Geoffrey Dobb

Intravenous flecainide versus Amiedarone fof recent-onset atrial fibrillation

In a randomized, double-blind, controlled study of 98 patients with atrial fibrillation (AF) (present for > or = 30 minutes, < or = 72 hours, and a ventricular response of > or = 100 beats/min), intravenous flecainide (2 mg/kg, maximum 150 mg) was compared with intravenous amiodarone (7 mg/kg) and placebo. Exclusion criteria included significant left ventricular dysfunction, inotrope dependence, recent antiarrhythmic therapy, hypokalemia, and pacemaker dependence. Reversion to stable sinus rhythm within 2 hours of starting medication was considered likely to be due to drug effect. Twenty of 34 patients (59%) given flecainide, 11 of 32 (34%) given amiodarone, and 7 of 32 (22%) given placebo reverted to stable sinus rhythm in < or = 2 hours after starting medication (chi-square 9.87, p = 0.007). More patients reverted to stable rhythm with flecainide than with placebo (p = 0.005; odds ratio 5.1, 95% confidence interval 1.54 to 17.5). There was no significant difference between amiodarone and placebo or between flecainide and amiodarone. However, after 8 hours there were no significant differences in reversion between the treatment groups: flecainide (n = 23, 68%), amiodarone (n = 19, 59%), and placebo (n = 18, 56%). Amiodarone promptly reduced the ventricular rate, and this effect was maintained for 8 hours in those whose reversion to stable sinus rhythm was unsuccessful: flecainide was no more effective than placebo in controlling ventricular rate. Adverse effects were not significantly different in the 3 groups. Thus, intravenous flecainide results in earlier reversion of AF than does intravenous amiodarone or placebo. Amiodarone, although less effective in reverting AF, slows the rapid ventricular response.(ABSTRACT TRUNCATED AT 250 WORDS)

Determinants of long-term survival after intensive care

Objective:To identify prognostic determinants of long-term survival for patients treated in intensive care units (ICUs) who survived to hospital discharge. Design:An ICU clinical cohort linked to state-wide hospital records and death registers. Setting and Patients:Adult patients admitted to a 22-bed ICU at a major teaching hospital in Perth, Western Australia, between 1987 and 2002 who survived to hospital discharge (n = 19,921) were followed-up until December 31, 2003. Measurements:The main outcome measures are crude and adjusted survival. Main Results:The risk of death in the first year after hospital discharge was high for patients who survived the ICU compared with the general population (standardized mortality rate [SMR] at 1 yr = 2.90, 95% confidence interval [CI] 2.73–3.08) and remained higher than the general population for every year during 15 yrs of follow up (SMR at 15 yrs = 2.01, 95% CI 1.64–2.46). Factors that were independently associated with survival during the first year were older age (hazard ratio [HR] = 4.09; 95% CI 3.20–5.23), severe comorbidity (HR = 5.23; 95% CI 4.25–6.43), ICU diagnostic group (HR range 2.20 to 8.95), new malignancy (HR = 4.60; 95% CI 3.68–5.76), high acute physiology score on admission (HR = 1.55; 95% CI 1.23–1.96), and peak number of organ failures (HR = 1.51; 95% CI 1.11–2.04). All of these factors were independently associated with subsequent survival for those patients who were alive 1 yr after discharge from the hospital with the addition of male gender (HR = 1.17; 95% CI 1.10–1.25) and prolonged length of stay in ICU (HR = 1.42; 95% CI 1.29–1.55). Conclusions:Patients who survived an admission to the ICU have worse survival than the general population for at least 15 yrs. The factors that determine long-term survival include age, comorbidity, and primary diagnosis. Severity of illness was also associated with long-term survival and this suggests that an episode of critical illness, or its treatment, may shorten life-expectancy.

Promoting Global Research Excellence in Severe Sepsis (PROGRESS): Lessons from an International Sepsis Registry

Background:The PROGRESS Registry (Promoting Global Research Excellence in Severe Sepsis) was designed to provide comparative data reflecting everyday clinical practice, thereby allowing participating institutions to explore and benchmark medical interventions in severe sepsis.Materials and Methods:PROGRESS was an international, noninterventional, prospective, observational registry collecting data that describe the management and outcomes of severe sepsis patients in intensive care units (ICUs). Patients were enrolled who had been diagnosed with severe sepsis (suspected or proven infection and ≥ 1 acute sepsis-induced organ dysfunction) at the participating institutions, where de-identified data were entered directly into a secured website. PROGRESS was governed by an independent international medical advisory board.Results:PROGRESS took place in 276 ICUs in 37 countries, and 12,881 patients were identified as having severe sepsis. There was considerable variation among countries in enrollment levels, provision of standard treatment and supportive therapies, and ICU and hospital outcomes. Eight countries accounted for 65.2% of the enrolled patients. Males (59.3%) and Caucasian (48.6%) patients predominated the patient cohort. Diagnosis of severe sepsis was prior to ICU admission in 45.7% of patients, at ICU admission in 29.1% of patients, and after ICU admission in the remainder. Globally, ICU and hospital mortality rates were 39.2% and 49.6%, respectively. The mean length of ICU and hospital stay was 14.6 days and 28.2 days, respectively.Conclusions:The PROGRESS international sepsis registry demonstrates that a large web-based sepsis registry is feasible. Wide variations in outcomes and use of sepsis therapies were observed between countries. These results also suggest that additional opportunities exist across countries to improve severe sepsis outcomes.

Comparison of transthoracic electrical impedance and thermodilution methods for measuring cardiac output.

Cardiac output was measured 120 times in 27 critically ill patients using the thermodilution and transthoracic electrical impedance methods. Both the minimum and mean values for the distance between the inner electrodes, and a variety of values for the resistivity of blood (p) were substituted in the Kubiceks empiric formula for calculating cardiac output by transthoracic electrical impedance. Using the mean distance between the inner electrodes and a p-value of 150 ohmċcm gave the best agreement between the methods (mean difference 0.17 ± 2.4 L/min). Ventilation alone or with positive end-expiratory pressure did not significantly affect the bias of the estimate, but both affected its precision when compared with measurements in spontaneously breathing patients (SD of mean difference 2.4 and 3.2 L/min, respectively, vs. 1.5 L/min). The pulmonary artery wedge pressure was significantly higher in patients with an abnormal diastolic impedance waveform (zero-wave), but there was no relationship between wedge pressure and base impedance per unit length between the measuring electrodes.

Magnesium in cardiac arrest (the magic trial).

The prognosis of out of hospital cardiac arrest (OHCA) is dismal. Recent reports indicate that high dose magnesium may improve survival. A prospective randomized double blind placebo controlled trial was conducted at the emergency department (ED) of Royal Perth Hospital, a University teaching hospital. Patients with OHCA of cardiac origin received either 5 g MgSO4 or placebo as first line drug therapy. The remainder of their management was standard advanced cardiac life support (ACLS). Study endpoints were: (1) ECG rhythm 2 min after the trial drug; (2) return of spontaneous circulation; (3) survival to leave the ED; (4) survival to leave intensive care; and (5) survival to hospital discharge. Of 67 patients enrolled, 31 received magnesium and 36 placebo. There were no significant differences between groups for all criteria, except that there were significantly more arrests witnessed after arrival of EMS personnel in the magnesium group (11 or 35% vs 4 or 11%). Return of spontaneous circulation occurred in seven (23%) patients receiving magnesium and eight (22%) placebo. Four patients in each group survived to leave the ED and one from the magnesium group survived to hospital discharge. There were no survivors in the placebo group. In this study, the use of high dose magnesium as first line drug therapy for OHCA was not associated with a significantly improved survival. Early defibrillation remains the single most important treatment for ventricular fibrillation (VF). Further studies are required to evaluate the role of magnesium in cardiac and cerebral resuscitation.

Diarrhoea during enteral feeding in the critically ill: a comparison of feeds with and without fibre.

This randomised double-blind study examined the frequency of diarrhoea in intensive care unit patients given a fibre-containing feed, Enrich, and a fibre-free feed, Ensure. A daily ‘diarrhoea score’ was calculated from the frequency, volume and consistency of the stools. A score greater than 12 indicated diarrhoea, and greater than 50 severe diarrhoea. Ninety one patients met the criteria for participation: Enrich 45, Ensure 46. The groups were similar in age, sex ratio, feed volume, antibiotic usage, upper gastro-intestinal bleeding prophylaxis and plasma albumin concentrations. Diarrhoea occurred in 16 patients given Enrich and 13 given Ensure, severe diarrhoea affecting 5 and 9 respectively (NS). Forty seven of 343 (14%) Enrich feeding days and 51 of 342 (15%) Ensure feeding days were complicated by diarrhoea — severe diarrhoea: 8 and 12 feeding days (NS). We conclude soy polysaccharide (21 g/L) did not reduce diarrhoea in intensive care unit patients given enteral feeds.

a systematic review and meta-analysis of clinical trials of thyroid hormone administration to brain dead potential organ donors*

Objectives: To review all published clinical studies of thyroid hormone administration to brain-dead potential organ donors. Methods: A search of PubMed using multiple search terms retrieved 401 publications including 35 original reports describing administration of thyroid hormone to brain-dead potential organ donors. Detailed review of the 35 original reports led to identification of two additional publications not retrieved in the original search. The 37 original publications reported findings from 16 separate case series or retrospective audits and seven randomized controlled trials, four of which were placebo-controlled. Meta-analysis was restricted to the four placebo-controlled randomized controlled trials. Results: Whereas all case series and retrospective audits reported a beneficial effect of thyroid hormone administration, all seven randomized controlled trials reported no benefit of thyroid hormone administration either alone or in combination with other hormonal therapies. In four placebo-controlled trials including 209 donors, administration of thyroid hormone (n = 108) compared with placebo (n = 101) had no significant effect on donor cardiac index (pooled mean difference, 0.15 L/min/m2; 95% confidence interval –0.18 to 0.48). The major limitation of the case series and retrospective audits was the lack of consideration of uncontrolled variables that confound interpretation of the results. A limitation of the randomized controlled trials was that the proportion of donors who were hemodynamically unstable or marginal in other ways was too small to exclude a benefit of thyroid hormone in this subgroup. Conclusions: The findings of this systematic review do not support a role for routine administration of thyroid hormone in the brain-dead potential organ donor. Existing recommendations regarding the use of thyroid hormone in marginal donors are based on low-level evidence.

Global utilization of low-dose corticosteroids in severe sepsis and septic shock: a report from the PROGRESS registry

IntroductionThe benefits and use of low-dose corticosteroids (LDCs) in severe sepsis and septic shock remain controversial. Surviving sepsis campaign guidelines suggest LDC use for septic shock patients poorly responsive to fluid resuscitation and vasopressor therapy. Their use is suspected to be wide-spread, but paucity of data regarding global practice exists. The purpose of this study was to compare baseline characteristics and clinical outcomes of patients treated or not treated with LDC from the international PROGRESS (PROmoting Global Research Excellence in Severe Sepsis) cohort study of severe sepsis.MethodsPatients enrolled in the PROGRESS registry were evaluated for use of vasopressor and LDC (equivalent or lesser potency to hydrocortisone 50 mg six-hourly plus 50 μg 9-alpha-fludrocortisone) for treatment of severe sepsis at any time in intensive care units (ICUs). Baseline characteristics and hospital mortality were analyzed, and logistic regression techniques used to develop propensity score and outcome models adjusted for baseline imbalances between groups.ResultsA total of 8,968 patients with severe sepsis and sufficient data for analysis were studied. A total of 79.8% (7,160/8,968) of patients received vasopressors, and 34.0% (3,051/8,968) of patients received LDC. Regional use of LDC was highest in Europe (51.1%) and lowest in Asia (21.6%). Country use was highest in Brazil (62.9%) and lowest in Malaysia (9.0%). A total of 14.2% of patients on LDC were not receiving any vasopressor therapy. LDC patients were older, had more co-morbidities and higher disease severity scores. Patients receiving LDC spent longer in ICU than patients who did not (median of 12 versus 8 days; P <0.001). Overall hospital mortality rates were greater in the LDC than in the non-LDC group (58.0% versus 43.0%; P <0.001). After adjusting for baseline imbalances, in all mortality models (with vasopressor use), a consistent association remained between LDC and hospital mortality (odds ratios varying from 1.30 to 1.47).ConclusionsWidespread use of LDC for the treatment of severe sepsis with significant regional and country variation exists. In this study, 14.2% of patients received LDC despite the absence of evidence of shock. Hospital mortality was higher in the LDC group and remained higher after adjustment for key determinates of mortality.

A comparison of admission and worst 24-hour Acute Physiology and Chronic Health Evaluation II scores in predicting hospital mortality: a retrospective cohort study

IntroductionThe Acute Physiology and Chronic Health Evaluation (APACHE) II score is widely used in the intensive care unit (ICU) as a scoring system for research and clinical audit purposes. Physiological data for calculation of the APACHE II score are derived from the worst values in the first 24 hours after admission to the ICU. The collection of physiological data on admission only is probably logistically easier, and this approach is used by some ICUs. This study compares the performance of APACHE II scores calculated using admission data with those obtained from the worst values in the first 24 hours.Materials and MethodsThis was a retrospective cohort study using prospectively collected data from a tertiary ICU. There were no missing physiological data and follow-up for mortality was available for all patients in the database. The admission and the worst 24-hour physiological variables were used to generate the admission APACHE II score and the worst 24-hour APACHE II score, and the corresponding predicted mortality, respectively.ResultsThere were 11,107 noncardiac surgery ICU admissions during 11 years from 1 January 1993 to 31 December 2003. The mean admission and the worst 24-hour APACHE II score were 12.7 and 15.4, and the derived predicted mortality estimates were 15.5% and 19.3%, respectively. The actual hospital mortality was 16.3%. The overall discrimination ability, as measured by the area under the receiver operating characteristic curve, of the admission APACHE II model (83.8%, 95% confidence interval = 82.9–84.7) and the worst 24-hour APACHE II model (84.6%, 95% confidence interval = 83.7–85.5) was not significantly different (P = 1.00).ConclusionSubstitution of the worst 24-hour physiological variables with the admission physiological variables to calculate the admission APACHE II score maintains the overall discrimination ability of the traditional APACHE II model. The admission APACHE II model represents a potential alternative model to the worst 24-hour APACHE II model in critically ill nontrauma patients.

The effect of comorbidities on risk of intensive care readmission during the same hospitalization: A linked data cohort study

PURPOSE The aim of this study is to assess the effect of comorbidities on risk of readmission to an intensive care unit (ICU) and the excess hospital mortality associated with ICU readmissions. MATERIALS AND METHODS A cohort study used clinical data from a 22-bed multidisciplinary ICU in a university hospital and comorbidity data from the Western Australian hospital morbidity database. RESULTS From 16,926 consecutive ICU admissions between 1987 and 2002, and 654 (3.9%) of these patients were readmitted to ICU readmissions within the same hospitalization. Patients with readmission were older, more likely to be originally admitted from the operating theatre or hospital ward, had a higher Acute Physiology and Chronic Health Evaluation (APACHE)-predicted mortality, and had more comorbidities when compared with patients without readmission. The number of Charlson comorbidities was significantly associated with late readmission (>72 hours) but not early readmission (<or=72 hours) in the multivariate analysis. Both early and late ICU readmissions were associated with an increased risk of hospital mortality (odds ratio, 1.68; 95% confidence interval, 1.18-2.39; P = .004; odds ratio, 1.45; 95% confidence interval, 1.05-1.99; P = .022, respectively) after adjusting for age, admission source, type of admission, the APACHE-predicted mortality, and the number of Charlson comorbidities and APACHE chronic health conditions. CONCLUSIONS Comorbidity was a risk factor for late ICU readmission. Comorbidities could not account for the excess mortality associated with ICU readmissions.