Faculty Bibliography

Objective: Warfarin is a high risk medication whose safety can be greatly improved by patient education. This study was designed to evaluate patients' understanding of their warfarin medication instructions and evaluate readability of the FDA's Warfarin Medication Guide. Methods: Qualitative structured interviews were conducted with 50 patients prescribed warfarin within the last year at two hospital-based outpatient clinics. 19 questions were asked to examine (1) patient understanding of specific sections in the medication guide, (2) prior provision of warfarin medication instructions, (3) numeracy issues specific to warfarin, (4) general medication management, and 5) patient recommendations for better ways to present warfarin information. The study was approved by the IRB at both institutions. Patients were given an incentive that included a tote bag, medicine box, medical ID bracelet, and brochures about the Poison Center. Results: Of the 50 patients who were surveyed, 49 responses were included for analysis. There were slightly more female respondents than male (53.1% vs. 46.9% respectively). 70% of the patients were between 36-64 years old and reported taking 1-18 medications daily. Most patients (75%) had received information about warfarin when they were first prescribed the medi- cine, 65% were given written information, and 48% discussed the medication with their doctors. Only 12% of patients spoke with the pharmacist about their warfarin. When asked to identify specific content in the medication guide, 16% had difficulty with information about diet, and 21% were not able to identify when to call their provider. Numeracy analysis showed that 19% had trouble with both dosing and interpretation of their INR. Patients' suggested alternative ways to present warfarin information including more graphics, in-person counseling, DVD instructional videos, and multilingual translations of the warfarin medication guide. Conclusion: About 20% of patients were unable to identify key messages in the !

Objective: Carbon monoxide (CO) generation is a known complication of methylene chloride (MeCl) exposure. We report a patient exposed to 36.5 hours of elevated carboxyhemoglobin (COHb) following MeCl exposure without neuro-psychiatric sequelae. We consider this in the context of similar cases treated with hyperbaric oxygen (HBO) due to concern for "soaking" in the setting of ongoing endogenous CO production. Case report: A 51 year-old man was found unresponsive in his car surrounded by rags and an empty bottle of paint stripper. ED vital signs: BP 160/70 mmHg; HR 118 beats/min; RR 14 breaths/min; SpO₂ 100% RA. VBG on supplemental oxygen: pH 7.4; PCO₂ 5.2 kPa; PO₂ 13.3 kPa. He was intubated and placed on 100% O₂. The paint thinner label revealed components: MeCl 90%; methanol 7%; toluene 2%. COHb one hour after arrival was 3.9%. Serial concentrations revealed a rising CO that reached 7% by 5.5 hours, 8% by 10.7 hours, and peaked at 12.1%, 18.2 hours after presentation, before falling to 3.6% at 36.5 hours. He was extubated 36 hours after arrival and remained neurologically intact until discharge. Telephone follow up was performed one month later and he was well and without complaints. Conclusion: In acute CO poisoning loss of consciousness and a long time span of exposure ("soaking") are risk factors for neuropsychiatric sequelae.¹ In cases of acute CO poisoning, evidence suggests that HBO prevents development of these cognitive deficits.² While HBO has also been used to treat CO poisoning following MeCl exposure with similar COHb peaks (11%, 13%), 3 there is no prospective evaluation of the role of HBO. CO poisoning following MeCl exposure can cause neuropsychiatric sequelae.³ While HBO may be considered in such cases due to a concern for prolonged exposure due to continuous endogenous CO production, patients may recover fully with only 100% O₂

Buprenorphine is a partial mu-opioid receptor agonist that is approved for the treatment of opioid dependency. It is generally believed to be safer than methadone because of its ceiling effect on respiratory depression. As more adults in US households use buprenorphine, an increasing number of children are being exposed. We report a fatal exposure to buprenorphine in a small child that occurred after ingestion of a caretaker's buprenorphine/naloxone. Postmortem toxicology analysis showed free serum concentrations of 52 ng/mL and 39 ng/mL for buprenorphine and norbuprenorphine, respectively. No other drugs were detected. Autopsy did not find signs of injury or trauma. The theoretical safety provided by the ceiling effect in respiratory depression from buprenorphine may not apply to children, and buprenorphine may cause dose-dependent respiratory depression.

OBJECTIVES: Oximes such as pralidoxime (2-PAM) are essential antidotes for life-threatening organophosphate poisoning. Unfortunately, oximes are expensive, have limited use, and have short shelf lives. As such, maintaining large stockpiles in preparation for terrorist activity is not always possible. We have demonstrated that atropine is stable well beyond its labeled shelf life and that recently expired 2-PAM was clinically efficacious in a series of poisoned patients. Because 2-PAM is often dosed empirically, clinical improvement does not guarantee pharmacological stability. We therefore chose to analyze the chemical stability of expired 2-PAM. METHODS: Samples of lyophylized 2-PAM were maintained according to the manufacturer's recommendations for 20 years beyond the published shelf life. We studied 2-PAM contained in a MARK I autoinjector that was stored properly for 3 years beyond its expiration date. An Agilent LC/MSD 1100 with diode-array detector and an Agilent Sorbax SB-C-18, 4.6 x 150-mm, 5-mum column were used with the following solvent systems: water with 0.01% trifluoroacetic acid and methanol with 0.01% trifluoroacetic acid. Fresh reagent grade 2-PAM was used as a standard. Results were repeated for consistency. RESULTS: Lyophylized 2-PAM was a white powder that was clear and colorless in solution. Liquid chromatography was identical to the standard and resulted in 2 isolated peaks with identical mass spectra, suggesting that they are stereoisomers. The autoinjector discharged a clear, yellowish solution. In addition to the 2 peaks identified for lyophylized 2-PAM, a small third peak was identified with a mass spectra corresponding to the reported N -methyl pyridinium carboxaldehyde degradation product. CONCLUSIONS: When properly stored, lyophylized 2-PAM appears to be chemically stable well beyond its expiration date. Although the relative amount of degradation product found in solubilized (autoinjector) 2-PAM was small, it is unclear whether this may be toxic and therefore is of concern. Further studies performed with lots of drug stored under varied conditions would be required to fully determine the stability of expired 2-PAM.