Marc Moss

The effect of age on the development and outcome of adult sepsis

Objective:Sepsis is an increasingly common and lethal medical condition that occurs in people of all ages. The influence of age on sepsis risk and outcome is incompletely understood. We sought to determine the independent effect of age on the incidence, severity, and outcome of adult sepsis. Design:Longitudinal observational study using national hospital discharge data. Setting:Approximately 500 geographically separated nonfederal acute care hospitals in the United States. Patients:Patients were 10,422,301 adult sepsis patients hospitalized over 24 yrs, from 1979 to 2002. Interventions:None. Measurements and Main Results:Incident sepsis cases were age adjusted and characterized by demographics, sources and types of infection, comorbid medical conditions, and hospital discharge status. Elderly patients (≥65 yrs of age) accounted for 12% of the U.S. population and 64.9% of sepsis cases, yielding a relative risk of 13.1 compared with younger patients (95% confidence interval, 12.6–13.6). Elderly patients were more likely to have Gram-negative infections, particularly in association with pneumonia (relative risk, 1.66; 95% confidence interval, 1.63–1.69) and to have comorbid medical conditions (relative risk, 1.99; 95% confidence interval, 1.92–2.06). Case-fatality rates increased linearly by age; age was an independent predictor of mortality in an adjusted multivariable regression (odds ratio, 2.26; 95% confidence interval, 2.17–2.36). Elderly sepsis patients died earlier during hospitalization, and elderly survivors were more likely to be discharged to a nonacute health care facility. Conclusions:The incidence of sepsis is disproportionately increased in elderly adults, and age is an independent predictor of mortality. Compared with younger sepsis patients, elderly nonsurvivors of sepsis die earlier during hospitalization and elderly survivors more frequently require skilled nursing or rehabilitative care after hospitalization. These findings have implications for patient care and health care resource prioritization and provide insights for expanded scientific investigations and potential patient interventions.

Postoperative Delirium in the Elderly : Risk Factors and Outcomes

Objective:The purpose of this study was to describe the natural history, identify risk factors, and determine outcomes for the development of postoperative delirium in the elderly. Background:Postoperative delirium is a common and deleterious complication in geriatric patients. Methods:Subjects older than 50 years scheduled for an operation requiring a postoperative intensive care unit admission were recruited. After preoperative informed written consent, enrolled subjects had baseline cognitive and functional assessments. Postoperatively, subjects were assessed daily for delirium using the confusion assessment method-intensive care unit. Patients were also followed for outcomes. Results:During the study period, 144 patients were enrolled before major abdominal (40%), thoracic (53%), or vascular (7%) operations. The overall incidence of delirium was 44% (64/144). The average time to onset of delirium was 2.1 ± 0.9 days and the mean duration of delirium was 4.0 ± 5.1 days. Several preoperative variables were associated with an increased risk of delirium including older age (P < 0.001), hypoalbuminemia (P < 0.001), impaired functional status (P < 0.001), pre-existing dementia (P < 0.001), and pre-existing comorbidities (P < 0.001). In a multivariable logistic regression model, pre-existing dementia remains the strongest risk factor for the development of postoperative delirium. Worse outcomes, including increased length of stay (P < 0.001), postdischarge institutionalization (P < 0.001), and 6 month mortality (P = 0.001), occurred in subjects who developed delirium. Conclusions:In the current study, delirium occurred in 44% of elderly patients after a major operation. Pre-existing cognitive dysfunction was the strongest predictor of the development of postoperative delirium. Outcomes, including an increased rate of 6 month mortality, were worse in patients who developed postoperative delirium.

Redefining geriatric preoperative assessment using frailty, disability and co-morbidity.

Objectives:(1) Determine the relationship of geriatric assessment markers to 6-month postoperative mortality in elderly patients. (2) Create a clinical prediction rule using geriatric markers from preoperative assessment. Background:Geriatric surgery patients have unique physiologic vulnerability requiring preoperative assessment beyond the traditional evaluation of older adults. The constellation of frailty, disability and comorbidity predict poor outcomes in elderly hospitalized patients. Methods:Prospectively, subjects ≥65 years undergoing a major operation requiring postoperative intensive care unit admission were enrolled. Preoperative geriatric assessments included: Mini-Cog Test (cognition), albumin, having fallen in the past 6-months, hematocrit, Katz Score (function), and Charlson Index (comorbidities). Outcome measures included 6-month mortality (primary) and postdischarge institutionalization (secondary). Results:One hundred ten subjects (age 74 ± 6 years) were studied. Six-month mortality was 15% (16/110). Preoperative markers related to 6-month mortality included: impaired cognition (P < 0.01), recent falls (P < 0.01), lower albumin (P < 0.01), greater anemia (P < 0.01), functional dependence (P < 0.01), and increased comorbidities (P < 0.01). Similar statistical relationships were found for all 6 markers and postdischarge institutionalization. Logistic regression identified any functional dependence (odds ratio 13.9) as the strongest predictor of 6-month mortality. Four or more markers in any one patient predicted 6-month mortality with a sensitivity of 81% (13/16) and specificity of 86% (81/94). Conclusions:Geriatric assessment markers for frailty, disability and comorbidity predict 6-month postoperative mortality and postdischarge institutionalization. The preoperative presence of ≥4 geriatric-specific markers has high sensitivity and specificity for 6-month mortality. Preoperative assessment using geriatric-specific markers is a substantial paradigm shift from the traditional preoperative evaluation of older adults.

The epidemiology of sepsis.

Sepsis is a common and devastating syndrome that represents a significant healthcare burden worldwide. The average annual cost to care for patients with sepsis has been estimated to being

Accumulated Frailty Characteristics Predict Postoperative Discharge Institutionalization in the Geriatric Patient

16.7 billion. Uniform definitions have been developed for the spectrum of sepsis syndrome, including the systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis and septic shock. SIRS describes the clinical manifestations derived from an acute yet nonspecific illness, whereas an infectious etiology is required for the diagnosis of sepsis. As sepsis progresses, organ system dysfunction becomes apparent (severe sepsis) with the final development of fluid refractory cardiovascular dysfunction (septic shock). Pulmonary, gastrointestinal, genitourinary, and primary bloodstream infections account for the majority of infectious sources in septic patients. Since 1987, gram positive bacteria have become the most common organisms responsible for the development of sepsis. Several risk factors for the development of sepsis have been identified including male sex, race, age, comorbid medical conditions, alcohol abuse, and a lower socioeconomic status. Seasonal variations also exist, with sepsis being more common in the winter months. Fortunately, the case fatality rates for both sepsis and severe sepsis have diminished over the last two decades. However, patients who survive their episode of sepsis continue to have increased morbidity and mortality up to five years after their initial illness.

The role of infection and comorbidity: Factors that influence disparities in sepsis.

BACKGROUND Frailty is a state of increased vulnerability to health-related stressors and can be measured by summing the number of frailty characteristics present in an individual. Discharge institutionalization (rather than discharge to home) represents disease burden and functional dependence after hospitalization. Our aim was to determine the relationship between frailty and need for postoperative discharge institutionalization. STUDY DESIGN Subjects ≥ 65 years undergoing major elective operations requiring postoperative ICU admission were enrolled. Discharge institutionalization was defined as need for institutionalized care at hospital discharge. Fourteen preoperative frailty characteristics were measured in 6 domains: comorbidity burden, function, nutrition, cognition, geriatric syndromes, and extrinsic frailty. RESULTS A total of 223 subjects (mean age 73 ± 6 years) were studied. Discharge institutionalization occurred in 30% (n = 66). Frailty characteristics related to need for postoperative discharge institutionalization included: older age, Charlson index ≥ 3, hematocrit <35%, any functional dependence, up-and-go ≥ 15 seconds, albumin <3.4 mg/dL, Mini-Cog score ≤ 3, and having fallen within 6 months (p < 0.0001 for all comparisons). Multivariate logistic regression retained prolonged timed up-and-go (p < 0.0001) and any functional dependence (p < 0.0001) as the variables most closely related to need for discharge institutionalization. An increased number of frailty characteristics present in any one subject resulted in increased rate of discharge institutionalization. CONCLUSIONS Nearly 1 in 3 geriatric patients required discharge to an institutional care facility after major surgery. The frailty characteristics of prolonged up-and-go and any functional dependence were most closely related to the need for discharge institutionalization. Accumulation of a higher number of frailty characteristics in any one geriatric patient increased their risk of discharge institutionalization.

Toll-like Receptor 1 Polymorphisms Affect Innate Immune Responses and Outcomes in Sepsis

Objective:Large healthcare disparities exist in the incidence of sepsis based on both race and gender. We sought to determine factors that may influence the occurrence of these healthcare disparities, with respect to the source of infection, causal organisms, and chronic comorbid medical conditions. Design:Historical cohort study. Setting:U.S. acute care hospitals from 1979 to 2003. Patients:Hospitalized patients with a diagnosis of sepsis were identified from the National Hospital Discharge Survey per codes of the International Statistical Classification of Diseases, Ninth Revision (ICD-9CM). Chronic comorbid medical conditions and the source and type of infection were characterized by corresponding ICD-9CM diagnoses. Interventions:None. Measurements and Main Results:Sepsis incidence rates are mean cases per 100,000 after age adjustment to the 2000 U.S. Census. Males and nonwhite races were confirmed at increased risk for sepsis. Both proportional source distribution and incidence rates favored respiratory sources of sepsis in males (36% vs. 29%, p < .01) and genitourinary sources in females (35% vs. 27%, p < .01). Incidence rates for all common sources of sepsis were greater in nonwhite races, but proportional source distribution was approximately equal. After stratification by the source of infection, males (proportionate ratio 1.16, 95% confidence interval 1.04–1.29) and black persons (proportionate ratio 1.25, 95% confidence interval 1.18–1.32) remained more likely to have Gram-positive infections. Chronic comorbid conditions that alter immune function (chronic renal failure, diabetes mellitus, HIV, alcohol abuse) were more common in nonwhite sepsis patients, and cumulative comorbidities were associated with greater acute organ dysfunction. Compared with white sepsis patients, nonwhite sepsis patients had longer hospital length of stay (2.0 days, 95% confidence interval 1.9–2.1) and were less likely to be discharged to another medical facility (30% whites, 25% blacks, 18% other races). Case-fatality rates were not significantly different across racial and gender groups. Conclusions:Healthcare disparities exist in the incidence of sepsis within all major sources of infection, and males and blacks have greater frequency of Gram-positive infections independent of the infection source. The differential distribution of specific chronic comorbid medical conditions may contribute to these disparities. Large cohort and administrative studies are required to confirm discrete root causes of sepsis disparities.

Diabetic patients have a decreased incidence of acute respiratory distress syndrome

RATIONALE Polymorphisms affecting Toll-like receptor (TLR)-mediated responses could predispose to excessive inflammation during an infection and contribute to an increased risk for poor outcomes in patients with sepsis. OBJECTIVES To identify hypermorphic polymorphisms causing elevated TLR-mediated innate immune cytokine and chemokine responses and to test whether these polymorphisms are associated with increased susceptibility to death, organ dysfunction, and infections in patients with sepsis. METHODS We screened single-nucleotide polymorphisms (SNPs) in 43 TLR-related genes to identify variants affecting TLR-mediated inflammatory responses in blood from healthy volunteers ex vivo. The SNP associated most strongly with hypermorphic responses was tested for associations with death, organ dysfunction, and type of infection in two studies: a nested case-control study in a cohort of intensive care unit patients with sepsis, and a case-control study using patients with sepsis, patients with sepsis-related acute lung injury, and healthy control subjects. MEASUREMENTS AND MAIN RESULTS The SNP demonstrating the most hypermorphic effect was the G allele of TLR1(-7202A/G) (rs5743551), which associated with elevated TLR1-mediated cytokine production (P < 2 x 10(-20)). TLR1(-7202G) marked a coding SNP that causes higher TLR1-induced NF-kappaB activation and higher cell surface TLR1 expression. In the cohort of patients with sepsis TLR1(-7202G) predicted worse organ dysfunction and death (odds ratio, 1.82; 95% confidence interval, 1.07-3.09). In the case-control study TLR1(-7202G) was associated with sepsis-related acute lung injury (odds ratio, 3.40; 95% confidence interval, 1.59-7.27). TLR1(-7202G) also associated with a higher prevalence of gram-positive cultures in both clinical studies. CONCLUSIONS Hypermorphic genetic variation in TLR1 is associated with increased susceptibility to organ dysfunction, death, and gram-positive infection in sepsis.

Extravascular lung water in patients with severe sepsis: a prospective cohort study.

Objective Our ability to predict which critically ill patients will develop acute respiratory distress syndrome (ARDS) is imprecise. Based on the effects of diabetes mellitus on the inflammatory cascade, we hypothesized that a history of diabetes might alter the incidence of ARDS. Design A prospective multicenter study. Setting Intensive care units at four university medical centers. Patients One hundred thirteen consecutive patients with septic shock. Interventions None. Measurements and Main Results All patients were prospectively followed during their intensive care course for the development of ARDS. A history of diabetes was identified in 28% (32/113) of the patients. In this study, nondiabetics were more likely to develop septic shock from a pulmonary source (48%, 39/81) compared with diabetics (25%, 8/32) (p = .02). Forty-one percent (46/113) of the patients with septic shock developed ARDS. Forty-seven percent of the nondiabetic patients developed ARDS compared with only 25% of those with diabetes (p = .03, relative risk = 0.53, 95% confidence interval = 0.28–0.98). In a multivariate logistic regression analysis, when we adjusted for several variables including source of infection, the effect of diabetes on the incidence of ARDS remained significant (p = .03, odds ratio = 0.33, 95% confidence interval = 0.12–0.90). Conclusions In patients with septic shock, a history of diabetes is associated with a lower risk of developing ARDS compared with nondiabetics.

Frailty predicts increased hospital and six-month healthcare cost following colorectal surgery in older adults.

IntroductionFew investigations have prospectively examined extravascular lung water (EVLW) in patients with severe sepsis. We sought to determine whether EVLW may contribute to lung injury in these patients by quantifying the relationship of EVLW to parameters of lung injury, to determine the effects of chronic alcohol abuse on EVLW, and to determine whether EVLW may be a useful tool in the diagnosis of acute respiratory distress syndrome (ARDS).MethodsThe present prospective cohort study was conducted in consecutive patients with severe sepsis from a medical intensive care unit in an urban university teaching hospital. In each patient, transpulmonary thermodilution was used to measure cardiovascular hemodynamics and EVLW for 7 days via an arterial catheter placed within 72 hours of meeting criteria for severe sepsis.ResultsA total of 29 patients were studied. Twenty-five of the 29 patients (86%) were mechanically ventilated, 15 of the 29 patients (52%) developed ARDS, and overall 28-day mortality was 41%. Eight out of 14 patients (57%) with non-ARDS severe sepsis had high EVLW with significantly greater hypoxemia than did those patient with low EVLW (mean arterial oxygen tension/fractional inspired oxygen ratio 230.7 ± 36.1 mmHg versus 341.2 ± 92.8 mmHg; P < 0.001). Four out of 15 patients with severe sepsis with ARDS maintained a low EVLW and had better 28-day survival than did ARDS patients with high EVLW (100% versus 36%; P = 0.03). ARDS patients with a history of chronic alcohol abuse had greater EVLW than did nonalcoholic patients (19.9 ml/kg versus 8.7 ml/kg; P < 0.0001). The arterial oxygen tension/fractional inspired oxygen ratio, lung injury score, and chest radiograph scores correlated with EVLW (r2 = 0.27, r2 = 0.18, and r2 = 0.28, respectively; all P < 0.0001).ConclusionsMore than half of the patients with severe sepsis but without ARDS had increased EVLW, possibly representing subclinical lung injury. Chronic alcohol abuse was associated with increased EVLW, whereas lower EVLW was associated with survival. EVLW correlated moderately with the severity of lung injury but did not account for all respiratory derangements. EVLW may improve both risk stratification and management of patients with severe sepsis.