Hani Tamim

Intensive versus conventional insulin therapy: A randomized controlled trial in medical and surgical critically ill patients

Objective:The role of intensive insulin therapy in medical surgical intensive care patients remains unclear. The objective of this study was to examine the effect of intensive insulin therapy on mortality in medical surgical intensive care unit patients. Design:Randomized controlled trial. Settings:Tertiary care intensive care unit. Patients:Medical surgical intensive care unit patients with admission blood glucose of >6.1 mmol/L or 110 mg/dL. Intervention:A total of 523 patients were randomly assigned to receive intensive insulin therapy (target blood glucose 4.4–6.1 mmol/L or 80–110 mg/dL) or conventional insulin therapy (target blood glucose 10–11.1 mmol/L or 180–200 mg/dL). Measurements and Main Outcomes:The primary end point was intensive care unit mortality. Secondary end points included hospital mortality, intensive care unit and hospital length of stay, mechanical ventilation duration, the need for renal replacement therapy and packed red blood cells transfusion, and the rates of intensive care unit acquired infections as well as the rate of hypoglycemia (defined as blood glucose ≤2.2 mmol/L or 40 mg/dL). There was no significant difference in intensive care unit mortality between the intensive insulin therapy and conventional insulin therapy groups (13.5% vs. 17.1%, p = 0.30). After adjustment for baseline characteristics, intensive insulin therapy was not associated with mortality difference (adjusted hazard ratio 1.09, 95% confidence interval 0.70–1.72). Hypoglycemia occurred more frequently with intensive insulin therapy (28.6% vs. 3.1% of patients; p < 0.0001 or 6.8/100 treatment days vs. 0.4/100 treatment days; p < 0.0001). There was no difference between the intensive insulin therapy and conventional insulin therapy in any of the other secondary end points. Conclusions:Intensive insulin therapy was not associated with improved survival among medical surgical intensive care unit patients and was associated with increased occurrence of hypoglycemia. Based on these results, we do not advocate universal application of intensive insulin therapy in intensive care unit patients. Trial Registration:Current Controlled Trials registry (ISRCTN07413772) http://www.controlled-trials.com/ISRCTN07413772/07413772; 2005.

Permissive underfeeding and intensive insulin therapy in critically ill patients: a randomized controlled trial

BACKGROUND Nutritional support has been recognized as an essential part of intensive care unit management. However, the appropriate caloric intake for critically ill patients remains ill defined. OBJECTIVE We examined the effect of permissive underfeeding compared with that of target feeding and of intensive insulin therapy (IIT) compared with that of conventional insulin therapy (CIT) on the outcomes of critically ill patients. DESIGN This study had a 2 × 2 factorial, randomized, controlled design. Eligible patients were randomly assigned to permissive underfeeding or target feeding groups (caloric goal: 60-70% compared with 90-100% of calculated requirement, respectively) with either IIT or CIT (target blood glucose: 4.4-6.1 compared with 10-11.1 mmol/L, respectively). RESULTS Twenty-eight-day all-cause mortality was 18.3% in the permissive underfeeding group compared with 23.3% in the target feeding group (relative risk: 0.79; 95% CI: 0.48, 1.29; P = 0.34). Hospital mortality was lower in the permissive underfeeding group than in the target group (30.0% compared with 42.5%; relative risk: 0.71; 95% CI: 0.50, 0.99; P = 0.04). No significant differences in outcomes were observed between the IIT and CIT groups. CONCLUSION In critically ill patients, permissive underfeeding may be associated with lower mortality rates than target feeding. This trial was registered at controlled-trials.com as ISRCTN96294863.

Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults

BACKGROUND The appropriate caloric goal for critically ill adults is unclear. We evaluated the effect of restriction of nonprotein calories (permissive underfeeding), as compared with standard enteral feeding, on 90-day mortality among critically ill adults, with maintenance of the full recommended amount of protein in both groups. METHODS At seven centers, we randomly assigned 894 critically ill adults with a medical, surgical, or trauma admission category to permissive underfeeding (40 to 60% of calculated caloric requirements) or standard enteral feeding (70 to 100%) for up to 14 days while maintaining a similar protein intake in the two groups. The primary outcome was 90-day mortality. RESULTS Baseline characteristics were similar in the two groups; 96.8% of the patients were receiving mechanical ventilation. During the intervention period, the permissive-underfeeding group received fewer mean (±SD) calories than did the standard-feeding group (835±297 kcal per day vs. 1299±467 kcal per day, P<0.001; 46±14% vs. 71±22% of caloric requirements, P<0.001). Protein intake was similar in the two groups (57±24 g per day and 59±25 g per day, respectively; P=0.29). The 90-day mortality was similar: 121 of 445 patients (27.2%) in the permissive-underfeeding group and 127 of 440 patients (28.9%) in the standard-feeding group died (relative risk with permissive underfeeding, 0.94; 95% confidence interval [CI], 0.76 to 1.16; P=0.58). No serious adverse events were reported; there were no significant between-group differences with respect to feeding intolerance, diarrhea, infections acquired in the intensive care unit (ICU), or ICU or hospital length of stay. CONCLUSIONS Enteral feeding to deliver a moderate amount of nonprotein calories to critically ill adults was not associated with lower mortality than that associated with planned delivery of a full amount of nonprotein calories. (Funded by the King Abdullah International Medical Research Center; PermiT Current Controlled Trials number, ISRCTN68144998.).

Hypoglycemia with intensive insulin therapy in critically ill patients: Predisposing factors and association with mortality

Objectives:To examine the predisposing factors for hypoglycemia in medical-surgical intensive care unit patients treated with intensive insulin therapy and to assess its association with mortality. Design:Nested-cohort study within a randomized controlled trial. Setting:Tertiary care intensive care unit. Participants:Medical-surgical intensive care unit patients with admission blood glucose of >6.1 mmol/L or 110 mg/dL who were enrolled in a randomized controlled trial comparing intensive insulin therapy with conventional insulin therapy. Interventions:None. Exposure:Hypoglycemia was defined as blood glucose ≤2.2 mmol/L or 40 mg/dL and intensive care unit mortality was the primary outcome. Measurements and Main Results:Among the 523 patients included in the study, hypoglycemia occurred in 84 (16%). Intensive insulin therapy was independently associated with increased risk of hypoglycemia (adjusted odds ratio, 50.65; 95% confidence interval, 17.36–147.78; p < .0001). Other variables associated with an increased risk of hypoglycemia included female gender, diabetes, Acute Physiology and Chronic Health Evaluation II, mechanical ventilation, continuous veno-venous hemodialysis, and intensive care unit length of stay. When adjusted to potential confounders, hypoglycemia was not significantly associated with increased mortality (adjusted hazard ratio, 1.31; 95% confidence interval, .70–2.46; p = .40). Patients with admission blood glucose of ≤10 mmol/L had an increased mortality with hypoglycemia (adjusted hazard ratio, 4.43; 95% confidence interval, 1.36–14.44; p = .01). Crude analysis showed significant association of mortality with blood glucose levels of ≤1.2 mmol/L (adjusted hazard ratio, 2.92; 95% confidence interval, 1.05–8.11; p = .04). When adjusted analysis was performed, similar trend was seen but was not statistically significant (adjusted hazard ratio, 2.56; 95% confidence interval, .85–7.70; p = .10). Conclusions:Our study showed significant increase of hypoglycemia with intensive insulin therapy. Although hypoglycemia was not independently associated with increased risk of death, increased mortality could not be excluded with severe hypoglycemia and in patients admitted with blood glucose of ≤10 mmol/L.

Elevated liver iron concentration is a marker of increased morbidity in patients with β thalassemia intermedia

Background Patients with β thalassemia intermedia can have substantial iron overload, irrespectively of their transfusion status, secondary to increased intestinal iron absorption. This study evaluates whether iron overload in patients with β thalassemia intermedia is associated with morbidity. Design and Methods This was a cross-sectional study of 168 patients with β thalassemia intermedia treated at two centers in Lebanon and Italy. Data on demographics, splenectomy status, transfusion status, and presence of co-morbidities were retrieved. Laboratory values of serum ferritin, fetal and total hemoglobin levels, as well as platelet and nucleated red blood cell counts were also obtained. Iron burden was determined directly by measuring liver iron concentration using magnetic resonance imaging. Patients were subdivided according to transfusion and splenectomy status into groups with phenotypes of different severity. Results The mean age of the patients was 35.2±12.6 years and 42.9% of them were male. The mean liver iron concentration was 8.4±6.7 mg Fe/g dry weight. On multivariate logistic regression analysis, after adjusting for age, gender, splenectomy status, transfusion status, and laboratory indices, an increase in 1 mg Fe/g dry weight liver iron concentration was independently and significantly associated with higher odds of thrombosis, pulmonary hypertension, hypothyroidism, osteoporosis, and hypogonadism. A liver iron concentration of at least 7 and at least 6 mg Fe/g dry weight were the best thresholds for discriminating the presence and absence of vascular and endocrine/bone morbidities, respectively (area under the receiver-operating characteristic curve: 0.72, P<0.001). Elevated liver iron concentration was associated with an increased rate of morbidity in patients with phenotypes of all severity, with a steeper increase in the rate of vascular morbidity being attributed to aging, and an earlier appearance of endocrine and bone disease. Conclusions Elevated liver iron concentration in patients with β thalassemia intermedia is a marker of increased vascular, endocrine, and bone disease.

Low-dose hydrocortisone in patients with cirrhosis and septic shock: a randomized controlled trial

Background Recent studies have reported a high prevalence of relative adrenal insufficiency in patients with liver cirrhosis. However, the effect of corticosteroid replacement on mortality in this high-risk group remains unclear. We examined the effect of low-dose hydrocortisone in patients with cirrhosis who presented with septic shock. Methods We enrolled patients with cirrhosis and septic shock aged 18 years or older in a randomized double-blind placebo-controlled trial. Relative adrenal insufficiency was defined as a serum cortisol increase of less than 250 nmol/L or 9 μg/dL from baseline after stimulation with 250 μg of intravenous corticotropin. Patients were assigned to receive 50 mg of intravenous hydrocortisone or placebo every six hours until hemodynamic stability was achieved, followed by steroid tapering over eight days. The primary outcome was 28-day all-cause mortality. Results The trial was stopped for futility at interim analysis after 75 patients were enrolled. Relative adrenal insufficiency was diagnosed in 76% of patients. Compared with the placebo group (n = 36), patients in the hydrocortisone group (n = 39) had a significant reduction in vasopressor doses and higher rates of shock reversal (relative risk [RR] 1.58, 95% confidence interval [CI] 0.98–2.55, p = 0.05). Hydrocortisone use was not associated with a reduction in 28-day mortality (RR 1.17, 95% CI 0.92–1.49, p = 0.19) but was associated with an increase in shock relapse (RR 2.58, 95% CI 1.04–6.45, p = 0.03) and gastrointestinal bleeding (RR 3.00, 95% CI 1.08–8.36, p = 0.02). Interpretation Relative adrenal insufficiency was very common in patients with cirrhosis presenting with septic shock. Despite initial favourable effects on hemodynamic parameters, hydrocortisone therapy did not reduce mortality and was associated with an increase in adverse effects. (Current Controlled Trials registry no. ISRCTN99675218.)

Clinical characteristics, sepsis interventions and outcomes in the obese patients with septic shock: an international multicenter cohort study

See related commentary by Dickerson, http://ccforum.com/content/17/3/154IntroductionData are sparse as to whether obesity influences the risk of death in critically ill patients with septic shock. We sought to examine the possible impact of obesity, as assessed by body mass index (BMI), on hospital mortality in septic shock patients.MethodsWe performed a nested cohort study within a retrospective database of patients with septic shock conducted in 28 medical centers in Canada, United States and Saudi Arabia between 1996 and 2008. Patients were classified according to the World Health Organization criteria for BMI. Multivariate logistic regression analysis was performed to evaluate the association between obesity and hospital mortality.ResultsOf the 8,670 patients with septic shock, 2,882 (33.2%) had height and weight data recorded at ICU admission and constituted the study group. Obese patients were more likely to have skin and soft tissue infections and less likely to have pneumonia with predominantly Gram-positive microorganisms. Crystalloid and colloid resuscitation fluids in the first six hours were given at significantly lower volumes per kg in the obese and very obese patients compared to underweight and normal weight patients (for crystalloids: 55.0 ± 40.1 ml/kg for underweight, 43.2 ± 33.4 for normal BMI, 37.1 ± 30.8 for obese and 27.7 ± 22.0 for very obese). Antimicrobial doses per kg were also different among BMI groups. Crude analysis showed that obese and very obese patients had lower hospital mortality compared to normal weight patients (odds ratio (OR) 0.80, 95% confidence interval (CI) 0.66 to 0.97 for obese and OR 0.61, 95% CI 0.44 to 0.85 for very obese patients). After adjusting for baseline characteristics and sepsis interventions, the association became non-significant (OR 0.80, 95% CI 0.62 to 1.02 for obese and OR 0.69, 95% CI 0.45 to 1.04 for very obese).ConclusionsThe obesity paradox (lower mortality in the obese) documented in other populations is also observed in septic shock. This may be related in part to differences in patient characteristics. However, the true paradox may lie in the variations in the sepsis interventions, such as the administration of resuscitation fluids and antimicrobial therapy. Considering the obesity epidemic and its impact on critical care, further studies are warranted to examine whether a weight-based approach to common therapeutic interventions in septic shock influences outcome.

Mortality reduction after implementing a clinical practice guidelines-based management protocol for severe traumatic brain injury.

INTRODUCTION The objective of this study was to examine the effect of implementing a clinical practice guidelines-based management protocol on the outcome of patients with severe traumatic brain injury (TBI). METHODS We carried out a pre-post guideline implementation study using previously collected data in the Intensive Care Unit (ICU). All patients older than 12 years with severe TBI, defined as a Glasgow Coma Scale score of 8 or less, from March 1999 to January 2001 (control group) and from February 2001 to December 2006 (protocol group) were identified and included in this study. Patients in the protocol group were managed using a clinical practice guidelines-based management protocol, derived from the guidelines published by the Brain Trauma Foundation. Primary outcome was hospital mortality, whereas the secondary outcome was ICU mortality. To assess whether the ICU protocol might have led to an increase in the number of surviving patients with severe disability, we examined the association of the protocol use and the need for tracheostomies, mechanical ventilation duration, and ICU and hospital length of stay (LOS) among survivors. RESULTS During the study period, a total of 434 patients met the inclusion criteria. After adjustment for several prognostic factors, the use of protocol was independently associated with a significant reduction in hospital and ICU mortality (odds ratio, 0.45; 95% confidence interval, 0.24-0.86; and odds ratio, 0.47; 95% confidence interval, 0.23-0.96, respectively). The use of the protocol was not associated with an increase in the need for tracheostomies, mechanical ventilation duration, ICU LOS, and hospital LOS. CONCLUSION The protocol implementation was associated with a reduction in hospital and ICU mortality. This improvement was not associated with an increase in the frequency of tracheostomies and in ICU or hospital LOS, suggesting that the improved survival was not associated with the increased number of surviving patients with severe disability and that the functional status might have also improved.

Near-Target Caloric Intake in Critically Ill Medical-Surgical Patients Is Associated With Adverse Outcomes

BACKGROUND The objective of this study was to determine whether caloric intake independently influences mortality and morbidity of critically ill patients. METHODS The study was conducted as a nested cohort study within a randomized controlled trial in a tertiary care intensive care unit (ICU). The main exposure in the study was average caloric intake/target for the first 7 ICU days. The primary outcomes were ICU and hospital mortality. Secondary outcomes included ICU-acquired infections, ventilator-associated pneumonia (VAP), duration of mechanical ventilation days, and ICU and hospital length of stay (LOS). The authors divided patients (n = 523) into 3 tertiles according to the percentage of caloric intake/target: tertile I <33.4%, tertile II 33.4%-64.6%, and tertile III >64.6%. To adjust for potentially confounding variables, the authors assessed the association between caloric intake/target and the different outcomes using multivariate logistic regression for categorical outcomes (tertile I was used as reference) and multiple linear regression for continuous outcomes. RESULTS Tertile III was associated with higher adjusted hospital mortality, higher risk of ICU-acquired infections, and a trend toward higher VAP rate. Increasing caloric intake was independently associated with a significant increase in duration of mechanical ventilation, ICU LOS, and hospital LOS. CONCLUSIONS The data demonstrate that near-target caloric intake is associated with significantly increased hospital mortality, ICU-acquired infections, mechanical ventilation duration, and ICU and hospital LOS. Further studies are needed to explore whether reducing caloric intake would improve the outcomes in critically ill patients.

Visual estimation versus gravimetric measurement of postpartum blood loss: a prospective cohort study

PurposeOne of the major problems in international literature is how to measure postpartum blood loss with accuracy. We aimed in this research to assess the accuracy of visual estimation of postpartum blood loss (by each of two main health-care providers) compared with the gravimetric calculation method.MethodsWe carried out a prospective cohort study at King Abdulaziz Medical City, Riyadh, Saudi Arabia between 1 November 2009 and 31 December 2009. All women who were admitted to labor and delivery suite and delivered vaginally were included in the study. Postpartum blood loss was visually estimated by the attending physician and obstetrics nurse and then objectively calculated by a gravimetric machine. Comparison between the three methods of blood loss calculation was carried out.ResultsA total of 150 patients were included in this study. There was a significant difference between the gravimetric calculated blood loss and both health-care providers’ estimation with a tendency to underestimate the loss by about 30%. The background and seniority of the assessing health-care provider did not affect the accuracy of the estimation. The corrected incidence of postpartum hemorrhage in Saudi Arabia was found to be 1.47%.ConclusionHealth-care providers tend to underestimate the volume of postpartum blood loss by about 30%. Training and continuous auditing of the diagnosis of postpartum hemorrhage is needed to avoid missing cases and thus preventing associated morbidity and mortality.