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1.  Toward evidence-based approach to deep venous thrombosis 
Annals of Thoracic Medicine  2015;10(1):1-2.
PMCID: PMC4286838  PMID: 25593600
2.  Venous Thromboembolism in Critically Ill Cirrhotic Patients: Practices of Prophylaxis and Incidence 
Thrombosis  2013;2013:807526.
Objectives. We compared venous thromboembolism (VTE) prophylaxis practices and incidence in critically ill cirrhotic versus noncirrhotic patients and evaluated cirrhosis as a VTE risk factor. Methods. A cohort of 798 critically ill patients followed for the development of clinically detected VTE were categorized according to the diagnosis of cirrhosis. VTE prophylaxis practices and incidence were compared. Results. Seventy-five (9.4%) patients had cirrhosis with significantly higher INR (2.2 ± 0.9 versus 1.3 ± 0.6, P < 0.0001), lower platelet counts (115,000 ± 90,000 versus 258,000 ± 155,000/μL, P < 0.0001), and higher creatinine compared to noncirrhotic patients. Among cirrhotics, 31 patients received only mechanical prophylaxis, 24 received pharmacologic prophylaxis, and 20 did not have any prophylaxis. Cirrhotic patients were less likely to receive pharmacologic prophylaxis (odds ratio, 0.08; 95% confidence interval (CI), 0.04–0.14). VTE occurred in only two (2.7%) cirrhotic patients compared to 7.6% in noncirrhotic patients (P = 0.11). The incidence rate was 2.2 events per 1000 patient-ICU days for cirrhotic patients and 3.6 events per 1000 patient-ICU days for noncirrhotics (incidence rate ratio, 0.61; 95% CI, 0.15–2.52). On multivariate Cox regression analysis, cirrhosis was not associated with VTE risk (hazard ratio, 0.40; 95% CI, 0.10–1.67). Conclusions. In critically ill cirrhotic patients, VTE incidence did not statistically differ from that in noncirrhotic patients.
PMCID: PMC3872442  PMID: 24386564
3.  Building capacity for quality and safety in critical care: A roundtable discussion from the second international patient safety conference in April 9-11, 2013, Riyadh, Saudi Arabia 
Annals of Thoracic Medicine  2013;8(4):183-185.
This paper summarizes the roundtable discussion from the Second International Patient Safety Conference held in April 9-11, 2013, Riyadh, Saudi Arabia. The objectives of the roundtable discussion were to: (1) review the conceptual framework for building capacity in quality and safety in critical care. (2) examine examples of leading international experiences in building capacity. (3) review the experience in Saudi Arabia in this area. (4) discuss the role of building capacity in simulation for patient safety in critical care and (5) review the experience in building capacity in an ongoing improvement project for severe sepsis and septic shock.
PMCID: PMC3821276  PMID: 24250730
Building capacity; critical care; safety culture; sepsis; simulation
4.  Knowledge of thromboprophylaxis guidelines pre- and post-didactic lectures during a venous thromboembolism awareness day at a tertiary-care hospital 
Annals of Thoracic Medicine  2013;8(3):165-169.
Didactic lectures are frequently used to improve compliance with practice guidelines. This study assessed the knowledge of health-care providers (HCPs) at a tertiary-care hospital of its evidence-based thromboprophylaxis guidelines and the impact of didactic lectures on their knowledge.
The hospital launched a multifaceted approach to improve thromboprophylaxis practices, which included posters, a pocket-size guidelines summary and didactic lectures during the annual thromboprophylaxis awareness days. A self-administered questionnaire was distributed to HCPs before and after lectures on thromboprophylaxis guidelines (June 2010). The questionnaire, formulated and validated by two physicians, two nurses and a clinical pharmacist, covered various subjects such as risk stratification, anticoagulant dosing and the choice of anticoagulants in specific clinical situations.
Seventy-two and 63 HCPs submitted the pre- and post-test, respectively (62% physicians, 28% nurses, from different clinical disciplines). The mean scores were 7.8 ± 2.1 (median = 8.0, range = 2-12, maximum possible score = 15) for the pre-test and 8.4 ± 1.8 for the post-test, P = 0.053. There was no significant difference in the pre-test scores of nurses and physicians (7.9 ± 1.7 and 8.2 ± 2.4, respectively, P = 0.67). For the 35 HCPs who completed the pre- and post-tests, their scores were 7.7 ± 1.7 and 8.8 ± 1.6, respectively, P = 0.003. Knowledge of appropriate anticoagulant administration in specific clinical situations was frequently inadequate, with approximately two-thirds of participants failing to adjust low-molecular-weight heparin doses in patients with renal failure.
Education via didactic lectures resulted in a modest improvement of HCPs′ knowledge of thromboprophylaxis guidelines. This supports the need for a multifaceted approach to improve the awareness and implementation of thromboprophylaxis guidelines.
PMCID: PMC3731859  PMID: 23922612
Clinical practice guidelines; continuing medical education; health knowledge; practice guidelines; questionnaires; venous thromboembolism
5.  What is the optimal blood glucose target in critically ill patients? A nested cohort study 
Annals of Thoracic Medicine  2011;6(4):207-211.
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.
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.
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.
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).
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.
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.
PMCID: PMC3183637  PMID: 21977065
Critically ill; hypoglycemia; insulin; intensive care; mortality; sepsis
6.  Low-dose hydrocortisone in patients with cirrhosis and septic shock: a randomized controlled trial 
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.
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.
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).
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.)
PMCID: PMC3001503  PMID: 21059778
7.  Scientific misconduct and medical publishing 
PMCID: PMC2732094  PMID: 19727364
8.  Diagnostic accuracy of a screening electronic alert tool for severe sepsis and septic shock in the emergency department 
Early recognition of severe sepsis and septic shock is challenging. The aim of this study was to determine the diagnostic accuracy of an electronic alert system in detecting severe sepsis or septic shock among emergency department (ED) patients.
An electronic sepsis alert system was developed as a part of a quality-improvement project for severe sepsis and septic shock. The system screened all adult ED patients for a combination of systemic inflammatory response syndrome and organ dysfunction criteria (hypotension, hypoxemia or lactic acidosis). This study included all patients older than 14 years who presented to the ED of a tertiary care academic medical center from Oct. 1, 2012 to Jan. 31, 2013. As a comparator, emergency medicine physicians or the critical care physician identified the patients with severe sepsis or septic shock.
In the ED, vital signs were manually entered into the hospital electronic heath record every hour in the critical care area and every two hours in other areas. We also calculated the time from the alert to the intensive care unit (ICU) referral.
Of the 49,838 patients who presented to the ED, 222 (0.4%) were identified to have severe sepsis or septic shock. The electronic sepsis alert had a sensitivity of 93.18% (95% CI, 88.78% - 96.00%), specificity of 98.44 (95% CI, 98.33% – 98.55%), positive predictive value of 20.98% (95% CI, 18.50% – 23.70%) and negative predictive value of 99.97% (95% CI, 99.95% – 99.98%) for severe sepsis and septic shock. The alert preceded ICU referral by a median of 4.02 hours (Q1 - Q3: 1.25–8.55).
Our study shows that electronic sepsis alert tool has high sensitivity and specificity in recognizing severe sepsis and septic shock, which may improve early recognition and management.
PMCID: PMC4261595  PMID: 25476738
Clinical decision support; Sepsis; Sensitivity and specificity; Septic shock; Emergency department; Electronic alert
9.  Antimicrobial therapeutic determinants of outcomes from septic shock among patients with cirrhosis 
Hepatology (Baltimore, Md.)  2012;56(6):2305-2315.
It is unclear whether practice-related aspects of antimicrobial therapy contribute to the high mortality from septic shock among patients with cirrhosis. We examined the relationship between aspects of initial empiric antimicrobial therapy and mortality in patients with cirrhosis and septic shock. This was a nested cohort study within a large retrospective database of septic shock from 28 medical centers in Canada, the United States, and Saudi Arabia by the Cooperative Antimicrobial Therapy of Septic Shock Database Research Group between 1996 and 2008. We examined the impact of initial empiric antimicrobial therapeutic variables on the hospital mortality of patients with cirrhosis and septic shock. Among 635 patients with cirrhosis and septic shock, the hospital mortality was 75.6%. Inappropriate initial empiric antimicrobial therapy was administered in 155 (24.4%) patients. The median time to appropriate antimicrobial administration was 7.3 hours (interquartile range, 3.2-18.3 hours). The use of inappropriate initial antimicrobials was associated with increased mortality (adjusted odds ratio [aOR], 9.5; 95% confidence interval [CI], 4.3-20.7], as was the delay in appropriate antimicrobials (aOR for each 1 hour increase, 1.1; 95% CI, 1.1-1.2). Among patients with eligible bacterial septic shock, a single rather than two or more appropriate antimicrobials was used in 226 (72.9%) patients and was also associated with higher mortality (aOR, 1.8; 95% CI, 1.0-3.3). These findings were consistent across various clinically relevant subgroups. Conclusion: In patients with cirrhosis and septic shock, inappropriate and delayed appropriate initial empiric antimicrobial therapy is associated with increased mortality. Monotherapy of bacterial septic shock is also associated with increased mortality. The process of selection and implementation of empiric antimicrobial therapy in this high-risk group should be restructured. (Hepatology 2012;56:2305–2315)
PMCID: PMC3556696  PMID: 22753144
10.  Association of compliance of ventilator bundle with incidence of ventilator-associated pneumonia and ventilator utilization among critical patients over 4 years 
Annals of Thoracic Medicine  2014;9(4):221-226.
Several studies showed that the implementation of the Institute for Healthcare Improvement (IHI) ventilator bundle alone or with other preventive measures are associated with reducing Ventilator-Associated Pneumonia (VAP) rates. However, the association with ventilator utilization was rarely examined and the findings were conflicting. The objectives were to validate the bundle association with VAP rate in a traditionally high VAP environment and to examine its association with ventilator utilization.
The study was conducted at the adult medical-surgical intensive care unit (ICU) at King Abdulaziz Medical City, Saudi Arabia, between 2010 and 2013. VAP data were collected by a prospective targeted surveillance as per Centers for Disease Control and Prevention (CDC)/National Healthcare Safety Network (NHSN) methodology while bundle data were collected by a cross-sectional design as per IHI methodology.
Ventilator bundle compliance significantly increased from 90% in 2010 to 97% in 2013 (P for trend < 0.001). On the other hand, VAP rate decreased from 3.6 (per 1000 ventilator days) in 2010 to 1.0 in 2013 (P for trend = 0.054) and ventilator utilization ratio decreased from 0.73 in 2010 to 0.59 in 2013 (P for trend < 0.001). There were negative significant correlations between the trends of ventilator bundle compliance and VAP rate (cross-correlation coefficients −0.63 to 0.07) and ventilator utilization (cross-correlation coefficients −0.18 to −0.63).
More than 70% improvement of VAP rates and approximately 20% improvement of ventilator utilization were observed during IHI ventilator bundle implementation among adult critical patients in a tertiary care center in Saudi Arabia. Replicating the current finding in multicenter randomized trials is required before establishing any causal link.
PMCID: PMC4166069  PMID: 25276241
Bundle; health-care-associated infection; Institute for Healthcare Improvement; quality improvement; ventilator-associated pneumonia; ventilator utilization
11.  Drug-resistant ventilator associated pneumonia in a tertiary care hospital in Saudi Arabia 
Annals of Thoracic Medicine  2014;9(2):104-111.
There is a wide geographic and temporal variability of bacterial resistance among microbial causes of ventilator-associated pneumonia (VAP). The contribution of multi-drug resistant (MDR) pathogens to the VAP etiology in Saudi Arabia was never studied. We sought to examine the extent of multiple-drug resistance among common microbial causes of VAP.
We conducted a retrospective susceptibility study in the adult intensive care unit (ICU) of King Abdulaziz Medical City, Riyadh, Saudi Arabia. Susceptibility results of isolates from patients diagnosed with VAP between October 2004 and June 2009 were examined. The US National Healthcare Safety Network definition of MDR was adopted.
A total of 248 isolates including 9 different pathogens were included. Acinetobacter spp. was highly (60-89%) resistant to all tested antimicrobials, including carbapenems (three- and four-class MDR prevalence were 86% and 69%, respectively). Pseudomonas aeruginosa was moderately (13-31%) resistant to all tested antimicrobials, including antipseudomonal penicillins (three- and four-class MDR prevalence were 13% and 10%, respectively). With an exception of ampicillin (fully resistant), Klebsiella spp. had low (0-13%) resistance to other tested antimicrobials with no detected MDR. Staphylococcus aureus was fully susceptible to vancomycin with 42% resistance to oxacillin. There were significant increasing trends of MDR Acinetobacter spp. however not P. aeruginosa during the study. Resistant pathogens were associated with worse profile of ICU patients but not patients’ outcomes.
Acinetobacter in the current study was an increasingly resistant VAP-associated pathogen more than seen in many parts of the world. The current finding may impact local choice of initial empiric antibiotics.
PMCID: PMC4005156  PMID: 24791174
Acinetobacter; antimicrobial resistance; microbiology; Saudi Arabia; ventilator-associated pneumonia
12.  Risk factors, management and outcomes of patients admitted with near fatal asthma to a tertiary care hospital in Riyadh 
Annals of Thoracic Medicine  2014;9(1):33-38.
Near-fatal asthma (NFA) has not been well studied in Saudi Arabia. We evaluated NFA risk factors in asthmatics admitted to a tertiary-care hospital and described NFA management and outcomes.
This was a retrospective study of NFA patients admitted to an ICU in Riyadh (2006-2010). NFA was defined as a severe asthma attack requiring intubation. To evaluate NFA risk factors, randomly selected patients admitted to the ward for asthma exacerbation were used as controls. Collected data included demographics, information on prior asthma control and various NFA treatments and outcomes.
Thirty NFA cases were admitted to the ICU in the five-year period. Compared to controls (N = 120), NFA patients were younger (37.5 ± 19.9 vs. 50.3 ± 23.1 years, P = 0.004) and predominantly males (70.0% vs. 41.7%, P = 0.005) and used less inhaled steroids/long-acting ß2-agonists combination (13.6% vs. 38.7% P = 0.024. Most (73.3%) NFA cases presented in the cool months (October-March). On multivariate analysis, age (odds ratio [OR] 0.96; 95% confidence interval [CI], 0.92-0.99, P = 0.015) and the number of ED visits in the preceding year (OR, 1.25; 95% CI, 1.00-1.55) were associated with NFA. Rescue NFA management included ketamine (50%) and theophylline (19%) infusions. NFA outcomes included: neuromyopathy (23%), mechanical ventilation duration = 6.4 ± 4.7 days, tracheostomy (13%) and mortality (0%). Neuromuscular blockade duration was associated with neuromyopathy (OR, 3.16 per one day increment; 95% CI, 1.27-7.83).
In our study, NFA risk factors were younger age and higher number of ED visits. NFA had significant morbidity. Reducing neuromuscular blockade duration during ventilator management may decrease neuromyopathy risk.
PMCID: PMC3912685  PMID: 24551016
Asthma; critical illness; mechanical ventilation; neuromyopathy
13.  The association between statin therapy during intensive care unit stay and the incidence of venous thromboembolism: a propensity score-adjusted analysis 
Studies have shown that statins have pleiotropic effects on inflammation and coagulation; which may affect the risk of developing venous thromboembolism (VTE). The objective of this study was to evaluate the association between statin therapy during intensive care unit (ICU) stay and the incidence of VTE in critically ill patients.
This was a post-hoc analysis of a prospective observational cohort study of patients admitted to the intensive care unit between July 2006 and January 2008 at a tertiary care medical center. The primary endpoint was the incidence of VTE during ICU stay up to 30 days. Secondary endpoint was overall 30-day hospital mortality. Propensity score was used to adjust for clinically and statistically relevant variables.
Of the 798 patients included in the original study, 123 patients (15.4%) received statins during their ICU stay. Survival analysis for VTE risk showed that statin therapy was not associated with a reduction of VTE incidence (crude hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.28-1.54, P = 0.33 and adjusted HR 0.63, 95% CI 0.25-1.57, P = 0.33). Furthermore, survival analysis for hospital mortality showed that statin therapy was not associated with a reduction in hospital mortality (crude HR 1.26, 95% CI 0.95-1.68, P = 0.10 and adjusted HR 0.98, 95% CI 0.72-1.36, P = 0.94).
Our study showed no statistically significant association between statin therapy and VTE risk in critically ill patients. This question needs to be further studied in randomized control trials.
PMCID: PMC3829807  PMID: 24206781
Venous thromboembolism; Outcome assessment; Intensive care; Hospital mortality; Propensity scores; Statins
14.  Even Mild Hyperlactatemia Is Associated with Increased Mortality in Critically Ill Patients 
Critical Care  2013;17(5):R197.
The clinical significance of elevation of lactate levels within the reference range is not well studied. The objective of this study was to determine the best cutoff threshold for serum lactate within the reference range (0.01 to 2.00 mM) that best discriminated between survivors and nonsurvivors of critical illness and to examine the association between relative hyperlactatemia (lactate above the identified threshold) and mortality.
This was a retrospective cohort study of adult patients admitted to the medical-surgical intensive care unit (ICU) of a tertiary care academic center. Youden index was calculated to identify the best lactate cutoff threshold that discriminated between survivors and nonsurvivors. Patients with lactate above the identified threshold were defined as having relative hyperlactatemia. Multivariate logistic regression, adjusting for baseline variables, was performed to determine the relationship between the above two ranges of lactate levels and mortality. In addition, a test of interaction was performed to assess the effect of selected subgroups on the association between relative hyperlactatemia and hospital mortality.
During the study period, 2,157 patients were included in the study with mean lactate of 1.3 ± 0.4 mM, age of 55.1 ± 20.3 years, and acute physiology and chronic health evaluation (APACHE) II score of 22.1 ± 8.2. Vasopressors were required in 42.4%. Lactate of 1.35 mM was found to be the best cutoff threshold for the whole cohort. Relative hyperlactatemia was associated with increased hospital mortality (adjusted odds ratio (aOR), 1.60, 95% confidence interval (CI) 1.29 to 1.98), and ICU mortality (aOR, 1.66; 95% CI, 1.26 to 2.17) compared with a lactate level of 0.01 to 1.35 mM. This association was consistent among all examined subgroups.
Relative hyperlactatemia (lactate of 1.36 to 2.00 mM) within the first 24 hours of ICU admission is an independent predictor of hospital and ICU mortality in critically ill patients.
PMCID: PMC4056896  PMID: 24025259
15.  Demographics and outcomes of critically ill patients transferred from other hospitals to a tertiary care academic referral center in Saudi Arabia 
The objective of this study was to examine the outcomes of critically ill patients who were transferred from other hospitals to a tertiary care center in Saudi Arabia as a quality improvement project.
This was a retrospective study of adult patients admitted to the medical-surgical intensive care unit (ICU) of a tertiary care hospital. Patients were divided according to the source of referral into three groups: transfers from other hospitals, and direct admissions from emergency department (ED) and from hospital wards. Standardized mortality ratio (SMR) was calculated. Multivariate analysis was performed to determine the independent predictors of mortality.
Of the 7,654 patients admitted to the ICU, 611 patients (8%) were transferred from other hospitals, 2,703 (35.3%) were direct admissions from ED and 4,340 (56.7%) from hospital wards. Hospital mortality for patients transferred from other hospitals was not significantly different from those who were directly admitted from ED (35% vs. 33.1%, p = 0.37) but was lower than those who were directly admitted from hospital wards (35% vs. 51.2%, p < 0.0001). SMRs did not differ significantly across the three groups.
Critically ill patients who were transferred from other hospitals constituted 8% of all ICU admissions. Mortality of these patients was similar to patients with direct admission from the ED and lower than that of patients with direct admission from hospital wards. However, risk-adjusted mortality was not different from the other two groups.
PMCID: PMC3751539  PMID: 23937989
Emergency department; Hospital mortality; Hospital wards; Intensive care unit; Mortality; Ambulance; Trauma
16.  Clinical characteristics, sepsis interventions and outcomes in the obese patients with septic shock: an international multicenter cohort study 
Critical Care  2013;17(2):R72.
Data 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.
We 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.
Of 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).
The 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.
PMCID: PMC3672731  PMID: 23594407
17.  Permissive underfeeding versus target enteral feeding in adult critically ill patients (PermiT Trial): a study protocol of a multicenter randomized controlled trial 
Trials  2012;13:191.
Nutritional support is an essential part of the management of critically ill patients. However, optimal caloric intake has not been systematically evaluated. We aim to compare two strategies of enteral feeding: permissive underfeeding versus target feeding.
This is an international multi-center randomized controlled trial in critically ill medical- surgical adult patients. Using a centralized allocation, 862 patients will be randomized to permissive underfeeding or target feeding. Patients in the permissive group receive 50% (acceptable range is 40% to 60%) of the calculated caloric requirement, while those in the targeted group receive 100% (acceptable range 70% to 100%) of the calculated caloric requirement. The primary outcome is 90-day all-cause mortality. Secondary outcomes include ICU and hospital mortality, 28-day, and 180-day mortality as well as health care-associated infections, organ failure, and length of stay in the ICU and hospital. The trial has 80% power to detect an 8% absolute reduction in 90-day mortality assuming a baseline risk of death of 25% at an alpha level of 0.05.
Patient recruitment started in November 2009 and is currently active in five centers. The Data Monitoring Committee advised continuation of the trial after the first interim analysis. The study is expected to finish by November 2013.
Trial registration
Current Controlled Trials ISRCTN68144998
PMCID: PMC3517534  PMID: 23057605
Enteral nutrition; Intensive Care Units; Caloric restriction; Infections; Insulin; Mortality
18.  Intra-abdominal pressure and abdominal perfusion pressure in cirrhotic patients with septic shock 
Annals of Intensive Care  2012;2(Suppl 1):S4.
The importance of intra-abdominal pressure (IAP) and abdominal perfusion pressure (APP) in cirrhotic patients with septic shock is not well studied. We evaluated the relationship between IAP and APP and outcomes of cirrhotic septic patients, and assessed the ability of these measures compared to other common resuscitative endpoints to differentiate survivors from nonsurvivors.
This study was a post hoc analysis of a randomized double-blind placebo-controlled trial in which mean arterial pressure (MAP), central venous oxygen saturation (ScvO2) and IAP were measured every 6 h in 61 cirrhotic septic patients admitted to the intensive care unit. APP was calculated as MAP - IAP. Intra-abdominal hypertension (IAH) was defined as mean IAP ≥ 12 mmHg, and abdominal hypoperfusion as mean APP < 60 mmHg. Measured outcomes included ICU and hospital mortality, need for renal replacement therapy (RRT) and ventilator- and vasopressor-free days.
IAH prevalence on the first ICU day was 82%, and incidence in the first 7 days was 97%. Compared to patients with normal IAP, IAH patients had significantly higher ICU mortality (74.0% vs. 27.3%, p = 0.005), required more RRT (78.0% vs. 45.5%, p = 0.06) and had lower ventilator- and vasopressor-free days. On a multivariate logistic regression analysis, IAH was an independent predictor of both ICU mortality (odds ratio (OR), 12.20; 95% confidence interval (CI), 1.92 to 77.31, p = 0.008) and need for RRT (OR, 6.78; 95% CI, 1.29 to 35.70, p = 0.02). Using receiver operating characteristic curves, IAP (area under the curve (AUC) = 0.74, p = 0.004), APP (AUC = 0.71, p = 0.01), Acute Physiology and Chronic Health Evaluation II score (AUC = 0.71, p = 0.02), but not MAP, differentiated survivors from nonsurvivors.
IAH is highly prevalent in cirrhotic patients with septic shock and is associated with increased ICU morbidity and mortality.
PMCID: PMC3390301  PMID: 22873420
liver cirrhosis; sepsis; compartment syndrome; septic shock; ascites; mortality.
19.  Critical care management of severe traumatic brain injury in adults 
Traumatic brain injury (TBI) is a major medical and socio-economic problem, and is the leading cause of death in children and young adults. The critical care management of severe TBI is largely derived from the "Guidelines for the Management of Severe Traumatic Brain Injury" that have been published by the Brain Trauma Foundation. The main objectives are prevention and treatment of intracranial hypertension and secondary brain insults, preservation of cerebral perfusion pressure (CPP), and optimization of cerebral oxygenation. In this review, the critical care management of severe TBI will be discussed with focus on monitoring, avoidance and minimization of secondary brain insults, and optimization of cerebral oxygenation and CPP.
PMCID: PMC3298793  PMID: 22304785
Traumatic brain injury; head injury; head trauma; critical care
20.  Etomidate and mortality in cirrhotic patients with septic shock 
Clinical 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.
This 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.
Sixty 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.
In 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.
PMCID: PMC3295685  PMID: 22208901
21.  Impact of computerized physician order entry (CPOE) system on the outcome of critically ill adult patients: a before-after study 
Computerized physician order entry (CPOE) systems are recommended to improve patient safety and outcomes. However, their effectiveness has been questioned. Our objective was to evaluate the impact of CPOE implementation on the outcome of critically ill patients.
This was an observational before-after study carried out in a 21-bed medical and surgical intensive care unit (ICU) of a tertiary care center. It included all patients admitted to the ICU in the 24 months pre- and 12 months post-CPOE (Misys®) implementation. Data were extracted from a prospectively collected ICU database and included: demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, admission diagnosis and comorbid conditions. Outcomes compared in different pre- and post-CPOE periods included: ICU and hospital mortality, duration of mechanical ventilation, and ICU and hospital length of stay. These outcomes were also compared in selected high risk subgroups of patients (age 12-17 years, traumatic brain injury, admission diagnosis of sepsis and admission APACHE II > 23). Multivariate analysis was used to adjust for imbalances in baseline characteristics and selected clinically relevant variables.
There were 1638 and 898 patients admitted to the ICU in the specified pre- and post-CPOE periods, respectively (age = 52 ± 22 vs. 52 ± 21 years, p = 0.74; APACHE II = 24 ± 9 vs. 24 ± 10, p = 0.83). During these periods, there were no differences in ICU (adjusted odds ratio (aOR) 0.98, 95% confidence interval [CI] 0.7-1.3) and in hospital mortality (aOR 1.00, 95% CI 0.8-1.3). CPOE implementation was associated with similar duration of mechanical ventilation and of stay in the ICU and hospital. There was no increased mortality or stay in the high risk subgroups after CPOE implementation.
The implementation of CPOE in an adult medical surgical ICU resulted in no improvement in patient outcomes in the immediate phase and up to 12 months after implementation.
PMCID: PMC3248372  PMID: 22098683
Intensive care unit; critical illness; CPOE; safety management; mortality; morbidity
22.  In-Hospital Mortality Among a Cohort of Cirrhotic Patients Admitted to a Tertiary Hospital 
To determine the mortality rate in a cohort of hospitalized patients with cirrhosis and examine their resuscitation status at admission.
Materials and Methods:
A retrospective chart review was conducted of patients with cirrhosis who were admitted to a tertiary care hospital in Riyadh, Saudi Arabia, from January 1, 2009, to December 31, 2009.
We reviewed 226 cirrhotic patients during the study period. The hospital mortality rate was 35%. A univariate analysis revealed that worse outcomes were seen in patients with advanced age or who had worse child-turcotte-pugh (CPT) scores, worse model for end-stage liver disease (MELD) scores, low albumin and high serum creatinine. Using a multivariate analysis, we found that advanced age (P=0.004) and high MELD (P=0.001) scores were independent risk factors for the mortality of cirrhotic patients. The end-of-life decision were made in 34% of cirrhotic patients, and the majority of deceased patients were “no resuscitation” status (90% vs. 4%, P<0.001).
The relatively high mortality in cirrhotic patients admitted for care in a tertiary hospital, Saudi Arabia was comparable to that reported in the literature. Furthermore, end-of-life discussions should be addressed early in the hospitalization of cirrhotic patients.
PMCID: PMC3221112  PMID: 22064336
Cirrhosis; MELD score; mortality
23.  sRAGE in diabetic and non-diabetic critically ill patients: effects of intensive insulin therapy 
Critical Care  2011;15(4):R203.
Hyperglycemia represents an independent prognostic factor in critically ill non-diabetic patients but not in those with diabetes. In this context, there is an ongoing debate on the benefit of an intensive insulin therapy, particularly in diabetic patients. We tested the hypothesis that expression of the receptor for advanced glycation end-products (RAGE), an important signal transduction receptor that elicits long-lasting nuclear factor kappa B (NF-κB) activation, may underlie this difference. RAGE expression is regulated by multiple ligands, including high mobility group box-1 (HMGB-1), and is reflected by its released soluble form (sRAGE).
A predesigned analysis was conducted of prospectively collected samples from 76 hyperglycemic critically ill patients (33 type-2 diabetes, 43 non-diabetes) aged ≥18 years with blood glucose of > 6.1 mmol/L enrolled in a randomized controlled trial comparing intensive insulin therapy with conventional insulin therapy. sRAGE and its ligand HMGB-1 together with IL-6, and soluble thrombomodulin (as markers of inflammation and endothelial cell injury, respectively) were evaluated in ICU, at Days 1, 3, 5 and 7. Plasma samples from 18 healthy subjects were used as controls.
Both diabetic and non-diabetic hyperglycemic patients showed increased plasma sRAGE, HMGB-1 and soluble thrombomodulin levels at the time of admission to ICU. Plasma IL-6 concentration was only increased in non-diabetic patients. Plasma levels of sRAGE were higher in diabetic compared with non-diabetic patients. Intensive insulin therapy resulted in a significant decrease of sRAGE and thrombomodulin at Day 7, in diabetic but not in non-diabetic patients. Circulating sRAGE levels correlated positively with IL-6 and soluble thrombomodulin levels and inversely with HMGB-1. Multivariate regression analysis demonstrated that sRAGE remains independently correlated with HMGB-1 only in diabetic patients. Neither sRAGE nor any inflammatory markers are associated with mortality.
These findings support the hypothesis that sRAGE release, time-course and response to intensive insulin therapy differ between hyperglycemic diabetic and non-diabetic critically ill patients. Whether this difference underlies the dissimilarity in clinical outcome of hyperglycemia in these two conditions warrants further studies.
PMCID: PMC3387645  PMID: 21871056
24.  Association between statin therapy and outcomes in critically ill patients: a nested cohort study 
The effect of statin therapy on mortality in critically ill patients is controversial, with some studies suggesting a benefit and others suggesting no benefit or even potential harm. The objective of this study was to evaluate the association between statin therapy during intensive care unit (ICU) admission and all-cause mortality in critically ill patients.
This was a nested cohort study within two randomised controlled trials conducted in a tertiary care ICU. All 763 patients who participated in the two trials were included in this study. Of these, 107 patients (14%) received statins during their ICU stay. The primary endpoint was all-cause ICU and hospital mortality. Secondary endpoints included the development of sepsis and severe sepsis during the ICU stay, the ICU length of stay, the hospital length of stay, and the duration of mechanical ventilation. Multivariate logistic regression was used to adjust for clinically and statistically relevant variables.
Statin therapy was associated with a reduction in hospital mortality (adjusted odds ratio [aOR] = 0.60, 95% confidence interval [CI] 0.36-0.99). Statin therapy was associated with lower hospital mortality in the following groups: patients >58 years of age (aOR = 0.58, 95% CI 0.35-0.97), those with an acute physiology and chronic health evaluation (APACHE II) score >22 (aOR = 0.54, 95% CI 0.31-0.96), diabetic patients (aOR = 0.52, 95% CI 0.30-0.90), patients on vasopressor therapy (aOR = 0.53, 95% CI 0.29-0.97), those admitted with severe sepsis (aOR = 0.22, 95% CI 0.07-0.66), patients with creatinine ≤100 μmol/L (aOR = 0.14, 95% CI 0.04-0.51), and patients with GCS ≤9 (aOR = 0.34, 95% CI 0.17-0.71). When stratified by statin dose, the mortality reduction was mainly observed with statin equipotent doses ≥40 mg of simvastatin (aOR = 0.53, 95% CI 0.28-1.00). Mortality reduction was observed with simvastatin (aOR = 0.37, 95% CI 0.17-0.81) but not with atorvastatin (aOR = 0.80, 95% CI 0.84-1.46). Statin therapy was not associated with a difference in any of the secondary outcomes.
Statin therapy during ICU stay was associated with a reduction in all-cause hospital mortality. This association was especially noted in high-risk subgroups. This potential benefit needs to be validated in a randomised, controlled trial.
PMCID: PMC3199769  PMID: 21819615
25.  Management of severe sepsis in patients admitted to Asian intensive care units: prospective cohort study 
Objectives To assess the compliance of Asian intensive care units and hospitals to the Surviving Sepsis Campaign’s resuscitation and management bundles. Secondary objectives were to evaluate the impact of compliance on mortality and the organisational characteristics of hospitals that were associated with higher compliance.
Design Prospective cohort study.
Setting 150 intensive care units in 16 Asian countries.
Participants 1285 adult patients with severe sepsis admitted to these intensive care units in July 2009. The organisational characteristics of participating centres, the patients’ baseline characteristics, the achievement of targets within the resuscitation and management bundles, and outcome data were recorded.
Main outcome measure Compliance with the Surviving Sepsis Campaign’s resuscitation (six hours) and management (24 hours) bundles.
Results Hospital mortality was 44.5% (572/1285). Compliance rates for the resuscitation and management bundles were 7.6% (98/1285) and 3.5% (45/1285), respectively. On logistic regression analysis, compliance with the following bundle targets independently predicted decreased mortality: blood cultures (achieved in 803/1285; 62.5%, 95% confidence interval 59.8% to 65.1%), broad spectrum antibiotics (achieved in 821/1285; 63.9%, 61.3% to 66.5%), and central venous pressure (achieved in 345/870; 39.7%, 36.4% to 42.9%). High income countries, university hospitals, intensive care units with an accredited fellowship programme, and surgical intensive care units were more likely to be compliant with the resuscitation bundle.
Conclusions While mortality from severe sepsis is high, compliance with resuscitation and management bundles is generally poor in much of Asia. As the centres included in this study might not be fully representative, achievement rates reported might overestimate the true degree of compliance with recommended care and should be interpreted with caution. Achievement of targets for blood cultures, antibiotics, and central venous pressure was independently associated with improved survival.
PMCID: PMC3113333  PMID: 21669950

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