A one-year observational study of all hospitalized acute poisonings in Oslo: complications, treatment and sequelae.

OBJECTIVES: Changes in poisoning trends may affect both complications and outcomes in patients with acute poisoning. This study reports the treatments given and the frequency of complications, also related to treatment, mortality and sequelae related to various toxic agents. METHODS: All acute poisonings in adults (≥ 16 years) admitted to the five hospitals in Oslo were included consecutively during one year (2008 to 2009) in an observational cross-sectional multicenter study. A standardized form was completed by the treating physician, which covered the study aims. RESULTS: There were 1065 admissions in 912 patients. The median length of hospital stay was one day, and 49% were observed in an intensive care unit (ICU). Active treatment was given to 83%, and consisted of supportive therapy (70%), antidote(s) (38%), activated charcoal (16%) and gastric lavage (9%). The most commonly used antidotes were flumazenil (19%), naloxone (17%) and N-acetylcysteine (11%). The rate of treatment-related complications was 2.4% (21/884). Neither flumazenil, naloxone, nor the combination, was associated with convulsions or other complications. Among those receiving N-acetylcysteine, 5% (6/120) developed allergic reactions, one of which mandated discontinuation of treatment. Nineteen percent presented in a coma. Complications developed in 30%, compared with 18% in a 2003 study, mainly respiratory depression (12%), prolonged QTc interval (6%) and hypotension (5%). Eight patients died (0.8%) and five (0.5%) survived with permanent sequelae, mainly anoxic brain damage. DISCUSSION: Few patients stayed more than two days. The use of the ICU was liberal, considering that only one out of five presented in a coma. Antidotes were frequently given diagnostically. Although N-acetylcysteine induced allergic reactions, most were mild and treatment discontinuation was only necessary once. The frequency of complications had almost doubled in five years, although the poisoning pattern was largely unchanged. However, few patients developed permanent sequelae.

Incidence and causes of new-onset dyspnea in 3,719 patients treated with clopidogrel and aspirin combination after coronary stenting.

The experimental oral antiplatelet agent AZD6140 causes dyspnea in randomized trials. Whether clopidogrel may also cause dyspnea remains controversial. We sought to define the incidence and causes of dyspnea in a large post-percutaneous coronary intervention (PCI) cohort based on open-labeled consecutive registry analysis of in-hospital charts and discharge diagnoses. Data were collected at six-month follow-up by means of telephone interviews or returned questionnaires during outpatient visits. Patients undergoing coronary stent implantation were loaded with 600 mg clopidogrel followed by 75 mg/daily in combination with 75-325 mg of aspirin daily for at least six months. Data from 3,719 patients were analyzed. Dyspnea was diagnosed in 157 (4.2%) patients caused by chronic obstructive pulmonary disease (n = 43 or 27% of the dyspnea group), heart failure (n = 30 or 19%), cancer (n = 22 or 14%), pneumonia (n = 17 or 11%); asthma (n = 8 or 5%), pulmonary hypertension (n = 8 or 5%); pericarditis (n = 5 or 3%); cardiac arrhythmias (n = 4 or 2.5%); pleural effusion (n = 1), pulmonary embolism (n = 1), anxiety (n = 1), or unknown (n = 17, or 11%). The incidence of dyspnea at six months in a post-stent cohort treated with aspirin and clopidogrel is low (4.2%). The majority of patients with dyspnea (140/157) exhibit a distinct underlying disease or condition, in contrast to only 17 patients (0.45% of total cohort) in whom the pathogenesis of dyspnea remained unidentified. These data closely match the frequency of dyspnea that was observed in the CAPRIE trial, suggesting that therapy with clopidogrel, and/or aspirin holds very small (if any) risk for dyspnea.

Bleeding risks of combination vs. single antiplatelet therapy: a meta-analysis of 18 randomized trials comprising 129,314 patients.

A number of antiplatelet drugs, principally aspirin alone or in combination, have been evaluated in randomized trials of survivors of prior occlusive vascular disease events or of individuals at high risk because of multiple cardiovascular risk factors. In this meta-analysis we compare single and dual antiplatelet regimens to quantitate the risks of bleeding. Data from randomized trials published in English in 1988-2006 were retrieved from MEDLINE, OVID, and CARDIOSOURCE. Inclusion criteria were clinical follow-up for at least 1 month and the presence of data on bleeding complications. Information was compiled on sample size, antiplatelet agents tested, patient characteristics as well as major, minor, fatal and intracranial bleeding. Using these criteria, we identified 18 randomized trials, which included 129,314 patients. For each endpoint, relative risk (RR) and 95% confidence intervals (CI) were calculated. Dual antiplatelet therapy is associated with a significantly increased risk of major (RR 1.47, CI = 1.36-1.60) and minor bleeding events (RR 1.56, CI = 1.47-1.66) compared to single agent therapy. Although based on small numbers, there were no significant differences in fatal (RR 1.10, CI = 0.87-1.40) or intracranial (RR 1.07, CI = 0.85-1.35) bleedings although the CIs are wide to make definite assessments. Patients treated with dual antiplatelet therapy have an approximately 40-50% increase in risks of major and minor bleeding compared to those receiving single agent therapy during the duration of the scrutinized trials. The magnitude of this excess risk is not so remote from the approximately 60% increase observed in trials comparing single antiplatelet agents to placebo. This excess risk should be considered when choosing the optimal antiplatelet strategy for long-term treatment of patients with prior occlusive vascular events or those at high risk of developing occlusive vascular disease.