Victor Novack

Mechanical Ventilation Guided by Esophageal Pressure in Acute Lung Injury

BACKGROUND Survival of patients with acute lung injury or the acute respiratory distress syndrome (ARDS) has been improved by ventilation with small tidal volumes and the use of positive end-expiratory pressure (PEEP); however, the optimal level of PEEP has been difficult to determine. In this pilot study, we estimated transpulmonary pressure with the use of esophageal balloon catheters. We reasoned that the use of pleural-pressure measurements, despite the technical limitations to the accuracy of such measurements, would enable us to find a PEEP value that could maintain oxygenation while preventing lung injury due to repeated alveolar collapse or overdistention. METHODS We randomly assigned patients with acute lung injury or ARDS to undergo mechanical ventilation with PEEP adjusted according to measurements of esophageal pressure (the esophageal-pressure-guided group) or according to the Acute Respiratory Distress Syndrome Network standard-of-care recommendations (the control group). The primary end point was improvement in oxygenation. The secondary end points included respiratory-system compliance and patient outcomes. RESULTS The study reached its stopping criterion and was terminated after 61 patients had been enrolled. The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen at 72 hours was 88 mm Hg higher in the esophageal-pressure-guided group than in the control group (95% confidence interval, 78.1 to 98.3; P=0.002). This effect was persistent over the entire follow-up time (at 24, 48, and 72 hours; P=0.001 by repeated-measures analysis of variance). Respiratory-system compliance was also significantly better at 24, 48, and 72 hours in the esophageal-pressure-guided group (P=0.01 by repeated-measures analysis of variance). CONCLUSIONS As compared with the current standard of care, a ventilator strategy using esophageal pressures to estimate the transpulmonary pressure significantly improves oxygenation and compliance. Multicenter clinical trials are needed to determine whether this approach should be widely adopted. (ClinicalTrials.gov number, NCT00127491.)

Prior Statin Therapy Is Associated With a Decreased Rate of Severe Sepsis

Background—Statins have anti-inflammatory properties that are independent of their lipid-lowering abilities. We hypothesized that statin therapy before the onset of an acute bacterial infection may have a protective effect against severe sepsis. The aim of this study was to determine whether patients treated with statins develop severe sepsis less frequently. Methods and Results—In this prospective observational cohort study, consecutive patients admitted with presumed or documented acute bacterial infection were enrolled. The primary outcomes were the rate of severe sepsis and intensive care unit (ICU) admission. Of the 361 patients enrolled, 82 (22.7%) were treated with statins before their admission. Both groups had a similar severity of illness on admission. Severe sepsis developed in 19% of patients in the no-statin group and in only 2.4% of the statin group (P<0.001). Statin treatment was associated with a relative risk of developing severe sepsis of 0.13 (95% CI, 0.03 to 0.52) and an absolute risk reduction of 16.6%. The overall ICU admission rate was 10.2% (37/361): 12.2% of the no-statin group required ICU admission, whereas in the statin group only 3.7% were admitted to the ICU (P=0.025), reflecting a relative risk of ICU admission of 0.30 (95% CI, 0.1 to 0.95). Conclusions—Prior therapy with statins may be associated with a reduced rate of severe sepsis and ICU admission. If supported by prospective controlled trials, statins may have a role in the primary prevention of sepsis.

Iatrogenic Gastric Acid Suppression and the Risk of Nosocomial Clostridium difficile Infection

BACKGROUND The incidence and severity of Clostridium difficile infections are increasing. Acid-suppressive therapy has been suggested as a risk factor for C difficile, but this remains controversial. METHODS We conducted a pharmacoepidemiologic cohort study, performing a secondary analysis of data collected prospectively on 101 796 discharges from a tertiary care medical center during a 5-year period. The primary exposure of interest was acid suppression therapy, classified by the most intense acid suppression therapy received (no acid suppression, histamine(2)-receptor antagonist [H(2)RA] therapy, daily proton pump inhibitor [PPI], and PPI more frequently than daily). RESULTS As the level of acid suppression increased, the risk of nosocomial C difficile infection increased, from 0.3% (95% confidence interval [CI], 0.21%-0.31%) in patients not receiving acid suppressive therapy to 0.6% (95% CI, 0.49%-0.79%) in those receiving H(2)RA therapy, to 0.9% (95% CI, 0.80%-0.98%) in those receiving daily PPI treatment, and to 1.4% (1.15%-1.71%) in those receiving more frequent PPI therapy. After adjustment for comorbid conditions, age, antibiotics, and propensity score-based likelihood of receipt of acid-suppression therapy, the association persisted, increasing from an odds ratio of 1 (no acid suppression [reference]) to 1.53 (95% CI, 1.12-2.10) (H(2)RA), to 1.74 (95% CI, 1.39-2.18) (daily PPI), and to 2.36 (95% CI, 1.79-3.11) (more frequent PPI). Similar estimates were found with a matched cohort analysis and with nested case-control techniques. CONCLUSIONS Increasing levels of pharmacologic acid suppression are associated with increased risks of nosocomial C difficile infection. This evidence of a dose-response effect provides further support for the potentially causal nature of iatrogenic acid suppression in the development of nosocomial C difficile infection.

The effect of statin therapy on infection-related mortality in patients with atherosclerotic diseases*

Objective:Statins have pleiotropic effects that are independent of their lipid-lowering ability. We have previously shown that prior statin therapy is associated with a decreased risk of severe sepsis in patients admitted with acute bacterial infection. The aim of this study was to determine whether statin therapy is associated with a decreased risk of infection-related mortality. Design:A prospective, observational, population-based study. Setting:Tertiary university medical center. Patients:Using a computerized database, 11,490 patients with atherosclerotic diseases were identified and followed for up to 3 yrs. Two groups of patients were compared: those receiving statins in the final month before follow-up termination and those who were not. Interventions:None. Measurements and Main Results:The primary outcome was infection-related mortality. Of the 11,362 patients included in the final analysis, 5,698 (50.1%) belonged to the statin group. Median follow-up was 19.8 months (interquartile range, 14.3–33.3). The risk of infection-related mortality was significantly lower in the statin compared with the no-statin group (0.9% vs. 4.1%), reflecting a relative risk of 0.22 (95% confidence interval, 0.17–0.28). Stepwise Cox proportional hazard survival analysis including a propensity score for receiving statins revealed that the protective effect of statins adjusted for all known potential confounders remained highly significant (hazard ratio, 0.37; 95% confidence interval, 0.27–0.52). Conclusions:Therapy with statins may be associated with a reduced risk of infection-related mortality. This protective effect is independent of all known comorbidities and dissipates when the medication is discontinued. If this finding is supported by prospective controlled trials, statins may play an important role in the primary prevention of infection-related mortality.

The costs and cost-effectiveness of an integrated sepsis treatment protocol

Context:Sepsis is associated with high mortality and treatment costs. International guidelines recommend the implementation of integrated sepsis protocols; however, the true cost and cost-effectiveness of these are unknown. Objective:To assess the cost-effectiveness of an integrated sepsis protocol, as compared with conventional care. Design:Prospective cohort study of consecutive patients presenting with septic shock and enrolled in the institutions integrated sepsis protocol. Clinical and economic outcomes were compared with a historical control cohort. Setting:Beth Israel Deaconess Medical Center. Patients:Overall, 79 patients presenting to the emergency department with septic shock in the treatment cohort and 51 patients in the control group. Interventions:An integrated sepsis treatment protocol incorporating empirical antibiotics, early goal-directed therapy, intensive insulin therapy, lung-protective ventilation, and consideration for drotrecogin alfa and steroid therapy. Main Outcome Measures:In-hospital treatment costs were collected using the hospitals detailed accounting system. The cost-effectiveness analysis was performed from the perspective of the healthcare system using a lifetime horizon. The primary end point for the cost-effectiveness analysis was the incremental cost per quality-adjusted life year gained. Results:Mortality in the treatment group was 20.3% vs. 29.4% in the control group (p = .23). Implementing an integrated sepsis protocol resulted in a mean increase in cost of ∼

Association of lipid levels during gestation with preeclampsia and gestational diabetes mellitus: a population-based study

8,800 per patient, largely driven by increased intensive care unit length of stay. Life expectancy and quality-adjusted life years were higher in the treatment group; 0.78 and 0.54, respectively. The protocol was associated with an incremental cost of

Troponin Criteria for Myocardial Infarction After Percutaneous Coronary Intervention

11,274 per life-year saved and a cost of

Esophageal pressures in acute lung injury: do they represent artifact or useful information about transpulmonary pressure, chest wall mechanics, and lung stress?

16,309 per quality-adjusted life year gained. Conclusions:In patients with septic shock, an integrated sepsis protocol, although not cost-saving, appears to be cost-effective and compares very favorably to other commonly delivered acute care interventions.

Continuous perioperative insulin infusion decreases major cardiovascular events in patients undergoing vascular surgery: a prospective, randomized trial.

OBJECTIVE The study evaluates lipids profile changes during gestation in pregnancies with and without preeclampsia and/or gestational diabetes. STUDY DESIGN Lipid profiles were assessed between year prior and after pregnancy in 9911 women without cardiovascular comorbidities. RESULTS Lipid levels during gestation varied substantially with a nadir following conception and a peak at delivery. Compared to preconception levels total cholesterol levels increased from 164.4 mg/dL to 238.6 mg/dL and triglycerides (TGs) from 92.6 mg/dL to 238.4 mg/dL. The composite endpoint (gestational diabetes mellitus or preeclampsia) occurred in 1209 women (12.2%). Its prevalence increased with levels of TG-from 7.2% in the group with low TGs (<25th percentile adjusted for the gestational month) to 19.8% in the group with high TGs (>75th percentile), but was not associated with high-density lipoprotein levels. In multivariate analysis higher TGs levels, but not low high-density lipoprotein, were associated with the primary endpoint. CONCLUSION Lipid levels change substantially during gestation. Abnormal levels of TGs are associated with pregnancy complications.

The role of cardiac troponin I as a prognosticator in critically ill medical patients: a prospective observational cohort study

BACKGROUND The universal definition of myocardial infarction specifies creatine kinase-MB fraction (CKMB) or troponin values more than 3 times the 99th percentile of the upper reference limit as diagnostic after percutaneous coronary intervention, with a preference for the use of troponin. METHODS Outcomes of 4930 patients with elective coronary stent placement between July 1, 2004, and September 30, 2007, as part of the EVENT (Evaluation of Drug Eluting Stents and Ischemic Events) registry were analyzed to test the association between 1-year mortality and postprocedure elevation of either CKMB or troponin. All values were normalized to the individual clinical center myocardial infarction diagnostic levels. RESULTS Myocardial infarction occurred in 7.2% of patients by the CKMB criteria and in 24.3% of patients by the troponin criteria of greater than 3 times the diagnostic level. Both CKMB (hazard ratio [HR], 1.38; 95% CI, 1.22-1.55) and troponin (HR, 1.35; 95% CI, 1.18-1.54) as continuous values were associated with 1-year mortality. The mortality effect of a more than 3-fold increase was greater for CKMB (adjusted HR, 2.5; 95% CI, 1.5-4.1) than for troponin (adjusted HR, 1.7; 95% CI, 1.1-2.5). A troponin threshold more than 20 times the diagnostic level provided similar frequency (7.0%) and mortality risk (adjusted HR, 2.6; 95% CI, 1.6-4.3) as a 3-fold increase in CKMB. A regression spline model of the relationship between troponin and 1-year mortality demonstrated that the hazard of mortality increased from 1.02 at 3-fold to 1.67 at 20-fold troponin elevation. CONCLUSION Troponin and CKMB elevations after percutaneous coronary intervention are associated with increased 1-year mortality rates, but thresholds for similar event frequency and mortality hazard are much higher for troponin than for CKMB.