James A. Chenoweth

Is It Prime Time for Alpha2-Adrenocepter Agonists in the Treatment of Withdrawal Syndromes?

The need to treat withdrawal syndromes is a common occurrence in outpatient, inpatient ward, and intensive care unit (ICU) settings. A PubMed and Google Scholar search using alpha2-adrenoreceptor agonist (A2AA), specific A2AA agents, withdrawal syndrome and nicotine, and alcohol and opioid withdrawal terms was performed. A2AA agents appear to be able to modulate many of the signs and symptoms of significant withdrawal syndromes but are also capable of significant side effects, which can limit clinical use. Non-opioid oral A2AA agent use for opioid withdrawal has been well established. Pharmacologic combination therapy that utilizes A2AA agents for withdrawal syndromes appears promising but requires further formal testing to better define which other agents, under what condition(s), and at what A2AA doses are needed. The A2AA dexmedetomidine may be useful as an adjunctive agent in treating severe alcohol withdrawal syndromes in the ICU. In general, the current data does not support the routine use of A2AA as the primary or sole agent to treat ethanol/alcohol or nicotine withdrawal syndromes. Specific A2AA agents such as lofexidine has been shown to have a primary role in non-opioid-based treatment of opioid withdrawal syndrome and dexmedetomidine in combination with benzodiazepines has been shown to have potential in the treatment of severe ICU-based alcohol withdrawal syndrome.

The Changing Use of Intravenous Opioids in an Emergency Department

Introduction Government agencies are increasingly emphasizing opioid safety in hospitals. In 2012, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) started a sentinel event program, the “Safe Use of Opioids in Hospitals.” We sought to determine if opioid use patterns in our emergency department (ED) changed from 2011, before the program began, to 2013, after start of the program. Methods This was a retrospective study of all adult ED patients who received an intravenous opioid and had a serum creatinine measured. We recorded opioids used, dose prescribed, and serum creatinine. As an index of the safety of opioids, uses of naloxone after administration of an opioid was recorded. Results Morphine is still the most commonly used opioid by doses given, but its percentage of opioids used decreased from 68.9% in 2011 to 52.8% in 2013. During the same period, use of hydromorphone increased from 27.5% to 42.9%, while the use of fentanyl changed little (3.6% to 4.3%). Naloxone administration was rare after an opioid had been given. Opioids were not dosed in an equipotent manner. Conclusion The use of hydromorphone in our ED increased by 56% (absolute increase of 15.4%), while the use of morphine decreased by 30.5% (absolute decrease 16.1%) of total opioid use from 2011 to 2013. The JCAHO program likely was at least indirectly responsible for this change in relative dosing of the opioids. Based on frequency of naloxone administered after administration of an opioid, the use of opioids was safe.

Massive diltiazem and metoprolol overdose rescued with extracorporeal life support.

ABSTRACT The management of overdoses of cardioactive medications in the emergency department can be challenging. The reversal of severe toxicity from one or more types of cardioactive medication may fail maximal medical therapies and require extreme invasive measures such as transvenous cardiac pacing and extracorporeal life support. We present a case of massive diltiazem and metoprolol overdose refractory to maximal medical therapy, including intravenous calcium, glucagon, vasopressors, high dose insulin, and lipid emulsion. The patient experienced refractory bradydysrhythmia that responded only to transvenous pacing. Extracorporeal life support was initiated and resulted in successful organ perfusion and complete recovery of the patient. This case highlights the potential utility of extracorporeal life support in cases of severe toxicity due to multiple cardioactive medications.

Altered Mental Status and End Organ Damage Associated with the use of Gacyclidine: A Case Series

IntroductionOver the past decade, there has been a sharp increase in the number of newly identified synthetic drugs. These new drugs are often derivatives of previously abused substances but have unpredictable toxicity. One of these drugs is gacyclidine, a derivative of phencyclidine (PCP). Gacyclidine has been studied as a neuroprotective agent in trauma and as a therapy of soman toxicity. There are no previous reports of its use as a drug of abuse.Case ReportsDuring a two-month period in the summer of 2013, a series of patients with severe agitation and end-organ injury were identified in an urban academic Emergency Department (ED). A urine drug of abuse screen was performed on all patients, and serum samples were sent for comprehensive toxicology analysis. A total of five patients were identified as having agitation, rhabdomyolysis, and elevated troponin (Table 1). Three of the five patients reported use of methamphetamine, and all five patients had urine drug screens positive for amphetamine. Comprehensive serum analysis identified methamphetamine in three cases, cocaine metabolites in one case, and a potential untargeted match for gacyclidine in all five cases. No other drugs of abuse were identified.DiscussionThis is the first series of cases describing possible gacyclidine intoxication. The possible source of the gacyclidine is unknown but it may have been an adulterant in methamphetamine as all patients who were questioned reported methamphetamine use. These cases highlight the importance of screening for new drugs of abuse when patients present with atypical or severe symptoms. Gacyclidine has the potential to become a drug of abuse both by itself and in conjunction with other agents and toxicity from gacyclidine can be severe. It is the role of the medical toxicology field to identify new agents such as gacyclidine early and to attempt to educate the community on the dangers of these new drugs of abuse.

Incidence of Delayed Intracranial Hemorrhage in Older Patients After Blunt Head Trauma

Importance Current guidelines conflict on the management of older adults who have blunt head trauma taking anticoagulant and antiplatelet medications. This is partially due to the limited data comparing patients who are taking these medications with those who are not. Objective To investigate the incidence of delayed traumatic intracranial hemorrhage in older adults with head trauma, including those taking anticoagulant and antiplatelet medications. Design, Setting, and Participants This prospective observational cohort study included patients 55 years and older who had blunt head trauma and were transported via emergency medical services between August 1, 2015, and September 30, 2016. The setting was a multicenter study conducted at 11 hospitals in northern California. Patients were excluded if they had traumatic intracranial hemorrhage on the initial cranial computed tomographic scan, did not have a cranial computed tomographic scan performed at the initial emergency department visit, refused consent for a follow-up telephone call, or did not have reliable means of follow-up. Main Outcome and Measure The primary outcome of this study was the incidence of delayed traumatic intracranial hemorrhage within 14 days of injury. Results Among 859 patients enrolled in the study, the median age was 75 years (interquartile range, 64-85 years), and 389 (45.3%) were male. A total of 343 patients (39.9%) were taking an anticoagulant or antiplatelet medication. Three patients (0.3%; 95% CI, 0.1%-1.0%) had a delayed traumatic intracranial hemorrhage. Of the 3 patients, 1 of 75 patients (1.3%; 95% CI, 0.0%-7.2%) who were taking warfarin sodium alone and 2 of 516 patients (0.4%; 95% CI, 0.1%-1.4%) who were not taking any anticoagulant or antiplatelet medication had a delayed traumatic intracranial hemorrhage. Thirty-nine patients (4.5%; 95% CI, 3.2%-6.2%) were lost to follow-up. Conclusions and Relevance Overall, the incidence of delayed intracranial hemorrhage in older adults who have blunt head trauma is low, including patients taking an anticoagulant or antiplatelet medication. These findings suggest that routine observation and serial cranial computed tomography may not be necessary in these patients.

Management of atrial fibrillation in the acute setting

Purpose of reviewThe review aims to describe the scope of the problem and potential therapeutic intervention for the management and risk stratification of patients with atrial fibrillation in the emergency department and acute care setting. Recent findingsAtrial fibrillation is the most common arrhythmia prompting admission to the hospital. Management strategies include determining the trigger of the arrhythmia, rate control, and potential cardioversion. In the acute care setting the treatment is often dependent on the timing of the onset of arrhythmia. In those patients presenting with symptoms of less than 48 h of duration management may consist of rate control, pharmacologic, or electrical cardioversion. Recent studies suggest no difference in long-term outcomes with rate and rhythm control. In patients with symptoms greater that 48 h rate control is the initial option with potential for cardioversion as an outpatient. There are recent advances in ablation that provide additional options to patients with paroxysmal atrial fibrillation. An essential component of the treatment strategy for these patients is risk stratification for stroke and the initiation of long-term anticoagulation in appropriate patients. SummaryManagement of atrial fibrillation is guided by underlying causes of the atrial fibrillation and duration of symptoms.

Prevalence of Intracranial Hemorrhage after Blunt Head Trauma in Patients on Pre-injury Dabigatran

Introduction Dabigatran etexilate was the first direct-acting oral anticoagulant approved in the United States. The prevalence of intracranial hemorrhage after blunt head trauma in patients on dabigatran is currently unknown, complicating adequate ability to accurately compare the risks and benefits of dabigatran to alternative anticoagulants. We aimed to determine the prevalence of intracranial hemorrhage for patients on dabigatran presenting to a Level I trauma center. Methods This is a retrospective observational study of adult patients on dabigatran who presented to a Level I trauma center and received cranial computed tomography (CT) following blunt head trauma. Patients who met inclusion criteria underwent manual chart abstraction. Our primary outcome was intracranial hemorrhage on initial cranial CT. Results We included a total of 33 eligible patient visits for analysis. Mean age was 74.8 years (SD 11.2, range 55–91). The most common cause of injury was ground-level fall (n = 22, 66.7%). One patient (3.0%, 95% confidence interval [CI] 0.[1–15.8%]) had intracranial hemorrhage on cranial CT. No patients (0%, 95% CI [0–8.7%]) required neurosurgical intervention. One in-hospital death occurred from infection. Conclusion To our knowledge, this is the first study to evaluate the prevalence of intracranial hemorrhage after blunt head trauma for patients on dabigatran presenting to the emergency department, including those not admitted. The intracranial hemorrhage prevalence in our study is similar to previous reports for patients on warfarin. Further studies are needed to determine if the prevalence of intracranial hemorrhage seen in our patient population is true for a larger patient population in more diverse clinical settings.

The Salford Lung Study: a pioneering comparative effectiveness approach to COPD and asthma in clinical trials

The Salford Lung Study (SLS) of patients with asthma and chronic obstructive pulmonary disease (COPD) is a practical, community-based, randomized, open-label pragmatic study on the efficacy and safety of the once-daily dry powder inhaler that combines the inhaled corticosteroid fluticasone furoate (FF) with the long-acting beta2 agonist vilanterol (VI). The asthma component of the SLS is not yet reported but the COPD component, done over a 12-month period, found a statistically significant 8.4% reduction in COPD exacerbations when compared to usual care. No differences in adverse events, including serious adverse events and pneumonia, were noted. The importance of real-world findings, such as those found in the SLS COPD trial with inhaled FF/VI, is discussed in comparison to classical randomized controlled trials (RCTs) with inhaled FF/VI in COPD patients. The real-world, community-based pragmatic RCT like the SLS provides additional generalizable data with direct clinical applicability and potential usefulness in the development of practice guidelines. The results from the SLS, along with those of large and small RCTs, are supportive of the use of once-daily FF/VI in COPD maintenance therapy.

Transaminase and creatine kinase ratios for differentiating delayed acetaminophen overdose from rhabdomyolysis

Introduction Rhabdomyolysis and delayed acetaminophen hepatotoxicity may be associated with elevated serum transaminase values. Establishing the cause of elevated transaminases may be especially difficult because of limited or inaccurate histories of acetaminophen ingestion. We hypothesized that the comparative ratios of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK) can differentiate acetaminophen hepatotoxicity from rhabdomyolysis. Methods A retrospective chart review of patients in four hospitals from 2006 to 2011 with a discharge diagnosis of acetaminophen toxicity or rhabdomyolysis was performed. Subjects were classified into three groups: rhabdomyolysis, acetaminophen overdose (all), and acetaminophen overdose with undetectable serum acetaminophen concentrations [acetaminophen(delayed)]. Ratios of AST, ALT, and CK were compared using non-parametric statistical methods. Results 1,353 subjects were identified and after applying our exclusion criteria there were 160 in the rhabdomyolysis group, 68 in the acetaminophen overdose (all) group, and 29 in the acetaminophen (delayed) group. The AST/ALT ratio for the rhabdomyolysis group was 1.66 (Interquartile range: 1.18–2.22), for the acetaminophen overdose (all) group was 1.38 (1.08–1.69, statistically lower than the rhabdomyolysis group, p = 0.018), and for the acetaminophen (delayed)group was 1.30 (1.06–1.63, p = 0.037). CK/AST ratios were 21.3 (12.8–42.2), 5.49 (2.52–15.1, p < 0.001), and 3.80 (1.43–13.8, p < 0.001) respectively. CK/ALT ratios were 37.1 (16.1–80.0), 5.77 (2.79–25.2, p < 0.001), and 5.03 (2.20–17.4, p < 0.001) respectively. Increasing CK to transaminase ratio cutoffs resulted in increasing test sensitivity but lower specificity. Conclusion AST/ALT, CK/AST and CK/ALT ratios are significantly larger in rhabdomyolysis when compared to patients with acetaminophen toxicity. This result suggests that the ratios could be used to identify patients with rhabdomyolysis who otherwise might have been diagnosed as delayed acetaminophen toxicity. Such patients may not require treatment with N-acetylcysteine, resulting in cost savings and improved resource utilization.

Muscarinic antagonists in early stage clinical development for the treatment of asthma

ABSTRACT Introduction: Parasympathetic neurons utilize the neurotransmitter acetylcholine to modulate and constrict airway smooth muscles at the muscarinic acetylcholine receptor. Inhaled agents that antagonize the muscarinic (M) acetylcholine receptor, particularly airway M3 receptors, have increasing data supporting use in persistent asthma. Areas covered: Use of inhaled long-acting muscarinic antagonists (LAMA) in asthma is explored. The LAMA tiotropium is approved for maintenance in symptomatic asthma patients despite the use of inhaled corticosteroids (ICS), leukotriene receptor antagonists (LTRA) and/or long-acting beta2 agonists (LABA). LAMA agents currently approved for chronic obstructive pulmonary disease (COPD) include tiotropium, glycopyrrolate/glycopyrronium, umeclidinium and aclidinium. These agents are reviewed for their pharmacological differences and clinical trials in asthma. Expert opinion: Current guidelines place inhaled LAMAs as adjunctive maintenance therapy in symptomatic asthma not controlled by an ICS and/or a LTRA. LAMA agents will play an increasing role in moderate to severe symptomatic asthma patients. Additional LAMA agents are likely to seek a maintenance indication perhaps as a combined inhaler with an ICS or with an ICS and a LABA. These fixed-dose combination inhalers are being tested in COPD and asthma patients. Once-a-day dosing of inhaled LAMA agents in severe asthma patients will likely become the future standard.