESULTS: The patient sample of 169 was 65% male with an average age of 59.7 years, a mean APACHE II score of 20.6, and a median ICU stay of 11 days. While ventilator-associated pneumonia was identified using a specific 4-item checklist in 29 patients, agreement between the checklist and independent physician diagnosis was only 17%. Sputum microbe culture reporting was sparse. Approximately 75% of the sample was administered an antimicrobial (main indications: lung infection [54%] and prophylaxis [11%]). No clinical justification was documented for 20% of prescriptions. Piperacillin/tazobactam was most frequently prescribed (1/3rd of all antimicrobial prescriptions) with about half of those for prophylaxis. Variations in prescribing practices were identified, including apparent gaps in antimicrobial stewardship; particularly in relation to prescribing for prophylaxis and therapy de-escalation. Sputum microbe culture reports for VAP did not appear to contribute to prescribing decisions but physician suspicion of lung infection and empiric therapy rather than ventilator-associated pneumonia criteria and guideline concordance.

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.

Intravenous amino acid therapy for kidney function in critically ill patients: a randomized controlled trial.

IMPORTANCE: Acute kidney injury (AKI) is characterized by severe loss of glomerular filtration rate (GFR) and is associated with a prolonged intensive care unit (ICU) stay and increased risk of death. No interventions have yet been shown to prevent AKI or preserve GFR in critically ill patients. Evidence from mammalian physiology and small clinical trials suggests higher amino acid intake may protect the kidney from ischemic insults and thus may preserve GFR during critical illness. OBJECTIVE: To determine whether amino acid therapy, achieved through daily intravenous (IV) supplementation with standard amino acids, preserves kidney function in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, phase II, randomized clinical trial conducted between December 2010 and February 2013 in the ICUs of 16 community and tertiary hospitals in Australia and New Zealand. Participants were adult critically ill patients expected to remain in the study ICU for longer than 2 days. INTERVENTIONS: Random allocation to receive a daily supplement of up to 100 g of IV amino acids or standard care. MAIN OUTCOMES AND MEASURES: Duration of renal dysfunction (primary outcome); estimated GFR (eGFR) derived from creatinine; eGFR derived from cystatin C; urinary output; renal replacement therapy (RRT) use; fluid balance and other measures of renal function. RESULTS: 474 patients were enrolled and randomized (235 to standard care, 239 to IV amino acid therapy). At time of enrollment, patients allocated to receive amino acid therapy had higher APACHE II scores (20.2 ± 6.8 vs. 21.7 ± 7.6, P = 0.02) and more patients had pre-existing renal dysfunction (29/235 vs. 44/239, P = 0.07). Duration of renal dysfunction after enrollment did not differ between groups (mean difference 0.21 AKI days per 10 patient ICU days, 95 % CI -0.27 to 1.04, P = 0.45). Amino acid therapy significantly improved eGFR (treatment group × time interaction, P = 0.004), with an early peak difference of 7.7 mL/min/1.73 m(2) (95 % CI 1.0-14.5 mL/min/1.73 m(2), P = 0.02) on study day 4. Daily urine output was also significantly increased (+300 mL/day, 95 % CI 145-455 mL, P = 0.0002). There was a trend towards increased RRT use in patients receiving amino acid therapy (13/235 vs. 25/239, P = 0.062); however, this trend was not present after controlling for baseline imbalance (P = 0.21). CONCLUSION AND RELEVANCE: Treatment with a daily IV supplement of standard amino acids did not alter our primary outcome, duration of renal dysfunction. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12609001015235.

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).

Prediction of death in less than 60 minutes after withdrawal of cardiorespiratory support in potential organ donors after circulatory death.

BACKGROUND: Given the stable number of potential organ donors after brain death, donors after circulatory death have been an increasing source of organs procured for transplant. Among the most important considerations for donation after circulatory death (DCD) is the prediction that death will occur within a reasonable period of time after the withdrawal of cardiorespiratory support (WCRS). Accurate prediction of time to death is necessary for the procurement process. We aimed to develop simple predictive rules for death in less than 60 min and test the accuracy of these rules in a pool of potential DCD donors. METHODS: A multicenter prospective longitudinal cohort design of DCD eligible patients (n=318), with the primary binary outcome being death in less than 60 min after withdrawal of cardiorespiratory support conducted in 28 accredited intensive care units (ICUs) in Australia. We used a random split-half method to produce two samples, first to develop the predictive classification rules and then to estimate accuracy in an independent sample. RESULTS: The best classification model used only three simple classification rules to produce an overall efficiency of 0.79 (0.72-0.85), sensitivity of 0.82 (0.73-0.90), and a positive predictive value of 0.80 (0.70-0.87) in the independent sample. Using only intensive care unit specialist prediction (a single classification rule) produced comparable efficiency 0.80 (0.73-0.86), sensitivity 0.87 (0.78-0.93), and positive predictive value 0.78 (0.68-0.86). CONCLUSION: This best predictive model missed only 18% of all potential donors. A positive prediction would be incorrect on only 20% of occasions, meaning there is an acceptable level of lost opportunity costs involved in the unnecessary assembly of transplantation teams and theatres.

Prediction of death in less than 60 minutes following withdrawal of cardiorespiratory support in ICUs.

OBJECTIVES: Half of all ICU patients die within 60 minutes of withdrawal of cardiorespiratory support. Prediction of which patients die before and after 60 minutes would allow changes in service organization to improve patient palliation, family grieving, and allocation of ICU beds. This study tested various predictors of death within 60 minutes and explored which clinical variables ICU specialists used to make their prediction. DESIGN AND SETTINGS: Prospective longitudinal cohort design (n = 765) of consecutive adult patients having withdrawal of cardiorespiratory support, in 28 ICUs in Australia. Primary outcome was death within 60 minutes following withdrawal of cardiorespiratory support. A random split-half method was used to make two independent samples for development and testing of the predictive indices. The secondary outcome was ICU Specialist prediction of death within 60 minutes. MEASUREMENTS AND MAIN RESULTS: Death within 60 minutes of withdrawal of cardiorespiratory support occurred in 377 (49.3%). ICU specialist opinion was the best individual predictor, with an unadjusted odds ratio of 15.42 (95% CI, 9.33-25.49) and an adjusted odds ratio of 8.44 (4.30-16.58). A predictive index incorporating the ICU specialist opinion and clinical variables had an area under the curve of 0.89 (0.86-0.92) and 0.84 (0.80-0.88) in the development and test sets, respectively; and a second index using only clinical variables had an area under the curve of 0.86 (0.82-0.89) and 0.78 (0.73-0.83). The ICU specialist prediction of death within 60 minutes was independently associated with five clinical variables: pH, Glasgow Coma Scale, spontaneous respiratory rate, positive end-expiratory pressure, and systolic blood pressure. CONCLUSION: ICU specialist opinion is probably the current clinical standard for predicting death within 60 minutes of withdrawal of cardiorespiratory support. This approach is supported by this study, although predictive indices restricted to clinical variables are only marginally inferior. Either approach has a clinically useful level of prediction that would allow ICU service organization to be modified to improve care for patients and families and use ICU beds more efficiently.

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.

Ability of pulse contour and esophageal Doppler to estimate rapid changes in stroke volume.

OBJECTIVE: Two technologies to acquire beat-to-beat stroke volume values exist, pulse contour analysis and esophageal Doppler monitoring. Pulse contour analysis assumes fixed aortic impedance. Esophageal Doppler assumes a constant proportional descending aortic flow and diameter. These assumptions may not be correct as arterial tone or myocardial contractility vary. We tested these relationships in the setting of rapidly changing stroke volumes and different cardiovascular states over a period of 10-15 cardiac cycles. DESIGN AND SETTING: In a university research facility we compared beat-to-beat changes in stroke volume as measure by aortic root flow probe or conductance catheter to pulse contour analysis and stroke distance as measured by esophageal Doppler. SUBJECTS: Five purpose-bred research hounds. INTERVENTIONS: To obtain a wide range of rapidly changing stroke volumes measurements were made during transient inferior vena cava occlusion. Data were gathered under baseline conditions and during norepinephrine, nitroprusside, and dobutamine infusions. MEASUREMENTS AND RESULTS: The pulse contour stroke volumes and esophageal Doppler stroke distance paralleled flow probe stroke volumes under all conditions (R(2)=0.89 for all measures). However, the absolute changes and proportional changes and the absolute values for both surrogate measures differed from absolute stroke volumes. Bland-Altman analysis showed no consistent bias or degree of precision across all animals under any given cardiovascular state. CONCLUSIONS: Both pulse contour stroke volumes and esophageal Doppler derived stroke distance estimates yield significant correlations with aortic root flow probe. However, the absolute values, absolute changes, or proportional changes may not reflect actual stroke volumes as cardiovascular state varies, making their use in estimating absolute changes in stroke volume potentially inaccurate.