Adverse events related to medications identified by a Canadian poison centre.

BACKGROUND: Poison centres are an underutilized source of information on adverse events related to medications, including therapeutic errors and adverse drug reactions. OBJECTIVE: To demonstrate the feasibility of using a poison centres' electronic data to identify and describe adverse events related to medications. METHODS: This one-year, retrospective cross-sectional pilot study was conducted at one Canadian Poison Centre. All records from the IWK Regional Poison Centre database in Nova Scotia between November 1, 2007 and October 31, 2008 for unintentional exposures were abstracted for a descriptive data analysis. RESULTS: An issue related to use of a medication was the main reason for 1,525 (32.5%) of 4,697 eligible calls. Of the 1,525 calls, 970 (63.6%) were coded as 'unintentional-general.' There were 470 (30.8%) calls for unintentional therapeutic errors and 61 (4.0%) for adverse drug reactions. The majority of calls involving medications were judged to have resulted in minimal or no toxic effect (78.4%). However, 3.3% of calls involving adverse drug reactions resulted in admission to a critical care unit (n=2). Approximately 1% of calls involving unintentional therapeutic errors resulted in admission to hospital (n=6). CONCLUSIONS: Calls to poison centres provide a potentially valuable source of information on adverse events related to medications that are likely not reported elsewhere. Establishment of a mechanism to routinely share information from all Canadian poison centres with relevant national drug safety programs (e.g., MedEffect™ Canada) will provide a supplementary source of information and contribute to building capacity for detection of sentinel events and pharmacosurveillance.

Does ketamine have a role in managing severe exacerbation of asthma in adults?

OBJECTIVE: To evaluate the role of ketamine in management of severe exacerbation of asthma in adults. METHODS: Qualitative systematic search using MEDLINE (January 1966-September 2000), EMBASE (January 1988-September 2000), and the Cochrane Database of Systematic Reviews (Issue 2, 2000). RESULTS: One prospective, randomized, double-blind, placebo-controlled trial and five case reports were retrieved. In the clinical trial, low-dosage ketamine as an adjunct to standard therapy offered no benefit in improving outcomes in nonventilated patients. In the case reports, all patients with refractory severe exacerbation of asthma requiring mechanical ventilation appeared to receive some benefit from ketamine, with alleviation of bronchospasm and improved oxygenation. Adverse effects included dysphoria, hallucinations, and increased pulmonary secretions. CONCLUSION: Limited evidence is available in the literature to support administration of ketamine in severe exacerbation of asthma. Although a few cases suggest possible benefit from ketamine, it should not be considered until controlled clinical trials demonstrate that benefits outweigh risks for patients for whom other standard therapies failed.

Meta-analysis of proton pump inhibitors in treatment of bleeding peptic ulcers.

OBJECTIVE: To evaluate the efficacy of proton pump inhibitors (PPIs) compared with placebo and histamine receptor antagonists (H2RAs) for reducing the incidence of rebleeding, surgery, and death in acute gastrointestinal bleeding (GIB) associated with peptic ulcer disease. DATA SOURCES: A systematic search of the English-language literature was performed using MEDLINE, EMBASE, and Pre-MEDLINE (from 1966 to September 2000) and a manual search of references. STUDY SELECTION: Randomized, controlled trials evaluating any PPI for acute GIB in adults with the end points of rebleeding, surgery of death. DATA SYNTHESIS: Nine trials (1829 pts.) were included. The relative odds of rebleeding indicated a 50% reduction in the PPI-treated group (OR 0.50, 95% CI 0.33 to 0.77; p = 0.002, NNTB 9; 95% CI NNTB 6 to 13). The relative odds of surgery indicated a 53% reduction in the PPI-treated group (OR 0.47, 95% CI 0.29 to 0.77; p = 0.003; NNTB 17, 95% CI 12 to 35). The relative odds for mortality indicated a nonsignificant 8% decrease in the odds of death in the PPI-treated group (OR 0.92, 95% CI 0.46 to 1.83, p = 0.81; NNTB 323, 95% CI NNTB 47 to infinity to NNTH 33). CONCLUSIONS: PPIs are superior to H2RAs and placebo in preventing rebleeding and the need for surgery in patients with GIB, although they do not appear to reduce mortality.

Is propofol an optimal agent for procedural sedation and rapid sequence intubation in the emergency department?

OBJECTIVE: We conducted a qualitative systematic review to evaluate the efficacy and safety of propofol for direct current cardioversion (DCC), rapid sequence intubation (RSI) and procedural sedation in adult emergency department (ED) patients. DATA SOURCE: MEDLINE (1966 to September 2000), PubMed (to September 2000), EMBASE (1988 to September 2000), Database of Systematic Reviews (to September 2000), Best Evidence (1991 to September 2000) and Current Contents (1996 to September 2000) databases. STUDY SELECTION: English-language, randomized, comparative evaluations of propofol for procedures routinely conducted in adults (>18 years) were included. Direct current cardioversion, RSI and procedural sedation were considered. DATA EXTRACTION: Efficacy and safety endpoints were evaluated for all trials. For DCC and procedural sedation trials, efficacy measures included induction and recovery times, as well as the association for successful procedure. For the RSI trials, optimal intubating conditions were evaluated as the primary efficacy endpoint. Safety measures included hemodynamic changes, apnea rates and adverse effects. DATA SYNTHESIS: In the setting of DCC, efficacy and safety outcomes were similar for propofol, thiopental, etomidate and methohexital. All of these agents provided markedly shorter induction and recovery times than midazolam. Patients who were pre-medicated with fentanyl exhibited prolonged recovery times and greater decreases in blood pressure. When used for RSI, propofol administration was associated with satisfactory intubating conditions that were comparable to those seen with thiopental and etomidate. Blood pressure reductions were seen in both DCC and RSI studies. Apneic episodes (>30 seconds) occurred in 23% of propofol recipients, 28% of thiopental recipients and 7% of etomidate and midazolam recipients. Apart from the DCC studies described, no procedural sedation studies met our predefined review eligibility criteria. CONCLUSION: The body of literature evaluating propofol for DCC and RSI in the ED is limited. There is evidence to support the use of propofol for DCC and RSI, but this evidence comes from stable patients in non-ED settings. Further ED-based randomized comparative trials should be conducted before propofol is adopted for widespread use in the ED.

Severe methemoglobinemia from topical anesthetic spray: case report, discussion and qualitative systematic review.

Few health care professionals realize that topical anesthetic spray can cause methemoglobinemia. We describe a 56-year-old woman who was transferred to our emergency department when severe cyanosis and chest pain developed after administration of topical oropharyngeal benzocaine and lidocaine during outpatient endoscopy. Investigations revealed a methemoglobin level of 51%. Despite rapid diagnosis and treatment with methylene blue, pulmonary edema consistent with adult respiratory distress syndrome developed, endotracheal intubation was required, and the patient suffered a lengthy course in the intensive care unit. This article presents a detailed discussion of the pathophysiology, diagnosis and treatment of methemoglobinemia, as well as a qualitative systematic review of the English literature on methemoglobinemia induced by topical anesthetic. The implications of this condition for emergency physicians are also outlined.

5-HT3 receptor antagonists vs traditional agents for the prophylaxis of postoperative nausea and vomiting.

PURPOSE: Numerous antiemetics have been studied for the prevention of postoperative nausea and vomiting (PONV) including traditional agents (metoclopramide, perphenazine, prochlorperazine, cyclizine and droperidol) and the 5-HT3 receptor antagonists (ondansetron, dolasetron, granisetron and tropisetron). The results have been divergent and inconsistent. The purpose of this quantitative systematic review was to evaluate the effectiveness of 5HT3 receptor antagonists compared to traditional antiemetics for the prevention of PONV METHODS: A systematic search of the English language literature using computerized MEDLINE, EMBASE, and Pre-MEDLINE databases from 1966 to October 1999 and a manual search of references from retrieved articles were performed. Individual efficacy and adverse effect data was extracted from each of the studies according to a predefined protocol. The summary odds ratios were calculated using the Dersimonian and Laird method under a random effects model. RESULTS: A total of 41 trials met our pre-defined inclusion criteria and were included in our analysis. Results in the 32 studies examining PONV indicated a 46% reduction in the odds of PONV in the 5-HT3-treated group (0.54 [95% CI 0.42-0.71], P < 0.001). Evaluation of PONV by traditional antiemetic agent demonstrated a 39% reduction compared with droperidol (0.61 [95% CI 0.42-0.89], P < 0.001) and a 56% reduction compared with metoclopramide (0.44 [95% CI 0.31-0.62], P < 0.001). Results in the 34 studies examining vomiting indicated a 38% reduction in the odds of vomiting in the 5-HT3-treated group (0.62 [95% CI 0.48-0.81], P < 0.001). CONCLUSIONS: The 5-HT3 receptor antagonists are superior to traditional antiemetic agents for the prevention of PONV and vomiting. The reduction in the odds of PONV and vomiting is significant in the overall analysis and the subgroup analyses comparing 5-HT3 receptor antagonists with droperidol and metoclopramide.

Low molecular weight heparins and coronary artery disease.

Coronary artery disease encompasses a wide spectrum of conditions including silent ischemia, exertional angina, unstable angina, and myocardial infarction. Acute coronary syndromes (unstable angina and myocardial infarction) are caused by the rupture of an atherosclerotic plaque, platelet activation, and fibrin deposition resulting in thrombosis. Aspirin and unfractionated heparin (UFH) have traditionally been the treatment of choice in patients with acute coronary syndromes; however, low molecular weight heparins (LMWHs) offer potential advantages over UFH. Available evidence indicates that LMWH is superior to UFH in reducing ischemic events or death in the acute phase of unstable angina or non-Q-wave myocardial infarction. Long-term therapy with lower doses of LMWH may not offer any advantage to aspirin in the prevention of coronary events or death. Major bleeding complications are similar for LMWH and UFH although minor bleeding complications are more common with LMWH, primarily due to injection-site hematomas. Finally, use of LMWH appears to be cost- effective compared with UFH. The available evidence supports improved clinical outcomes, favorable safety profile, and cost savings associated with LMWH use in the management of unstable angina and non-Q-wave myocardial infarction and should be favored over UFH.

Continuous intrathecal pump infusion of baclofen with antibiotic drugs for treatment of pump-associated meningitis. Case report.

Intrathecal baclofen administered by means of an implantable pump is being increasingly used for successful treatment of spasticity. Meningitis following intrathecally administered baclofen is a rare but serious complication that is difficult to treat without removal of the pump. Because success rates with intravenously administered antibiotic drugs for the treatment of meningitis have been low, intrathecal administration of antibiotic agents is often required to eradicate the pathogen. The authors report the case of a patient in whom Staphylococcus epidermidis meningitis developed after insertion of an intrathecal baclofen pump. The patient was successfully treated by intrathecal coadministration of vancomycin and baclofen.

Low-molecular-weight heparins in the management of acute coronary syndromes.

Acute coronary syndromes (unstable angina and non-Q-wave myocardial infarction) are caused by the rupture of an atherosclerotic plaque, platelet activation, and fibrin deposition resulting in thrombosis. Aspirin and unfractionated heparin have traditionally been the treatments of choice for patients with acute coronary syndromes. Low-molecular-weight heparins offer potential advantages over unfractionated heparin, having proven equally effective for the treatment and prevention of many thromboembolic processes. Recently, a number of randomized controlled trials have been conducted to evaluate the role of low-molecular-weight heparins in the management of patients with unstable angina or non-Q-wave myocardial infarction. The purpose of this article is to review and evaluate the available literature on the use of low-molecular-weight heparins in the management of acute coronary syndromes to establish their role in therapy.

Low-molecular-weight heparin should replace unfractionated heparin in the management of acute coronary syndromes.

Acute coronary syndromes (unstable angina and non-Q-wave myocardial infarction) are caused by the rupture of an atherosclerotic plaque, platelet activation, and fibrin deposition, resulting in thrombosis. Aspirin and unfractionated heparin (UFH) have traditionally been the treatment of choice in patients with acute coronary syndromes. Low-molecular-weight heparins (LMWHs) offer potential advantages over UFH and have been shown to be equally effective as UFH for the treatment and prevention of many venous thromboembolic processes. Results of prospective, randomized, controlled trials evaluating the role of LMWH in the management of patients with unstable angina or non-Q-wave myocardial infarction have indicated improved outcomes when compared with UFH. In addition, despite the increased acquisition cost of LMWH compared with UFH, an overall cost saving was associated with LMWH use, primarily as a result of a reduction in cardiovascular events. The available evidence supports improved clinical outcomes, favorable safety profile, and cost savings associated with LMWH use in the management of unstable angina and non-Q-wave myocardial infarction. Thus, LMWH should replace UFH as the antithrombotic agent of first choice in the management of acute coronary syndromes.

Treatment of acetaminophen overdose.

The therapeutic management of patients with acetaminophen overdose is reviewed. Acetaminophen overdose results in more calls to poison control centers in the United States than overdose with any other pharmacologic substance. Although the optimal management strategy remains controversial, the literature suggests a general approach that can be followed until there is evidence supporting a different strategy. A single dose of activated charcoal should be administered within one hour of acetaminophen overdose. Other means of gastric decontamination are not warranted. Acetylcysteine should be given if the acetaminophen concentration exceeds the treatment line in the Rumack-Matthew nomogram. If a patient is treated within 10 hours of acetaminophen ingestion, the risk of hepatoxicity is low. In patients 10-24 hours after ingestion, a 72-hour oral or 48-hour i.v. acetylcysteine regimen should be used. Among patients with fulminant hepatic failure, acetylcysteine should be given until recovery or death occurs. In patients who have taken extended-release acetaminophen, the acetaminophen concentration should be measured at four hours and, if this level exceeds the treatment line, acetylcysteine should be started immediately. If the concentration is below the treatment line, a second acetaminophen concentration should be determined four to six hours later. If this level is above the treatment line, acetylcysteine therapy should be started. Cimetidine appears to have no role in the management of acetaminophen overdose. Children should be diagnosed and treated the same way as adults, and pregnant patients should be managed no differently than nonpregnant patients. An evaluation of the literature on acetaminophen poisoning verifies the usefulness of acetylcysteine as a hepatoprotective agent. A single dose of activated charcoal may also be useful if given within one hour of acetaminophen ingestion.

Medication-induced headache: overview and systematic review of therapeutic approaches.

OBJECTIVE: To review medication-induced headache (MIH) through a systematic evaluation of the literature regarding the pharmacologic management of this condition. METHODOLOGY: To identify and evaluate all pharmacologic interventions for MIH, we conducted a qualitative systematic review of the English-language literature from 1966 to June 1998 using MEDLINE. The following search terms were used: chronic daily headache, transformed migraine, analgesic withdrawal headache, analgesic rebound headache, drug-associated headache, medication-induced headache, detoxification, and dihydroergotamine. In addition, a review of the references from relevant literature was also conducted to collect reports not identified in the MEDLINE search. RESULTS: Numerous therapies for acute management of MIH have been evaluated, although no rigorously conducted clinical trials were identified. Therapies evaluated include abrupt withdrawal of analgesics, initiation of dihydroergotamine, nonsteroidal antiinflammatory agents, methylergonovine, dihydroergotamine, sumatriptan, amitriptyline, dexamethasone, piracetam, prothipendyl, and valproate. Epidemiology, diagnosis, clinical features, pathophysiology, and long-term prognosis of therapy are discussed and therapeutic guidelines are offered. CONCLUSIONS: MIH is an underrecognized and difficult condition affecting headache-prone patients. The published literature concerning treatment of patients with MIH is scant and of poor quality, making it difficult for clinicians to decide on appropriate therapy. Recognition and treatment of MIH may lead to a long-term improvement in headache relief for many patients. It appears that complete withdrawal of the medications being overused is required for favorable long-term results.

Cost-effectiveness analysis of enoxaparin versus unfractionated heparin for acute coronary syndromes. A Canadian hospital perspective.

OBJECTIVE: To determine the cost effectiveness of enoxaparin therapy versus unfractionated heparin (UFH) therapy for patients with unstable coronary artery disease from the perspective of a Canadian hospital. DESIGN: A predictive decision analysis model using published clinical and economic evaluations and costs of medical care in Canada. PATIENTS: A hypothetical cohort of patients presenting to hospital with unstable angina or non-Q-wave myocardial infarction as defined by the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) trial. INTERVENTIONS: Two antithrombotic treatment strategies were compared: (i) enoxaparin 1 mg/kg subcutaneously every 12 hours, and (ii) UFH intravenous bolus and constant infusion adjusted to maintain a therapeutic activated partial thromboplastin time. Both treatment strategies included 100 to 325 mg of oral aspirin daily. Enoxaparin or UFH was continued for a minimum of 48 hours to a maximum of 8 days. Cumulative outcomes were considered up to 30 days after initial presentation to hospital. RESULTS: At 30 days, 19.8% of patients who received enoxaparin compared with 23.3% of patients who received UFH reached one of the primary composite events. There was no difference in major bleeding between the 2 treatment groups (6.5% enoxaparin vs 6.8% UFH). The average total direct medical cost per patient was $Can848 with the enoxaparin strategy versus $Can892 with the UFH strategy (1999 values). Therapy with enoxaparin was, therefore, considered to be the dominant strategy. Univariate sensitivity analysis indicated that the decision model was not robust to changes in the 30-day composite end-point, probability of recurrent angina, or base costs for treatment of recurrent angina or enoxaparin therapy. CONCLUSION: Enoxaparin is the dominant antithrombotic pharmacotherapeutic strategy for patients with unstable coronary artery disease.

Cost-effectiveness analysis of abciximab: a Canadian hospital perspective.

OBJECTIVE: To assess the cost-effectiveness of abciximab therapy versus traditional practice in high-risk patients receiving percutaneous transluminal coronary angioplasty (PTCA) from a Canadian hospital perspective. DESIGN: A predictive decision analytic model using published clinical and economic evaluations, as well as costs of medical care in Canada. SUBJECTS: High-risk PTCA patients as defined by the Evaluation of c7E3 for Prevention of Ischemic Complications trial and the c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina trial. INTERVENTIONS: Two treatment strategies were compared: (1) abciximab 0.25 mg/kg intravenous bolus 10 minutes prior to PTCA followed by abciximab 10 micrograms/min intravenous infusion for 12 hours after the procedure, and (2) no abciximab adjunctive therapy at the time of PTCA. Both treatment strategies were combined with intravenous heparin up to 100 units/kg bolus pre-PTCA followed by bolus doses for 1 hour after PTCA per the protocol. Cumulative outcomes were considered up to 6 months after initial PTCA. RESULTS: At 6 months, 29% of the patients in the abciximab treatment arm compared with 33% in the no abciximab arm achieved one of the primary events. The most common adverse event experienced was major bleeding at 4% in the abciximab treatment arm versus 1.6% in the no abciximab arm. The average cost per patient for each strategy was $3261 Can ($1 Can = $0.686 US) (abciximab arm) versus $2073 Can (no abciximab arm), resulting in an incremental cost-effectiveness ratio of $29,700 Can per event-free patient. In univariate sensitivity analyses, the only controllable factor that changed the results of the cost-effectiveness outcome was the cost of abciximab. CONCLUSIONS: Although the use of abciximab as an adjunct to PTCA results in a reduction in event rates in high-risk patients compared with traditional treatment, there is an increased cost associated with this strategy.