Faculty Bibliography

Objective: At low-to-moderate concentrations, ethanol elimination follows zero-order kinetics. It is unknown whether renal, pulmonary or other first-order processes become significant in patients with very high serum ethanol concentrations. Additionally, it is unclear whether ethanol naive subjects induce their metabolism during acute intoxication. We present the toxicokinetic analysis in a child with a massive ingestion of ethanol. Case report: A 15-year-old girl without significant medical history presented to the Emergency Department after drinking 24 ounces of tequila. She was found unresponsive at home with a Glasgow Coma Score of 3. Her presenting vitals were as follows: 118/69 mmHg blood pressure; pulse rate was 88 beats per minute; respiratory rate of 20 breaths per minute; pulse-oximetry is 96% on room air. Other than obtundation, her physical examination was normal. She was intubated for airway protection and admitted to the ICU. Her initial serum ethanol concentration was 543 mg/dL. A repeat level 3 h later was 722 mg/dL. Post-absorptive ethanol concentrations decreased from 693 mg/dL to 291 mg/dL over the following 15.5 h. The patient had spontaneous eye opening 24 h after presentation. Her projected serum ethanol concentration at that time was 215 mg/dL. She was extubated 2 h later and had an uneventful recovery. Results: The elimination of ethanol in the post-absorptive phase remained zero-order at a rate of 26.3 mg/dL/h (5.7 mmol/L/h) with a Pearson's correlation coefficient (R (2)) of 0.9968 (p < 0.01). There was no evidence of acute induction in metabolism although pharmacodynamic tolerance likely occurred. Conclusion: Even at very high ethanol concentrations in ethanol naive subjects, elimination of ethanol follows a zero-order toxicokinetic model.

A 60-year-old man with a history of hepatic cirrhosis and cardiomyopathy underwent transoesophageal echocardiogram. He received mild sedation and topical lidocaine. During the recovery period the patient developed ataxia and diplopia for about 30 mins, a result of lidocaine toxicity. The patient was administered a commonly used local anaesthetic, a combination of 2% viscous lidocaine, 4% lidocaine gargle and 5% lidocaine ointment topically to the oropharnyx. The total dose was at least 280 mg. Oral lidocaine undergoes extensive first pass metabolism and its clearance is quite dependent on rates of liver blood flow as well as other factors. The patient's central nervous system symptoms were mild and transient but remind us that to avoid adverse side effects, orally administered drugs with fairly high hepatic extraction ratio given to patients with chronic liver disease need to be given in reduced dosages. Even 'Safe' medications need to be carefully administered.

Objective. Dabigatran is a direct thrombin inhibitor approved for anticoagulation in non-valvular atrial fibrillation and, in some countries, for thromboembolism prophylaxis following select orthopedic surgeries. Despite decreased rates of thromboembolism, bleeding remains a risk due to the inability to conveniently monitor anticoagulant effect and the lack of a reversal agent. Case series. We present four cases of dabigatran-related bleeding. A 79-year-old man on aspirin, clopidogrel, and dabigatran presented with rectal bleeding and epistaxis. He died despite transfusion and administration of prothrombin complex concentrate. A 73-year-old woman on dabigatran and aspirin survived after transfusion and an emergent sternotomy for cardiac tamponade. An 86 year-old man with kidney disease and thrombocytopenia received packed red blood cells, platelets, and fresh frozen plasma for rectal bleeding while on dabigatran. An 80 year-old man on dabigatran had a subdural hematoma after falling and hitting his head. Serial imaging showed no progression. Conclusion. The absence of a reversal agent for dabigatran raises concern for uncontrollable bleeding and death. Dabigatran's listed contraindications include active bleeding and a history of dabigatran hypersensitivity reaction. Wider use may result in bleeding rates higher than anticipated from clinical trials. Risks factors that may have contributed to bleeding in these patients include concomitant bleeding diathesis, antiplatelet agent use, renal insufficiency, advanced age, and fall risks.