Physiologic oxygen responses to smoking opioids: an observational study using continuous pulse oximetry at overdose prevention services in British Columbia, Canada.

BACKGROUND: In British Columbia, Canada, smoking is the most common modality of drug use among people who die of opioid toxicity. We aimed to assess oxygen saturation (SpO2) while people smoked opioids during a pilot study that introduced continuous pulse oximetry at overdose prevention services (OPS) sites. METHODS: This was an observational cohort study, using a participatory design. We implemented our monitoring protocol from March to August 2021 at four OPS. We included adults (≥ 18 years) presenting to smoke opioids. A sensor taped to participants' fingers transmitted real-time SpO2 readings to a remote monitor viewed by OPS staff. Peer researchers collected baseline data and observed the timing of participants' inhalations. We analyzed SpO2 on a per-event basis. In mixed-effects logistic regression models, drop in minimum SpO2 ≤ 90% in the current minute was our main outcome variable. Inhalation in that same minute was our main predictor. We also examined inhalation in the previous minute, cumulative inhalations, inhalation rate, demographics, co-morbidities, and substance use variables. RESULTS: We recorded 599 smoking events; 72.8% (436/599) had analyzable SpO2 data. Participants' mean age was 38.6 years (SD 11.3 years) and 73.1% were male. SpO2 was highly variable within and between individuals. Drop in SpO2 ≤ 90% was not significantly associated with inhalation in that same minute (OR: 1.2 [0.8-1.78], p = 0.261) or inhalation rate (OR 0.47 [0.20-1.10], p = 0.082). There was an association of SpO2 drop with six cumulative inhalations (OR 3.38 [1.04-11.03], p = 0.043); this was not maintained ≥ 7 inhalations. Demographics, co-morbidities, and drug use variables were non-contributory. CONCLUSIONS: Continuous pulse oximetry SpO2 monitoring is a safe adjunct to monitoring people who smoke opioids at OPS. Our data reflect challenges of real-world monitoring, indicating that greater supports are needed for frontline responders at OPS. Inconsistent association between inhalations and SpO2 suggests that complex factors (e.g., inhalation depth/duration, opioid tolerance, drug use setting) contribute to hypoxemia and overdose risk while people smoke opioids.

Feeling safer: effectiveness, feasibility, and acceptability of continuous pulse oximetry for people who smoke opioids at overdose prevention services in British Columbia, Canada.

BACKGROUND: Smoking is the most common mode of unregulated opioid consumption overall and implicated in fatal overdoses in British Columbia (BC). In part, perception of decreased risk (e.g., fewer who smoke carry naloxone kits) and limited smoking-specific harm reduction services contribute to overdose deaths. Overdose prevention services (OPS) offer supervised settings for drug use. Continuous pulse oximetry, common in acute care, allows real-time, remote oxygen monitoring. We evaluated the effectiveness of a novel continuous pulse oximetry protocol aimed at allowing physical distancing (as required by COVID-19, secluded spaces, and to avoid staff exposure to vaporized opioids), its feasibility, and acceptability at OPS for people who smoke opioids. METHODS: This was a mixed methods survey study. We developed a continuous pulse oximetry protocol in collaboration with clinical experts and people with lived/living experience of substance use. We implemented our protocol from March to August 2021 at four OPS in BC permitting smoking. We included adults (≥ 18 years) presenting to OPS to smoke opioids. Peer researchers collected demographic, health, and substance use information, and conducted structured observations. OPS clients participating in our study, OPS staff, and peer researchers completed post-monitoring surveys. We analyzed responses using a thematic inductive approach and validated themes with peer researchers. RESULTS: We included 599 smoking events. OPS clients participating in our study had a mean age of 38.5 years; 73% were male. Most (98%) reported using "down", heroin, or fentanyl; 48% concurrently used other substances (32% of whom reported stimulants); 76% reported smoking alone in the last 3 days; and 36% reported an overdose while smoking. Respondents reported that the protocol facilitated physical distancing, was easy to use, high satisfaction, improved confidence, improved sense of safety, and that they would use it again. CONCLUSIONS: Continuous pulse oximetry allowed safe physical distancing, was feasible, and acceptable in monitoring people who smoke opioids at OPS.

Do emergency physicians attribute drug-related emergency department visits to medication-related problems?

STUDY OBJECTIVE: Adverse drug events represent the most common cause of preventable nonsurgical adverse events in medicine but may remain undetected. Our objective is to determine the proportion of drug-related visits emergency physicians attribute to medication-related problems. METHODS: This prospective observational study enrolled adults presenting to a tertiary care emergency department (ED) during 12 weeks. Drug-related visits were defined as ED visits caused by adverse drug events. The definition of adverse drug event was varied to examine both narrow and broad adverse drug event classification systems. Clinical pharmacists evaluated all patients for drug-related visits, using standardized assessment algorithms, and then followed patients until hospital discharge. Interrater agreement for the clinical pharmacist diagnosis of drug-related visit was assessed. Emergency physicians, blinded to the clinical pharmacist opinion, were interviewed at the end of each shift to determine whether they attributed the visit to a medication-related problem. An independent committee reviewed and adjudicated all cases in which the emergency physicians' and clinical pharmacists' assessments were discordant, or either the emergency physician or clinical pharmacist was uncertain. The primary outcome was the proportion of drug-related visits attributed to a medication-related problem by emergency physicians. RESULTS: Nine hundred forty-four patients were enrolled, of whom 44 patients received a diagnosis of the narrowest definition of an adverse drug event, an adverse drug reaction (4.7%; 95% confidence interval [CI] 3.5% to 6.2%). Twenty-seven of these were categorized as medication-related by emergency physicians (61.4%; 95% CI 46.5% to 74.3%), 10 were categorized as uncertain (22.7%; 95% CI 12.9% to 37.1%), and 7 categorized as a non-medication-related problem (15.9%; 95% CI 8.0% to 29.5%). Seventy-eight patients (8.3%; 95% CI 6.7% to 10.2%) received a diagnosis of an adverse drug event caused by an adverse drug reaction, a drug interaction, drug withdrawal, a medication error, or noncompliance. Emergency physicians attributed 49 of these to a medication-related problem (62.8%; 95% CI 51.7% to 72.7%), were uncertain about 15 (19.2%; 95% CI 12.0% to 29.4%), and attributed 14 to non-medication-related problems (17.9%; 95% CI 11.0% to 27.9%). Twenty-five of 29 (86.2%; 95% CI 69.3% to 94.4%) adverse drug events not considered medication related by emergency physicians were rated at least moderate in severity. CONCLUSION: A significant proportion of drug-related visits are not deemed medication related by emergency physicians. Drug-related visits not attributed to medication-related problems by emergency physicians may be missed in ongoing outpatient adverse drug event surveillance programs intended to develop strategies to enhance drug safety. Further research is needed to determine what the effect may be of not attributing adverse drug events to medication-related problems.

Adverse drug events associated with the antidotes for methanol and ethylene glycol poisoning: a comparison of ethanol and fomepizole.

STUDY OBJECTIVE: We investigate adverse drug events associated with antidotes ethanol and fomepizole in methanol or ethylene glycol poisonings. An "adverse drug event" is harm associated with normal or incorrect drug use. We describe type, frequency, severity, seriousness, and onset time of adverse drug events and test the hypothesis that fomepizole results in fewer adverse drug events than ethanol. METHODS: This cohort study included patients aged 13 years or older, hospitalized between 1996 and 2005 for methanol or ethylene glycol poisoning (identified by International Classification of Diseases, Ninth Revision or 10th Revision codes) and treated with at least 1 dose of ethanol or fomepizole. Two abstractors separately reviewed each chart, identifying new clinical events during antidote treatment. Three toxicologists determined, by consensus, which events were adverse drug events. The primary outcome was at least 1 adverse drug event, expressed as adverse drug event rate per person-day of antidote treatment. Association between time to first adverse drug event and antidote type was modeled by Cox regression, adjusted for confounders. RESULTS: Two hundred twenty-three charts were reviewed and 172 analyzed. Toxicologists identified at least 1 adverse drug event in 74 of 130 (57%) ethanol-treated and 5 of 42 (12%) fomepizole-treated cases. Central nervous system symptoms accounted for most adverse drug events (48% ethanol-treated, 2% fomepizole-treated). Severe adverse drug events occurred in 26 of 130 (20%) ethanol-treated (coma, extreme agitation, cardiovascular) and 2 of 42 (5%) fomepizole-treated (coma, cardiovascular). Serious (life-threatening) adverse drug events occurred in 11 of 130 (8%) ethanol-treated (respiratory depression, hypotension) and 1 of 42 (2%) fomepizole-treated (hypotension, bradycardia) cases. Median adverse drug event onset was within 3 hours after the start of either antidote. Ethanol and fomepizole adverse drug event rates were 0.93 and 0.13 adverse drug events per treatment-day, respectively. Adjusted hazard ratio was 0.16 (95% confidence interval 0.06, 0.40). CONCLUSION: Given observational study limitations, results suggest lower occurrence of adverse drug events with fomepizole than ethanol.

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.

Cannabis use as a risk factor for causing motor vehicle crashes: a prospective study.

AIM: We conducted a responsibility analysis to determine whether drivers injured in motor vehicle collisions who test positive for Δ-9-tetrahydrocannabinol (THC) or other drugs are more likely to have contributed to the crash than those who test negative. DESIGN: Prospective case-control study. SETTING: Trauma centres in British Columbia, Canada. PARTICIPANTS: Injured drivers who required blood tests for clinical purposes following a motor vehicle collision. MEASUREMENTS: Excess whole blood remaining after clinical use was obtained and broad-spectrum toxicology testing performed. The analysis quantified alcohol and THC and gave semiquantitative levels of other impairing drugs and medications. Police crash reports were analysed to determine which drivers contributed to the crash (responsible) and which were 'innocently involved' (non-responsible). We used unconditional logistic regression to determine the likelihood (odds ratio: OR) of crash responsibility in drivers with 0 < THC < 2 ng/ml, 2 ng/ml ≤ THC < 5 ng/ml and THC ≥ 5 ng/ml (all versus THC = 0 ng/ml). Risk estimates were adjusted for age, sex and presence of other impairing substances. FINDINGS: We obtained toxicology results on 3005 injured drivers and police reports on 2318. Alcohol was detected in 14.4% of drivers, THC in 8.3%, other drugs in 8.9% and sedating medications in 19.8%. There was no increased risk of crash responsibility in drivers with THC < 2 ng/ml or 2 ≤ THC < 5 ng/ml. In drivers with THC ≥ 5 ng/ml, the adjusted OR was 1.74 [95% confidence interval (CI) = 0.59-6.36; P = 0.35]. There was significantly increased risk of crash responsibility in drivers with blood alcohol concentration (BAC) ≥ 0.08% (OR = 6.00;95% CI = 3.87-9.75; P < 0.01), other recreational drugs detected (OR = 1.82;95% CI = 1.21-2.80; P < 0.01) or sedating medications detected (OR = 1.45; 95%CI = 1.11-1.91; P < 0.01). CONCLUSIONS: In this sample of non-fatally injured motor vehicle drivers in British Columbia, Canada, there was no evidence of increased crash risk in drivers with Δ-9-tetrahydrocannabinol < 5 ng/ml and a statistically non-significant increased risk of crash responsibility (odds ratio = 1.74) in drivers with Δ-9-tetrahydrocannabinol ≥ 5 ng/ml.

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.

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

BACKGROUND: The 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. METHODS: Electronic 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. RESULTS: One 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. CONCLUSION: In 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.

Police documentation of drug use in injured drivers: Implications for monitoring and preventing drug-impaired driving.

INTRODUCTION: Most countries have laws against driving while impaired by drugs. However, in many countries, including Canada and the United States, police must have individualized suspicion that the driver has recently used an impairing substance before they can gather the evidence required for laying a criminal charge. This report studies police documentation of drug involvement among drivers who had a motor-vehicle crash after using an impairing substance. METHODS: We obtained blood samples and police reports on injured drivers treated in participating British Columbia trauma centres following a crash. Blood was analyzed for alcohol, cannabinoids, other recreational drugs, and impairing medications. Corresponding police reports were examined to determine whether police recorded that the driver's ability was impaired by alcohol, drug or medication, or that one of these substances was a possible contributory factor in the crash. RESULTS: We obtained blood samples and corresponding police reports on 1816 injured drivers. Mean driver age was 44 years, 63.2% were male, and 25.8% were admitted to hospital. Alcohol was detected in 272 drivers (15.0%), THC (tetrahydrocannabinol - the principal psychoactive ingredient in cannabis) in 136 (7.5%), other recreational drugs in 166 (9.1%), and potentially impairing medications in 363 (20.0%). Police reported that the driver's ability was impaired by alcohol or that alcohol was a possible contributory factor in 64.1% of the crashes involving alcohol-positive drivers. Drug impairment or drugs as a possible contributory factor was reported in 5.9% of the crashes involving THC-positive drivers, and in 16.9% of the crashes involving drivers who tested positive for other recreational drugs. Medication impairment was reported in only 2.2% of the crashes involving medication-positive drivers. CONCLUSION: Police seldom document drug involvement in drivers who were in a crash after using cannabis, other recreational drugs or potentially impairing medications. This finding raises serious concerns about the ability of the police to effectively enforce current drug-impaired driving laws and public health officials' continued reliance on police crash reports to monitor the prevalence of drug-impaired driving.

Aluminum toxicity following IV use of oral methadone solution.

BACKGROUND: Aluminum toxicity has been reported in renal failure patients exposed to aluminum-contaminated dialysate and oral phosphate binders. We report a case of significant aluminum toxicity in a non-hemodialysis patient. CASE REPORT: A 43-year-old male IV drug user presented to the hospital with a seizure disorder of recent onset, progressive cognitive decline, ataxia, and dysarthria. The serum aluminum concentration was 180 micrograms/L (6.65 micromol/L). For 3 to 4 years prior, the patient had injected 'cooked' oral methadone. The methadone solution was heated in an aluminum pot to reduce the volume and then injected intravenously (IV). He was treated with IV deferoxamine over 9 months until he failed to return. Serum aluminum level after 9 months of treatment was 64.5 microgram/L (2.39 micromol/L). Neurological symptoms were partially improved. CONCLUSION: Chronic IV injection of oral methadone solution heated in an aluminum-based cooking utensil may result in significant aluminum toxicity.

Adequacy of antidote stocking in British Columbia hospitals: the 2005 Antidote Stocking Study.

BACKGROUND: Inadequate hospital stocking and the unavailability of essential antidotes is a worldwide problem with potentially disastrous repercussions for poisoned patients. Research indicates minimal progress has been made in the resolution of this issue in both urban and rural hospitals. In response to this issue the British Columbia Drug and Poison Information Centre developed provincial antidote stocking guidelines in 2003. We sought to determine the compliance with antidote stocking in BC hospitals and any factors associated with inadequate supply. METHODS: A 2-part survey, consisting of hospital demographics and antidote stocking information, was distributed in 2005 to all acute care hospital pharmacy directors in BC. The 32 antidotes examined (21 deemed essential) and the definitions of adequacy were based on the 2003 BC guidelines. Availability was reported as number of antidotes stocked per hospital and proportion of hospitals stocking each antidote. For secondary purposes, we assessed factors potentially associated with inadequate stocking. RESULTS: Surveys were completed for all 79 (100%) hospitals. A mean of 15.6+/-4.9 antidotes were adequately stocked per hospital. Over 90% of hospitals had adequate stocks of N-acetylcysteine, activated charcoal, naloxone, calcium salts, flumazenil and vitamin K; 71%-90% had adequate dextrose 50% in water (D50W), ethyl alcohol or fomepizole, polyethylene glycol electrolyte solution, protamine sulfate, and cyanide antidotes; 51%-70% had adequate folic acid, glucagon, methylene blue, atropine, pralidoxime, leucovorin, pyridoxine, and deferoxamine; and <50% had adequate isoproterenol and digoxin immune Fab. Only 7 (8.9%) hospitals sufficiently stocked all 21 essential antidotes. Factors predicting poor stocking included small hospital size (p < 0.0001), isolation (p = 0.01) and rural location (p < 0.0001). CONCLUSION: Although antidote stocking has improved since the implementation of the 2003 guidelines, essential antidotes are absent in many BC hospitals. Future research should focus on determining the reasons for this situation and the effects of corrective interventions.

Deaths from exposure to paramethoxymethamphetamine in Alberta and British Columbia, Canada: a case series.

BACKGROUND: Paramethoxymethamphetamine (PMMA) is a ring-substituted amphetamine similar in structure to 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"), but substantially more toxic. We describe the clinical features of fatal exposures in the provinces of Alberta and British Columbia, Canada. METHODS: We conducted a retrospective case series on deaths in Alberta and BC between June 2011 and April 2012 for which forensic toxicologic analysis was positive for PMMA and the drug was implicated as the primary toxic agent. Data collected included patient demographics, exposure history, clinical features, investigations, therapy provided and postmortem toxicologic findings. RESULTS: A total of 27 PMMA-associated deaths (20 in Alberta, 7 in BC) were reported in the 11-month period. The median age was 24 (range 14-52) years, and 22 (81%) were male. Ten patients were pronounced dead at the scene, and 17 died in hospital. The median time from exposure to death was 17 (range 5-264) hours. The median first-recorded vital signs (and ranges) were: heart rate 160 (86-201) beats/min, blood pressure 89/43 (69/30-162/83) mm Hg, respiratory rate 40 (26-48) breaths/min, oxygen saturation 81% (68%-100%) and temperature 39.4°C (34-43.8°C). Sixteen of the 17 people who died in hospital presented with clinical features consistent with serotonin syndrome. End-organ dysfunction included hepatic (30%) and acute kidney injury (85%), rhabdomyolysis (54%), coagulopathy (61%) and cardiac ischemia (15%). Other drugs identified on toxicologic analysis were MDMA (n = 27), cocaine or its metabolite benzoylecgonine (n = 14) and methamphetamine (n = 12). INTERPRETATION: Exposure to PMMA was characterized by multiorgan dysfunction and serotonin syndrome, followed by cardiovascular collapse. In addition to PMMA, multiple synthetic amphetamines were present on toxicologic analysis. When evaluating patients suspected of exposure to sympathomimetic drugs of abuse, clinicians must anticipate multiple clinical effects from the increased release of dopamine, serotonin, norepinephrine and other neurotransmitters.

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 (Osm(m)) 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=Osm(m)-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 Osm(m) (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.

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 (phi). 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.

Antidote stocking in British Columbia hospitals.

INTRODUCTION: Previous studies have demonstrated that antidotes are insufficiently stocked in Canadian and US health care facilities. The purpose of this study was to determine the adequacy of antidote stocking in British Columbia hospitals based on the current guidelines. METHODS: A written survey was mailed to hospital pharmacy directors at all 93 acute care facilities in BC. Availability of 14 essential antidotes was classified as sufficient or insufficient based on the current guidelines. Facilities were stratified into small (<50 beds), medium (50-250 beds) or large (>250 beds); teaching or non-teaching; trauma or non-trauma, urban or rural, and isolated or non-isolated. RESULTS: Complete responses were received from 75 (81%) of 93 hospitals. No hospital had adequate stock of all 14 antidotes. Overall, the average number (+/- standard deviation) of antidotes adequately stocked was 4.2 +/- 2.9 per hospital. Urban hospitals had adequate stocks of 6.5 +/- 2.6 antidotes while rural centres had adequate stocks of 2.6 +/- 1.8 (p < 0.001). Corresponding figures were 9.0 +/- 1.8 for teaching hospitals vs. 3.7 +/- 2.4 for non-teaching hospitals (p < 0.001), 8.9 +/- 2.0 for trauma centres vs. 3.8 +/- 2.5 non-trauma centres (p < 0.001), and 2.5 +/- 2.1 for isolated hospitals vs. 4.6 +/- 2.9 for non-isolated hospitals (p = 0.018). Small, medium, and large hospitals adequately stocked 2.3 +/- 1.7, 5.7 +/- 2.2, and 7.7 +/- 3.0 antidotes, respectively (p < 0.001). The 4 antidotes most adequately stocked were sodium bicarbonate (77%), N-acetylcysteine (64%), ethanol (49%) and naloxone (47%). Digoxin immune Fab fragments, glucagon, pyridoxine and rattlesnake antivenin were poorly stocked with sufficient supplies of 5%, 7%, 7% and 13%, respectively. CONCLUSION: BC hospitals do not have adequate antidote stocks. Provincial stocking guidelines and coordination of antidote purchasing and stocking are necessary to correct these deficiencies.

Proportion of injured alcohol-impaired drivers subsequently convicted of an impaired driving criminal code offence in British Columbia.

BACKGROUND: Alcohol is a frequent contributing factor to motor vehicle collision injuries. Our objective was to determine the proportion of intoxicated drivers hospitalized following motor vehicle crashes who were subsequently convicted of an impaired driving criminal code offence. METHODS: We reviewed British Columbia Trauma Registry records from Jan. 1, 1992, to Mar. 31, 2000, and identified drivers of motor vehicles who were hospitalized for treatment of crash-related injuries. Patient identifiers were then used to link with the Insurance Corporation of British Columbia's (ICBC) contraventions database and the ICBC Traffic Accident System collisions database. RESULTS: Of 6067 patients identified in the Trauma Registry, 4042 had not been administered a blood ethanol test, 209 had no driver's licence match in the relevant databases and 119 died, leaving 1697 eligible patients. Mean age was 34 years, and 79.6% were male. The average Injury Severity Score was 20, the average hospital stay was 14 days and, among ethanol-positive patients, the mean ethanol level was 34.0 mmol/L (156.4 mg/dL). In patients with levels >17.3 mmol/L, the police had listed ethanol as a contributing factor in 70.6% of cases. Despite this, only 11.0% were convicted of impaired driving and 8.4% of another criminal offence; 10.7% received a 24-hour roadside prohibition, 3.9% received a 90-day administrative driving prohibition and 25.0% were convicted of a contravention of the Motor Vehicle Act. Forty-one percent were not convicted of any offence at all. CONCLUSIONS: Intoxicated drivers in British Columbia requiring hospitalization as a result of alcohol-related motor vehicle crashes are seldom convicted of impaired driving or other criminal code offences.

Risk factors for subsequent impaired driving by injured passengers.

OBJECTIVES: The purpose of this study was to evaluate the rate of, and risk factors for, subsequent impaired driving activity (IDA) in a cohort of injured passengers who were treated for injuries in a Canadian trauma center. METHODS: We studied adult passengers who were occupants in vehicles involved in motor vehicle crashes (MVCs) and either included in the British Columbia (BC) trauma registry (January 1, 1992-December 31, 2004) or treated in the emergency department (ED) of Vancouver General Hospital (VGH; January 1, 1999-December 31, 2003). Passengers were linked to their driver's license and hence to their driving record using personal health number and demographic information. Injured passengers were stratified into 3 groups based on their blood alcohol concentration (BAC) at time of ED presentation: group 1: BAC = 0, group 2: 0 < BAC ≤ 17.3 mM (0.08%), group 3: BAC > 17.3 mM (0.08%). Two outcome variables were studied: involvement in a subsequent IDA and time to their first subsequent IDA. IDA was defined as a criminal code conviction for impaired driving, a 24-h or 90-day license suspension for impaired driving, and/or involvement in an MVC where police cited alcohol as a factor. Time to first IDA following the index event among passenger BAC groups was compared with Kaplan-Meier survival analysis. Cox proportional hazards models were employed to examine the effect of various potential risk factors on time to engage in first IDA. RESULTS: Injured passengers with any BAC at the time of ED visit were more likely to engage in IDA and had their first IDA sooner after the index event than those with zero BAC. Among this cohort of injured passengers, 12.1 percent with BAC = 0, 29.9 percent with 0 < BAC ≤ 17.3 mM (0.08%), and 37.8 percent with a BAC > 17.3 mM (0.08%) engaged in IDA. Compared to passengers with BAC = 0, group 3 passengers and group 2 passengers were 2.06 times and 1.79 times more likely to engage in future IDA. Twenty-five percent of injured passengers engaged their first IDA by 57 and 38 months in groups 2 and 3, respectively. Previous IDA and being male were also significant risk factors for future IDA. Those with a history of IDA before the index event were 2.37 times more likely to engage in subsequent IDA. CONCLUSIONS: Injured alcohol-impaired passengers are at high risk for IDA and should be included in impaired driving prevention programs.

Medication errors associated with the use of ethanol and fomepizole as antidotes for methanol and ethylene glycol poisoning.

INTRODUCTION: Little is known about medication errors which occur with the antidotes ethanol and fomepizole, used for treatment of methanol and ethylene glycol poisoning. Study objectives were to describe and compare the frequency, type, outcome and underlying causes of medication errors associated with ethanol and fomepizole. METHODS: Patients aged ≥13 years were included if they were hospitalized in 1996-2005 for methanol or ethylene glycol poisoning and treated with ethanol or fomepizole. Charts from 10 hospitals were separately reviewed by two abstracters who recorded case details. A consensus panel of clinicians used the abstracted data to identify medication errors and classify error outcome. Fisher's exact test determined significant differences in the proportion of ethanol and fomepizole-treated cases with medication error and univariate logistic regression identified risk factors associated with harmful dosage errors. RESULTS: There were 145 ethanol- and 44 fomepizole-treated cases. There was ≥1 medication error in 113/145 (78%) ethanol- and 20/44 (45%) fomepizole-treated cases (p = 0.0001) with more ethanol-related errors involving excessive dose, inadequate monitoring and inappropriate antidote duration. Harmful errors occurred in 19% of ethanol- and 7% of fomepizole-treated cases (p = 0.06) and were largely due to excessive antidote dose or delayed antidote initiation. Occurrence of harmful dosage error was reduced in cases with Poison Control Centre consultation, odds ratio (95% confidence interval) 0.39 (0.17, 0.91), hemodialysis 0.37 (0.16, 0.88), or fomepizole versus ethanol 0.24 (0.06, 1.04). CONCLUSION: Fomepizole was less prone to medication error than ethanol. Error-related harm was most commonly due to excessive antidote dose or delayed antidote initiation.

Patient-reported adverse drug-related events from emergency department discharge prescriptions.

OBJECTIVE: The tolerability of drugs prescribed on emergency department (ED) discharge is unknown. Our objectives were to quantify and describe adverse drug-related events (ADREs) as reported by patients triaged as Canadian Emergency Department Triage and Acuity Scale scores 3, 4 or 5, discharged from the ED with prescriptions. METHODS: This prospective observational study was a planned substudy of a larger study on adherence to discharge prescriptions. This study was conducted in a tertiary care centre with an annual ED census of 69 000 visits. The primary outcome was the frequency of ADREs reported during a structured telephone questionnaire 2 weeks after ED discharge. An ADRE was deemed to have occurred if the patient reported a symptom consistent with a known ADRE that began and resolved within a plausible time frame after starting and stopping the drug, and if no alternative diagnosis was probable. RESULTS: Research assistants contacted 258/301 (85.7%) patients discharged from the ED with a prescription. An ADRE was reported by 54/258 patients (20.9%, 95% confidence interval [CI] 16.4%-26.3%). The most commonly reported ADREs were nausea, constipation and drowsiness. None required hospital admission or caused death. Participants reporting ADREs were not more likely to make an unplanned ED or clinic revisit (crude odds ratio [OR] 1.1, 95% CI 0.6-2.2; adjusted OR 1.2, 95% CI 0.6-2.4). CONCLUSION: Approximately one-fifth of low-acuity patients prescribed medication on discharge from the ED report ADREs, but most of these are neither severe nor associated with an increase in use of health services. Attention to common preventable ADREs, such as opioid-associated constipation, could reduce the rate of ADREs in this 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.