Nicholas J. Connors

The Evolution of Recommended Naloxone Dosing for Opioid Overdose by Medical Specialty

IntroductionOpioid abuse and opioid overdose deaths have increased significantly over the past decade. Naloxone is a potentially life-saving medication that can reverse opioid-induced respiratory depression, though precipitated opioid withdrawal can pose acute risks to the patient and medical personnel. The optimal naloxone dose is unclear and few studies address this question.MethodsA convenience sample of commonly available references were queried for the recommended IV naloxone dose. When dosing recommendations were different for opioid-tolerant patients these were also recorded.ResultsTwenty-five references were located. 48% recommended a starting dose ≤ 0.05 mg while 36% recommend a dose ten-fold higher. More than half of medical toxicology and general medical sources recommended a low-dose strategy with a starting dose lower than 0.05 mg IV.ConclusionThere are variations in the recommended doses for naloxone with ranges spanning an order of magnitude. Further exploration is needed to determine the dose that balances reversal of respiratory depression with mitigation of withdrawal.

Methotrexate toxicity treated with continuous venovenous hemofiltration, leucovorin and glucarpidase

High-dose methotrexate (MTX) can produce acute kidney injury, impairing MTX elimination. Continuous venovenous hemofiltration (CVVH) may enhance elimination in this setting, although its use is largely unstudied. A 79-year-old man received IV MTX for central nervous system lymphoma, and over a 34-h period his serum creatinine increased from 1.09 to 2.24 mg/dL. His serum MTX concentration (sMTX) at the end of this time period was 59.05 µmol/L. After urinary alkalinization and leucovorin and glucarpidase (CPDG2) treatment, sMTX decreased. Fluid overload ensued and CVVH was initiated. The initial MTX extraction ratio and clearance were 0.22 and 47.0 mL/min, respectively. No MTX extraction occurred at an sMTX of 0.15 µmol/L. Continuous venovenous hemodialysis was initiated, and sMTX further declined. CVVH may help eliminate MTX and provide renal replacement at moderate sMTX.

The Devil Is in the Details but the Details Are Not in NHAMCS

Given the current epidemic of harmful consequences from prescription opioids and heroin in the USA including 28,647 deaths due to opioids in 2014, naloxone has received widespread attention for use in hospital, prehospital, and bystander settings [1–3]. While naloxone can be a highly effective reversal agent for opioid poisoning, there appears to be a general assumption that it is substantially effective and always safe. This is highlighted by the inclusion of naloxone as part of a Bcoma cocktail,^ given indiscriminately to patients with suspected overdose decades ago. Given changes in the opioid pharmacopoeia, this is no longer appropriate [4, 5]. Under optimal circumstances (opioid-naïve patient, no co-intoxicant, shortly after exposure), administration of the opioid receptor antagonist naloxone definitively and safely reverses the dangerous respiratory depression caused by opioids. In the setting of opioid overdose, naloxone is appropriately recommended for those patients with depressed mental status and hypoventilation, often defined as a respiratory rate less than 12/min to maximize sensitivity and specificity of response to the antidote [4]. However, naloxone has never been a risk-free medication. Precipitated opioid withdrawal produces a catecholamine surge that can result in myocardial ischemia or pulmonary edema. Similarly, delirium, severe agitation, and combativeness may occur, as can other, less consequential, effects such as vomiting and diarrhea [6, 7]. Thus, clinicians are increasingly introspective about to whom they administer naloxone in the ED. In this issue, Frank et al. utilize National Hospital Ambulatory Medical Care Survey (NHAMCS) data to describe the use of naloxone in the ED [8]. Their inclusion criteria were any adult in whom naloxonewas among the eight administered medications recorded in NHAMCS or whether any of the three recorded diagnoses were opioid abuse, dependence, or withdrawal. Although it is unclear why the authors included opioid withdrawal in these criteria, it may reflect iatrogenic withdrawal that occurred after a patient was treated with naloxone. Since the authors were most interested in the use of naloxone as an antidote for opioid toxicity, it may have been cleaner to have limited their search criteria to only opioid abuse, overdose, and dependence. There were an estimated 1.7 million visits for opioid overdose over the 10-year period they searched, and naloxonewas one of the administeredmedications recorded by NHAMCS in 16 % of cases. Note that it is not possible fromNHAMCS data to decipher why naloxone was administered. It is equally not possible to determine the reason that naloxone was not administered to the vast majority of potential recipients: Did they not manifest respiratory depression? Did they receive prehospital or bystander naloxone? Were they in withdrawal?Were they already intubated? Given the low percentage of naloxone administration, this result may also reflect ED providers being appropriately judicious with the use of naloxone. Interestingly, of the patients who received naloxone, only 19 % had an opioid-related diagnosis included in the three diagnoses NHAMCS recorded. Explanations for this odd finding include the administration of naloxone to reverse procedural sedation or the use of naloxone as a diagnostic tool in patients with altered mental status or undifferentiated respiratory depression. In patients who present somnolent with respiratory depression, many potential causes exist including * Nicholas J. Connors nicholasconnors@gmail.com

Electromyographic and laboratory findings in acute Solanum torvum poisoning.

Abstract Context: Solanum torvum berries, known as susumber or turkey berries, are prepared as part of traditional Jamaican dishes usually served with cod and rice. Poisoning is rare. Although toxic compounds have never been definitively isolated, previous reports suggest toxicity results from inhibition of acetylcholinesterases. We present a case of susumber berry poisoning with detailed electromyographic studies and laboratory analysis. Case details: A 54-year-old woman presented to the Emergency Department (ED) complaining of vision, speech, and gait changes; emesis; and diffuse myalgias following consumption of susumber berries. The physical examination demonstrated an intact, lucid mental status, miosis, opsoclonus, severe dysarthria, dysmetria, mild extremity tenderness and weakness, and inability to ambulate. Her symptom constellation was interpreted as a stroke. Discussion: Electromyography demonstrated a pattern of early full recruitment as well as myotonia during the period of acute toxicity. Additionally, solanaceous compounds, in particular solasonine and solanidine, were identified in leftover berries and the patient’s serum. Store-bought commercial berries and subsequent serum samples were free of such toxic compounds. EMG studies, together with a laboratory analysis of berries or serum can assist in the differential diagnosis of stroke, and provide both a prognostic screening and confirmation of suspected glycoside toxicity.

Case 6 Medication Error in the Delivery Room

Neonatal medication errors occur in the delivery room, particularly when maternal medications are given in the same location by the same personnel. Ergot derivatives, given to control maternal postpartum hemorrhage, may cause seizures and vasoconstriction in the newborn. Treatment is directed at supportive management to reverse these effects. Other medications which may be involved in a delivery room error are discussed.

Man With Abdominal Swelling

[Ann Emerg Med. 2016;68:163.] A 46-year-old man presented to the emergency department with abdominal swelling for 2 weeks. He had a history of hepatitis C that he treated with milk thistle for 20 years. He denied significant alcohol intake. His vital signs were normal and his examination revealed a distended abdomen that was tympanic to percussion with mild tenderness. Paracentesis was performed and milky white fluid was aspirated (Figure 1).

Comments on ‘Spectrum of toxic hepatitis following intentional paraquat ingestion’

To the Editor: We read with interest the recent work by Yang and colleagues describing liver injury following intentional paraquat ingestion (1). While the possibility of paraquat-induced liver injury is interesting, significant questions remain as to whether this phenomenon is either real or clinically significant. The authors define acute hepatitis as a serum ALT greater than two times the upper limit of normal (2ULN), 72 U/L, or total bilirubin >1.5 mg/dl. While this is consistent with a consensus statement from 1990 (2), more recently, authorities defined a clinically significant elevation of ALT as at least 3ULN (3). This improved definition would disqualify nearly half of the patients in the hepatitis group. Additionally, there was no relationship between mortality and liver injury, suggesting that the finding has little or no clinical relevance. Furthermore, besides paraquat, there are several other potential causes of elevated ALT. Cyclophosphamide, a known hepatotoxin even at low doses (4), was given with a statistically significant higher rate to the hepatitis group, suggesting the possibility of iatrogenic liver injury. Also, 65% of patients reported alcohol consumption, suggesting that alcoholic hepatitis could have caused ALT elevation. While Hepatitis B status was determined for subjects, the possibility of Hepatitis C, known to be prevalent in the region (5), should have been considered. Finally, it is unclear whether noted transaminase elevations were due to liver injury at all. Rhabdomyolysis could be consistent with the ALT abnormalities and a possible aetiology for the described renal injury. Paraquat is a pulmonary toxin with high mortality. While Yang and colleagues report an association between liver injury and renal and respiratory failure, with a definition of liver injury below what is thought to be clinically significant and many potential confounders, we conclude that there is insufficient evidence to link paraquat ingestion to acute liver injury, and look forward to future work to further elucidate a potential relationship. A final consideration is that pesticide ingestion is believed to be the cause of one-third of global suicides. Following the ban of WHO class I toxicity pesticides in Sri Lanka, suicide deaths decreased by 50% (6). Given the high mortality associated with paraquat ingestion, the limited intensive care resources available in the developing world and the lack of an antidote, we suggest directing attention towards banning paraquat and replacing it with a safer pesticide.