Fomepizole as an adjunct in acetylcysteine treated acetaminophen overdose patients: a case series.

INTRODUCTION: Acetaminophen (N-acetyl-para-aminophenol or APAP) is the leading cause of acute liver failure worldwide. Standard therapy for APAP overdose is with IV N-acetylcysteine (NAC). However, overdose patients treated with NAC can still incur hepatotoxicity in some circumstances. Fomepizole has proven safety in methanol and ethylene glycol poisoning and is a potent CYP2E1 and c-Jun-N-terminal Kinase (JNK) inhibitor that is effective even in the metabolic phase. METHODS: We present a prospective case series of 14 consecutive, high-risk patients who had elevated APAP levels after overdose who were treated with fomepizole as an adjunct to standard IV-NAC. The attending toxicologist utilized clinical judgement to determine the use of fomepizole, especially if APAP levels persisted due to altered half-life or risk factors for toxicity. RESULTS: There were no unfavorable outcomes in any patient, which were better than expected. CONCLUSIONS: This case series has demonstrated the safety of fomepizole in high-risk APAP overdose. The efficacy of fomepizole needs to be further elucidated through controlled clinical trials on a larger scale. In massive APAP overdoses, fomepizole should be considered as an adjunct due to the known failure rate of NAC and the safety profile of fomepizole.

Effect of Very Low-Dose Hydrocortisone on Shock Reversal in Patients With Septic Shock.

In patients with septic shock, hydrocortisone 200-400 mg/d has been shown to reverse shock compared with placebo. Lower doses of hydrocortisone have not previously been studied, and there are no previous studies comparing two different doses of hydrocortisone. At our institution, some clinicians routinely prescribe doses less than 200 mg/d. This study aims to compare the effect of lower doses of hydrocortisone to standard doses on shock reversal and adverse events in septic shock. DESIGN: Retrospective cohort study. SETTING: Single-center medical ICU. SUBJECTS: Patients who received hydrocortisone for septic shock. INTERVENTIONS: Electronic chart review. MEASUREMENTS AND MAIN RESULTS: Patients were divided into low-dose hydrocortisone (75-150 mg/d) and standard-dose hydrocortisone (200-400 mg/d) cohorts based on initial prescribed hydrocortisone dose. Rates of shock reversal and adverse events in the two cohorts were compared. Two-hundred thirteen patients were included-41 in low-dose and 172 in standard-dose cohorts. Baseline characteristics including initial vasopressor requirement and Sequential Organ Failure Assessment scores were similar. Average rates of change in vasopressor needs, conditional hazard rate for vasopressor withdrawal, and cumulative probability for vasopressor withdrawal were all quantitatively similar for low-dose and standard-dose hydrocortisone. Insulin requirement (particularly in those with diabetes mellitus), blood glucose in those with diabetes mellitus, and frequency of secondary infections seemed to be lower in the low-dose hydrocortisone cohort. Mortality and other secondary outcomes were similar. CONCLUSIONS: In septic shock, hydrocortisone dosed 75-150 mg/d appears to reverse shock as effectively 200-400 mg/d and may cause a lower frequency of adverse events.

Accelerated lymphocyte death in sepsis occurs by both the death receptor and mitochondrial pathways.

Patients with sepsis are immune compromised, as evidenced by their failure to clear their primary infection and their propensity to develop secondary infections with pathogens that are often not particularly virulent in normal healthy individuals. A potential mechanism for immunosuppression in sepsis is lymphocyte apoptosis, which may occur by either a death receptor or a mitochondrial-mediated pathway. A prospective study of blood samples from 71 patients with sepsis, 55 nonseptic patients, and 6 healthy volunteers was undertaken to quantitate lymphocyte apoptosis and determine cell death pathways and mechanisms of apoptosis. Apoptosis was evaluated by flow cytometry and Western blotting. Lymphocyte apoptosis was increased in CD4 and CD8 T cells, B cells (CD20), and NK cells (CD56) in septic vs nonseptic patients. Samples taken sequentially from 10 patients with sepsis showed that the degree of CD3 T cell apoptosis correlated with the activity of his/her sepsis. In septic patients, apoptotic lymphocytes were positive for active caspases 8 and 9, consistent with death occurring by both mitochondrial-mediated and receptor-mediated pathways. In support of the concept that both death pathways were operative, lymphocyte apoptosis occurred in cells with markedly decreased Bcl-2 (an inhibitor of mitochondrial-mediated apoptosis) as well as cells with normal concentrations of Bcl-2. In conclusion, apoptosis occurs in a broad range of lymphocyte subsets in patients with sepsis and correlates with the activity of the disease. Lymphocyte loss occurs by both death receptor and mitochondrial-mediated apoptosis, suggesting that there may be multiple triggers for lymphocyte apoptosis.

Prevention of pneumonia in the hospital setting.

Although the optimal approach to reducing ventilator-associated pneumonia (VAP) is unclear, recent studies indicate that mandatory education of health care workers caring for mechanically ventilated patients can decrease overall VAP rates. Among the available interventions, shortening the duration of mechanical ventilation and providing measures to prevent the aspiration of contaminated secretions are most important. Given the evidence supporting greater morbidity, hospital mortality, and medical care costs among patients who have VAP, the prevention of this nosocomial infection should be an important priority in the hospital setting.

Reporting of medical errors: an intensive care unit experience.

OBJECTIVE: To determine the occurrence and type of medical errors in an intensive care setting using a voluntary reporting method. DESIGN: Prospective, single-center, observational study. SETTING: The medical intensive care unit (19 beds) at an urban teaching hospital. PATIENTS: Adult patients requiring at least 48 hrs of intensive care. INTERVENTIONS: Prospective reporting of medical errors. MEASUREMENTS AND MAIN RESULTS: During a 6-month period, 232 medical events were reported involving 147 patients. A total of 2598 patient days were surveyed yielding 89.3 medical events reported per 1000 intensive care unit days. The source of the reports included nurses, who reported most of the medical events (59.1%), followed by physicians-in-training (27.2%) and intensive care unit attending physicians (2.6%). One hundred thirty (56.2%) medical events occurred within the intensive care unit and were judged to involve patient careproviders who were working directly in the intensive care unit area. One hundred and two (43.8%) medical events were commissions or omissions that occurred outside of the intensive care unit during patient transports or in the emergency department and hospital floors. Twenty-three (9.9%) medical events leading to a medical error resulted in the need for additional life-sustaining treatment, and seven (3.0%) medical errors may have contributed to patient deaths. CONCLUSION: Medical errors appear to be common among patients requiring intensive care. Medical events resulting in an error can result in the need for additional life-sustaining treatments and, in some circumstances, can contribute to patient death. Patient healthcare providers appear to be in a unique position to identify medical errors. Institutions should develop formalized methods for the reporting and analysis of medical errors to improve patient care.

Hospital mortality for patients with bacteremia due to Staphylococcus aureus or Pseudomonas aeruginosa.

STUDY OBJECTIVES: To evaluate the relationship between hospital mortality and bloodstream infections due to Staphylococcus aureus or Pseudomonas aeruginosa. DESIGN: Prospective cohort study. SETTING: A 1,400-bed, university-affiliated urban teaching hospital. PATIENTS: Between December 2001 and September 2002, 314 patients with bacteremia due to S aureus or P aeruginosa were prospectively evaluated. INTERVENTION: Prospective patient surveillance and data collection. RESULTS: Thirteen patients (4.1%) received inadequate initial antibiotic treatment. Fifty-four patients (17.2%) died during hospitalization. Hospital mortality was statistically greater for patients with bloodstream infections due to P aeruginosa (n = 49) compared to methicillin-sensitive S aureus (MSSA) [n = 117; 30.6% vs 16.2%, p = 0.036] and methicillin-resistant S aureus (MRSA) [n = 148; 30.6% vs 13.5%, p = 0.007]. Multiple logistic regression analysis identified the lack of response to initial medical treatment (adjusted odds ratio [AOR], 2.69; 95% confidence interval [CI], 1.83 to 3.94; p = 0.010) and endocarditis (AOR, 4.62; 95% CI, 2.45 to 8.73; p = 0.016) as independent determinants of hospital mortality. Patients with bloodstream infections due to P aeruginosa were statistically more likely to be nonresponders to early medical treatment compared to patients with MSSA (73.5% vs 11.1%, p < 0.001) and MRSA (73.5% vs 16.9%, p < 0.001) bloodstream infections. CONCLUSIONS: These data suggest that bloodstream infections due to P aeruginosa have a greater risk of hospital mortality compared to bloodstream infections due to S aureus despite adequate antibiotic treatment.