Kathryn M Rowan

Trial of early, goal-directed resuscitation for septic shock.

BACKGROUND Early, goal-directed therapy (EGDT) is recommended in international guidelines for the resuscitation of patients presenting with early septic shock. However, adoption has been limited, and uncertainty about its effectiveness remains. METHODS We conducted a pragmatic randomized trial with an integrated cost-effectiveness analysis in 56 hospitals in England. Patients were randomly assigned to receive either EGDT (a 6-hour resuscitation protocol) or usual care. The primary clinical outcome was all-cause mortality at 90 days. RESULTS We enrolled 1260 patients, with 630 assigned to EGDT and 630 to usual care. By 90 days, 184 of 623 patients (29.5%) in the EGDT group and 181 of 620 patients (29.2%) in the usual-care group had died (relative risk in the EGDT group, 1.01; 95% confidence interval [CI], 0.85 to 1.20; P=0.90), for an absolute risk reduction in the EGDT group of -0.3 percentage points (95% CI, -5.4 to 4.7). Increased treatment intensity in the EGDT group was indicated by increased use of intravenous fluids, vasoactive drugs, and red-cell transfusions and reflected by significantly worse organ-failure scores, more days receiving advanced cardiovascular support, and longer stays in the intensive care unit. There were no significant differences in any other secondary outcomes, including health-related quality of life, or in rates of serious adverse events. On average, EGDT increased costs, and the probability that it was cost-effective was below 20%. CONCLUSIONS In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment Programme; ProMISe Current Controlled Trials number, ISRCTN36307479.).

Referral to an Extracorporeal Membrane Oxygenation Center and Mortality Among Patients With Severe 2009 Influenza A(H1N1)

CONTEXT Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients with severe acute respiratory distress syndrome (ARDS), but its role has remained controversial. ECMO was used to treat patients with ARDS during the 2009 influenza A(H1N1) pandemic. OBJECTIVE To compare the hospital mortality of patients with H1N1-related ARDS referred, accepted, and transferred for ECMO with matched patients who were not referred for ECMO. DESIGN, SETTING, AND PATIENTS A cohort study in which ECMO-referred patients were defined as all patients with H1N1-related ARDS who were referred, accepted, and transferred to 1 of the 4 adult ECMO centers in the United Kingdom during the H1N1 pandemic in winter 2009-2010. The ECMO-referred patients and the non-ECMO-referred patients were matched using data from a concurrent, longitudinal cohort study (Swine Flu Triage study) of critically ill patients with suspected or confirmed H1N1. Detailed demographic, physiological, and comorbidity data were used in 3 different matching techniques (individual matching, propensity score matching, and GenMatch matching). MAIN OUTCOME MEASURE Survival to hospital discharge analyzed according to the intention-to-treat principle. RESULTS Of 80 ECMO-referred patients, 69 received ECMO (86.3%) and 22 died (27.5%) prior to discharge from the hospital. From a pool of 1756 patients, there were 59 matched pairs of ECMO-referred patients and non-ECMO-referred patients identified using individual matching, 75 matched pairs identified using propensity score matching, and 75 matched pairs identified using GenMatch matching. The hospital mortality rate was 23.7% for ECMO-referred patients vs 52.5% for non-ECMO-referred patients (relative risk [RR], 0.45 [95% CI, 0.26-0.79]; P = .006) when individual matching was used; 24.0% vs 46.7%, respectively (RR, 0.51 [95% CI, 0.31-0.81]; P = .008) when propensity score matching was used; and 24.0% vs 50.7%, respectively (RR, 0.47 [95% CI, 0.31-0.72]; P = .001) when GenMatch matching was used. The results were robust to sensitivity analyses, including amending the inclusion criteria and restricting the location where the non-ECMO-referred patients were treated. CONCLUSION For patients with H1N1-related ARDS, referral and transfer to an ECMO center was associated with lower hospital mortality compared with matched non-ECMO-referred patients.

Effect of a perioperative, cardiac output-guided hemodynamic therapy algorithm on outcomes following major gastrointestinal surgery: a randomized clinical trial and systematic review

IMPORTANCE Small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm. OBJECTIVE To evaluate the clinical effectiveness of a perioperative, cardiac output-guided hemodynamic therapy algorithm. DESIGN, SETTING, AND PARTICIPANTS OPTIMISE was a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom. An updated systematic review and meta-analysis were also conducted including randomized trials published from 1966 to February 2014. INTERVENTIONS Patients were randomly assigned to a cardiac output-guided hemodynamic therapy algorithm for intravenous fluid and inotrope (dopexamine) infusion during and 6 hours following surgery (n=368) or to usual care (n=366). MAIN OUTCOMES AND MEASURES The primary outcome was a composite of predefined 30-day moderate or major complications and mortality. Secondary outcomes were morbidity on day 7; infection, critical care-free days, and all-cause mortality at 30 days; all-cause mortality at 180 days; and length of hospital stay. RESULTS Baseline patient characteristics, clinical care, and volumes of intravenous fluid were similar between groups. Care was nonadherent to the allocated treatment for less than 10% of patients in each group. The primary outcome occurred in 36.6% of intervention and 43.4% of usual care participants (relative risk [RR], 0.84 [95% CI, 0.71-1.01]; absolute risk reduction, 6.8% [95% CI, -0.3% to 13.9%]; P = .07). There was no significant difference between groups for any secondary outcomes. Five intervention patients (1.4%) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group. Findings of the meta-analysis of 38 trials, including data from this study, suggest that the intervention is associated with fewer complications (intervention, 488/1548 [31.5%] vs control, 614/1476 [41.6%]; RR, 0.77 [95% CI, 0.71-0.83]) and a nonsignificant reduction in hospital, 28-day, or 30-day mortality (intervention, 159/3215 deaths [4.9%] vs control, 206/3160 deaths [6.5%]; RR, 0.82 [95% CI, 0.67-1.01]) and mortality at longest follow-up (intervention, 267/3215 deaths [8.3%] vs control, 327/3160 deaths [10.3%]; RR, 0.86 [95% CI, 0.74-1.00]). CONCLUSIONS AND RELEVANCE In a randomized trial of high-risk patients undergoing major gastrointestinal surgery, use of a cardiac output-guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality. However, inclusion of these data in an updated meta-analysis indicates that the intervention was associated with a reduction in complication rates. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN04386758.

Variation in critical care services across North America and Western Europe

Objective:Critical care represents a large percentage of healthcare spending in developed countries. Yet, little is known regarding international variation in critical care services. We sought to understand differences in critical care delivery by comparing data on the distribution of services in eight countries. Design:Retrospective review of existing national administrative data. We identified sources of data in each country to provide information on acute care hospitals and beds, intensive care units and beds, intensive care admissions, and definitions of intensive care beds. Data were all referenced and from as close to 2005 as possible. Setting:United States, France, United Kingdom, Canada, Belgium, Germany, The Netherlands, and Spain. Patients:Not available. Interventions:None. Measurements and Main Results:No standard definition existed for acute care hospital or intensive care unit beds across countries. Hospital beds varied three-fold from 221/100,000 population in the United States to 593/100,000 in Germany. Adult intensive care unit beds also ranged seven-fold from 3.3/100,000 population in the United Kingdom to 24.0/100,000 in Germany. Volume of intensive care unit admissions per year varied ten-fold from 216/100,000 population in the United Kingdom to 2353/100,000 in Germany. The ratio of intensive care unit beds to hospital beds was highly correlated across all countries except the United States (r = .90). There was minimal correlation between the number of intensive care unit beds per capita and health care spending per capita (r = .45), but high inverse correlation between intensive care unit beds and hospital mortality for intensive care unit patients across countries (r = −.82). Conclusions:Absolute critical care services vary dramatically between countries with wide differences in both numbers of beds and volume of admissions. The number of intensive care unit beds per capita is not strongly correlated with overall health expenditure, but does correlate strongly with mortality. These findings demonstrate the need for critical care data from all countries, as they are essential for interpretation of studies, and policy decisions regarding critical care services.

Intensive Care Society's APACHE II study in Britain and Ireland--II: Outcome comparisons of intensive care units after adjustment for case mix by the American APACHE II method.

OBJECTIVES--To compare outcome between intensive care units in Britain and Ireland both before and after adjustment for case mix with the American APACHE II method and to validate the American APACHE II method in Britain and Ireland. DESIGN--Prospective, cohort study of consecutive admissions to intensive care units. SETTING--26 general intensive care units in Britain and Ireland. SUBJECTS--8796 admissions to the study intensive care units. MAIN OUTCOME MEASURE--Death or survival at discharge from intensive care unit and hospital. RESULTS--At discharge from both intensive care unit and hospital there was a greater than twofold variation in crude mortality between the 26 units. After adjustment for case mix, variations in mortality were still apparent. For four intensive care units the observed numbers of deaths were significantly different from the number predicted by the American APACHE II equation. The overall goodness of fit, or predictive ability, of the APACHE II equation for the British and Irish data was good, being only slightly inferior to that obtained when the equation was tested on the data from which it had been derived. When patients were grouped by various factors such as age and diagnosis, the equation did not adjust across the subgroups in a uniform manner. CONCLUSIONS--The American APACHE II equation did not fit the British and Irish data. Use of the American equation could be of advantage or disadvantage to individual intensive care units, depending on the mix of patients treated.

Outcome following admission to UK intensive care units after cardiac arrest: a secondary analysis of the ICNARC Case Mix Programme Database.

Using a retrospective analysis of the Intensive Care National Audit and Research Centre Case Mix Programme Database (ICNARC CMPD), we have summarised the characteristics and outcomes for mechanically ventilated patients admitted to UK intensive care units (ICUs) after cardiac arrest. Descriptive statistics on case mix, physiology, treatment, service delivery, outcome and activity were described separately for community cardiac arrest, in‐hospital cardiac arrest (peri‐operative) and in‐hospital cardiac arrest (not peri‐operative). The impact on outcome of several patient characteristics and physiological values were analysed using multivariable logistic regression. Mechanically ventilated survivors of cardiac arrest accounted for 24 132 (5.8%) of all admissions to the 174 ICUs in the ICNARC CMP. Of these, 10 347 (42.9%) survived to leave the ICU and 6778 (28.6%) survived to acute hospital discharge. The ICNARC model gives much better discrimination than APACHE II for predicting hospital mortality after admission to ICU following cardiac arrest: the predicted hospital mortality based on the APACHE II and ICNARC model was 41.9% and 79.7%, respectively.

Trial of the Route of Early Nutritional Support in Critically Ill Adults

BACKGROUND Uncertainty exists about the most effective route for delivery of early nutritional support in critically ill adults. We hypothesized that delivery through the parenteral route is superior to that through the enteral route. METHODS We conducted a pragmatic, randomized trial involving adults with an unplanned admission to one of 33 English intensive care units. We randomly assigned patients who could be fed through either the parenteral or the enteral route to a delivery route, with nutritional support initiated within 36 hours after admission and continued for up to 5 days. The primary outcome was all-cause mortality at 30 days. RESULTS We enrolled 2400 patients; 2388 (99.5%) were included in the analysis (1191 in the parenteral group and 1197 in the enteral group). By 30 days, 393 of 1188 patients (33.1%) in the parenteral group and 409 of 1195 patients (34.2%) in the enteral group had died (relative risk in parenteral group, 0.97; 95% confidence interval, 0.86 to 1.08; P=0.57). There were significant reductions in the parenteral group, as compared with the enteral group, in rates of hypoglycemia (44 patients [3.7%] vs. 74 patients [6.2%]; P=0.006) and vomiting (100 patients [8.4%] vs. 194 patients [16.2%]; P<0.001). There were no significant differences between the parenteral group and the enteral group in the mean number of treated infectious complications (0.22 vs. 0.21; P=0.72), 90-day mortality (442 of 1184 patients [37.3%] vs. 464 of 1188 patients [39.1%], P=0.40), in rates of 14 other secondary outcomes, or in rates of adverse events. Caloric intake was similar in the two groups, with the target intake not achieved in most patients. CONCLUSIONS We found no significant difference in 30-day mortality associated with the route of delivery of early nutritional support in critically ill adults. (Funded by the United Kingdom National Institute for Health Research; CALORIES Current Controlled Trials number, ISRCTN17386141.).

Intensive Care Society's APACHE II study in Britain and Ireland--I: Variations in case mix of adult admissions to general intensive care units and impact on outcome.

OBJECTIVES--To describe the extent of variation in the case mix of adult admissions to general intensive care units in Britain and Ireland and investigate the impact of such variation on outcome. DESIGN--Prospective, cohort study of consecutive admissions to intensive care units. SETTING--26 general intensive care units in Britain and Ireland. SUBJECTS--9099 admissions to the intensive care units studied. MAIN OUTCOME MEASURE--Death or survival at discharge before and after adjustment of case mix (age, history of chronic conditions, surgical status, diagnosis, and severity of illness) according to the APACHE II method. RESULTS--Important differences in case mix were found, with large variations between the units. Hospital mortality was significantly associated with most of the case mix factors investigated. CONCLUSIONS--Comparing crude death rates in hospital between intensive care units may be misleading indicators of performance. The collection of data on case mix needs to be standardised and differences in case mix adjusted for when comparing outcome between different intensive care units.

Comparison of Medical Admissions to Intensive Care Units in the United States and United Kingdom

RATIONALE The United States has seven times as many intensive care unit (ICU) beds per capita as the United Kingdom; the effect on care of critically ill patients is unknown. OBJECTIVES To compare medical ICU admissions in the United States and United Kingdom. METHODS Retrospective (2002-2004) cohort study of 172,785 ICU admissions (137 United States ICUs, Project IMPACT database; 160 United Kingdom ICUs, Case Mix Program) with patients followed until initial hospital discharge. MEASUREMENT AND MAIN RESULTS United Kingdom (vs. United States) admissions were less likely to be admitted directly from the emergency room (ER) (33.4% vs. 58%); had longer hospital stays before ICU admission (mean days 2.6 ± 8.2 vs. 1 ± 3.6); and fewer were greater than or equal to 85 years (3.2% vs. 7.8%). United Kingdom patients were more frequently mechanically ventilated within 24 hours after ICU admission (68% vs. 27.4%); were sicker (mean Acute Physiology Score 16.7 ± 7.6 vs. 10.6 ± 6.8); and had higher primary hospital mortality (38% vs. 15.9%; adjusted odds ratio, 1.73; 95% confidence interval, 1.50-1.99). There was no mortality difference for mechanically ventilated patients admitted from the ER (adjusted odds ratio, 1.09; 95% confidence interval, 0.89-1.33). Comparisons of hospital mortality were confounded by differences in case mix; hospital length of stay (United Kingdom median 10 d [interquartile range {IQR}, 3-24] vs. United States 6 d [IQR, 3-11]; and discharge practices (more United States patients were discharged to skilled care facilities [29% of survivors vs. 6% in the United Kingdom]). CONCLUSIONS Lower United Kingdom ICU bed availability is associated with fewer direct admissions from the ER, longer hospital stays before ICU admission, and higher severity of illness. Interpretation of between-country hospital outcomes is confounded by differences in case mix, processes of care, and discharge practices.

Do intensivist staffing patterns influence hospital mortality following ICU admission? A systematic review and meta-analyses.

Objective:To determine the effect of different intensivist staffing models on clinical outcomes for critically ill patients. Data Sources:A sensitive search of electronic databases and hand-search of major critical care journals and conference proceedings was completed in October 2012. Study Selection:Comparative observational studies examining intensivist staffing patterns and reporting hospital or ICU mortality were included. Data Extraction:Of 16,774 citations, 52 studies met the inclusion criteria. We used random-effects meta-analytic models unadjusted for case-mix or cluster effects and quantified between-study heterogeneity using I2. Study quality was assessed using the Newcastle-Ottawa Score for cohort studies. Data Synthesis:High-intensity staffing (i.e., transfer of care to an intensivist-led team or mandatory consultation of an intensivist), compared to low-intensity staffing, was associated with lower hospital mortality (risk ratio, 0.83; 95% CI, 0.70–0.99) and ICU mortality (pooled risk ratio, 0.81; 95% CI, 0.68–0.96). Significant reductions in hospital and ICU length of stay were seen (–0.17 d, 95% CI, –0.31 to –0.03 d and –0.38 d, 95% CI, –0.55 to –0.20 d, respectively). Within high-intensity staffing models, 24-hour in-hospital intensivist coverage, compared to daytime only coverage, did not improved hospital or ICU mortality (risk ratio, 0.97; 95% CI, 0.89–1.1 and risk ratio, 0.88; 95% CI, 0.70–1.1). The benefit of high-intensity staffing was concentrated in surgical (risk ratio, 0.84; 95% CI, 0.44–1.6) and combined medical-surgical (risk ratio, 0.76; 95% CI, 0.66–0.83) ICUs, as compared to medical (risk ratio, 1.1; 95% CI, 0.83–1.5) ICUs. The effect on hospital mortality varied throughout different decades; pooled risk ratios were 0.74 (95% CI, 0.63–0.87) from 1980 to 1989, 0.96 (95% CI, 0.69–1.3) from 1990 to 1999, 0.70 (95% CI, 0.54–0.90) from 2000 to 2009, and 1.2 (95% CI, 0.84–1.8) from 2010 to 2012. These findings were similar for ICU mortality. Conclusions:High-intensity staffing is associated with reduced ICU and hospital mortality. Within a high-intensity model, 24-hour in-hospital intensivist coverage did not reduce hospital, or ICU, mortality. Benefits seen in mortality were dependent on the type of ICU and decade of publication.