Gordon Jacobsen

Early lactate clearance is associated with improved outcome in severe sepsis and septic shock

Objective:Serial lactate concentrations can be used to examine disease severity in the intensive care unit. This study examines the clinical utility of the lactate clearance before intensive care unit admission (during the most proximal period of disease presentation) as an indicator of outcome in severe sepsis and septic shock. We hypothesize that a high lactate clearance in 6 hrs is associated with decreased mortality rate. Design:Prospective observational study. Setting:An urban emergency department and intensive care unit over a 1-yr period. Patients:A convenience cohort of patients with severe sepsis or septic shock. Interventions:Therapy was initiated in the emergency department and continued in the intensive care unit, including central venous and arterial catheterization, antibiotics, fluid resuscitation, mechanical ventilation, vasopressors, and inotropes when appropriate. Measurements and Main Results:Vital signs, laboratory values, and Acute Physiology and Chronic Health Evaluation (APACHE) II score were obtained at hour 0 (emergency department presentation), hour 6, and over the first 72 hrs of hospitalization. Therapy given in the emergency department and intensive care unit was recorded. Lactate clearance was defined as the percent decrease in lactate from emergency department presentation to hour 6. Logistic regression analysis was performed to determine independent variables associated with mortality. One hundred and eleven patients were enrolled with mean age 64.9 ± 16.7 yrs, emergency department length of stay 6.3 ± 3.2 hrs, and overall in-hospital mortality rate 42.3%. Baseline APACHE II score was 20.2 ± 6.8 and lactate 6.9 ± 4.6 mmol/L. Survivors compared with nonsurvivors had a lactate clearance of 38.1 ± 34.6 vs. 12.0 ± 51.6%, respectively (p = .005). Multivariate logistic regression analysis of statistically significant univariate variables showed lactate clearance to have a significant inverse relationship with mortality (p = .04). There was an approximately 11% decrease likelihood of mortality for each 10% increase in lactate clearance. Patients with a lactate clearance ≥10%, relative to patients with a lactate clearance <10%, had a greater decrease in APACHE II score over the 72-hr study period and a lower 60-day mortality rate (p = .007). Conclusions:Lactate clearance early in the hospital course may indicate a resolution of global tissue hypoxia and is associated with decreased mortality rate. Patients with higher lactate clearance after 6 hrs of emergency department intervention have improved outcome compared with those with lower lactate clearance.

Utility assessment among patients with dry eye disease

PURPOSE To determine utilities (patient preferences) for dry eye disease. DESIGN Survey study. PARTICIPANTS Fifty-six patients with mild, moderate, or severe dry eye treated by ophthalmologists in the Eye Care Services department of Henry Ford Health Care System. TESTING Patients completed interactive software utility assessment questionnaires by the time trade-off (TTO) method. Utility scores were scaled such that a score of 1.0 = perfect health and 0 = death. Dry eye severity was independently classified using clinical parameters and physician/patient assessments. Global health status, visual functioning, and ocular symptoms were assessed by the Short Form-36 Health Survey, 25-Item National Eye Institute Visual Function Questionnaire (NEI VFQ-25), and Ocular Surface Disease Index survey instruments. MAIN OUTCOME MEASURES Utility scores for a range of dry eye severity states. These utilities were compared with utilities reported for other disease states. Correlations with the general and vision-related health status measures were conducted. RESULTS Fifty-six patients completed the utility assessments with acceptable reliability. Mean utilities for moderate (0.78) and severe dry eye (0.72) by TTO were similar to historical reports for moderate (0.75) and more severe (class III/IV) angina (0.71), respectively. Utility scores correlated with the NEI VFQ-25 composite score (rho = 0.32; P = 0.037) and with components of other health measures. CONCLUSIONS Utilities for the more severe forms of dry eye are in the range of conditions like class III/IV angina (0.71) that are widely recognized as lowering health utilities. Our results underscore how significantly dry eye impacts patients compared with other medical conditions.

The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock.

Background:Despite abundant experimental studies of biomarker patterns in early severe sepsis and septic shock, human data are few. Further, the impact of the severity of global tissue hypoxia resulting from resuscitative strategies on these early biomarker patterns remains unknown. Methods:The temporal patterns of interleukin-1 receptor antagonist, intercellular adhesion molecule-1, tumor necrosis factor-&agr;, caspase-3, and interleukin-8 were serially examined over the first 72 hrs of hospitalization after early hemodynamic optimization strategies of early goal-directed vs. standard therapy for severe sepsis and septic shock patients. The relationship of these biomarker patterns to each hemodynamic optimization strategy, severity of global tissue hypoxia (reflected by lactate and central venous oxygen saturation), organ dysfunction, and mortality were examined. Results:Abnormal biomarker levels were present upon hospital presentation and modulated to distinct patterns within 3 hrs based on the hemodynamic optimization strategy. The temporal expression of these patterns over 72 hrs was significantly associated with the severity of global tissue hypoxia, organ dysfunction, and mortality. Conclusion:In early severe sepsis and septic shock, within the first 3 hrs of hospital presentation, distinct biomarker patterns emerge in response to hemodynamic optimization strategies. A significant association exists between temporal biomarker patterns in the first 72 hrs, severity of global tissue hypoxia, organ dysfunction, and mortality. These findings identify global tissue hypoxia as an important contributor to the early inflammatory response and support the role of hemodynamic optimization in supplementing other established therapies during this diagnostic and therapeutic “window of opportunity.”

Effects of Increasing Maintenance Dose of Digoxin on Left Ventricular Function and Neurohormones in Patients With Chronic Heart Failure Treated With Diuretics and Angiotensin-Converting Enzyme Inhibitors

BACKGROUND Despite almost three centuries of use, the appropriate dosage of digitalis in patients with chronic heart failure and normal sinus rhythm has not been well studied. METHODS AND RESULTS We studied 22 patients with heart failure who were receiving constant daily doses of digoxin, diuretics, and angiotensin-converting enzyme (ACE) inhibitors. In 18 patients, the oral daily dose of digoxin was increased from a mean of 0.20 +/- 0.07 to 0.39 +/- 0.11 mg/day corresponding to an increase in the serum digoxin concentration from 0.67 +/- 0.22 to 1.22 +/- 0.35 ng/mL. Radionuclide and echocardiographic left ventricular ejection fraction; maximal treadmill time; heart failure score; serum concentrations of norepinephrine, aldosterone, atrial natriuretic factor, and antidiuretic hormone; and plasma renin activity were obtained before and after the increase in digoxin dose. Subsequently, 9 patients were randomized to receive digoxin and 9 to receive placebo and radionuclide ejection fraction measured after 12 weeks. With the higher dose of digoxin compared with the lower dose, there was a significant increase in radionuclide ejection fraction from 23.7 +/- 9.6% to 27.1 +/- 11.8% (P = .007). No significant changes were noted in heart failure score; exercise tolerance; serum concentrations of norepinephrine, atrial natriuretic factor, and antidiuretic hormone; and plasma renin activity. There was, however, an increase in serum aldosterone concentration. Twelve weeks after the patients were randomized to receive digoxin or placebo, there was a significant decrease in ejection fraction (from 29.4 +/- 10.4% to 23.7 +/- 8.9%) in the placebo group but not in patients who continued to receive digoxin (P = .002). CONCLUSIONS The increase in maintenance digoxin dose, while maintaining serum concentrations within therapeutic range, resulted in a significant increase in left ventricular ejection fraction that was not associated with significant changes in heart failure score, exercise tolerance, and neurohumoral profile.

Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock

BackgroundLactate clearance, a surrogate for the magnitude and duration of global tissue hypoxia, is used diagnostically, therapeutically and prognostically. This study examined the association of early lactate clearance with selected inflammatory, coagulation, apoptosis response biomarkers and organ dysfunction scores in severe sepsis and septic shock.MethodsMeasurements of serum arterial lactate, biomarkers (interleukin-1 receptor antagonist, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha, intercellular adhesion molecule-1, high mobility group box-1, D-Dimer and caspase-3), and organ dysfunction scores (Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology Score II, Multiple Organ Dysfunction Score, and Sequential Organ Failure Assessment) were obtained in conjunction with a prospective, randomized study examining early goal-directed therapy in severe sepsis and septic shock patients presenting to the emergency department (ED). Lactate clearance was defined as the percent change in lactate levels after six hours from a baseline measurement in the ED.ResultsTwo-hundred and twenty patients, age 65.0 +/- 17.1 years, were examined, with an overall lactate clearance of 35.5 +/- 43.1% and in-hospital mortality rate of 35.0%. Patients were divided into four quartiles of lactate clearance, -24.3 +/- 42.3, 30.1 +/- 7.5, 53.4 +/- 6.6, and 75.1 +/- 7.1%, respectively (p < 0.01). The mean levels of all biomarkers and organ dysfunction scores over 72 hours were significantly lower with higher lactate clearance quartiles (p < 0.01). There was a significant decreased in-hospital, 28-day, and 60-day mortality in the higher lactate clearance quartiles (p < 0.01).ConclusionsEarly lactate clearance as a surrogate for the resolution of global tissue hypoxia is significantly associated with decreased levels of biomarkers, improvement in organ dysfunction and outcome in severe sepsis and septic shock.

Central venous-arterial carbon dioxide difference as an indicator of cardiac index

Abstract Objective: The mixed venous-arterial (v-a) pCO2 difference has been shown to be inversely correlated with the cardiac index (CI). A central venous pCO2, which is easier to obtain, may provide similar information. The purpose of this study was to examine the correlation between the central venous-arterial pCO2 difference and CI. Design: Prospective, cohort study. Setting: Intensive care unit of an urban tertiary care hospital. Patients and participants: Eighty-three consecutive intensive care unit patients. Measurements: Simultaneous blood gases from the arterial, pulmonary artery (PA), and central venous (CV) catheters were obtained. At the same time point, cardiac indices were measured by the thermodilution technique (an average of three measurements). The cardiac indices obtained by the venous-arterial differences were compared with those determined by thermodilution. Results: The correlation (R2) between the mixed venous-arterial pCO2 difference and cardiac index was 0.903 ( p <0.0001), and the correlation between the central venous-arterial pCO2 difference and cardiac index was 0.892 ( p <0.0001). The regression equations for these relationships were natural log (CI)=1.837−0.159 (v-a) CO2 for the PA and natural log (CI)=1.787−0.151 (v-a) CO2 for the CV ( p <0.0001 for both). The root-mean-squared error for the PA and CV regression equations were 0.095 and 0.101, respectively. Conclusion: Venous-arterial pCO2 differences obtained from both the PA and CV circulations inversely correlate with the cardiac index. Substitution of a central for a mixed venous-arterial pCO2 difference provides an accurate alternative method for calculation of cardiac output.

The utility of a double-lumen tube for one-lung ventilation in a variety of noncardiac thoracic surgical procedures

To determine the utility of one-lung ventilation (OLV) in a variety of noncardiac thoracic surgical procedures, 200 patients were studied to document the ease of double-lumen tube (DLT) placement, associated complications, intraoperative respiratory changes, and methods for managing hypoxic events. Most tubes could be placed, repositioned when necessary, and secured within 12 minutes. By defining tube position with fiberoptic bronchoscopy, auscultatory assessment of placement was found to be incorrect in 38.0% of patients. The tip occluded the respective upper lobe orifice in 40.5% of this subgroup, the endobronchial cuff was at or above the carina in 38.7%, and in the wrong mainstem bronchus in 20.8%. During OLV, PaO2 initially fell to approximately 200 mmHg in most patients but gradually rose during the balance of the operation. Hypoxia (PaO2 less than 80 mmHg) during OLV developed in 28.5% of patients. Preoperative spirometry and arterial blood gases had no predictive value for this complication. Pulse oximetry values between 95% and 100% reliably reflected systemic arterial oxygen saturation. Hypoxia occurring during OLV was successfully reversed in 40.0% of instances by positive end-expiratory pressure (PEEP) to the ventilated lung. The addition of continuous positive airway pressure (CPAP) to the nonventilated lung reversed persistent hypoxia in virtually all cases. There was no difference in oxygenation, carbon dioxide elimination, airway pressures, or intraoperative complications noted between right and left double-lumen tubes. In conclusion, a DLT for OLV can expeditiously and safely be placed. Because auscultation for tube position is unreliable, bronchoscopic assessment of final position should be performed in every instance. Hypoxia during OLV can be detected reliably by pulse oximetry.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of three treatment strategies for esophageal cancer within a single institution

Fifty-seven patients with esophageal cancer were treated with curative intent between January 1979 and June 1985. Seventeen were treated with radical radiation therapy alone (TD 4000-6500 cGy in 200-250 cGy fractions). Twenty-five were treated using radiation therapy (3000 cGy in 200 cGy fractions, day 1-19, and 2600-3000 cGy in 200 cGy fractions, day 50-68) and concomitant chemotherapy (5-FU and Cis-platinum). Fifteen were treated preoperatively by radiation therapy (3000 cGy at 200 cGy fractions) and concomitant chemotherapy (5-FU and Cis-platinum) followed by esophagectomy in 2-3 weeks. Chi square tests showed no significant baseline differences between the patients in the three different treatment groups with respect to A.J.C. stage, T status, location of tumor or histology. Median survival and 2-year survival for the three treatment groups were RT alone: 5 months and 0%, RT and chemotherapy: 12 months and 37%, RT, chemotherapy and surgery 13 months and 38%. A Cox multivariate analysis revealed significant predictor variables for increased survival were treatment strategy, RT dose delivered and T status. Increased local control was seen with either multimodality approach compared to radiation therapy alone. Our data suggests that a multimodality approach is superior as a curative treatment strategy, compared to RT alone, in esophageal cancer. In our series no significant differences were seen with respect to treatment outcome between the two multimodality approaches used.

The increased need for a permanent pacemaker after reoperative cardiac surgery

OBJECTIVE The requirement for permanent pacemaker implantation after most initial cardiac surgical procedures generally is less than 3%. To identify the incidence and factors related to permanent pacemaker need after repeat cardiac surgery, we retrospectively studied 558 consecutive patients undergoing at least one repeat cardiac operation. METHOD Univariable and multivariable analyses of comorbidity, preoperative catheterization values, and operative data were performed to identify factors related to pacemaker implantation. RESULTS In this group, 54 patients (9.7%) required a permanent pacemaker. A multivariable model showed a relationship between a permanent pacemaker and tricuspid valve replacement/annuloplasty associated with aortic/mitral valve replacement, preoperative endocarditis, increasing number of reoperations, the degree of hypothermia during cardiopulmonary bypass, and advanced age. Additional univariable predictors of pacemaker need included multiple valve replacement, increased cardiopulmonary bypass and aortic crossclamp times, and aortic valve replacement. Over 90% of patients who have or have not received permanent pacemaker implantation were in New York Heart Association class I to II, with a mean follow-up time of 6 years. Kaplan-Meier survival curves were statistically similar for both groups at 5 and 10 years after the operation. CONCLUSION Permanent pacemaker implantation was required in 9.7% of patients undergoing repeat cardiac surgery. This represented approximately a fourfold increase compared with similar primary operations reported in other series. Factors strongly related to this need included valve replacement, preoperative endocarditis, number of reoperations, advanced age, and degree of hypothermia during cardiopulmonary bypass. The need for a permanent pacemaker after reoperations did not result in significant long-term impairment of functional status or longevity compared with those who did not require a permanent pacemaker.

Relationship among p53, stage, and prognosis of large bowel cancer

PURPOSE: We designed a study to determine whether increases inp53protein in primary carcinomas of the colon or rectum correlate with overall survival. Mutations of the tumor suppressor genep53are detectable by immunocytochemical methods in colorectal cancers because of accumulation of nuclearp53protein. METHODS: IgG1 monoclonal antibody to humanp53protein (PAb 1801) was used to detectp53in formalin-fixed, paraffin-embedded archival tumors resected from 84 patients with tumor limited to the bowel wall. A multivariate analysis was performed using five prognostic pathobiologic variables compared with the level of staining of thep53product. RESULTS: Nuclearp53protein was observed in 52 (62 percent) of 84 colorectal cancer patients with Stage T2 or T3, N0, M0 disease. Patients with strong expression (3+ and 4+) ofp53appeared to die from their disease sooner than those with weak expression (1+ and 2+), although this was not statistically significant (P >0.59). Thirty-two patients did not express nuclearp53by immunocytochemical methods. When these patients were analyzed in combination with the strongp53expressors, the trend toward decreased survival increased (P>0.15). CONCLUSIONS: This data suggest that lack ofp53expression may also predict an adverse outcome in colorectal cancer. However, before the immunocytochemical method can be used clinically as a prognostic indicator, the colorectal cancer patients with zero expression should be studied further to clarify the functional status ofp53in their tumors.