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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Use of intermittent pneumatic compression and not graduated compression stockings is associated with lower incident VTE in critically ill patients: a multiple propensity scores adjusted analysis.

BACKGROUND: A limited amount of data exist regarding the effect of intermittent pneumatic compression (IPC) and graduated compression stockings (GCS) on the incidence of VTE in the ICU setting. The objective of this study was to examine the association of mechanical thromboprophylaxis with IPC or GCS with the risk of VTE and hospital mortality among critically ill medical-surgical patients. METHODS: In this prospective cohort study of patients admitted to the ICU of a tertiary-care medical center between July 2006 and January 2008, we used multiple propensity scores adjustment to examine the association of IPC and GCS with VTE. The primary outcome was incident VTE, including DVT and pulmonary embolism. The following data were collected: patient demographics, admission physiologic data, VTE risk factors, pharmacologic thromboprophylaxis, and mechanical thromboprophylaxis. RESULTS: Among 798 patients enrolled in the study, incident VTE occurred in 57 (7.1%). The use of IPC was associated with a significantly lower VTE incidence compared with no mechanical thromboprophylaxis (propensity scores adjusted hazard ratio, 0.45; 95% CI, 0.22-0.95; P=.04). GCS were not associated with decreased VTE incidence. No significant interaction was found between the mechanical thromboprophylaxis group and the type of prophylactic heparin used (P=.99), recent trauma (P=.66), or recent surgery (P=.07) on VTE risk. CONCLUSIONS: The use of IPC, but not GCS, was associated with a significantly lower VTE risk. This association was consistent regardless of the type of prophylactic heparin used and was not modified by trauma or surgical admission.

Antimicrobial therapeutic determinants of outcomes from septic shock among patients with cirrhosis.

UNLABELLED: 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.

Preparedness lessons from modern disasters and wars.

Disasters come in all shapes and forms, and in varying magnitudes and intensities. Nevertheless, they offer many of the same lessons for critical care practitioners and responders. Among these, the most important is that well thought out risk assessment and focused planning are vital. Such assessment and planning require proper training for providers to recognize and treat injury from disaster, while maintaining safety for themselves and others. This article discusses risk assessment and planning in the context of disasters. The article also elaborates on the progress toward the creation of portable, credible, sustainable, and sophisticated critical care outside the walls of an intensive care unit. Finally, the article summarizes yields from military-civilian collaboration in disaster planning and response.

Prolonged coma from refractory status epilepticus.

OBJECTIVE: Status epilepticus is a life-threatening medical condition. In its most severe form, refractory status epilepticus (RSE) seizures may not respond to first and second-line anti-epileptic drugs. RSE is associated with a high mortality and significant medical complications in survivors with prolonged hospitalizations. METHODS: We describe the clinical course of RSE in the setting of new onset lupus in a 31-year-old male who required prolonged barbiturate coma. RESULTS: Seizure stopped on day 64 of treatment. Prior to the resolution of seizures, discussion around withdrawal of care took place between the physicians and patient's family. Medical care was continued because of the patient's age, normal serial MRI studies, and the patient's reversible medical condition. CONCLUSION: Few evidence-based data exist to guide management of RSE. Our case emphasizes the need for continuous aggressive therapy when neuroimaging remains normal.

Fresh frozen plasma transfusion in critically ill medical patients with coagulopathy.

OBJECTIVE: Although restrictive red cell transfusion practice has become a standard of care in the critically ill, data on the use of fresh frozen plasma (FFP) are limited. We hypothesized that the practice of FFP transfusion in the medical intensive care unit is variable and that liberal use may not be associated with improved outcome. DESIGN: Retrospective cohort study. SETTING: A 24-bed medical intensive care unit in a tertiary referral center. PATIENTS: All patients admitted to a medical intensive care unit during a 5-month period who had abnormal coagulation defined as international normalized ratio (INR) of > or = 1.5-times normal. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We collected data on demographics, severity of illness as measured by Acute Physiology and Chronic Health Evaluation (APACHE) III scores, INR, bleeding episodes, and transfusion complications. We identified 115 patients with coagulopathy (INR of > or = 1.5) but without active bleeding. A total of 44 patients (38.3%) received FFP transfusion. INR was corrected in 16 of 44 patients (36%) who received transfusion. Median dose of FFP was 17 mL/kg in patients who had INR corrected vs. 10 mL/kg in those who did not (p = .018). There was no difference in age, sex, APACHE III scores, liver disease, Coumadin treatment, or INR level between those who did and did not receive FFP. Invasive procedures (68.2% vs. 40.8%, p = .004) and history of recent gastrointestinal bleeding (41% vs. 7%, p < .001) were more frequent in the group with transfusion. Although there was no difference in new bleeding episodes (6.8% in transfused vs. 2.8% in nontransfused group, p = .369), new onset acute lung injury was more frequent in the transfused group (18% vs. 4%, p = .021). Adjusted for severity of illness, hospital mortality and intensive care unit length of stay among survivors were not different between the two groups. CONCLUSION: The risk-benefit ratio of FFP transfusion in critically ill medical patients with coagulopathy may not be favorable. Randomized controlled trials evaluating restrictive vs. liberal FFP transfusion strategies are warranted.

Intensivist-to-bed ratio: association with outcomes in the medical ICU.

OBJECTIVE: With an increasing number of critical care beds, a shortage of critical care physicians, and pressure from purchasers, there is a need to define the optimal intensivist-to-ICU bed ratio. The objective of this study was to determine if there are any associations between the intensivist-to-ICU bed ratio and the outcome of patients admitted to the medical ICU. DESIGN: Retrospective cohort study. SETTING: A tertiary care medical center. PATIENTS: All critically ill patients admitted to a medical ICU between December 8, 2001, and July 14, 2003. INTERVENTIONS: None. MEASUREMENTS: Demographics, APACHE (acute physiology and chronic health evaluation) III-predicted mortality, ICU length of stay (LOS), hospital LOS, and ICU and hospital mortality rates. Four time periods based on intensivist-to-ICU bed ratios of 1:7.5, 1:9.5, 1:12, and 1:15 were identified. Regression analyses were performed to develop customized models to predict ICU and hospital LOS and mortality. The ICU LOS ratio, defined as the ratio of the observed to predicted LOS, and standardized mortality ratio (SMR) were calculated for each of the four periods. RESULTS: A total of 2,492 patients were included in the study. There was no difference in the severity of illness at the time of ICU admission among the four periods. The mean ICU LOS ratio was longer for an intensivist-to-ICU bed ratio of 1:15 compared to the other periods. The ICU and hospital SMR did not differ significantly among the four periods. CONCLUSION: Differences in intensivist-to-ICU bed ratios, ranging from 1:7.5 to 1:15, were not associated with differences in ICU or hospital mortality. However, a ratio of 1:15 was associated with increased ICU LOS.

Engendering enthusiasm for sustainable disaster critical care response: why this is of consequence to critical care professionals?

Disaster medical response has historically focused on the pre-hospital and initial treatment needs of casualties. In particular, the critical care component of many disaster response plans is incomplete. Equally important, routinely available critical care resources are almost always insufficient to respond to disasters that generate anything beyond a 'modest' casualty stream. Large-scale monetary funding to effectively remedy these shortfalls is unavailable. Education, training, and improved planning are our most effective initial steps. We suggest several areas for further development, including dual usage of resources that may specifically augment critical care disaster medical capabilities over time.

Worldwide disaster medical response: an historical perspective.

OBJECTIVE: Disaster medicine and disaster medical response is a complex and evolving field that has existed for millennia. The objective of this article is to provide a brief review of significant milestones in the history of disaster medicine with emphasis on applicability to present and future structures for disaster medical response. RESULTS: Disaster medical response is an historically necessary function in any society. These range from response to natural disasters, to the ravages of warfare, and most recently, to medical response after terrorist acts. Our current disaster response systems are largely predicated on military models derived over the last 200 yrs. Their hallmark is a structured and graded response system based on numbers of casualties. In general, all of these assume that there is an identifiable "ground zero" and then proceed with echelons of casualty retrieval and care that proceeds rearward to a hospital(s). In a civil response setting, most civilian models of disaster medical response similarly follow this military model. This historical approach may not be applicable to some threats such as bioterrorism. A "new" model of disaster medical response for this type of threat is still evolving. Using history to guide our future education and planning efforts is discussed. CONCLUSION: We can learn much from an historical perspective that is still applicable to many current disaster medical threats. However, a new response model may be needed to address the threats of bioterrorism.

Outcome of patients with end-stage renal disease admitted to the intensive care unit.

OBJECTIVES: To describe the clinical course of patients with end-stage renal disease (ESRD) admitted to the intensive care unit (ICU) and to compare the performance of Acute Physiology and Chronic Health Evaluation (APACHE) III and Sequential Organ Failure Assessment (SOFA) in predicting their outcome. PATIENTS AND METHODS: This retrospective cohort study consisted of patients with ESRD admitted to 3 ICUs between January 1, 1997, and November 30, 2002. Data on demographics, APACHE III score, SOFA score, development of sepsis and organ failure, use of mechanical ventilation, and mortality were collected. RESULTS: Of the 476 patients with ESRD who underwent dialysis during the study period, 93 (20%) required admission to the ICU. The most common ICU admission diagnosis was gastrointestinal bleeding. The first day median (Interquartile range) APACHE III score, SOFA score, and APACHE III predicted hospital mortality rate were 64 (47-79), 6 (5-8), and 12.9% (4.2%-30.8%), respectively. The observed ICU, hospital, and 30-day mortality rates were 9%, 16%, and 22%, respectively. Nonrenal organ failure developed in 48 patients (52%) and sepsis in 15 patients (16%). Mechanical ventilation was required In 26 patients (28%). The area under the receiver operating characteristic curve for the first-day APACHE III probability of hospital death in predicting 30-day mortality was 0.78 (95% confidence interval, 0.68-0.86) compared with 0.66 (95% confidence interval, 0.55-0.76) for the SOFA score (P = .16). CONCLUSIONS: The observed hospital mortality of patients with ESRD admitted to the ICU is relatively low. There is no statistically significant difference in the performance of APACHE III and SOFA prognostic models in discriminating between 30-day survivors and nonsurvivors.

Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation.

OBJECTIVE: Although ventilation with small tidal volumes is recommended in patients with established acute lung injury, most others receive highly variable tidal volume aimed in part at normalizing arterial blood gas values. We tested the hypothesis that acute lung injury, which develops after the initiation of mechanical ventilation, is associated with known risk factors for ventilator-induced lung injury such as ventilation with large tidal volume. DESIGN: Retrospective cohort study. SETTING: Four intensive care units in a tertiary referral center. PATIENTS: Patients who received invasive mechanical ventilation for > or = 48 hrs between January and December 2001. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome of interest, acute lung injury, was assessed by independent review of daily digital chest radiographs and arterial blood gases. Ventilator settings, hemodynamics, and acute lung injury risk factors were extracted from the Acute Physiology and Chronic Health Evaluation III database and the patients' medical records. Of 332 patients who did not have acute lung injury from the outset, 80 patients (24%) developed acute lung injury within the first 5 days of mechanical ventilation. When expressed per predicted body weight, women were ventilated with larger tidal volume than men (mean 11.4 vs. 10.4 mL/kg predicted body weight, p <.001) and tended to develop acute lung injury more often (29% vs. 20%, p =.068). In a multivariate analysis, the main risk factors associated with the development of acute lung injury were the use of large tidal volume (odds ratio 1.3 for each mL above 6 mL/kg predicted body weight, p <.001), transfusion of blood products (odds ratio, 3.0; p < 0.001), acidemia (pH < 7.35; odds ratio, 2.0; p =.032) and a history of restrictive lung disease (odds ratio, 3.6; p =.044). CONCLUSIONS: The association between the initial tidal volume and the development of acute lung injury suggests that ventilator-associated lung injury may be an important cause of this syndrome. Height and gender should be considered when setting up the ventilator. Strong consideration should be given to limiting large tidal volume, not only in patients with established acute lung injury but also in patients at risk for acute lung injury.