The American journal of gastroenterology 2013 Jun
Authors: Ehrenpreis ED, Deepak P, Sifuentes H, Devi R, Du H, Leikin JB,
We examined the effects of the black box warning about the risk of tardive dyskinesia (TD) with chronic use of metoclopramide on management of gastroparesis within a single clinical practice, and on reporting of adverse events.
Medical records of gastroparesis patients were evaluated for physician management choices. The FDA Adverse Event Reporting System (FAERS) was analyzed for event reports, and for lawyer-initiated reports, with metoclopramide from 2004 to 2010. Google Scholar was searched for court opinions against metoclopramide manufacturers.
Before the black box warning, 69.8% of patients received metoclopramide for gastroparesis, compared with 23.7% after the warning. Gastroenterologists prescribed domperidone more often after than before the warning. Metoclopramide prescriptions decreased after 2008. Adverse event reporting increased after the warning. Only 3.6% of all FAERS reports but 70% of TD reports were filed by lawyers, suggesting a distortion in signal. Forty-seven legal opinions were identified, 33 from 2009-2010.
The black box warning for metoclopramide has decreased its usage and increased its rate of adverse event reporting. Lawyer-initiated reports of TD hinder pharmacovigilance.
PMID: 23735907 [PubMed - as supplied by publisher]
Clinical toxicology (Philadelphia, Pa.) 2013 May
Authors: Leikin JB, Karydes HC, Whiteley PM, Wills BK, Cumpston KL, Jacobs JJ,
With regard to biological effects, the increasing number of early failure of metal-on-metal (MoM) hip arthroplasties and possible parenteral exposure to orthopedic metal alloys have caused concern for patients and providers alike.
We sought to characterize our outpatient clinical experience of patients with MoM and other forms of hip implants and associated serum/blood chromium and cobalt levels, with a focus on possible systemic sequelae.
This was an observational and retrospective chart review of consecutive patients presenting to two outpatient medical toxicology clinics from January 1, 2010-June 1, 2012 with history of hip implants. Presenting signs, symptoms, and interventions were reviewed. Available cobalt and chromium levels were summarized as median concentration with interquartile range.
A total of 39 patients were analyzed; of the 39 patients, 26 had MoM hip implants while 13 did not. Twelve patients exhibited no symptoms and nine sought evaluation for fatigue while two other patients had been previously diagnosed with fibromyalgia. Tinnitus/hearing loss was also a frequent complaint noted in 12 patients (one presenting complaint), however there was no difference between the incidence of this symptom between the MoM and non-MoM groups. Three patients were provisionally diagnosed with demyelinating neuropathy with one patient demonstrating marked (subjective and objective) improvement after revision. Patients with MoM arthroplasties generally exhibit an approximately tenfold increase in metal ion levels than traditional arthroplasties. Finally, 20 (51.2%) patients had replacement or revision of their hip implant with subsequent decreases in metal ion levels.
A majority of our patients had minor symptoms (fatigue and muscle aches) or no symptoms (n = 23 or 59%). Documented peripheral neurotoxicity is uncommon. The decision for hip revision solely for toxicologic reasons is rare and usually involves a multidisciplinary approach.
Most patients seeking toxicologic referral may be minimally symptomatic and seek guidance regarding elevated blood or serum metal ions; however, solely toxicologic-based interventions are unusual. Revision was associated with a decrease in metal ion levels; however, subjective complaints did not correlate with metal ion levels.
PMID: 23421810 [PubMed - as supplied by publisher]
Disease-a-month : DM 2013 Mar
Authors: Hoyte CO, Leikin JB,
Diethylene glycol is a toxic alcohol used as an industrial solvent in various products. Human exposure to diethylene glycol has resulted in multisystem organ dysfunction and death in cases of acute intentional ingestions as well as epidemics of mass poisoning. Debate remains as to whether the parent compound or metabolite, 2-hydroxyethoxyacetic acid, is responsible for the majority of the toxicity seen in diethylene glycol poisoning. Therefore, cases of diethylene glycol poisoning create management dilemmas when deciding whether to administer alcohol dehydrogenase inhibitors, hemodialysis, or both.
A 35-year-old male was presented to the emergency department reporting that he intentionally ingested brake fluid containing diethylene glycol 8 hours prior to arrival. The patient complained only of epigastric abdominal pain, had a normal physical exam, with a serum bicarbonate of 22 mmol/L, serum creatinine of 0.9 mg/dL, and an undetectable serum ethanol. The management dilemma in this case was whether to initiate fomepizole therapy, administer hemodialysis, or both given the high risk circumstances of the presentation. The decision was made not to administer any therapy other than usual supportive care. Serial basic metabolic panels were sent showing the development of no acidosis or renal dysfunction until his serum diethylene glycol concentration returned undetectable.
Diethylene glycol ingestion can be life threatening. This case highlights the difficulty regarding management of these cases while attempting to balance resource utilization, diagnosis, monitoring, and therapy. Due to continued debate, these decisions remain practitioner specific.
PMID: 23410666 [PubMed - as supplied by publisher]
Disease-a-month : DM 2012 Jan
Authors: Matlock A, Allan N, Wills B, Kang C, Leikin JB,
The boxed warning is increasingly utilized by the Food and Drug Administration (FDA) as a clinical warning to prescribers of dangerous adverse drug reactions. As these warnings have expanded, we feel the utility and application of boxed warnings are becoming more nebulous. The use of drugs following issuance of a boxed warning has been variable. Droperidol sales decreased 10-fold in the year following the warning, yet there has been essentially no change in the methadone usage over a similar time period after its boxed warning. Including more information, such as estimation of incidence for the adverse drug reaction, would be more clinically useful to the prescriber. Reasonable standards using supplemental databases outside of the FDA (such as national poison center data) could be helpful in developing an integrated and balanced approach to boxed warnings.
PMID: 22221547 [PubMed - as supplied by publisher]
The Annals of pharmacotherapy 2011 Apr
Authors: Mork TA, Killeen CT, Patel NK, Dohnal JM, Karydes HC, Leikin JB,
We present a case of a significant insulin overdose that was managed by monitoring daily plasma insulin levels. A 39-year-old male with poorly controlled diabetes mellitus presented to the Emergency Department via emergency medical services after an attempted suicide by insulin overdose. In the attempted suicide, he injected 800 U of insulin lispro and 3800 U of insulin glargine subcutaneously over several parts of his abdomen. The patient was conscious upon arrival to the emergency department. His vital parameters were within normal range. The abdominal examination, in particular, was nonfocal and showed no evidence of hematomas. He was awake, alert, conversant, tearful, and without any focal deficits. An infusion of 10% dextrose was begun at 100 mL/h with hourly blood glucose (BG) checks. The patient was transferred to the intensive care unit where his BG began to decrease and fluctuate between 50 and 80 mg/dL, and the rate of 10% dextrose was increased to 200 mL/h where it was maintained for the next 48 hours. The initial plasma insulin level was found to be 3712.6 uU/mL (reference range 2.6-31.1 uU/mL). At 10 hours, this had decreased to 1582.1 uU/ml. On five occasions, supplemental dextrose was needed when the BG was <70 mg/dL. Thirty-four hours after admission, the plasma insulin level was 724.8 uU/mL. Fifty-eight hours after admission, the plasma insulin level was 321.2 uU/mL, and the 10% dextrose infusion was changed to 5% dextrose solution at 200 mL/h. The plasma insulin levels continued to fall daily to 112.7 uU/mL at 80 hours and to 30.4 uU/mL at 108 hours. He was transferred to an inpatient psychiatric facility 109 hours after initial presentation. Monitoring daily plasma insulin levels and adjusting treatment on a day-to-day basis in terms of basal glucose infusions provides fewer opportunities for episodic hypoglycemia. Furthermore, it was easier to predict daily glucose requirements and eventual medical clearance based on the plasma levels.
PMID: 21467261 [PubMed - as supplied by publisher]
American journal of therapeutics 2013 Jan
Authors: Zell-Kanter M, Coleman P, Whiteley PM, Leikin JB,
The objective of this report is to describe an acidemic patient with one of the largest recorded acetaminophen ingestions in a patient with acidemia who was treated with supportive care and intravenous (IV) N-acetylcysteine. A 59-year-old female with a history of depression was found comatose. In the Emergency Department, she was obtunded with agonal respirations and immediately intubated. Activated charcoal was given through a nasogastric tube. An initial acetaminophen serum level was 1141 mg/L. The patient was started on IV N-acetylcysteine. The acetaminophen level peaked 2 hours later at 1193 mg/L. She was continued on the IV N-acetylcysteine protocol. The next day her aspartate aminotransferase was 3150 U/L, alanine aminotransferase was 2780 U/L, and creatinine phosphokinase was 16,197 U/L. There was no elevation in bilirubin or international normalized ratio (INR). Transaminase levels decreased on day 3 and normalized by day 4 when she was transferred to a psychiatric unit. Few cases have been reported of strikingly elevated acetaminophen levels in poisoned patients who did not receive hemodialysis. These patients did have increased lactate levels, and some had normal liver function tests. All of these patients received N-acetylcysteine and survived the poisoning without sequelae. This patient in this report was unique in that she had the highest reported serum acetaminophen level with acidosis and was treated successfully with only IV N-acetylcysteine and supportive care.
PMID: 21248620 [PubMed - as supplied by publisher]