Rahul Kashyap

Predictors of Acute Kidney Injury in Septic Shock Patients: An Observational Cohort Study

BACKGROUND AND OBJECTIVES Acute kidney injury (AKI) is a frequent complication in critically ill patients and sepsis is the most common contributing factor. We aimed to determine the risk factors associated with AKI development in patients with septic shock. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Observational cohort study consisted of consecutive adults with septic shock admitted to a medical intensive care unit (ICU) of a tertiary care academic hospital from July 2005 to September 2007. AKI was defined according to RIFLE criteria (urine output and creatinine criteria). Demographic, clinical, and treatment variables were reviewed. Main outcomes measured were AKI occurrence, all-cause hospital mortality, and hospital and ICU length of stay. RESULTS Three hundred ninety patients met inclusion criteria, of which 237 (61%) developed AKI. AKI development was independently associated with delay to initiation of adequate antibiotics, intra-abdominal sepsis, blood product transfusion, use of angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker, and body mass index (kg/m²). Higher baseline GFR and successful early goal directed resuscitation were associated with a decreased risk of AKI. Hospital mortality was significantly greater in patients who developed AKI (49 versus 34%). CONCLUSIONS In a contemporary cohort of patients with septic shock, both patient and health care delivery risk factors seemed to be important for AKI development.

Fresh Red Blood Cell Transfusion and Short-Term Pulmonary, Immunologic, and Coagulation Status A Randomized Clinical Trial

RATIONALE Transfusion-related pulmonary complications are leading causes of morbidity and mortality attributed to transfusion. Observational studies suggest an important role for red blood cell (RBC) storage duration in these adverse outcomes. OBJECTIVES To evaluate the impact of RBC storage duration on short-term pulmonary function as well as immunologic and coagulation status in mechanically ventilated patients receiving RBC transfusion. METHODS This is a double-blind, randomized, clinical trial comparing fresh (≤5 d of storage) versus standard issue single-unit RBC transfusion in adult intubated and mechanically ventilated patients. The primary outcome is the change in pulmonary gas exchange as assessed by the partial pressure of arterial oxygen to fraction of inspired oxygen concentration ratio (ΔPa(O(2))/Fi(O(2))). Secondary outcomes include changes in immune and coagulation status. MEASUREMENTS AND MAIN RESULTS Fifty patients were randomized to receive fresh RBCs and an additional 50 patients to standard issue RBCs. Median storage age was 4.0 days (interquartile range, 3.0-5.0) and 26.5 days (interquartile range, 21.0-36.0) in the fresh RBC group and standard issue RBC group, respectively. No differences were noted in the primary outcome of ΔPa(O(2))/Fi(O(2)) (difference between the mean ΔPa(O(2))/Fi(O(2)) in the standard issue RBC group vs. the fresh RBC group, -11.5; 95% confidence interval, -35.3 to 12.3; P = 0.22). Similarly, no significant differences were noted in markers of immunologic or coagulation status. CONCLUSIONS In this randomized clinical trial, no differences were noted in early measures of pulmonary function or in immunologic or coagulation status when comparing fresh versus standard issue single-unit RBC transfusion. Clinical trial registered with ClinicalTrials.gov (NCT00751322).

Derivation and Diagnostic Accuracy of the Surgical Lung Injury Prediction Model

Background:Acute lung injury (ALI) is a serious postoperative complication with limited treatment options. A preoperative risk-prediction model would assist clinicians and scientists interested in ALI. The objective of this investigation was to develop a surgical lung injury prediction (SLIP) model to predict risk of postoperative ALI based on readily available preoperative risk factors. Methods:Secondary analysis of a prospective cohort investigation including adult patients undergoing high-risk surgery. Preoperative risk factors for postoperative ALI were identified and evaluated for inclusion in the SLIP model. Multivariate logistic regression was used to develop the model. Model performance was assessed with the area under the receiver operating characteristic curve and the Hosmer-Lemeshow goodness-of-fit test. Results:Out of 4,366 patients, 113 (2.6%) developed early postoperative ALI. Predictors of postoperative ALI in multivariate analysis that were maintained in the final SLIP model included high-risk cardiac, vascular, or thoracic surgery, diabetes mellitus, chronic obstructive pulmonary disease, gastroesophageal reflux disease, and alcohol abuse. The SLIP score distinguished patients who developed early postoperative ALI from those who did not with an area under the receiver operating characteristic curve (95% CI) of 0.82 (0.78–0.86). The model was well calibrated (Hosmer-Lemeshow, P = 0.55). Internal validation using 10-fold cross-validation noted minimal loss of diagnostic accuracy with a mean ± SD area under the receiver operating characteristic curve of 0.79 ± 0.08. Conclusions:Using readily available preoperative risk factors, we developed the SLIP scoring system to predict risk of early postoperative ALI.

Septic shock: A multidisciplinary response team and weekly feedback to clinicians improve the process of care and mortality

Objective:To evaluate the impact of weekly feedback to clinicians and the activation of a sepsis response team on the process of care and hospital mortality in patients with severe sepsis or septic shock. Design:Prospective, interventional cohort study. Setting:The medical intensive care unit of a tertiary, academic medical center. Study Subjects:Patients with severe sepsis or septic shock consecutively treated in a medical intensive care unit. Interventions:Daily auditing and weekly feedback, and sepsis response team activation. Measurements and Main Results:During a 33-month study period, from January 2007 through September 2009, we performed daily screening of patients for severe sepsis or septic shock. Study periods were divided into baseline (screening only), daily auditing with weekly feedback, and sepsis response team activation. Comparisons among the three periods were made by using univariate and multiple logistic regression analyses. Compliance with the overall sepsis resuscitation bundle and its individual elements and hospital mortality were used as outcome measures. A total of 984 episodes of severe sepsis and septic shock were identified during the study periods, severe sepsis in 52 (5.3%) and septic shock in 932 (94.7%). The compliance rate with all elements of the sepsis resuscitation bundle increased from 12.7% at baseline to 37.7% and 53.7% during the weekly feedback and sepsis response team activation periods, respectively (p < .001). Overall hospital mortality rate was 30.3%, 28.3%, and 22.0% during baseline, weekly feedback, and sepsis response team periods, respectively (p = .029). Multiple logistic regression analysis showed that the sepsis response team was associated with reduced risk of hospital death (odds ratio, 0.657; 95% confidence interval, 0.456–0.945; p = .023) whereas hepatic cirrhosis, hepatic failure, leukemia, multiple myeloma, transfer from the same hospital ward, do-not-resuscitate status at the recognition of severe sepsis/septic shock, and lactate level were associated with increased risk of death. Conclusions:In septic shock, the activation of the sepsis response team in combination with weekly feedback increases the compliance with the process of care and reduces hospital mortality rate.

Acute lung injury prediction score: derivation and validation in a population-based sample.

Early recognition of patients at high risk of acute lung injury (ALI) is critical for successful enrolment of patients in prevention strategies for this devastating syndrome. We aimed to develop and prospectively validate an ALI prediction score in a population-based sample of patients at risk. In a retrospective derivation cohort, predisposing conditions for ALI were identified at the time of hospital admission. The score was calculated based on the results of logistic regression analysis. Prospective validation was performed in an independent cohort of patients at risk identified at the time of hospital admission. In a derivation cohort of 409 patients with ALI risk factors, the lung injury prediction score discriminated patients who developed ALI from those who did not with an area under the curve (AUC) of 0.84 (95% CI 0.80–0.89; Hosmer–Lemeshow p = 0.60). The performance was similar in a prospective validation cohort of 463 patients at risk of ALI (AUC 0.84, 95% CI 0.77–0.91; Hosmer–Lemeshow p = 0.88). ALI prediction scores identify patients at high risk for ALI before intensive care unit admission. If externally validated, this model will serve to define the population of patients at high risk for ALI in whom future mechanistic studies and ALI prevention trials will be conducted.

Long-Term Survival and Quality of Life After Transfusion-Associated Pulmonary Edema in Critically III Medical Patients

BACKGROUND Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) commonly complicate transfusion in critically ill patients. Prior outcome studies of TACO and TRALI have focused on short-term morbidity and mortality, but the long-term survival and quality of life (QOL) of these patients remain unknown. METHODS In a nested case-control study, we compared survival and QOL between critically ill medical patients who developed pulmonary edema after transfusion (TRALI or TACO) and medical critically ill transfused controls, matched by age, gender, and admission diagnostic group. QOL in survivors was assessed with a 36-item short form health survey 1 year after initial hospitalization. RESULTS Hospital, 1-year, and 2-year mortality among the 74 TRALI cases and 74 matched controls were 43.2% vs 24.3% (P = .020), 63.8% vs 46.4% (P = .037) and 74.3% vs 54.3% (P = .031), whereas among the 51 TACO cases and 51 matched controls these values were 7.8% vs 11.8% (P = .727), 38.0% vs 28.0% (P = .371), and 44.9% vs 38.8% (P = .512). When adjusted for age and baseline severity of illness in a Cox proportional hazard analysis, the development of TRALI remained associated with decreased survival (hazard ratio 1.86; 95% CI, 1.19-2.93; P = .006). Both TRALI (P = .006, P = .03) and TACO (P = .03, P = .049) were associated with prolonged ICU and hospital lengths of stay. CONCLUSIONS In critically ill medical patients, development of TRALI, but not TACO, is independently associated with decreased long-term survival.

Timing of the Onset of Acute Respiratory Distress Syndrome: A Population-Based Study

BACKGROUND: Many patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) have had recent healthcare interventions prior to developing ALI/ARDS. OBJECTIVE: To determine the timing of ALI/ARDS onset in relation to hospital admission and other healthcare interventions. METHODS: We conducted a population-based observational cohort study with a validated electronic surveillance tool, and identified patients with possible ALI/ARDS among critically ill adults at Mayo Clinic hospitals that provide critical care services for Olmsted County, Minnesota, in 2006. Trained investigators independently reviewed electronic medical records and confirmed the presence and timing of ALI/ARDS based on the American-European consensus definition. RESULTS: Of 124 episodes of ALI in 118 patients, only 5 did not fulfill the ARDS criteria. The syndrome developed a median 30 hours (IQR 10–82 h) after hospital admission in 79 patients (67%). ARDS was present on admission in 39 patients (33%), of whom 14 had recent hospitalization, 6 were transferred from nursing homes, and 3 had recent out-patient contact (1 antibiotic prescription, 1 surgical intervention, and 1 chemotherapy). Only 16 ARDS patients (14%) did not have known recent contact with a healthcare system. Compared to ARDS on admission, hospital-acquired ARDS was more likely to occur in surgery patients (54% vs 15%, P < .001), and had longer adjusted hospital stay (mean difference 8.9 d, 95% CI 0.3–17.4, P = .04). CONCLUSIONS: ARDS in the community most often develops either during hospitalization or in patients who recently had contact with a healthcare system. These findings have important implications for potential preventive strategies.

Increased fluid administration in the first three hours of sepsis resuscitation is associated with reduced mortality: a retrospective cohort study.

BACKGROUND The surviving sepsis guidelines recommend early aggressive fluid resuscitation within 6 h of sepsis onset. Although rapid fluid administration may offer benefit, studies on the timing of resuscitation are lacking. We hypothesized that there is an association between quicker, adequate fluid resuscitation and patient outcome from sepsis onset time. METHODS This is a retrospective cohort study of consecutive adults with severe sepsis and septic shock admitted to a quaternary care medical ICU between January 2007 and December 2009. Data were collected from a previously validated electronic medical database. Multivariate regression modeling was performed, adjusting for age, admission weight, Sequential Organ Failure Assessment score, APACHE (Acute Physiology and Chronic Health Examination) III score, and total fluid administration within the first 6 h of sepsis onset time. RESULTS Of 651 patients with severe sepsis and septic shock screened, 594 had detailed fluid data. In a univariate analysis, the median amount of fluid within the first 3 h for survivors at discharge was 2,085 mL (940-4,080 mL) and for nonsurvivors, 1,600 mL (600-3,010 mL; P = .007). In comparison, during the latter 3 h, the median amount was 660 mL (290-1,485 mL) vs 800 mL (360-1,680 mL; P = .09), respectively. After adjusting for confounders, the higher proportion of total fluid received within the first 3 h was associated with decreased hospital mortality (OR, 0.34; 95% CI, 0.15-0.75; P = .008). CONCLUSIONS Earlier fluid resuscitation (within the first 3 h) is associated with a greater number of survivors with severe sepsis and septic shock.

Epidemiology of critical care syndromes, organ failures, and life-support interventions in a suburban US community

BACKGROUND ICU services represent a significant and increasing proportion of medical care. Population-based epidemiologic studies are essential to inform physicians and policymakers about current and future ICU demands. We aimed to determine the incidence of critical care syndromes, organ failures, and life-support interventions in a defined US suburban community with unrestricted access to critical care services. METHODS This population-based observational cohort from January 1 to December 31, 2006, in Olmsted County, Minnesota, included all consecutive critically ill adult residents admitted to the ICU. Main outcomes were incidence of critical care syndromes, life-support interventions, and organ failures as defined by standard criteria. Incidences are reported per 100,000 population (95% CIs) and were age adjusted to the 2006 US population. RESULTS A total of 1,707 ICU admissions were identified from 1,461 patients. Incidences of critical care syndromes were respiratory failure, 430 (390-470); acute kidney injury, 290 (257-323); severe sepsis, 286 (253-319); all-cause shock, 194 (167-221); acute lung injury, 86 (68-105); all-cause coma, 43 (30-55); and overt disseminated intravascular coagulation, 18 (10-26). Incidence of mechanical ventilation was invasive, 310 (276-344); noninvasive, 180 (154-206); vasopressors and inotropes, 183(155-208). Renal replacement therapy incidence was 96 (77-116). Of the cohort, 1,330 patients (91%) survived to hospital discharge. Short- and long-term survival decreased by the number of failing organs. CONCLUSIONS In a suburban US community with high access to critical care services, cumulative incidences of critical care syndromes and life-support interventions were higher than previously reported. The results of this study have important implications for future planning of critical care delivery.

The role of potentially preventable hospital exposures in the development of acute respiratory distress syndrome: a population-based study.

Objective:Acute respiratory distress syndrome is a common complication of critical illness, with high mortality and limited treatment options. Preliminary studies suggest that potentially preventable hospital exposures contribute to acute respiratory distress syndrome development. We aimed to determine the association between specific hospital exposures and the rate of acute respiratory distress syndrome development among at-risk patients. Design:Population-based, nested, Matched case-control study. Patients:Consecutive adults who developed acute respiratory distress syndrome from January 2001 through December 2010 during their hospital stay (cases) were matched to similar-risk patients without acute respiratory distress syndrome (controls). They were matched for 6 baseline characteristics. Interventions:None. Measurements and Main Results:Trained investigators blinded to outcome of interest reviewed medical records for evidence of specific exposures, including medical and surgical adverse events, inadequate empirical antimicrobial treatment, hospital-acquired aspiration, injurious mechanical ventilation, transfusion, and fluid and medication administration. Conditional logistic regression was used to calculate the risk associated with individual exposures. During the 10-year period, 414 patients with hospital-acquired acute respiratory distress syndrome were identified and matched to 414 at-risk, acute respiratory distress syndrome-free controls. Adverse events were highly associated with acute respiratory distress syndrome development (odds ratio, 6.2; 95% CI, 4.0–9.7), as were inadequate antimicrobial therapy, mechanical ventilation with injurious tidal volumes, hospital-acquired aspiration, and volume of blood products transfused and fluids administered. Exposure to antiplatelet agents during the at-risk period was associated with a decreased risk of acute respiratory distress syndrome. Rate of adverse hospital exposures and prevalence of acute respiratory distress syndrome decreased during the study period. Conclusions:Prevention of adverse hospital exposures in at-risk patients may limit the development of acute respiratory distress syndrome.