Heparin-induced thrombocytopenia in extra-corporeal membrane oxygenation: epidemiology, outcomes, and diagnostic challenges.

To describe the prevalence of heparin-induced thrombocytopenia (HIT) in patients on extracorporeal membrane oxygenation (ECMO) and to explore ways to improve the diagnostic accuracy of the HIT enzyme-linked immunosorbent assay (ELISA). Retrospective review of all patients needing ECMO between September 2011 and September 2020 who underwent evaluation for HIT while on ECMO. The diagnosis of HIT required a confirmatory serotonin release assay (SRA). Various break points for the optical density (OD) that defines a positive HIT ELISA were examined to estimate their utility as screening tests for HIT. Patient outcomes served as a secondary endpoint. Among 417 ECMO patients, 162 (38.8%) had a HIT ELISA. Of these, 114 (70.4%) had a subsequent SRA. Although the HIT ELISA was positive at an OD ≥ 0.4 in 1/3rd of subjects, only 15 subjects met criteria for HIT by SRA. Hence, the prevalence of HIT equaled 3.6%. At an OD ≥ 0.4 the ELISA had both poor specificity (71.7%) and accuracy (74.6%). Changing the definition of the ELISA to an OD ≥ 1.2 improved both specificity and accuracy with only a limited impact on sensitivity. Nearly 60% of those with HIT developing during ECMO died. HIT is infrequent in persons requiring ECMO. However, HIT remains associated with substantial mortality. The HIT ELISA as currently implemented performs poorly as a screening test and likely results in the unnecessary overuse of alternatives to unfractionated heparin. Altering the definition of a positive OD improves the HIT ELISA's accuracy.

Preferences in traumatic intracranial hemorrhage: bleeding vs. clotting.

Patients with traumatic brain injury and resultant intracranial hemorrhage (ICH) are at high risk for developing venous thromboembolism (VTE). The use of thromboprophylaxis is effective at decreasing the rate of VTE, but at the potential expense of an increased risk of ICH progression. Physicians must carefully consider both the benefits and risks of VTE prophylaxis before prescribing chemical anticoagulants to these patients. To help clarify this difficult choice, Scales and colleagues performed a decision analysis to determine whether the benefits of thromboprophylaxis outweigh the potential risk of worsening ICH. There is increasing evidence that bleeding risks are not as prominent as previously thought. Although the results were largely inconclusive, the present study has identified areas for future research.

Venous thromboembolic disease in the intensive care unit.

Critically ill patients are at increased risk of developing venous thromboemboli (VTE). Risk factors that predispose them to acquiring VTE encompass factors that usually afflict the general medical population as well as factors attained in the intensive care unit (ICU) (e.g., sedation, mechanical ventilation). The poor cardiopulmonary reserve of this patient population is intolerant of even small pulmonary emboli (PE), which emphasizes the importance of preventing VTE from ever occurring. Indeed, the complications associated with hospital-acquired VTE increase morbidity, mortality, hospital length of stay, and costs. Without thromboprophylaxis, the incidence of VTE in the ICU ranges from 15 to 60%. Systematic implementation of VTE prophylaxis significantly reduces this rate and as a consequence, morbidity and mortality. In fact, prevention of VTE is so important that the American College of Chest Physicians (ACCP) developed guidelines on the use of routine VTE prophylaxis in critically ill patients. Therefore, upon admission, all ICU patients should be evaluated for and immediately prescribed the appropriate thromboprophylaxis therapy.

The Role for Optical Density in Heparin-Induced Thrombocytopenia: A Cohort Study.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin utilization. An enzyme-linked immunosorbent assay (ELISA) is usually performed to assist in the diagnosis of HIT. ELISAs tend to be sensitive but lack specificity. We sought to use a new cutoff to define a positive HIT ELISA. METHODS: We conducted a prospective observational study of hospitalized patients undergoing ELISA testing. All patients who underwent ELISA testing were eligible for inclusion (n = 496). Irrespective of the results, all subjects had confirmatory testing with a serotonin release assay (SRA). We compared a threshold optical density (OD) > 1.00 to the current definition of a positive ELISA (OD > 0.40) as a screening test for a positive SRA. We used sensitivity, specificity, and area under the receiver operating curve to determine whether an OD > 1.00 would improve diagnostic accuracy for HIT. RESULTS: The SRA was positive in 10 patients (prevalence, 2.0%). Adjusting the definition of a positive HIT ELISA to > 1.00 maintained the sensitivity and negative predictive value at 100% in the cohort. The positive predictive value of the higher cutoff OD was more than triple the positive predictive value of an OD > 0.40 (41.7% vs 13.3%). No patient with a positive SRA had an OD measurement ≤ 1.00. CONCLUSIONS: Increasing the OD threshold enhances specificity without noticeably compromising sensitivity. Altering the definition of the HIT ELISA could prevent unnecessary testing and/or treatment with non-heparin-based anticoagulants in patients with possible HIT. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00946400; URL: www.clinicaltrials.gov.

Economic and outcomes aspects of venous thromboembolic disease.

Critically ill patients clearly face an increased risk for developing venous thromboembolic disease (VTE). Upon admission, all critical care patients should be immediately assessed for and prescribed VTE prophylaxis as it can significantly reduce VTE occurrence, its potential sequelae,and costs associated with VTE treatment. The financial burden associated with VTE is substantial. Longer ICU and hospital lengths of stay, pharmacy costs, and further outpatient management all contribute considerably to the economic burden of disease. The importance of this healthcare issue should motivate hospital administrators and physicians to systematically initiate thromboprophylaxis in all ICU patients.

Factors associated with acute lung injury in combat casualties receiving massive blood transfusions: a retrospective analysis.

PURPOSE: We sought to determine if use of warm fresh whole blood (WFWB), rather than blood component therapy, alters rates of acute lung injury (ALI) in patients with trauma. MATERIALS AND METHODS: We retrospectively analyzed rates of ALI in patients undergoing massive blood transfusions while at a combat support hospital. Patients with ALI were compared with those not developing ALI with respect to demographics, trauma type, severity of illness, crystalloid volume given, and exposure to WFWB. Logistic regression was used to identify variables associated with ALI. RESULTS: The cohort included 591 subjects (mean age, 28 ± 8.1 years; male, 96.7%). Acute lung injury occurred in 11.2%, and 34.4% received WFWB. After adjusting for the type of trauma, severity of illness, and volume of crystalloid administered, WFWB remained independently associated with ALI (adjusted odds ratio [AOR], 1.06; 95% confidence interval [CI], 1.00-1.13). Nearly two thirds of persons with ALI never received WFWB; factors associated with the use of WFWB were also examined. Severity of illness (AOR, 1.18; 95% CI, 1.02-1.35), crystalloid volume (AOR, 1.12; 95% CI, 1.06-1.18), recombinant factor VIIa use (AOR, 1.94; 95% CI, 1.06-3.57), and US citizenship (AOR, 3.06; 95% CI, 1.74-5.37) correlated with WFWB use. CONCLUSIONS: Warm fresh whole blood may be associated with an increased risk of ALI, but this is confounded by increased injury and crystalloid use in patients receiving WFWB.

Comparing the pulmonary embolism severity index and the prognosis in pulmonary embolism scores as risk stratification tools.

BACKGROUND: Multiple risk stratification scoring systems exist to forecast outcomes in patients with acute pulmonary embolism (PE). OBJECTIVE: We evaluated the comparative validity of the PE severity index (PESI) and the prognosis in pulmonary embolism (PREP) scores to predict mortality in acute PE. DESIGN: Retrospective observational cohort study. SETTING: Washington Hospital Center, Washington, DC. PATIENTS: Consecutive adults (aged >18 years) diagnosed with acute PE. INTERVENTION: The PESI and PREP scores were calculated. MEASUREMENTS: Raw PESI scores were segregated into risk class (I-V) and then dichotomized into low (I-II) versus high (III-V) risk groups; the raw PREP scores were divided into low (0-7) versus high (>7) risk groups. The primary endpoint was 30-day and 90-day mortality. We determined the negative predictive value and computed the area under the receiver operating characteristics (AUROC) curves to compare the ability of these scoring tools. RESULTS: The cohort consisted of 302 subjects. Thirty-day mortality was 3.0%, and 4.0% died within 90 days. The PESI and the PREP performed similarly (PESI AUROC: 0.858 [95% confidence interval (CI), 0.773-0.943] vs 0.719 [95% CI, 0.563-0.875] for PREP). Segregating these scores into risk categories did not affect their discriminatory power (AUROC: 0.684 [95% CI, 0.559-0.810] for PESI and 0.790 [95% CI, 0.679-0.903] for PREP). The negative predictive value for death of being classified as low risk by the PESI or PREP was 100% and 99%, respectively. CONCLUSIONS: The PREP score performed comparably to the PESI score for identifying PE patients at low risk for short-term and intermediate-term mortality.

Diagnostics and epidemiology in ventilator-associated pneumonia.

Ventilator-associated pneumonia (VAP) represents a common nosocomial complication arising in the intensive care unit. Owing to concerns regarding the excess morbidity related to VAP, multiple interventions for preventing this syndrome exist. Despite controversy regarding the optimal diagnostic approach to VAP, clinicians now face many external pressures to try to reduce, if not eliminate, VAP. In fact, some organizations consider VAP an entirely preventable event. However, any dialog regarding the outcomes and burden of VAP must rest on an understanding and appreciation of both the diagnostic complexities surrounding VAP and the epidemiology of this condition. In addition, the issues of diagnostics and epidemiology are closely linked. The means employed for diagnosing VAP certainly affect the observed prevalence of VAP. Despite these concerns, several general themes emerge in the literature describing VAP epidemiology. First, VAP rates vary based on the diagnostic approach employed. Second, select cohorts of patients are at high risk for VAP, and patient case-mix clearly influences the epidemiology of VAP. Third, rates of VAP appear higher outside the US, irrespective of the diagnostic paradigm utilized.

Bacteremia in Staphylococcus aureus pneumonia: outcomes and epidemiology.

PURPOSE: Staphylococcus aureus represents a major cause of pneumonia in critically ill patients. Although bacteremia may complicate S aureus pneumonia, the epidemiology of and outcomes associated with bacteremia in this syndrome are poorly described. MATERIALS AND METHODS: We retrospectively identified (January 2005-December 2007) all patients admitted to the hospital with S aureus pneumonia necessitating mechanical ventilation. All subjects underwent lower airway and concurrent blood cultures. The prevalence of bacteremia served as a primary end point. We assessed the impact of bacteremia on mortality and length of stay via either logistic regression or a Cox proportional hazard model, respectively. In both models, we controlled for multiple covariates (eg, demographics, severity of illness, comorbidities, and appropriateness of initial antibiotics). We subsequently developed a prediction rule to identify subjects likely to have concurrent bacteremia based on variables assessed at the time of presentation. RESULTS: The cohort included 59 patients (mean ± SD age, 58.0 ± 17.4 years; 55.9% male, 59.3% methicillin resistant, 39.0% crude mortality). Bacteremia complicated nearly 20% of cases. The mortality rate in those with bacteremia was 39.1% vs 8.3% in persons without bacteremia (P = .007). Three variables were independently associated with mortality in S aureus pneumonia: age, need for vasopressors, and concurrent bacteremia. Bacteremia independently conferred a 6-fold increase in the risk for death (adjusted odds ratio, 5.96; 95% confidence interval [CI], 1.08-33.10). Bacteremia also correlated with a longer length of stay. The adjusted hazard ratio for remaining hospitalized if bacteremic was 2.65 (95% CI, 1.14-6.18). For the clinical prediction rule for concurrent bacteremia, we assigned points as follows: 2 points if the patient had received prior antibiotic therapy and 1 point each for acute lung injury and for the need for vasopressors. As the total score increased, the prevalence of bacteremia increased (P < .001). As a screening test for bacteremia in S aureus pneumonia, the scoring system had good predictive value. The area under the receiver operating curve measured 0.83 (95% CI, 0.72-0.94). CONCLUSIONS: Bacteremia often arises in S aureus pneumonia and is associated with both increased morbidity and mortality. Several simple clinical factors to determine clinical features identify patients with S aureus pneumonia likely to have simultaneous bacteremia.

Resistant pathogens in nonnosocomial pneumonia and respiratory failure: is it time to refine the definition of health-care-associated pneumonia?

BACKGROUND: The concept of health-care-associated pneumonia (HCAP) exists to identify patients infected with highly resistant pathogens. It is unclear how precise this concept is and how well it performs as a screening tool for resistance. METHODS: We retrospectively identified patients presenting to the hospital with pneumonia complicated by respiratory failure. We examined the microbiology of these infections based on pneumonia type and determined the sensitivity and specificity of HCAP as a screen for resistance. Through logistic regression and modeling, we created a scoring tool for determining who may be infected with resistant pathogens. RESULTS: The cohort included 190 subjects (37% with ARDS) and we noted resistant pathogens in 33%. Resistance was more common in HCAP (78% vs 44%, P = .001). HCAP alone performed poorly as a screening test (sensitivity and specificity 78.3% and 56.2%, respectively). Variables independently associated with a resistant organism included immunosuppression (adjusted odds ratio [AOR] 4.85, P < .001), long-term care admission (AOR 2.36, P = .029), and prior antibiotics (AOR 2.12, P = .099). A decision rule based only on these factors performed moderately well at identifying resistant infections. The presence of HCAP itself, based on meeting defined criteria, was not independently associated with resistance using logistic regression to control for covariates. CONCLUSIONS: HCAP is common in patients presenting to the hospital with pneumonia leading to respiratory failure. The HCAP concept does not correlate well with the presence of infection due to a resistant pathogen. A simpler clinical decision rule based on select HCAP criteria performs as well as the HCAP concept for potentially guiding antibiotic decision making.

The right ventricle in sepsis.

Right ventricular dysfunction is common in sepsis and septic shock because of decreased myocardial contractility and elevated pulmonary vascular resistance despite a concomitant decrease in systemic vascular resistance. The mainstay of treatment for acute right heart failure includes treating the underlying cause of sepsis and reversing circulatory shock to maintain tissue perfusion and oxygen delivery. Decreasing pulmonary vascular resistance with selective pulmonary vasodilators is a reasonable approach to improving cardiac output in septic patients with right ventricular dysfunction. Treatment for right ventricular dysfunction in the setting of sepsis should concentrate on fluid repletion, monitoring for signs of RV overload, and correction of reversible causes of elevated pulmonary vascular resistance, such as hypoxia, acidosis, and lung hyperinflation.