Lynn J. Hydo

Hypothermia during elective abdominal aortic aneurysm repair: The high price of avoidable morbidity

PURPOSE Adverse outcomes apparently associated with hypothermia led us to examine patients undergoing elective abdominal aortic aneurysm (AAA) repairs to test the hypothesis that hypothermia (temperature less than 34.5 degrees C) is associated with increased morbidity and excess mortality rates. METHODS Two hundred sixty-two elective AAA repairs were retrospectively reviewed for preoperative and intraoperative risk factors. Core temperature, age, Acute Physiology and Chronic Health Evaluation (APACHE) II and APACHE III scores (raw and temperature-adjusted), fluid resuscitation, and perioperative organ dysfunction were recorded prospectively. Outcome measures included lengths of stay in the intensive care unit and in the hospital, and hospital mortality rates. RESULTS Except for a higher risk of hypothermia in women (p < 0.05), by univariate analysis, preoperative risk factors were similar in patients in the hypothermic and normothermic groups. After operation, patients with hypothermia had significantly greater APACHE scores (p < 0.0001), and patients in the hypothermic nonsurvivor group took significantly longer to rewarm (p < 0.05), suggesting marked hypoperfusion. Patients with hypothermia had significantly greater fluid (p < 0.05), transfusion (p < 0.01), vasopressor (p < 0.05), and inotrope (p < 0.05) requirements, resulting in significantly higher incidences of organ dysfunction (53.0% vs 28.7%, p < 0.01) and death (12.1% vs 1.5%, p < 0.01) and markedly prolonged lengths of stay in the unit (9.2 +/- 2.0 vs 5.3 +/- 0.6, p < 0.05) and in the hospital (24.3 +/- 2.9 vs 15.0 +/- 0.08, p < 0.01). By multivariate analysis, female gender (p = 0.004) was the only predictor of intraoperative hypothermia, whereas initial hypothermia was significantly predictive of both prolonged hypothermia and development of organ failure (p < 0.05). Organ failure (p < 0.05) and acute myocardial infarction (p < 0.01) were independent predictors of death. CONCLUSIONS After AAA repair, patients with hypothermia have multiple physiologic derangements associated with adverse outcomes. Although multiple etiologic factors are interacting, body temperature is one variable that should be controlled during aortic surgery.

Factors influencing the development of decubitus ulcers in critically ill surgical patients.

IntroductionDecubitus ulcers confer significant morbidity to critically ill patients. We sought to determine which patient factors contributed to the formation of decubitus ulcers in our critically ill patients, and hypothesized that these ulcers occurred most often in elderly patients with lengths of stay >7 days and high severity of illness. MethodsThis study was conducted prospectively in two phases. Phase I provided an initial analysis of patients who developed decubitus ulcers in the surgical intensive care unit (ICU) of New York Weill Cornell Center from January 1, 1993, to June 1, 1997. In phase II of the study, a comparison study was made for patients with ICU length of stay (ULOS) >7 days admitted to the same ICU from January 1, 1998, to August 31, 1998. Age, APACHE III score, systemic inflammatory response syndrome (SIRS score), multiple organ dysfunction syndrome (MODS) score, admission status, days without nutrition, ULOS, mortality, days to formation of decubitus ulcers, Cornell ulcer risk score, and other demographic features were recorded. Univariate and multivariate analysis of variance were performed to analyze independent risk factors for development of decubitus ulcers;p < .05. ResultsIn phase I, 2,615 patients were admitted to surgical ICU over the study period. One hundred and one decubitus ulcers occurred (incidence 3.8%) during phase I, but the incidence of decubitus ulcers increased significantly over time to 9% (p < .01). Thirty-three decubitus ulcers occurred among the 412 patients (incidence 8.0%) during phase II. Multivariate analysis revealed that emergent admission (odds ratio [OR] 36.00, 95% confidence interval [CI] CI 0.2290–0.7694), age (OR 1.08, 95% CI 0.0026–0.0131), days in bed (OR 1.05, 95% CI −0.0013–0.0156, and days without nutrition (OR 0.51, 95% CI −0.1095–−0.0334) were independent predictors of a decubitus ulcer. ConclusionsThe incidence of decubitus ulcers is increasing in critically ill patients. Emergency ICU admission and ULOS >7 days in elderly patients confer significant risk for the formation of decubitus ulcers. Specific interventions targeting this high-risk population that may be instituted to decrease the incidence of decubitus ulcers include early nutrition, early mobilization, and possibly less noxious bedding surfaces.

Does de-escalation of antibiotic therapy for ventilator-associated pneumonia affect the likelihood of recurrent pneumonia or mortality in critically ill surgical patients?

BACKGROUND Ventilator-associated pneumonia (VAP) is a leading cause of mortality in critically ill patients. Although previous studies have shown that de-escalation therapy (DT) of antibiotics may decrease costs and the development of resistant pathogens, minimal data have shown its effect in surgical patients or in any patients with septic shock. We hypothesized that DT for VAP was not associated with an increased rate of recurrent pneumonia (RP) or mortality in a high acuity cohort of critically ill surgical patients. METHODS All surgical intensive care unit (SICU) patients from January 2005 to May 2007 with VAP diagnosed by quantitative bronchoalveolar lavage with a positive threshold of 10,000 CFU/mL were identified. Data collected included age, gender, Acute Physiologic and Chronic Health Evaluation Score III (A3), type of bacterial or other pathogen, antibiotics used for initial and final therapy, mortality, RP, and appropriateness of initial therapy (AIT). Patients were designated as receiving AIT, DT, or escalation of antibiotic therapy based on microbiology for their VAP. RESULTS One hundred thirty-eight of 1,596 SICU patients developed VAP during the study period (8.7%). For VAP patients, the mean Acute Physiologic and Chronic Health Evaluation III score was 82.7 points with a mean age of 63.8 years. The RP rate was 30% and did not differ between patients receiving DT (27.3%) and those who did not receive DT (35.1%). Overall mortality was 37% (55% predicted by A3 norms) and did not differ between those receiving DT (33.8%) or not (42.1%). The most common pathogens for primary VAP were methicillin-resistant Staphylococcus aureus (14%), Escherichia coli (11%), and Pseudomonas aeruginosa (9%) whereas P. aeruginosa was the most common pathogen in RP. The AIT for all VAP was 93%. De-escalation of therapy occurred in 55% of patients with AIT whereas 8% of VAP patients required escalation of antibiotic therapy. The most commonly used initial antibiotic choice was vancomycin/piperacillin-tazobactam (16%) and the final choice was piperacillin-tazobactam (20%). Logistic regression demonstrated no specific parameter correlated with development of RP. Higher A3 (Odds ratio, 1.03; 95% confidence interval, 1.01-1.05) was associated with mortality whereas lack of RP (odds ratio, 0.31; 95% confidence interval, 0.12-0.80), and AIT reduced mortality (odds ratio, 0.024; 95% confidence interval, 0.007-0.221). Age, gender, individual pathogen, individual antibiotic regimen, and the use of DT had no effect on mortality. CONCLUSION De-escalation therapy did not lead to RP or increased mortality in critically ill surgical patients with VAP. De-escalation therapy was also shown to be safe in patients with septic shock. Because of its acknowledged benefits and lack of demonstrable risks, de-escalation therapy should be used whenever possible in critically ill patients with VAP.

Beneficial effects of chest tube drainage of pleural effusion in acute respiratory failure refractory to positive end-expiratory pressure ventilation.

BACKGROUND As part of an ongoing prospective evaluation of the response of acute respiratory failure (ARF) to ventilation with titrated amounts of positive end-expiratory pressure (PEEP), a subset of patients with a poor response to the initial application of PEEP and radiographic evidence of pleural effusion was identified. The effusion(s) were treated by tube thoracostomy (TT) to test the hypothesis that drainage would have a favorable effect on oxygenation and compliance in critically ill patients with substantial pulmonary dysfunction. METHODS Consecutive patients with ARF underwent a titrated progressive application of PEEP if arterial oxygen saturation was less than 90% on fraction of inspired oxygen less than 0.5. One or two thoracostomy tubes (TT) were placed afterward in patients with radiologic evidence of effusion who had a poor response to PEEP therapy. The lung injury score (LIS), PaO2:FiO2 (P:F), peak airway pressure, dynamic compliance, and TT output were recorded. Changes over time were analyzed by one-way analysis of variance with repeated measures. RESULTS Nineteen of 199 patients needed TT. LIS was 3.0 +/- 0.1. Maximum PEEP was 16.6 +/ 1.0 cm H2O. TT drainage was 863 +/- 164 ml in the first 8 hours. Mortality was 63% (12 of 19) but only 41% (74 of 180) in the patients who did not require TT (p = 0.11). TT improved oxygenation and compliance immediately after insertion in 17 of 19 patients, and P:F remained statistically higher (245 +/- 29 versus 151 +/- 13, p < 0.01) 24 hours after TT drainage. There was no correlation between the volume of fluid removed and P:F either immediately (R2, 0.16) or 24 hours after TT (R2, 0.07). CONCLUSIONS Drainage of pleural fluid resulted in a significant improvement in oxygenation in ARF patients with pleural effusions who were refractory to treatment with mechanical ventilation and PEEP. TT represents a simple and safe alternative for aggressive management of selected patients, obviating the inherent risk of pneumothorax with thoracentesis and possibly avoiding the need for more complex forms of support in this critically ill patient population.

The Relationships of Hypocholesterolemia to Cytokine Concentrations and Mortality in Critically Ill Patients with Systemic Inflammatory Response Syndrome

BACKGROUND Decreased concentrations of total cholesterol, lipoproteins, and lipoprotein cholesterols occur early in the course of critical illness. Low cholesterol concentrations correlate with high concentrations of cytokines such as interleukin (IL)-6 and IL-10, and may be due to decreased synthesis or increased catabolism of cholesterol. Low cholesterol concentrations have been associated clinically with several adverse outcomes, including the development of nosocomial infections. The study was performed to test the hypothesis that a low cholesterol concentration predicts mortality and secondarily predicts the development of organ dysfunction in critical surgical illness. METHODS A prospective study was undertaken of 215 patients admitted to a university surgical ICU with systemic inflammatory response syndrome (SIRS). Serial blood samples were collected within 24 h of admission, as well as on the morning of days 2, 4, and 7 of the ICU stay for as long as the patients were in the ICU. Demographic data and predetermined outcomes were noted. RESULTS One hundred nine patients had at least two samples drawn and form the population for analysis. Sixty-two of the patients had three samples obtained, whereas 42 patients had four samples obtained. By univariate analysis, non-survivors were more severely ill on admission (APACHE III), more likely to have been admitted to the ICU as an emergency, more likely to develop a nosocomial infection, and more likely to develop severe organ dysfunction (MODS) (all, p < 0.05). Death was associated on day 1 with increased concentrations of sIL2R, IL-6, IL-10, and sTNFR-p75 (all, p < 0.01), but there were initially no differences in serum lipid concentrations. However, by day 2, concentrations of IL-6, IL-10, and cholesterol had decreased significantly (all, p < 0.05) from day 1 in non-survivors but not in survivors; the difference in serum cholesterol concentration persisted to day 7 (p < 0.05). Persistently elevated concentrations of IL-6 and IL-10 were observed in patients who developed severe MODS. By logistic regression, increased APACHE III score, development of a nosocomial infection, and decreased cholesterol concentration were independently associated with mortality. CONCLUSIONS Decreased serum cholesterol concentration is an independent predictor of mortality in critically ill surgical patients. Repletion of serum lipids is a feasible therapeutic approach for the management of critical illness.

Utility of illness severity scoring for prediction of prolonged surgical critical care.

OBJECTIVE To determine whether APACHE III and multiple organ dysfunction syndrome scores can predict a prolonged length of stay for critically ill surgical patients in the intensive care unit. DESIGN Prospective, inception-cohort study. SETTING Surgical intensive care unit (SICU) of an urban, tertiary care hospital. PATIENTS 2,295 consecutive admissions for critical surgical illness, postoperative complications, or postoperative monitoring in 2,058 patients. INTERVENTIONS Calculation of Acute Physiology and Chronic Health Evaluation (APACHE) II and APACHE III scores 24 hours after admission to the SICU. Serial quantitation of organ dysfunction for the duration of hospitalization according to the multiple organ dysfunction score. Patients were stratified by survival and time intervals for the duration of critical care, and followed until discharge or death. MAIN OUTCOME MEASURES Hospital mortality and length of stay in the SICU. RESULTS The mean APACHE II and APACHE III scores were 14.0 +/- 0.2 and 45.2 +/- 0.6 points, respectively (mean +/- SEM). The incidence of organ dysfunction was 43%, and the hospital mortality was 9.7%. The mean ICU length of stay was 6.1 +/- 0.2 days, but decreased progressively from 6.8 +/- 0.5 days in 1991 to 5.3 +/- 0.6 days in 1995 (p < 0.01) with no change in either illness severity or the number of admissions. By univariate analysis, increased length of stay in the ICU was associated with increasing APACHE scores, an increased incidence of emergency admissions, and the incidence and magnitude of organ dysfunction (all p < 0.01). Severity indices appeared to plateau in magnitude in patients whose ICU stay ultimately exceeded 21 days. By multivariate analysis of variance (MANOVA), independent predictors of a prolonged stay in the SICU were APACHE III (p = 0.0023), emergency admission (p = 0.0007), and the magnitude of organ dysfunction (p < 0.00001), but not APACHE II. Only an emergency admission (p = 0.0005) and the magnitude of organ dysfunction (p < 0.00001) predicted a prolonged stay independently in survivors. In contrast, only the admission APACHE III score(p = < 0.0001) and the magnitude of organ dysfunction (p = 0.0001) were independently predictive of mortality by MANOVA. CONCLUSIONS The development of multiple organ dysfunction syndrome is a powerful predictor of a prolonged ICU course in critical surgical illness, even in survivors. Increased risk of a prolonged stay in the ICU plateaued at 21 days, making 21 days an appropriate definition of prolonged care for future studies. Predictive models should account for organ dysfunction and very long stays in future estimations. The combined use of APACHE III and the multiple organ dysfunction score may provide improved prediction of a prolonged stay in the ICU, but further enhancements are needed before prediction of outcome in individual patients is reliable.

Secretory leukocyte protease inhibitor, an inhibitor of neutrophil activation, is elevated in serum in human sepsis and experimental endotoxemia.

Objectives: To document changes in serum secretory leukocyte protease inhibitor (SLPI) in human sepsis and in experimental endotoxemia in vivo. To compare changes in serum SLPI in human sepsis with changes in interleukin (IL)‐6, IL‐10, and tumor necrosis factor (TNF)‐α. To determine whether or not changes in SLPI correlate with the severity of multiple organ dysfunction syndrome as measured by the maximal multiple organ dysfunction score. Finally, because neutrophils have been implicated in tissue injury associated with organ dysfunction, to determine whether recombinant human SLPI blocks activation of isolated human neutrophils. Design: Case‐control study and ex‐vivo cellular assay. Setting: Surgical intensive care unit and clinical research center of university hospitals; laboratory of a medical school. Interventions: None. Measurements and Main Results: There was a significant dose‐dependent elevation (50.2 ± 4.0 ng/mL, p = .01) in plasma SLPI 12 hrs after administration of lipopolysaccharide to seven healthy adults (36.4 ± 2.3 ng/mL). Further, serum concentrations of SLPI (132 ± 15 ng/mL) were elevated in septic surgical patients compared with healthy controls (43 ± 2 ng/mL, p < .01) and nonseptic surgical controls (69 ± 10 ng/mL, p = .01). Serum SLPI concentrations correlated (r2 = .71, p < .01) better with organ dysfunction as measured by maximal multiple organ dysfunction score than did serum IL‐6 (r2 = .49, p < .01), IL‐10 (r2 = .05, p = .22), or TNF‐α (r2 = .02, p = .44). We found that recombinant human SLPI in vitro inhibits TNF‐α‐induced hydrogen peroxide production by human neutrophils (ID50 = 1‐2 μg/mL). Conclusions: Serum SLPI is elevated in human sepsis and experimental endotoxemia. Maximal concentrations of serum SLPI correlate significantly with maximal multiple organ dysfunction scores in patients with sepsis. Secretory leukocyte protease inhibitor may function to limit ongoing neutrophil‐mediated tissue injury associated with organ dysfunction.

Randomized, double-blind, placebo-controlled trial of effects of enteral iron supplementation on anemia and risk of infection during surgical critical illness.

BACKGROUND Critical illness is characterized by hypoferremia, iron-deficient erythropoiesis (IDE), and anemia. The relative risks and benefits of iron supplementation in this setting are unknown. METHODS Anemic, critically ill surgical patients with an expected intensive care unit length of stay (ULOS) >or= 5 days were randomized to either enteral iron supplementation (ferrous sulfate 325 mg three times daily) or placebo until hospital discharge. Outcomes included hematocrit, iron markers (i.e., serum concentrations of iron, ferritin, and erythrocyte zinc protoporphyrin [eZPP]), red blood cell (RBC) transfusion, transfusion rate (mL RBC/study day), nosocomial infection, antibiotic days, study length of stay (LOS), ULOS, and death. Iron-deficient erythropoiesis was defined as an elevated eZPP concentration. RESULTS Two hundred patients were randomized; 97 received iron, and 103 received placebo. Socio-demographics, baseline acuity, hematocrit, and iron markers were similar in the two groups. No differences were observed between the iron and placebo groups with respect to either hematocrit or iron markers following up to 28 days. However, patients treated with iron were significantly less likely to receive an RBC transfusion (29.9% vs. 44.7%, respectively; p = 0.03) and had a significantly lower transfusion rate (22.0 mL/day vs. 29.9 mL/day; p = 0.03). Subgroup analysis revealed that these differences were observed in patients with baseline IDE only. Iron and placebo groups did not differ with respect to incidence of infection (46.8% vs. 48.9%; p = 0.98), antibiotic days (14 vs. 16; p = 0.45), LOS (14 vs. 16 days; p = 0.24), ULOS (12 vs. 14 days; p = 0.69), or mortality rate (9.4% vs. 9.9%; p = 0.62). CONCLUSIONS Enteral iron supplementation of anemic, critically ill surgical patients does not increase the risk of infection and may benefit those with baseline IDE by decreasing the risk of RBC transfusion. A trial comparing enteral and parenteral iron supplementation in this setting is warranted (ClinicalTrials.gov number, NCT00450177).

Accuracy of short-duration creatinine clearance determinations in predicting 24-hour creatinine clearance in critically ill and injured patients.

BACKGROUND We hypothesized that measured 2-hour (CrCl2), 6-hour (CrCl6), and 16-hour (CrCl16) urine creatinine clearance accurately reflect measured (CrCl24meas) and calculated 24-hour CrCl (CrCl24calc) in critical illness. METHODS Urine was collected in consecutive specimens from 7 am to 9 am (CrCl2), 9 am to 3 pm (CrCl6), and 3 pm to 7 am (CrCl16) at surgical intensive care unit admission and weekly thereafter. CrCl2 and CrCl6 were added to obtain CrCl8, which was then added to CrCl16 to obtain CrCl24meas. CrCl24calc was estimated using the Cockcroft-Gault equation. RESULTS One hundred patients (45 with trauma) had 131 sets of CrCl2, CrCl6, and CrCl16. Trauma patients were younger; had a lower mean body surface area; and had higher CrCl2, CrCl6, and CrCl16 (all p < 0.0001). Correlation percentages (r2) comparing CrCl2, CrCl6, CrCl8, CrCl16, and CrCl24calc with CrCl24meas in trauma patients were 0.597, 0.760, 0.815, 0.958, and 0.670, respectively. In nontrauma patients, r2 values were 0.516, 0.693, 0.807, 0.946, and 0.649, respectively. CONCLUSION CrCl2, CrCl6, and CrCl24calc are unreliable for clinical decision making. A minimum collection period of at least 8 hours is recommended for determination of urine creatinine clearance.

A PROSPECTIVE COMPARISON OF TWO MULTIPLE ORGAN DYSFUNCTION/FAILURE SCORING SYSTEMS FOR PREDICTION OF MORTALITY IN CRITICAL SURGICAL ILLNESS

Multiple organ failure (MOF) is the primary cause of death in surgical intensive care units (SICU). Mortality increases with an increasing number of failed organs, but it has been recognized that lesser degrees of organ dysfunction occur commonly. Such gradations of the multiple organ dysfunction syndrome (MODS) are postulated to provide more descriptive and predictive power. We analyzed and compared two different MODS/MOF scoring systems and determined the utility of gradations of organ dysfunction for prediction of mortality in MODS/MOF. One of the scoring systems defines organ failure as an all-or-nothing phenomenon for each organ, whereas the other scoring system describes increasing organ dysfunction on a 24-point scale. Each scoring system assesses the same six organs. Admission APACHE II (AII) and AIII scores were calculated as independent estimates of mortality. In 867 consecutive SICU admissions, 261 patients (30%) had some degree of organ dysfunction, of whom 142 patients (54%) met criteria for single or multiple organ failure. The mean admission AII score was 19 (25 for nonsurvivors), and the AIII score was 62 (91 for nonsurvivors). Overall mortality was 5.8%, but among those patients with organ dysfunction, mortality was 19%. Death was equally likely for comparable degrees of organ dysfunction and failure. Mortality increased (p < 0.01, ANOVA) with higher scores in both systems. In patients with 9-12 organ dysfunction points, the number of failed organs was 1.5 +/- 0.2 in 34 survivors, versus 2.9 +/- 0.3 in the 14 nonsurvivors (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)