Simon Finfer

Introduction of the medical emergency team (MET) system: a cluster-randomised controlled trial.

BACKGROUND Patients with cardiac arrests or who die in general wards have often received delayed or inadequate care. We investigated whether the medical emergency team (MET) system could reduce the incidence of cardiac arrests, unplanned admissions to intensive care units (ICU), and deaths. METHODS We randomised 23 hospitals in Australia to continue functioning as usual (n=11) or to introduce a MET system (n=12). The primary outcome was the composite of cardiac arrest, unexpected death, or unplanned ICU admission during the 6-month study period after MET activation. Analysis was by intention to treat. FINDINGS Introduction of the MET increased the overall calling incidence for an emergency team (3.1 vs 8.7 per 1000 admissions, p=0.0001). The MET was called to 30% of patients who fulfilled the calling criteria and who were subsequently admitted to the ICU. During the study, we recorded similar incidence of the composite primary outcome in the control and MET hospitals (5.86 vs 5.31 per 1000 admissions, p=0.640), as well as of the individual secondary outcomes (cardiac arrests, 1.64 vs 1.31, p=0.736; unplanned ICU admissions, 4.68 vs 4.19, p=0.599; and unexpected deaths, 1.18 vs 1.06, p=0.752). A reduction in the rate of cardiac arrests (p=0.003) and unexpected deaths (p=0.01) was seen from baseline to the study period for both groups combined. INTERPRETATION The MET system greatly increases emergency team calling, but does not substantially affect the incidence of cardiac arrest, unplanned ICU admissions, or unexpected death.

Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care

BACKGROUND The safety and efficacy of hydroxyethyl starch (HES) for fluid resuscitation have not been fully evaluated, and adverse effects of HES on survival and renal function have been reported. METHODS We randomly assigned 7000 patients who had been admitted to an intensive care unit (ICU) in a 1:1 ratio to receive either 6% HES with a molecular weight of 130 kD and a molar substitution ratio of 0.4 (130/0.4, Voluven) in 0.9% sodium chloride or 0.9% sodium chloride (saline) for all fluid resuscitation until ICU discharge, death, or 90 days after randomization. The primary outcome was death within 90 days. Secondary outcomes included acute kidney injury and failure and treatment with renal-replacement therapy. RESULTS A total of 597 of 3315 patients (18.0%) in the HES group and 566 of 3336 (17.0%) in the saline group died (relative risk in the HES group, 1.06; 95% confidence interval [CI], 0.96 to 1.18; P=0.26). There was no significant difference in mortality in six predefined subgroups. Renal-replacement therapy was used in 235 of 3352 patients (7.0%) in the HES group and 196 of 3375 (5.8%) in the saline group (relative risk, 1.21; 95% CI, 1.00 to 1.45; P=0.04). In the HES and saline groups, renal injury occurred in 34.6% and 38.0% of patients, respectively (P=0.005), and renal failure occurred in 10.4% and 9.2% of patients, respectively (P=0.12). HES was associated with significantly more adverse events (5.3% vs. 2.8%, P<0.001). CONCLUSIONS In patients in the ICU, there was no significant difference in 90-day mortality between patients resuscitated with 6% HES (130/0.4) or saline. However, more patients who received resuscitation with HES were treated with renal-replacement therapy. (Funded by the National Health and Medical Research Council of Australia and others; CHEST ClinicalTrials.gov number, NCT00935168.).

Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients

BACKGROUND The optimal intensity of continuous renal-replacement therapy remains unclear. We conducted a multicenter, randomized trial to compare the effect of this therapy, delivered at two different levels of intensity, on 90-day mortality among critically ill patients with acute kidney injury. METHODS We randomly assigned critically ill adults with acute kidney injury to continuous renal-replacement therapy in the form of postdilution continuous venovenous hemodiafiltration with an effluent flow of either 40 ml per kilogram of body weight per hour (higher intensity) or 25 ml per kilogram per hour (lower intensity). The primary outcome measure was death within 90 days after randomization. RESULTS Of the 1508 enrolled patients, 747 were randomly assigned to higher-intensity therapy, and 761 to lower-intensity therapy with continuous venovenous hemodiafiltration. Data on primary outcomes were available for 1464 patients (97.1%): 721 in the higher-intensity group and 743 in the lower-intensity group. The two study groups had similar baseline characteristics and received the study treatment for an average of 6.3 and 5.9 days, respectively (P=0.35). At 90 days after randomization, 322 deaths had occurred in the higher-intensity group and 332 deaths in the lower-intensity group, for a mortality of 44.7% in each group (odds ratio, 1.00; 95% confidence interval [CI], 0.81 to 1.23; P=0.99). At 90 days, 6.8% of survivors in the higher-intensity group (27 of 399), as compared with 4.4% of survivors in the lower-intensity group (18 of 411), were still receiving renal-replacement therapy (odds ratio, 1.59; 95% CI, 0.86 to 2.92; P=0.14). Hypophosphatemia was more common in the higher-intensity group than in the lower-intensity group (65% vs. 54%, P<0.001). CONCLUSIONS In critically ill patients with acute kidney injury, treatment with higher-intensity continuous renal-replacement therapy did not reduce mortality at 90 days. (ClinicalTrials.gov number, NCT00221013.)

Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data

Background: Hyperglycemia is associated with increased mortality in critically ill patients. Randomized trials of intensive insulin therapy have reported inconsistent effects on mortality and increased rates of severe hypoglycemia. We conducted a meta-analysis to update the totality of evidence regarding the influence of intensive insulin therapy compared with conventional insulin therapy on mortality and severe hypoglycemia in the intensive care unit (ICU). Methods: We conducted searches of electronic databases, abstracts from scientific conferences and bibliographies of relevant articles. We included published randomized controlled trials conducted in the ICU that directly compared intensive insulin therapy with conventional glucose management and that documented mortality. We included in our meta-analysis the data from the recent NICE-SUGAR (Normoglycemia in Intensive Care Evaluation — Survival Using Glucose Algorithm Regulation) study. Results: We included 26 trials involving a total of 13 567 patients in our meta-analysis. Among the 26 trials that reported mortality, the pooled relative risk (RR) of death with intensive insulin therapy compared with conventional therapy was 0.93 (95% confidence interval [CI] 0.83–1.04). Among the 14 trials that reported hypoglycemia, the pooled RR with intensive insulin therapy was 6.0 (95% CI 4.5–8.0). The ICU setting was a contributing factor, with patients in surgical ICUs appearing to benefit from intensive insulin therapy (RR 0.63, 95% CI 0.44–0.91); patients in the other ICU settings did not (medical ICU: RR 1.0, 95% CI 0.78–1.28; mixed ICU: RR 0.99, 95% CI 0.86–1.12). The different targets of intensive insulin therapy (glucose level ≤ 6.1 mmol/L v. ≤ 8.3 mmol/L) did not influence either mortality or risk of hypoglycemia. Interpretation: Intensive insulin therapy significantly increased the risk of hypoglycemia and conferred no overall mortality benefit among critically ill patients. However, this therapy may be beneficial to patients admitted to a surgical ICU.

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.

Drotrecogin Alfa (Activated) in Adults with Septic Shock

BACKGROUND There have been conflicting reports on the efficacy of recombinant human activated protein C, or drotrecogin alfa (activated) (DrotAA), for the treatment of patients with septic shock. METHODS In this randomized, double-blind, placebo-controlled, multicenter trial, we assigned 1697 patients with infection, systemic inflammation, and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours to receive either DrotAA (at a dose of 24 μg per kilogram of body weight per hour) or placebo for 96 hours. The primary outcome was death from any cause 28 days after randomization. RESULTS At 28 days, 223 of 846 patients (26.4%) in the DrotAA group and 202 of 834 (24.2%) in the placebo group had died (relative risk in the DrotAA group, 1.09; 95% confidence interval [CI], 0.92 to 1.28; P=0.31). At 90 days, 287 of 842 patients (34.1%) in the DrotAA group and 269 of 822 (32.7%) in the placebo group had died (relative risk, 1.04; 95% CI, 0.90 to 1.19; P=0.56). Among patients with severe protein C deficiency at baseline, 98 of 342 (28.7%) in the DrotAA group had died at 28 days, as compared with 102 of 331 (30.8%) in the placebo group (risk ratio, 0.93; 95% CI, 0.74 to 1.17; P=0.54). Similarly, rates of death at 28 and 90 days were not significantly different in other predefined subgroups, including patients at increased risk for death. Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group (P=0.81). CONCLUSIONS DrotAA did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock. (Funded by Eli Lilly; PROWESS-SHOCK ClinicalTrials.gov number, NCT00604214.).

Resuscitation fluid use in critically ill adults: an international cross-sectional study in 391 intensive care units

IntroductionRecent evidence suggests that choice of fluid used for resuscitation may influence mortality in critically ill patients.MethodsWe conducted a cross-sectional study in 391 intensive care units across 25 countries to describe the types of fluids administered during resuscitation episodes. We used generalized estimating equations to examine the association between patient, prescriber and geographic factors and the type of fluid administered (classified as crystalloid, colloid or blood products).ResultsDuring the 24-hour study period, 1,955 of 5,274 (37.1%) patients received resuscitation fluid during 4,488 resuscitation episodes. The main indications for administering crystalloid or colloid were impaired perfusion (1,526/3,419 (44.6%) of episodes), or to correct abnormal vital signs (1,189/3,419 (34.8%)). Overall, colloid was administered to more patients (1,234 (23.4%) versus 782 (14.8%)) and during more episodes (2,173 (48.4%) versus 1,468 (32.7%)) than crystalloid. After adjusting for patient and prescriber characteristics, practice varied significantly between countries with country being a strong independent determinant of the type of fluid prescribed. Compared to Canada where crystalloid, colloid and blood products were administered in 35.5%, 40.6% and 28.3% of resuscitation episodes respectively, odds ratios for the prescription of crystalloid in China, Great Britain and New Zealand were 0.46 (95% confidence interval (CI) 0.30 to 0.69), 0.18 (0.10 to 0.32) and 3.43 (1.71 to 6.84) respectively; odds ratios for the prescription of colloid in China, Great Britain and New Zealand were 1.72 (1.20 to 2.47), 4.72 (2.99 to 7.44) and 0.39 (0.21 to 0.74) respectively. In contrast, choice of fluid was not influenced by measures of illness severity (for example, Acute Physiology and Chronic Health Evaluation (APACHE) II score).ConclusionsAdministration of resuscitation fluid is a common intervention in intensive care units and choice of fluid varies markedly between countries. Although colloid solutions are more expensive and may possibly be harmful in some patients, they were administered to more patients and during more resuscitation episodes than crystalloids were.

Epidemiology and 12-month outcomes from traumatic brain injury in Australia and New Zealand

BACKGROUND An epidemiologic profile of traumatic brain injury (TBI) in Australia and New Zealand was obtained following the publication of international evidence-based guidelines. METHODS Adult patients with TBI admitted to the intensive care units (ICU) of major trauma centers were studied in a 6-month prospective inception cohort study. Data including mechanisms of injury, prehospital interventions, secondary insults, operative and intensive care management, and outcome assessments 12-months postinjury were collected. RESULTS There were 635 patients recruited from 16 centers. The mean (+/-SD) age was 41.6 years +/- 19.6 years; 74.2% were men; 61.4% were due to vehicular trauma, 24.9% were falls in elderly patients, and 57.2% had severe TBI (Glasgow Coma Scale score </=8). Secondary brain insults were recorded in 28.5% and 34.8% underwent neurosurgical procedures before ICU admission. There was concordance with TBI and ICU practice guidelines, although intracranial pressure monitoring was used in 44.5% patients with severe TBI. Twelve-month mortality was 26.9% in all patients and 35.1% in patients with severe TBI. Favorable outcomes at 12 months were recorded in 58.8% of all patients and in 48.5% of patients with severe TBI. CONCLUSIONS In Australia and New Zealand, mortality and favorable neurologic outcomes after TBI were similar to published data before the advent of evidence-based guidelines. A high incidence of prehospital secondary brain insults and an ageing population may have contributed to these outcomes. Strategies to improve outcomes from TBI should be directed at preventive public health strategies and interventions to minimize secondary brain injuries in the prehospital period.

The role of albumin as a resuscitation fluid for patients with sepsis: A systematic review and meta-analysis*

Objective:To assess whether resuscitation with albumin-containing solutions, compared with other fluids, is associated with lower mortality in patients with sepsis. Data Sources:MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases, the metaRegister of Controlled Trials, and the Medical Editors Trial Amnesty Register. Study Selection:Prospective randomized clinical trials of fluid resuscitation with albumin-containing solutions compared with other fluid resuscitation regimens, which included a population or subgroup of participants with sepsis, were included. Data Extraction:Assessment of the validity of included studies and data extraction were conducted independently by two authors. Data Synthesis:For the primary analysis, the effect of albumin-containing solutions on all-cause mortality was assessed by using a fixed-effect meta-analysis. Results:Seventeen studies that randomized 1977 participants were included in the meta-analysis. There were eight studies that included only patients with sepsis and nine where patients with sepsis were a subgroup of the study population. There was no evidence of heterogeneity, I2 = 0%. The use of albumin for resuscitation of patients with sepsis was associated with a reduction in mortality with the pooled estimate of the odds ratio of 0.82 (95% confidence limits 0.67–1.0, p = .047). Conclusions:In this meta-analysis, the use of albumin-containing solutions for the resuscitation of patients with sepsis was associated with lower mortality compared with other fluid resuscitation regimens. Until the results of ongoing randomized controlled trials are known, clinicians should consider the use of albumin-containing solutions for the resuscitation of patients with sepsis.

Sedation and Delirium in the Intensive Care Unit

Patients in ICUs often require pain relief and sedation to treat both the underlying medical condition and the unpleasantness associated with being in an ICU. This review provides guidance on the identification and treatment of delirium and sedation.