Glucocorticoid Sensitivity Is Highly Variable in Critically Ill Patients With Septic Shock and Is Associated With Disease Severity.

OBJECTIVES: To measure tissue glucocorticoid sensitivity in patients with septic shock and determine its relationship to standard measurements of adrenal function and of outcome. DESIGN: Prospective observational trial. SETTING: Teaching hospital ICU. SUBJECTS: Forty-one patients and 20 controls were studied. INTERVENTIONS: Glucocorticoid sensitivity was measured by in vitro suppression of cytokine production from lipopolysaccharide-stimulated leukocytes. MEASUREMENTS AND MAIN RESULTS: There was no significant difference between the groups in the relative suppression of cytokine production, although there was a greater range and variance in the patient data. Patients in the lowest quartile of glucocorticoid sensitivity had higher Acute Physiology and Chronic Health Evaluation II scores (25 [24-28] vs 20 [14-23]; p = 0.02) and a trend toward higher mortality (30% vs 0%; p = 0.2) compared to those in the highest. The mRNA expression of the ß variant of the glucocorticoid receptor and the 11-ß hydroxysteroid dehydrogenase 2 isozyme were significantly higher in patients compared to controls (8.6-fold, p = 0.002 and 10.1-fold, p = 0.0002, respectively). Changes in mRNA expression of these genes did not correlate with measurements of glucocorticoid sensitivity. CONCLUSIONS: Patients with septic shock and controls do not differ in their median glucocorticoid sensitivity. However, patients exhibited a greater variability in glucocorticoid responsiveness and had evidence of association between increased sickness sensitivity and reduced glucocorticoid sensitivity. Sensitivity to glucocorticoids did not appear to be mediated by changes in the expression of the ß variant of the glucocorticoid receptor or the 11-ß hydroxysteroid dehydrogenase 2 isozyme.

Early mobilization and recovery in mechanically ventilated patients in the ICU: a bi-national, multi-centre, prospective cohort study.

INTRODUCTION: The aim of this study was to investigate current mobilization practice, strength at ICU discharge and functional recovery at 6 months among mechanically ventilated ICU patients. METHOD: This was a prospective, multi-centre, cohort study conducted in twelve ICUs in Australia and New Zealand. Patients were previously functionally independent and expected to be ventilated for >48 hours. We measured mobilization during invasive ventilation, sedation depth using the Richmond Agitation and Sedation Scale (RASS), co-interventions, duration of mechanical ventilation, ICU-acquired weakness (ICUAW) at ICU discharge, mortality at day 90, and 6-month functional recovery including return to work. RESULTS: We studied 192 patients (mean age 58.1 ± 15.8 years; mean Acute Physiology and Chronic Health Evaluation (APACHE) (IQR) II score, 18.0 (14 to 24)). Mortality at day 90 was 26.6% (51/192). Over 1,351 study days, we collected information during 1,288 planned early mobilization episodes in patients on mechanical ventilation for the first 14 days or until extubation (whichever occurred first). We recorded the highest level of early mobilization. Despite the presence of dedicated physical therapy staff, no mobilization occurred in 1,079 (84%) of these episodes. Where mobilization occurred, the maximum levels of mobilization were exercises in bed (N = 94, 7%), standing at the bed side (N = 11, 0.9%) or walking (N = 26, 2%). On day three, all patients who were mobilized were mechanically ventilated via an endotracheal tube (N = 10), whereas by day five 50% of the patients mobilized were mechanically ventilated via a tracheostomy tube (N = 18). CONCLUSIONS: Early mobilization of patients receiving mechanical ventilation was uncommon. More than 50% of patients discharged from the ICU had developed ICU-acquired weakness, which was associated with death between ICU discharge and day-90. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01674608. Registered 14 August 2012.

Agreement in electrocardiogram interpretation in patients with septic shock.

OBJECTIVE: The reliability of electrocardiogram interpretation to diagnose myocardial ischemia in critically ill patients is unclear. In adults with septic shock, we assessed intra- and inter-rater agreement of electrocardiogram interpretation, and the effect of knowledge of troponin values on these interpretations. DESIGN: Prospective substudy of a randomized trial of vasopressin vs. norepinephrine in septic shock. SETTING: Nine Canadian intensive care units. PATIENTS: Adults with septic shock requiring at least 5 µg/min of norepinephrine for 6 hrs. INTERVENTIONS: Twelve-lead electrocardiograms were recorded before study drug, and 6 hrs, 2 days, and 4 days after study drug initiation. MEASUREMENTS: Two physician readers, blinded to patient data and group, independently interpreted electrocardiograms on three occasions (first two readings were blinded to patient data; third reading was unblinded to troponin). To calibrate and refine definitions, both readers initially reviewed 25 trial electrocardiograms representing normal to abnormal. Cohen's Kappa and the φ statistic were used to analyze intra- and inter-rater agreement. RESULTS: One hundred twenty-one patients (62.2 ± 16.5 yrs, Acute Physiology and Chronic Health Evaluation II 28.6 ± 7.7) had 373 electrocardiograms. Blinded to troponin, readers 1 and 2 interpreted 46.4% and 30.0% of electrocardiograms as normal, and 15.3% and 12.3% as ischemic, respectively. Intrarater agreement was moderate for overall ischemia (κ 0.54 and 0.58), moderate/good for "normal" (κ 0.69 and 0.55), fair to good for specific signs of ischemia (ST elevation, T inversion, and Q waves, reader 1 κ 0.40 to 0.69; reader 2 κ 0.56 to 0.70); and good/very good for atrial arrhythmias (κ 0.84 and 0.79) and bundle branch block (κ 0.88 and 0.79). Inter-rater agreement was fair for ischemia (κ 0.29), moderate for ST elevation (κ 0.48), T inversion (κ 0.52), and Q waves (κ 0.44), good for bundle branch block (κ 0.78), and very good for atrial arrhythmias (κ 0.83). Inter-rater agreement for ischemia improved from fair to moderate (κ 0.52, p = .028) when unblinded to troponin. CONCLUSIONS: In patients with septic shock, inter-rater agreement of electrocardiogram interpretation for myocardial ischemia was fair, and improved with troponin knowledge.

Fibrinogen in traumatic haemorrhage: A narrative review.

Haemorrhage in the setting of severe trauma is associated with significant morbidity and mortality. There is increasing awareness of the important role fibrinogen plays in traumatic haemorrhage. Fibrinogen levels fall precipitously in severe trauma and the resultant hypofibrinogenaemia is associated with poor outcomes. Hence, it has been postulated that early fibrinogen replacement in severe traumatic haemorrhage may improve outcomes, although, to date there is a paucity of high quality evidence to support this hypothesis. In addition there is controversy regarding the optimal method for fibrinogen supplementation. We review the current evidence regarding the role of fibrinogen in trauma, the rationale behind fibrinogen supplementation and discuss current research.

The ICU Mobility Scale Has Construct and Predictive Validity and Is Responsive. A Multicenter Observational Study.

RATIONALE: The ICU Mobility Scale (IMS) is a measure of mobility milestones in critically ill patients. OBJECTIVES: This study aimed to determine the validity and responsiveness of the IMS from a prospective cohort study of adults admitted to the intensive care unit (ICU). METHODS: Construct and predictive validity were assessed by comparing IMS values at ICU discharge in 192 patients to other variables using Spearman rank correlation coefficient, Mann-Whitney U tests, and logistic regression. Responsiveness was assessed using change over time, effect size, floor and ceiling effects, and percentage of patients showing change. MEASUREMENTS AND MAIN RESULTS: The IMS at ICU discharge demonstrated a moderate correlation with muscle strength (r = 0.64, P < 0.001). There was a significant difference between the IMS at ICU discharge in patients with ICU-acquired weakness (median, 4.0; interquartile range, 3.0-5.0) compared with patients without (median, 8.0; interquartile range, 5.0-8.0; P < 0.001). Increasing IMS values at ICU discharge were associated with survival to 90 days (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.14-1.66) and discharge home (OR, 1.16; 95% CI, 1.02-1.32) but not with return to work at 6 months (OR, 1.09; 95% CI, 0.92-1.28). The IMS was responsive with a significant change from study enrollment to ICU discharge (d = 0.8, P < 0.001), with IMS values increasing in 86% of survivors during ICU admission. No substantial floor (14% scored 0) or ceiling (4% scored 10) effects were present at ICU discharge. CONCLUSIONS: Our findings support the validity and responsiveness of the IMS as a measure of mobility in the ICU.

Feasibility and inter-rater reliability of the ICU Mobility Scale.

OBJECTIVES: The objectives of this study were to develop a scale for measuring the highest level of mobility in adult ICU patients and to assess its feasibility and inter-rater reliability. BACKGROUND: Growing evidence supports the feasibility, safety and efficacy of early mobilization in the intensive care unit (ICU). However, there are no adequately validated tools to quickly, easily, and reliably describe the mobility milestones of adult patients in ICU. Identifying or developing such a tool is a priority for evaluating mobility and rehabilitation activities for research and clinical care purposes. METHODS: This study was performed at two ICUs in Australia. Thirty ICU nursing, and physiotherapy staff assessed the feasibility of the 'ICU Mobility Scale' (IMS) using a 10-item questionnaire. The inter-rater reliability of the IMS was assessed by 2 junior physical therapists, 2 senior physical therapists, and 16 nursing staff in 100 consecutive medical, surgical or trauma ICU patients. RESULTS: An 11 point IMS scale was developed based on multidisciplinary input. Participating clinicians reported that the scale was clear, with 95% of respondents reporting that it took <1 min to complete. The junior and senior physical therapists showed the highest inter-rater reliability with a weighted Kappa (95% confidence interval) of 0.83 (0.76-0.90), while the senior physical therapists and nurses and the junior physical therapists and nurses had a weighted Kappa of 0.72 (0.61-0.83) and 0.69 (0.56-0.81) respectively. CONCLUSION: The IMS is a feasible tool with strong inter-rater reliability for measuring the maximum level of mobility of adult patients in the ICU.

Effects of saline or albumin resuscitation on standard coagulation tests.

AIMS: To explore whether fluid resuscitation with normal saline or 4% albumin is associated with differential changes in routine clinical coagulation tests. DESIGN: Substudy from a large double-blind randomised controlled trial, the SAFE (Saline versus Albumin Fluid Evaluation) study. SETTING: Three general intensive care units. PATIENTS: Cohort of 687 critically ill patients. INTERVENTION: We randomly allocated patients to receive either 4% human albumin or normal saline for fluid resuscitation, and collected demographic and haematological data. METHODS AND MAIN RESULTS: Albumin was administered to 338 patients and saline to 349. At baseline, the two groups had similar mean activated partial thromboplastin time (APTT) of 37.2 s (albumin) v 39.1 s (saline); mean international normalised ratio (INR) of 1.38 v 1.34, and mean platelet count of 244 x 10(9)/L v 249 x 10(9)/L. After randomisation, during the first day of treatment, the APTT in the albumin group was prolonged by a mean of 2.7 s, but shortened slightly by a mean of -0.9 s in the saline group. The INR did not change in either group, while the platelet count decreased transiently in both groups. Using multivariate analysis of covariance to account for baseline coagulation status, albumin fluid resuscitation (P = 0.01) and a greater overall volume of resuscitation (P = 0.03) were independently associated with prolongation of APTT during the first day. CONCLUSIONS: Administration of albumin or of larger fluid volumes is associated with a prolongation of APTT. In ICU patients, the choice and amount of resuscitation fluid may affect a routinely used coagulation test.