Roy A. Purssell

Incidence, severity and preventability of medication-related visits to the emergency department: a prospective study

Background: Medication-related visits to the emergency department are an important but poorly understood phenomenon. We sought to evaluate the frequency, severity and preventability of drug-related visits to the emergency department. Methods: We performed a prospective observational study of randomly selected adults presenting to the emergency department over a 12-week period. Emergency department visits were identified as drug-related on the basis of assessment by a pharmacist research assistant and an emergency physician; discrepancies were adjudicated by 2 independent reviewers. Results: Among the 1017 patients included in the study, the emergency department visit was identified as drug-related for 122 patients (12.0%, 95% confidence interval [CI] 10.1%–14.2%); of these, 83 visits (68.0%, 95% CI 59.0%–76.2%) were deemed preventable. Severity was classified as mild in 15.6% of the 122 cases, moderate in 74.6% and severe in 9.8%. The most common reasons for drug-related visits were adverse drug reactions (39.3%), nonadherence (27.9%) and use of the wrong or suboptimal drug (11.5%). The probability of admission was significantly higher among patients who had a drug-related visit than among those whose visit was not drug-related (OR 2.18, 95% CI 1.46–3.27, p < 0.001), and among those admitted, the median length of stay was longer (8.0 [interquartile range 23.5] v. 5.5 [interquartile range 10.0] days, p = 0.06). Interpretation: More than 1 in 9 emergency department visits are due to drug-related adverse events, a potentially preventable problem in our health care system.

Comparison of the 20-hour intravenous and 72-hour oral acetylcysteine protocols for the treatment of acute acetaminophen poisoning.

STUDY OBJECTIVE To compare outcomes after acute acetaminophen poisoning in 2 large cohorts of patients treated with either the 20-hour intravenous or 72-hour oral acetylcysteine protocol. METHODS We conducted a retrospective cohort study with historical control comparing patients treated with one of 2 acetylcysteine regimens. Data for the 20-hour group were obtained from a medical record review of patients on whom the 20-hour intravenous protocol was initiated in Canadian hospitals from 1980 to 2005. The 72-hour group consisted of a historical cohort of patients treated in US hospitals with the 72-hour oral protocol from 1976 to 1985. The primary outcome was hepatotoxicity (aminotransferase levels >1,000 IU/L). RESULTS Of the 4,048 patients analyzed, 2,086 were in the 20-hour group and 1,962 were in the 72-hour group. The incidence of hepatotoxicity was 13.9% in the 20-hour group and 15.8% in the 72-hour group (-1.9% absolute difference; 95% confidence interval [CI] -4.2 to 0.3). The relative risk of hepatotoxicity was lower in the 20-hour group when acetylcysteine was initiated within 12 hours of ingestion. The relative risk was lower in the 72-hour group when acetylcysteine was initiated later than 18 hours after ingestion. There was no significant risk difference between groups when acetylcysteine treatment was started 12 to 18 hours after ingestion. One patient in the 20-hour group received a liver transplant and died because of acetaminophen toxicity compared with no liver transplants and 3 deaths in the 72-hour group. Anaphylactoid reactions to intravenous acetylcysteine were reported in 148 of 2,086 patients (7.1%; 95% CI 6.1% to 8.3%). This study is limited by comparison of 2 separate data sets from different countries and study years. CONCLUSION The risk of hepatotoxicity differed between the 20-hour and 72-hour protocols according to the time to initiation of acetylcysteine. It favored the 20-hour protocol for patients presenting early and favored the 72-hour protocol for patients presenting late after acute acetaminophen overdose.

Iatrogenic magnesium overdose: two case reports.

We report two cases of iatrogenic intravenous magnesium overdose. Both patients presented to the emergency department in alcohol withdrawal, and during the course of their therapy were ordered to receive 2 g of magnesium sulfate intravenously. The patients were erroneously given 20 g of magnesium sulfate, causing cardiac arrest in both cases. The patients were both successfully resuscitated. One patient was discharged neurologically intact and the other died three days later. Review of the literature identified one previous report of iatrogenic overdose of intravenous magnesium causing death. Hypermagnesemia is a rare occurrence, particularly in the absence of renal failure. The cause is often iatrogenic. The major life-threatening clinical manifestations are cardiac conduction delays, asystole, apnea, and coma. A particular hazard of intravenous magnesium therapy is the variety of units of measurement used in written orders and on drug labels. This can easily lead to errors in drug administration.

An evaluation of the osmole gap as a screening test for toxic alcohol poisoning

BackgroundThe osmole gap is used routinely as a screening test for the presence of exogenous osmotically active substances, such as the toxic alcohols ethylene glycol and methanol, particularly when the ability to measure serum concentrations of the substances is not available. The objectives of this study were: 1) to measure the diagnostic accuracy of the osmole gap for screening for ethylene glycol and methanol exposure, and 2) to identify whether a recently proposed modification of the ethanol coefficient affects the diagnostic accuracy.MethodsElectronic laboratory records from two tertiary-care hospitals were searched to identify all patients for whom a serum ethylene glycol and methanol measurement was ordered between January 1, 1996 and March 31, 2002. Cases were eligible for analysis if serum sodium, blood urea nitrogen, glucose, ethanol, ethylene glycol, methanol, and osmolality were measured simultaneously. Serum molarity was calculated using the Smithline and Gardner equation and ethanol coefficients of 1 and 1.25 mOsm/mM. The diagnostic accuracy of the osmole gap was evaluated for identifying patients with toxic alcohol levels above the recommended threshold for antidotal therapy and hemodialysis using receiver-operator characteristic curves, likelihood ratios, and positive and negative predictive values.ResultsOne hundred and thirty-one patients were included in the analysis, 20 of whom had ethylene glycol or methanol serum concentrations above the threshold for antidotal therapy. The use of an ethanol coefficient of 1.25 mOsm/mM yielded higher specificities and positive predictive values, without affecting sensitivity and negative predictive values. Employing an osmole gap threshold of 10 for the identification of patients requiring antidotal therapy resulted in a sensitivity of 0.9 and 0.85, and a specificity of 0.22 and 0. 5, with equations 1 and 2 respectively. The sensitivity increased to 1 for both equations for the identification of patients requiring dialysis.Table 1Equations used to calculate the serum molarity prior to the calculation of the osmole gap.Equation NumberEquation1Osmc = 2 * Na (mEq/L) + BUN (mmol/L) + glucose (mmol/L) + ethanol (mmol/L)2Osmc = 2 * Na (mEq/L) + BUN (mmol/L) + glucose (mmol/L) + 1.25 * ethanol (mmol/L)Equation 2 in effect inflates the ethanol concentration by 25% prior to calculating the osmole gap, as proposed by Purssell et al.[18]Osmc = calculated molarity; Na = sodium; BUN = blood urea nitrogenTo convert from SI units, use the following corrections: BUN/2.8 mg/dl, glucose/18.1 mg/dl, ethanol/0.217 mg/dlTable 2Area under the curve (diagnostic index) for osmole gap to identify toxic alcohol exposure.Exposure ThresholdAUC (95% CI)p valueAUC2 - AUC1 (95% CI)p valueANTIDOTAL THERAPY   Equation 10.736 (0.599, 0.873)< 0.0010.049 (-0.001, 0.099)0.057   Equation 20.785 (0.665, 0.905)< 0.001HEMODIALYSIS   Equation 10.827 (0.715, 0.939)< 0.0010.043 (-0.001, 0.086)0.056   Equation 20.870 (0.784, 0.956)< 0.001AUC = area under the curve; SE = standard error; CI = confidence intervalConclusionIn this sample, an osmole gap threshold of 10 has a sensitivity and negative predictive value of 1 for identifying patients for whom hemodialysis is recommended, independent of the ethanol coefficient applied. In patients potentially requiring antidotal therapy, applying an ethanol coefficient of 1.25 resulted in a higher specificity and positive predictive value without compromising the sensitivity.

Renal Failure Caused by Mushroom Poisoning

BACKGROUND In the Pacific Northwest region of the US and in southwestern British Columbia, Canada, isolated cases of renal failure have occurred following ingestion of wild mushrooms. We report four cases in which toxic mushrooms were mistaken for the edible pine mushroom or matsutake (Tricholoma magnivelare). CASE REPORTS Gastrointestinal symptoms started five to eight hours after ingestion and continued for several days. Three of the four patients were found to be in renal failure when they presented to the emergency department 5-6 days post ingestion. One patient, an elderly diabetic, had renal dysfunction the day following ingestion. All patients received hemodialysis and supportive care and regained renal function. DISCUSSION Symptoms and time of onset are similar to those reported in previous cases of Amanita smithiana poisoning. This suggests that the mushroom involved in these cases may also be Amanita smithiana which contains nephrotoxic compounds. In one of the cases, stem ends of the mushrooms were available for examination. Cellular elements conforming to those described as being present in the species Amanita smithiana were seen on light microscopy. CONCLUSION Mushroom field guides warn against mistaking Amanita smithiana for pine mushrooms. They are similar in size, color and habitat. It appears possible that Amanita smithiana mushrooms were eaten instead of pine mushrooms in these cases.

The Use of the Osmole Gap as a Screening Test for the Presence of Exogenous Substances

The rapid and accurate diagnosis of toxic alcohol poisoning due to methanol (methyl alcohol) [MeOH] and ethylene glycol (EG), is paramount in preventing serious adverse outcomes. The quantitative measurement of specific serum levels of these substances using gas chromatography is expensive, time consuming and generally only available at major tertiary-care facilities. Therefore, because these toxic substances are osmotically active and the measurement of serum osmolality is easily performed and more readily available, the presence of an osmole gap (OG) has been adopted as an alternative screening test. By definition, the OG is the difference between the measured serum osmolality determined using the freezing point depression (Osmm) and the calculated serum molarity (Mc), which is estimated from the known and readily measurable osmotically active substances in the serum, in particular sodium, urea, glucose, and potassium and ethanol (alcohol). Thus, the OG = Osmm − Mc, and an OG above a specific threshold (the threshold of positivity) suggests the presence of unmeasured osmotically active substances, which could be indicative of a toxic exposure. The objectives of this study were to review the principles of evaluating screening tests, the theory behind the OG as a screening test and the literature upon which the adoption of the OG as a screening test has been based.This review revealed that there have been numerous equations derived and proposed for the estimation of the Mc, with the objective of developing empirical evidence of the best equation for the determination of the OG and ultimately the utility of OG as a screening test. However, the methods and statistical analysis employed have generally been inconsistent with recommended guidelines for screening test evaluation and although many equations have been derived, they have not been appropriately validated.Specific evidence of the clinical utility of the OG requires that a threshold of positivity be definitively established, and the sensitivity and specificity of the OG in patients exposed to either EG or MeOH be measured. However, the majority of studies to date have only evaluated the relationship between the Osmm (mmol/kg H2O) and the Mc (mmol/L) in patients that have not been exposed to either MeOH or EG. While some studies have evaluated the relationship between the OG and serum ethanol concentration, these findings cannot be extrapolated to the use of the OG to screen for toxic alcohol exposure.This review shows that there has not been an appropriately designed empirical evaluation of the diagnostic utility of the OG and that its clinical utility remains hypothetical, having been theoretically extrapolated from the non-poisoned population.

Adherence to emergency department discharge prescriptions.

OBJECTIVE Nonadherence to prescribed medication is associated with increased morbidity and mortality as well as the increased use of health services. The main objective of our study was to assess the incidence of prescription-filling and medication adherence in patients discharged from the emergency department (ED). METHODS This was a prospective, observational study carried out at a Canadian tertiary care ED with an annual census of 69 000. We enrolled a convenience sample of patients being discharged with a prescription. We queried a provincial prescription-dispensing database 2 weeks later to determine whether prescriptions had been filled. We used a standardized follow-up interview to assess adherence and whether or not the patient experienced an adverse drug-related event (ADRE) or an unplanned revisit to an ED or clinic. RESULTS Of the 301 patients who agreed to participate, follow-up was successful for 258 (85.7%). Fifty-one patients (19.8%, 95% confidence interval [CI] 15.4%-25.1%) failed to fill their discharge prescriptions and 104 (40.3%, 95% CI 34.5%-46.4%) did not adhere to 1 or more medications. Antibiotics were associated with a lower odds ratio (OR) of nonadherence (OR 0.21, 95% CI 0.08-0.52). There was a trend toward increasing nonadherence in patients who reported an ADRE (OR 1.84, 95% CI 0.98-3.48) or had 2 or more medications coprescribed (OR 1.71, 95% CI 0.95-3.09). There was also a trend toward a higher risk of a revisit to an ED or clinic in nonadherent patients (OR 1.75, 95% CI 0.94-3.25). CONCLUSION Approximately 4 in 10 patients discharged from the ED did not adhere to his or her prescribed medication. Our results suggest that patients who are prescribed antibiotics are more likely to be adherent, and that further evaluation of the associations between nonadherence, ADREs, the coprescription of 2 or more medications and the use of health services is warranted.

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.

Reduction in Fatalities, Ambulance Calls, and Hospital Admissions for Road Trauma After Implementation of New Traffic Laws

OBJECTIVES We evaluated the public health benefits of traffic laws targeting speeding and drunk drivers (British Columbia, Canada, September 2010). METHODS We studied fatal crashes and ambulance dispatches and hospital admissions for road trauma, using interrupted time series with multiple nonequivalent comparison series. We determined estimates of effect using linear regression models incorporating an autoregressive integrated moving average error term. We used neighboring jurisdictions (Alberta, Saskatchewan, Washington State) as external controls. RESULTS In the 2 years after implementation of the new laws, significant decreases occurred in fatal crashes (21.0%; 95% confidence interval [CI]=15.3, 26.4) and in hospital admissions (8.0%; 95% CI=0.6, 14.9) and ambulance calls (7.2%; 95% CI=1.1, 13.0) for road trauma. We found a very large reduction in alcohol-related fatal crashes (52.0%; 95% CI=34.5, 69.5), and the benefits of the new laws are likely primarily the result of a reduction in drinking and driving. CONCLUSIONS These findings suggest that laws calling for immediate sanctions for dangerous drivers can reduce road trauma and should be supported.

The irrationality of the present use of the osmole gap: applicable physical chemistry principles and recommendations to improve the validity of current practices.

The present clinical use of serum osmometry is erroneous in two respects. The first, and the most important, is the incorrect assumption that serum behaves as a dilute ‘ideal’ solution and that the osmotic activity of a substance depends solely on the number of solute particles. The amount of variance from ideal behaviour of serum containing an exogenous substance is expressed by the osmotic coefficient (ϕ). We have calculated the osmotic coefficient for serum containing ethanol (alcohol) and recommend that the osmotic coefficient for serum containing other low molecular weight substances such as methanol (methyl alcohol), isopropyl alcohol and ethylene glycol also be calculated. This is necessary for the accurate calculation of the contribution of these substances to the serum osmolality.Secondly, the practice of subtracting the calculated serum molarity from measured serum osmolality is not valid since it represents a mathematically improper expression. The units of these two terms are different. The ‘osmole gap’ (OG) is typically viewed as the difference between serum osmolality determined by an osmometer and the estimated total molarity of solute in serum by directly measuring the concentration of several substances and then substituting them into a published formula. Some authors call this sum the calculated or estimated osmolarity but, because the concentrations are measured directly and not with an osmometer, the calculated term represents molarity. The units of osmolality are mmol/kg of H2O and the units of molarity are mmol/L. Therefore, the practice of subtracting calculated serum molarity from measured serum osmolality is not mathematically sound and is an oversimplification for ease of application. This mathematical transgression necessarily adds an error to the incorrectly calculated OG. Despite this, the OG is commonly used in clinical medicine. Serum osmolality can be converted to molarity provided the weight percentage and the density of the solution are known and thus, we recommend that this conversion be done prior to calculation of the gap. We recommend that the gap between measured serum osmolarity and calculated serum molarity be called the ‘osmolar gap’.After having corrected for non-ideality for serum and for inconsistency of units, the standard value and reference range for this gap must be determined in an adequate number of patient populations and in a variety of clinical settings. An example of this determination, using data from a group of ethanol-poisoned patients is given. This correction should be applied before the evaluation of the osmolar gap as a screening test for other low molecular weight substances proceeds.