Suzanne Doyon

Frequency of Medication Errors with Intravenous Acetylcysteine for Acetaminophen Overdose

Background: Acetadote, an intravenous preparation of acetylcysteine, became commercially available in the US in June 2004 for the treatment of acetaminophen poisoning. The dosing regimen is complex, consisting of a loading dose followed by 2 maintenance doses, each with different infusion rates. Objective: To analyze the frequency of medication errors related to the complex dosing regimen for intravenous acetylcysteine. Methods: A retrospective chart review of a regional poison centers records was performed for all patients treated with intravenous acetylcysteine from August 1, 2006, to August 31, 2007. Data collected included acetylcysteine dose, infusion rate, interruptions in therapy, unnecessary administration, and medical outcome. Records that revealed medication errors were further examined for the time and location of the errors. Results: There were 221 acetaminophen overdose cases treated with intravenous acetylcysteine that met inclusion criteria. Of these, 84 medication errors occurred in 74 (33%) patients. The frequency and types of errors were 1.4% incorrect dose, 5% incorrect infusion rate, 18.6% more than 1 hour of interruption in therapy, and 13.1% unnecessary administration. The frequency and types of medication errors in pediatric patients were similar to those in the total patient population. Errors occurred most frequently in the emergency department compared with Intensive care units or general medical floors. In addition, errors occurred most frequently on third shift, compared with first or second shift. Evaluation of medical outcomes in cases involving acetaminophen only found that medication errors did not have an impact on coded outcomes. Conclusions: Medication administration errors occur frequently with intravenous acetylcysteine. Awareness of this problem, coupled with increased vigilance in identifying factors associated with errors, should decrease medication errors with intravenous acetylcysteine therapy for acetaminophen poisoning.

Hepatotoxicity Despite Early Administration of Intravenous N-Acetylcysteine for Acute Acetaminophen Overdose

OBJECTIVES The objective was to evaluate the effectiveness of intravenous N-acetylcysteine (IV NAC; 300 mg/kg over 21 hours) in early acute acetaminophen (APAP) overdose patients. METHODS This observational case series included patients hospitalized between 2004 and 2007 for acute APAP overdoses and who were reported to a regional poison center. Inclusion criteria were plasma APAP concentrations on or above the treatment line on the Rumack-Matthew nomogram, administration of IV NAC within 8 hours of ingestion, and follow-up to known outcome. The hospital chart of each patient who received IV NAC for longer than the standard 21 hours was reviewed. Hepatotoxicity was defined as hepatic aminotransferase levels greater than 1,000 IU/L. RESULTS Seventy-seven patients met inclusion criteria and received at least 21 hours of IV NAC for an acute APAP overdose. Seven patients received antidotal therapy for greater than 21 hours. These patients tended to have ingested combination preparations, have very high initial plasma APAP concentrations, and had persistently elevated plasma concentrations during their hospital stay. Hepatotoxicity occurred in 4 patients (5.2%, 95% confidence interval [CI] = 0.2% to 10.1%), including 1 death and 1 liver transplantation. CONCLUSIONS Hepatotoxicity developed in 5.2% of cases, suggesting that the 21-hour IV NAC regimen is suboptimal in some patients. In addition to high initial plasma APAP concentrations, APAP product formulation and persistently elevated plasma APAP concentrations were identified as factors possibly associated with developing hepatotoxicity. The authors propose a tailored approach to the discontinuation of IV NAC and point out the need for reevaluation of optimal doses and duration of therapy.

Toxicity of Buprenorphine Overdoses in Children

OBJECTIVE. There are few reports in children of overdoses of buprenorphine, a partial opioid agonist used in the treatment of opioid dependence and pain. The purpose of this study was to analyze buprenorphine overdoses in young children reported by US poison centers to the Researched Abuse, Diversion, and Addiction-Related Surveillance System. METHODS. A retrospective review of buprenorphine overdoses in children <6 years of age reported to the Researched Abuse, Diversion, and Addiction-Related Surveillance System from November 2002 through December 2005 was performed. Patients lost to follow-up and those ingesting multiple substances were excluded. RESULTS. Eighty-six cases met inclusion criteria. In the 54 children who developed toxicity, the clinical effects included drowsiness or lethargy (55%), vomiting (21%), miosis (21%), respiratory depression (7%), agitation or irritability (5%), pallor (3%), and coma (2%). There were no fatalities. The mean time to onset of effects was 64.2 minutes, with a range of 20 minutes to 3 hours. Duration of clinical effects was under 2 hours in 11%, 2 to 8 hours in 59%, 8 to 24 hours in 26%, and >24 hours in 4%. Children who ingested ≥2 mg of buprenorphine were more likely to experience clinical effects, and all of the children who ingested >4 mg experienced some effect. No child ingesting <4 mg experienced a severe effect. Of the 22 children administered naloxone, 67% had at least a partial response. CONCLUSIONS. Buprenorphine overdoses are generally well tolerated in children, with significant central nervous system and respiratory depression occurring in only 7%. Any child ingesting >2 mg and children <2 years of age ingesting more than a lick or taste should be referred to the emergency department for a minimum of 6 hours of observation. Naloxone can be used to reverse respiratory depression.

Intravenous acetylcysteine for the treatment of acetaminophen overdose

Importance of the field: Acetaminophen is a leading cause of overdose-related hepatotoxicity. Although acetylcysteine prevents or minimizes acetaminophen-induced hepatotoxicity and reduces mortality, some patients presenting with complicated overdose scenarios (massive ingestions or combination or modified-release formulations) may develop toxicity despite administration of recommended dosage regimen. Areas covered in this review: The article evaluates evidence regarding intravenous acetylcysteines effectiveness in patients with acute overdoses who receive treatment within 10 h or > 10 h, patients with chronic supratherapeutic ingestions, and those with acetaminophen-induced fulminant hepatic failure. Intravenous and oral acetylcysteine are compared. What the reader will gain: A one-size-fits-all approach towards acetylcysteine therapy provides suboptimal care in some patients. High-risk patients are identified. Specific discontinuation criteria are presented. Take home message: The standard intravenous regimen will effectively treat most early-presenting uncomplicated overdoses. Acetylcysteine dosing should be individualized in patients with complicated presentations and in particular situations in which plasma acetaminophen concentrations may be persistently elevated at the end of the infusion or in late presenters. More studies are needed to evaluate the optimal intravenous dosage regimen and the role of oral acetylcysteine in these high-risk patients. Treatment decisions may be aided by consultation with a poison center and/or clinical toxicologist.

Impact of the voluntary withdrawal of over-the-counter cough and cold medications on pediatric ingestions reported to poison centers

To assess the impact of a voluntary withdrawal of over‐the‐counter cough and cold medications (OTC CCMs) labeled for children under age 2 years on pediatric ingestions reported to the American Association of Poison Control Centers.

Medical Outcomes Associated with Nonmedical Use of Methadone and Buprenorphine

BACKGROUND There exists a significant amount of misinformation regarding methadone and buprenorphine, and a belief that toxicity associated with nonmedical use of methadone and nonmedical use of buprenorphine is similar in severity and outcomes. OBJECTIVE The objective of this study is to compare outcomes associated with nonmedical use of methadone vs. nonmedical use of buprenorphine in patients presenting to the Emergency Department (ED) and reported to poison centers. METHODS This was a retrospective cohort study using data from the American Association of Poison Control Centers from January 1, 2003 to December 31, 2009 (7 years). Inclusion criteria were nonmedical use of methadone or buprenorphine (or buprenorphine/naloxone) as a single substance by history, age 18 years or older, ingestions only, evaluated in an ED. Outcome measures were clinical effects, treatments, disposition, and final medical outcomes. RESULTS Of 1,920 cases, 1,594 were in the methadone group and 326 were in the buprenorphine group. Frequently reported clinical effects were lethargy, 59.2% vs. 29.4%, and respiratory depression, 28.7% vs. 2.5%, for methadone and buprenorphine groups, respectively. Hospitalization rates were 67.4% in the methadone group and 32.2% in the buprenorphine group. Half of all patients in the methadone group were admitted to the intensive care unit (ICU) vs. only 15% of all the patients in the buprenorphine group. Twenty-six patients in the methadone group died vs. no deaths in the buprenorphine group. There were significant differences in the distribution of clinical effects, disposition, and medical outcomes (p < 0.001). CONCLUSIONS Patients who use methadone nonmedically have higher hospitalization rates, greater ICU utilization rates, and considerably worse medical outcomes when compared with patients who use buprenorphine nonmedically.

Decrease in Therapeutic Errors Involving Prescription Cough and Cold Medications in Young Children

OBJECTIVES This study sought to determine whether an increase in therapeutic errors involving prescription cough and cold medications (CCM) reported to poison centers was observed following the October 2007 voluntary withdrawal of over-the-counter CCM. METHODS Analysis of therapeutic errors involving prescription CCM in children under 2 years of age for the 33 months before and the 27 months after the October 2007 withdrawal. RESULTS Total counts of therapeutic errors involving prescription CCM in children under 2 years of age decreased from 452 to 337 per year. Rates of therapeutic errors decreased from 0.43 cases/100,000 person-month prewithdrawal to 0.32 postwithdrawal, a 25.6% decrease (p<0.0001). CONCLUSIONS An increase in harm as measured by the number of poison center calls for therapeutic errors involving prescription CCM was not observed in the 27-month time period after the withdrawal. A significant decrease in therapeutic errors involving these products is reported.

A Novel Approach to Informing the Public about the Risks of Overdose and Nonmedical Use of Prescription Medications

BACKGROUND Poison centers answer telephone calls from persons requesting identification of tablets. Many of these calls are from people for whom the tablets were not prescribed and potentially represent nonmedical use. Implementation of a telephone-based program of overdose prevention and screening for nonmedical use of prescription medications is examined. METHODS Social workers with experience in substance abuse disorders were hired by a poison center to answer telephone calls from persons asking for tablet identification. The social workers asked questions regarding demographics, provided the ingredients, provided overdose prevention/safety information, and offered referral to treatment to callers who desired it. RESULTS A total of 17,616 tablet identification calls from the public were answered by the social workers during the 20-month study period. Most callers were Caucasian with median age 33 years (range 18-93 years). Overdose prevention/safety information, aimed mostly at reducing polydrug use, was delivered to 6,635 (37.7%) callers. CONCLUSIONS Treatment resource information was provided to 3,775 (21.4%) callers. A telephone-based service made up of social workers interacted with several thousand individuals potentially at risk for adverse outcomes from nonmedical use of prescription medications and delivered overdose/safety information. Although further study is needed, this type of service can complement existing state/community efforts aimed at education regarding the nonmedical use of prescription medications.

Opioid overdose-related deaths.

To the Editor: Dr Bohnert and colleagues alerted the medical community to the dangers of higher opioid doses and their association with overdose death. Their study most likely missed cases of cardiac deaths from QTc prolongation, as the primary cause, methadone, was excluded from their investigation. However, the other major etiology of opioidrelated death is ventilatory suppression via opioid-induced central sleep apnea. Ventilation is consciously and reflexively controlled in the medulla with the nocturnal drive purely reflexive. If opioid ingestion is not restricted to the daytime, the suppression of ventilation by opioids can enhance the risk of nighttime hypoxemia with possible respiratory failure. Within 1 hour of ingestion of just 15 mg of oxycodone at 2 AM, precipitation of 91 central sleep apnea events occurred in a patient with chronic pain receiving longterm opiate therapy who previously showed no sleep apnea. Similarly, in a chronic pain patient taking regular hydrocodone and morphine, oxygen desaturation to 70% occurred within 2 hours following ingestion at about 1 AM of an additional 7.5 mg of hydrocodone, with events more prevalent during non–rapid eye movement (REM) sleep. Opioids prolong non-REM sleep by decreasing REM sleep duration, accentuating nocturnal breathing risks. Opioid-mediated ventilatory suppression does not attenuate with duration of use, such that patients are at risk for opioid-induced ventilatory suppression throughout their ingestion course. The suggestion from Bohnert et al to minimize opioid doses to reduce overdose-related deaths would also be useful in reducing ventilatory suppression, which is also dose dependent, although it can occur at even low doses. Dose limitation further serves patient safety and public health in that dose minimization also reduces iatrogenic dosedependent addiction as well as diminishes the risk of diversion of prescription narcotics. However, dose minimization may require clinicians to undertreat a portion of patients. If clinicians reflected on the mechanisms of death, educated patients about the ventilatory suppression risks, and informed patients not to ingest short-lasting opioids within several hours of sleep and to take long-lasting, sustainedrelease opioids in the early morning only, the risk of death might be greatly reduced.

Drug adsorption efficacy and palatability of a novel charcoal cookie formulation.

Study Objectives. To determine the effect of a novel charcoal cookie formulation compared with a standard aqueous charcoal product on the absorption of orally administered cimetidine, and to compare the palatability of the two charcoal products.