Asgar Rishu

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.

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.

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.

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.

The incidence of venous thromboembolism and practice of deep venous thrombosis prophylaxis in hospitalized cirrhotic patients

BackgroundCirrhotic patients are characterized by a decreased synthesis of coagulation and anticoagulation factors. The coagulopathy of cirrhotic patients is considered to be auto-anticoagulation. Our aim was to determine the incidence and predictors of venous thromboembolism (VTE) and examine the practice of deep venous thrombosis (DVT) prophylaxis among hospitalized cirrhotic patients.MethodsA retrospective cohort study was performed in a tertiary teaching hospital. We included all adult patients admitted to the hospital with a diagnosis of liver cirrhosis from January 1, 2009 to December 31, 2009. We grouped our cohort patients in two groups, cirrhotic patients without VTE and cirrhotic with VTE.ResultsOver one year, we included 226 cirrhotic patients, and the characteristics of both groups were similar regarding their clinical and laboratory parameters and their outcomes. Six patients (2.7%) developed VTE, and all of the VTEs were DVT. Hepatitis C was the most common (51%) underlying cause of liver cirrhosis, followed by hepatitis B (22%); 76% of the cirrhotic patients received neither pharmacological nor mechanical DVT prophylaxis.ConclusionCirrhotic patients are at risk for developing VTE. The utilization of DVT prophylaxis was suboptimal.

The results of a 6-year epidemiologic surveillance for ventilator-associated pneumonia at a tertiary care intensive care unit in Saudi Arabia.

BACKGROUND Ventilator-associated pneumonia (VAP) prevention is an important patient safety initiative. We describe the impact of a multidisciplinary surveillance program on VAP rates in a tertiary medical-surgical-trauma intensive care unit (ICU). METHODS An epidemiologic surveillance program was established in 2003 as a joint project between ICU and Infection Prevention and Control Department to regularly report VAP rates to guide evidence-based VAP preventive strategies. VAP cases were diagnosed according to predefined criteria and prospectively recorded by a research physician. VAP microbiology, risk factors, and outcomes were noted. RESULTS Of 2,812 ventilated patients, 433 (15.4%) developed VAP corresponding to 15.9 episodes per 1,000 ventilator-days. The rate decreased from 19.1 in 2003 to 6.3 per 1,000 ventilator-days in 2009. On multivariate analysis, VAP was associated with accidental extubation (hazard ratio [HR], 4.11; 95% confidence interval [CI]: 1.93-8.73), trauma versus medical diagnosis (HR, 2.59; 95% CI: 2.07-3.23), chronic obstructive pulmonary disease (HR, 1.55; 95% CI: 1.08-2.22), and neuromuscular blockade (HR, 1.39; 95% CI: 1.07-1.81). The most common isolated pathogens were Gram-negative organisms. VAP patients had longer mechanical ventilation duration, ICU and hospital length of stay, but similar ICU and hospital mortality compared with non-VAP patients. CONCLUSION The study showed a reduction in VAP rates with active surveillance, reporting and evidence-based preventive strategies and identified several modifiable risk factors, which should be the focus of additional interventions.

Acinetobacter is the most common pathogen associated with late-onset and recurrent ventilator-associated pneumonia in an adult intensive care unit in Saudi Arabia.

BACKGROUND The guidelines for initial empiric antimicrobial therapy for ventilator-associated pneumonia (VAP) are highly dependent on the type of causative pathogen and the time of diagnosis. The objective of this study was to examine the microbial causes of VAP and describe any variability by the timing of VAP onset and over time. METHODS A prospective surveillance study was conducted in the adult general intensive care unit of a tertiary care hospital in Riyadh, Saudi Arabia. Microbial isolates obtained from blood and different respiratory specimens of patients diagnosed with VAP (using the US Centers for Disease Control and Prevention definition) between August 2003 and June 2009 were included. RESULTS A total of 457 pathogens were identified during the study; 380 (83.2%) were associated with primary VAP and 77 (16.8%) were associated with recurrent VAP. Of primary VAP pathogens, 159 (41.8%) were associated with early-onset (<5 days) and 221 (58.2%) were associated with late-onset (≥5 days) VAP. The most common pathogen identified was Acinetobacter spp (26.5%), followed by Pseudomonas aeruginosa (21.7%), Staphylococcus aureus including methicillin-resistant S. aureus (MRSA) (15.3%), Klebsiella spp (6.8%), Haemophilus spp (6.1%), and Enterobacter spp (5.0%). Acinetobacter spp and MRSA were significantly associated with late-onset VAP while Haemophilus spp and Streptococcus pneumoniae were significantly associated with early-onset VAP. Acinetobacter spp was the only pathogen associated with recurrent VAP and its incidence showed a significant increasing trend during the study period. Acinetobacter spp was significantly associated with prolonged ventilation, sedation, and nasogastric intubation. CONCLUSIONS Acinetobacter baumannii is the most common and increasingly important pathogen associated with VAP in our patients, especially late-onset and recurrent VAP.

What is the optimal blood glucose target in critically ill patients? A nested cohort study

AIMS: There is an uncertainty about what constitutes an optimal level of blood glucose (BG) in critically ill patients. The objective of this study is to identify the optimal BG target for glycemic control in critically ill patients that is associated with survival benefit with the least hypoglycemia risk. SETTING AND DESIGN: This is a nested cohort study within a randomized control trial conducted in a tertiary care center in King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia. METHODS: The study was carried out in a single center to assess the effect of intensive insulin therapy [IIT; target BG 4.4-6.1 mmol/L (80-110 mg/dL)] versus conventional insulin therapy [CIT; target BG 10-11.1 mmol/L (180-200 mg/dL)] in a medical/surgical ICU. All patients were divided into six groups based on the mean daily BG levels. A logistic regression model was used to determine the association of BG and ICU mortality. We compared different outcomes below and above different BG thresholds of 0.1 mmol/L (2 mg/dL) increments using multivariate analyses. STATISTICAL ANALYSIS: Data are presented as mean ± SD or median with interquartile ranges, unless otherwise indicated. Differences between the six groups were assessed using the χ2 test. A P-value equal or less than 0.05 was considered to indicate statistical significance. The results were expressed as adjusted odds ratio (aOR) and 95% confidence intervals (CI). Statistical analyses were carried out using the Statistical Analysis Software (SAS, release 8, SAS Institute Inc., Cary, NC, USA). RESULTS: Among six groups, the ICU mortality was least in patients with BG <8.7 mmol/L (<157 mg/dL) compared with patients with BG ≥8.7 mmol/L (≥157 mg/dL) [11.5% vs. 21.5%, P = 0.002]. When analyzed using 0.1 mmol increments in average BG, we found that mortality remained unchanged by increasing thresholds of BG up to 8.0 mmol/L (144 mg/dL) and started to rise with thresholds of BG of 8.1 mmol/L (146 mg/dL) and above. The risk of hypoglycemia was the highest with a BG threshold of 6.1 mmol/L (110 mg/dL) and gradually decreased with increasing BG levels to plateau with a BG level of 7.2 mmol/L (130 mg/dL) and higher. CONCLUSION: Our study suggests that a BG level of 8.1 mmol/L (146 mg/dL) and below represents an optimal level in critically ill patients.

Etomidate and mortality in cirrhotic patients with septic shock.

BackgroundClinical effects and outcomes of a single dose etomidate prior to intubation in the intensive care setting is controversial. The aim of this study is to evaluate the association of a single dose effect of etomidate prior to intubation on the mortality of septic cirrhotic patients and the impact of the subsequent use of low dose hydrocortisone.MethodsThis is a nested-cohort study within a randomized double blind placebo controlled study evaluating the use of low dose hydrocortisone in cirrhotic septic patients. Cirrhotic septic patients ≥ 18 years were included in the study. Patients who received etomidate prior to intubation were compared to those who did not receive etomidate for all cause 28-day mortality as a primary outcome.ResultsSixty two intubated patients out of the 75 patients randomized in the initial trial were eligible for this study. Twenty three of the 62 intubated patients received etomidate dose prior to intubation. Etomidate use was not associated with all cause 28-day mortality or hospital mortality but was associated with significantly higher ICU mortality (91% vs. 64% for etomidate and controls groups, respectively; p = 0.02). Etomidate patients who received subsequent doses of hydrocortisone required lower doses of vasopressors and had more vasopressor-free days but no improvement in mortality.ConclusionsIn this group of septic cirrhotic patients with very high mortality, etomidate increased ICU mortality. Subsequent use of hydrocortisone appears to have no benefit beyond decreasing vasopressor requirements. The lowest mortality was observed in patients who did not receive etomidate but received hydrocortisone.