Induction of Therapeutic Hypothermia During Out-of-Hospital Cardiac Arrest Using a Rapid Infusion of Cold Saline: The RINSE Trial (Rapid Infusion of Cold Normal Saline).

BACKGROUND: Patients successfully resuscitated by paramedics from out-of-hospital cardiac arrest often have severe neurologic injury. Laboratory and observational clinical reports have suggested that induction of therapeutic hypothermia during cardiopulmonary resuscitation (CPR) may improve neurologic outcomes. One technique for induction of mild therapeutic hypothermia during CPR is a rapid infusion of large-volume cold crystalloid fluid. METHODS: In this multicenter, randomized, controlled trial we assigned adults with out-of-hospital cardiac arrest undergoing CPR to either a rapid intravenous infusion of up to 2 L of cold saline or standard care. The primary outcome measure was survival at hospital discharge; secondary end points included return of a spontaneous circulation. The trial was closed early (at 48% recruitment target) due to changes in temperature management at major receiving hospitals. RESULTS: A total of 1198 patients were assigned to either therapeutic hypothermia during CPR (618 patients) or standard prehospital care (580 patients). Patients allocated to therapeutic hypothermia received a mean (SD) of 1193 (647) mL cold saline. For patients with an initial shockable cardiac rhythm, there was a decrease in the rate of return of a spontaneous circulation in patients who received cold saline compared with standard care (41.2% compared with 50.6%, P=0.03). Overall 10.2% of patients allocated to therapeutic hypothermia during CPR were alive at hospital discharge compared with 11.4% who received standard care (P=0.71). CONCLUSIONS: In adults with out-of-hospital cardiac arrest, induction of mild therapeutic hypothermia using a rapid infusion of large-volume, intravenous cold saline during CPR may decrease the rate of return of a spontaneous circulation in patients with an initial shockable rhythm and produced no trend toward improved outcomes at hospital discharge. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01173393.

Delivering safe and effective analgesia for management of renal colic in the emergency department: a double-blind, multigroup, randomised controlled trial.

BACKGROUND: The excruciating pain of patients with renal colic on presentation to the emergency department requires effective analgesia to be administered in the shortest possible time. Trials comparing intramuscular non-steroidal anti-inflammatory drugs with intravenous opioids or paracetamol have been inconclusive because of the challenges associated with concealment of randomisation, small sample size, differences in outcome measures, and inadequate masking of participants and assessors. We did this trial to develop definitive evidence regarding the choice of initial analgesia and route of administration in participants presenting with renal colic to the emergency department. METHODS: In this three-treatment group, double-blind, randomised controlled trial, adult participants (aged 18-65 years) presenting to the emergency department of an academic, tertiary care hospital in Qatar, with moderate to severe renal colic (Numerical pain Rating Scale ≥ 4) were recruited. With the use of computer-generated block randomisation (block sizes of six and nine), participants were assigned (1:1:1) to receive diclofenac (75 mg/3 mL intramuscular), morphine (0.1 mg/kg intravenous), or paracetamol (1 g/100 mL intravenous). Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants achieving at least a 50% reduction in initial pain score at 30 min after analgesia, assessed by intention-to-treat analysis and per-protocol analysis, which included patients where a calculus in the urinary tract was detected with imaging. This trial is registered with ClinicalTrials.gov, number NCT02187614. FINDINGS: Between Aug 5, 2014, and March 15, 2015, we randomly assigned 1645 participants, of whom 1644 were included in the intention-to-treat analysis (547 in the diclofenac group, 548 in the paracetemol group, and 549 in the morphine group). Ureteric calculi were detected in 1316 patients, who were analysed as the per-protocol population (438 in the diclofenac group, 435 in the paracetemol group, and 443 in the morphine group). The primary outcome was achieved in 371 (68%) patients in the diclofenac group, 364 (66%) in the paracetamol group, and 335 (61%) in the morphine group in the intention-to-treat population. Compared to morphine, diclofenac was significantly more effective in achieving the primary outcome (odds ratio [OR] 1·35, 95% CI 1·05-1·73, p=0·0187), whereas no difference was detected in the effectiveness of morphine compared with intravenous paracetamol (1·26, 0·99-1·62, p=0·0629). In the per-protocol population, diclofenac (OR 1·49, 95% CI 1·13-1·97, p=0·0046) and paracetamol (1·40, 1·06-1·85, p=0·0166) were more effective than morphine in achieving the primary outcome. Acute adverse events in the morphine group occurred in 19 (3%) participants. Significantly lower numbers of adverse events were recorded in the diclofenac group (7 [1%] participants, OR 0·31, 95% CI 0·12-0·78, p=0·0088) and paracetamol group (7 [1%] participants, 0·36, 0·15-0·87, p=0·0175) than in the morphine group. During the 2 week follow-up, no additional adverse events were noted in any group. INTERPRETATION: Intramuscular non-steroidal anti-inflammatory drugs offer the most effective sustained analgesia for renal colic in the emergency department and seem to have fewer side-effects. FUNDING: Hamad Medical Corporation Medical Research Center, Doha, Qatar.

Predicting functional decline in older emergency patients-the Safe Elderly Emergency Discharge (SEED) project.

Objective: to profile the trajectory of, and risk factors for, functional decline in older patients in the 30 days following Emergency Department (ED) discharge. Methods: prospective cohort study of community-dwelling patients aged ≥65 years, discharged home from a metropolitan Melbourne ED, 31 July 2012 to 30 November 2013. The primary outcome was functional decline, comprising either increased dependency in personal activities of daily living (ADL) or in skills required for living independently instrumental ADL (IADL), deterioration in cognitive function, nursing home admission or death. Univariate analyses were used to select risk factors and logistic regression models constructed to predict functional decline. Results: at 30 days, 34.4% experienced functional decline; with 16.7% becoming more dependent in personal ADL, 17.5% more dependant in IADL and 18.4% suffering deterioration in cognitive function. Factors independently associated with decline were functional impairment prior to the visit in personal ADL (Odds Ratio [OR] 3.21, 95% confidence interval [CI] 2.26-4.53) or in IADL (OR 6.69, 95% CI 4.31-10.38). The relative odds were less for patients with moderately impaired cognition relative to those with normal cognition (OR 0.38, 95% CI 0.19-0.75). There was a 68% decline in the relative odds of functional decline for those with any impairment in IADL who used an aid for mobility (OR 0.32, 95% CI 0.14-0.7). Conclusion: older people with pre-existing ADL impairment were at high risk of functional decline in the 30 days following ED presentation. This effect was largely mitigated for those who used a mobility aid. Early intervention with functional assessments and appropriate implementation of support services and mobility aids could reduce functional decline after discharge.

Unplanned early return to the emergency department by older patients: the Safe Elderly Emergency Department Discharge (SEED) project.

BACKGROUND: an emergency department (ED) visit is a sentinel event for an older person, with increased likelihood of adverse outcomes post-discharge including early re-presentation. OBJECTIVES: to determine factors associated with early re-presentation. METHODS: prospective cohort study conducted in the ED of a large acute Melbourne tertiary hospital. Community-dwelling patients ≥65 years were interviewed including comprehensive assessment of cognitive and functional status, and mood. Logistic regression was used to identify risk factors for return within 30 days. RESULTS: nine hundred and fifty-nine patients, median age 77 years, were recruited. One hundred and forty patients (14.6%) re-presented within 30 days, including 22 patients (2.3%) on ≥2 occasions and 75 patients (7.8%) within 7 days. Risk factors for re-presentation included depressive symptoms, cognitive impairment, co-morbidity, triaged as less urgent (ATS 4) and attendance in the previous 12 months, with a decline in risk after 85 years of age. Logistic regression identified chronic obstructive pulmonary disease (OR 1.78, 95% CI 1.02-3.11), moderate cognitive impairment (OR 2.07, 95% CI 1.09-3.90), previous ED visit (OR 2.11, 95% CI 1.43-3.12) and ATS 4 (OR 2.34, 95% CI 1.10-4.99) as independent risk factors for re-presentation. Age ≥85 years was associated with reduced risk (OR 0.81, 95% CI 0.70-0.93). CONCLUSION: older discharged patients had a high rate of early re-presentation. Previously identified risk factors-increased age, living alone, functional dependence and polypharmacy-were not associated with early return in this study. It is not clear whether these inconsistencies represent a change in patient case-mix or strategies implemented to reduce re-attendance. This remains an important area for future research.

Trends in PICU Admission and Survival Rates in Children in Australia and New Zealand Following Cardiac Arrest.

OBJECTIVES: To describe the temporal trends in rates of PICU admissions and mortality for out-of-hospital cardiac arrests and in-hospital cardiac arrests admitted to PICU over the last decade. DESIGN: Multicenter, retrospective analysis of prospectively collected binational data of the Australian and New Zealand Paediatric Intensive Care Registry. All nine specialist PICUs in Australia and New Zealand were included. PATIENTS: All children admitted between 2003 and 2012 to PICU who were less than 16 years old at the time of admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were a total of 71,425 PICU admissions between 2003 and 2012. Overall, cardiac arrest accounted for 1.86% of all admissions (1,329 cases), including 677 cases of in-hospital cardiac arrest (51.0%) and 652 cases of out-of-hospital cardiac arrest (49.0%). Over the last decade, there has been a 29.6% increase in the odds of PICU survival for all pediatric admissions (odds ratio, 1.30; 95% CI, 1.09-1.54). By contrast, there was no significant improvement in the risk-adjusted odds of survival for out-of-hospital cardiac arrest admissions (odds ratio, 1.03; 95% CI, 0.50-2.10; p = 0.94) or in-hospital cardiac arrest admissions (odds ratio, 1.03; 95% CI, 0.54-1.98; p = 0.92). CONCLUSIONS: Despite improvements in overall outcomes in children admitted to Australian and New Zealand PICUs, survival of children admitted with out-of-hospital cardiac arrest or in-hospital cardiac arrest did not change significantly over the past decade.

Modelling risk-adjusted variation in length of stay among Australian and New Zealand ICUs.

PURPOSE: Comparisons between institutions of intensive care unit (ICU) length of stay (LOS) are significantly confounded by individual patient characteristics, and currently there is a paucity of methods available to calculate risk-adjusted metrics. METHODS: We extracted de-identified data from the Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database for admissions between January 1 2011 and December 31 2015. We used a mixed-effects log-normal regression model to predict LOS using patient and admission characteristics. We calculated a risk-adjusted LOS ratio (RALOSR) by dividing the geometric mean observed LOS by the exponent of the expected Ln-LOS for each site and year. The RALOSR is scaled such that values <1 indicate a LOS shorter than expected, while values >1 indicate a LOS longer than expected. Secondary mixed effects regression modelling was used to assess the stability of the estimate in units over time. RESULTS: During the study there were a total of 662,525 admissions to 168 units (median annual admissions = 767, IQR:426-1121). The mean observed LOS was 3.21 days (median = 1.79 IQR = 0.92-3.52) over the entire period, and declined on average 1.97 hours per year (95%CI:1.76-2.18) from 2011 to 2015. The RALOSR varied considerably between units, ranging from 0.35 to 2.34 indicating large differences after accounting for case-mix. CONCLUSIONS: There are large disparities in risk-adjusted LOS among Australian and New Zealand ICUs which may reflect differences in resource utilization.

Are sociodemographic characteristics associated with spatial variation in the incidence of OHCA and bystander CPR rates? A population-based observational study in Victoria, Australia.

BACKGROUND: Rates of out-of-hospital cardiac arrest (OHCA) and bystander cardiopulmonary resuscitation (CPR) have been shown to vary considerably in Victoria. We examined the extent to which this variation could be explained by the sociodemographic and population health characteristics of the region. METHODS: Using the Victorian Ambulance Cardiac Arrest Registry, we extracted OHCA cases occurring between 2011 and 2013. We restricted the calculation of bystander CPR rates to those arrests that were witnessed by a bystander. To estimate the level of variation between Victorian local government areas (LGAs), we used a two-stage modelling approach using random-effects modelling. RESULTS: Between 2011 and 2013, there were 15 830 adult OHCA in Victoria. Incidence rates varied across the state between 41.9 to 104.0 cases/100 000 population. The proportion of the population over 65, socioeconomic status, smoking prevalence and education level were significant predictors of incidence in the multivariable model, explaining 93.9% of the variation in incidence among LGAs. Estimates of bystander CPR rates for bystander witnessed arrests varied from 62.7% to 73.2%. Only population density was a significant predictor of rates in a multivariable model, explaining 73% of the variation in the odds of receiving bystander CPR among LGAs. CONCLUSIONS: Our results show that the regional characteristics which underlie the variation seen in rates of bystander CPR may be region specific and may require study in smaller areas. However, characteristics associated with high incidence and low bystander CPR rates can be identified and will help to target regions and inform local interventions to increase bystander CPR rates.

Regions of High Out-Of-Hospital Cardiac Arrest Incidence and Low Bystander CPR Rates in Victoria, Australia.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains a major public health issue and research has shown that large regional variation in outcomes exists. Of the interventions associated with survival, the provision of bystander CPR is one of the most important modifiable factors. The aim of this study is to identify census areas with high incidence of OHCA and low rates of bystander CPR in Victoria, Australia. METHODS: We conducted an observational study using prospectively collected population-based OHCA data from the state of Victoria in Australia. Using ArcGIS (ArcMap 10.0), we linked the location of the arrest using the dispatch coordinates (longitude and latitude) to Victorian Local Government Areas (LGAs). We used Bayesian hierarchical models with random effects on each LGA to provide shrunken estimates of the rates of bystander CPR and the incidence rates. RESULTS: Over the study period there were 31,019 adult OHCA attended, of which 21,436 (69.1%) cases were of presumed cardiac etiology. Significant variation in the incidence of OHCA among LGAs was observed. There was a 3 fold difference in the incidence rate between the lowest and highest LGAs, ranging from 38.5 to 115.1 cases per 100,000 person-years. The overall rate of bystander CPR for bystander witnessed OHCAs was 62.4%, with the rate increasing from 56.4% in 2008-2010 to 68.6% in 2010-2013. There was a 25.1% absolute difference in bystander CPR rates between the highest and lowest LGAs. CONCLUSION: Significant regional variation in OHCA incidence and bystander CPR rates exists throughout Victoria. Regions with high incidence and low bystander CPR participation can be identified and would make suitable targets for interventions to improve CPR participation rates.

Forest Fire Smoke Exposures and Out-of-Hospital Cardiac Arrests in Melbourne, Australia: A Case-Crossover Study.

BACKGROUND: Millions of people can potentially be exposed to smoke from forest fires, making this an important public health problem in many countries. OBJECTIVE: In this study we aimed to measure the association between out-of-hospital cardiac arrest (OHCA) and forest fire smoke exposures in a large city during a severe forest fire season, and estimate the number of excess OHCAs due to the fire smoke. METHODS: We investigated the association between particulate matter (PM) and other air pollutants and OHCA using a case-crossover study of adults (≥ 35 years of age) in Melbourne, Australia. Conditional logistic regression models were used to derive estimates of the percent change in the rate of OHCA associated with an interquartile range (IQR) increase in exposure. From July 2006 through June 2007, OHCA data were collected from the Victorian Ambulance Cardiac Arrest Registry. Hourly air pollution concentrations and meteorological data were obtained from a central monitoring site. RESULTS: There were 2,046 OHCAs with presumed cardiac etiology during our study period. Among men during the fire season, greater increases in OHCA were observed with IQR increases in the 48-hr lagged PM with diameter ≤ 2.5 µm (PM2.5) (8.05%; 95% CI: 2.30, 14.13%; IQR = 6.1 µg/m(3)) or ≤ 10 µm (PM10) (11.1%; 95% CI: 1.55, 21.48%; IQR = 13.7 µg/m(3)) and carbon monoxide (35.7%; 95% CI: 8.98, 68.92%; IQR = 0.3 ppm). There was no significant association between the rate of OHCA and air pollutants among women. One hundred seventy-four "fire-hours" (i.e., hours in which Melbourne's air quality was affected by forest fire smoke) were identified during 12 days of the 2006/2007 fire season, and 23.9 (95% CI: 3.1, 40.2) excess OHCAs were estimated to occur due to elevations in PM2.5 during these fire-hours. CONCLUSIONS: This study found an association between exposure to forest fire smoke and an increase in the rate of OHCA. These findings have implications for public health messages to raise community awareness and for planning of emergency services during forest fire seasons.

Trends in intensive care unit cardiac arrest admissions and mortality in Australia and New Zealand.

OBJECTIVES: To develop methods for distinguishing patients with in-hospital cardiac arrest (IHCA) from patients with out-of-hospital cardiac arrest (OHCA) in routinely collected intensive care unit registry data, and to explore the utility of the methods for describing trends in adult ICU cardiac arrest (CA) admissions and outcomes. DESIGN AND SETTING: A retrospective observational analysis of all ICU admissions entered in the Australian and New Zealand Intensive Care Society adult patient database between 2000 and 2011. Trends in admission and survival rates to hospital discharge over time were examined using eight different methods of classifying patients with IHCA and OHCA. RESULTS: There were 1 001 754 admissions to the ICUs between 2000 and 2011. Of these, postarrest admissions comprised 23 857 (2.4%), and increased annually by an average of 135 admissions (95% CI, 120-150 admissions). The annual volume of patients with IHCA as a fraction of total admissions declined by 0.4 patients/1000 admissions (95% CI, 0.3-0.5 patients/1000 admissions). In contrast, for patients with OHCA, each year was associated with an additional 0.2 patients/1000 admissions (95% CI, 0.1-0.4 patients/1000 admissions). This increase occurred in tertiary ICUs and declined in non-tertiary ICUs. Survival to hospital discharge for both groups improved, increasing annually by 1.2% (95% CI, 0.8%-1.6%) for patients with IHCA, and by 1.1% (95% CI, 0.7%-1.4%) for patients with OHCA. CONCLUSIONS: Use of routinely collected registry data uncovered important trends in adult ICU admission and survival rates for patients with IHCA and OHCA. The improved survival rates and increased number of admissions to tertiary centres requires further study to understand mechanisms and related factors.

Disentangling the effects of risk factors and clinical care on subnational variation in early neonatal mortality in the United States.

OBJECTIVE: Between 1990 and 2010, the U.S ranking in neonatal mortality slipped from 29(th) to 45(th) among countries globally. Substantial subnational variation in newborn mortality also exists. Our objective is to measure the extent to which trends and subnational variation in early neonatal mortality reflect differences in the prevalence of risk factors (gestational age and birth weight) compared to differences in clinical care. METHODS: Observational study using linked birth and death data for all births in the United States between 1996 and 2006. We examined health service area (HSA) level variation in the expected early neonatal mortality rate, based on gestational age (GA) and birth-weight (BW), and GA-BW adjusted mortality as a proxy for clinical care. We analyzed the relationship between selected health system indicators and GA-BW-adjusted mortality. RESULTS: The early neonatal death (ENND) rate declined 12% between 1996 and 2006 (2.39 to 2.10 per 1000 live births). This occurred despite increases in risk factor prevalence. There was significant HSA-level variation in the expected ENND rate (Rate Ratio: 0.73-1.47) and the GA-BW adjusted rate (Rate ratio: 0.63-1.68). Accounting for preterm volume (defined as <34 weeks), the number of neonatologist and NICU beds, 25.2% and 58.7% of the HSA-level variance in outcomes was explained among all births and very low birth weight babies, respectively. CONCLUSION: Improvements in mortality could be realized through the expansion or reallocation of clinical neonatal resources, particularly in HSAs with a high volume of preterm births; however, prevention of preterm births and low-birth weight babies has a greater potential to improve newborn survival in the United States.

Measuring efficiency in Australian and New Zealand paediatric intensive care units.

PURPOSE: To develop a measure of paediatric intensive care unit (PICU) efficiency and compare the efficiency of PICUs in Australia and New Zealand. METHODS: Separate outcome prediction models for estimating clinical performance and resource usage were constructed using patient data from 20,742 admissions between 2005 and 2007. A standardised mortality ratio was calculated using a recalibrated Paediatric Index of Mortality 2 model. A random effects length of stay (LoS) prediction model was used to provide an indicator of unit-level variation in resource use. A modified Rapoport-Teres plot of risk-adjusted mortality versus unit mean LoS provided a visual representation of efficiency. To account for potential differences in admission threshold, the calculation of performance measures was repeated on patients receiving mechanical respiratory support and compared to those estimated for all patients. RESULTS: The modified plot provides a useful tool for visualising ICU efficiency. Two units were identified as potentially inefficient with higher SMR and risk-adjusted mean LoS at the 95% level. One unit had a significantly lower SMR and significantly higher risk-adjusted mean LoS. The measures for both SMR and risk-adjusted mean LoS showed good agreement between all patients and those who received mechanical respiratory support. CONCLUSION: There is significant variation in efficiency among PICUs in Australia and New Zealand. Two units were designated as inefficient and one unit was considered to be effective at the expense of high resource use. Application of these methods may help to identify inefficiencies in units located in other countries or regions.