Faculty Bibliography

OBJECTIVES: To develop key messages for methadone and buprenorphine safety education material based on an analysis of calls to the NYC Poison Control Center (NYC PCC) and designed for distribution to caregivers of young children. METHODS: Retrospective review of all calls for children 5 years of age and younger involving methadone or buprenorphine from January 1, 2000, to June 15, 2014. A data abstraction form was completed for each case to capture patient demographics, exposure and caller sites, caller relation to patient, qualitative information regarding the exposure scenario, the product information, if naloxone was given, and the medical outcome of the case. RESULTS: A total of 123 cases were identified. The ages of the children ranged from 4 days to 5 years; 55% were boys. All exposures occurred in a home environment. The majority of the calls were made to the NYC PCC by the doctor (74%) or nurse (2%) at a health care facility. Approximately one-fourth of the calls came from the home and were made by the parent (22%) or grandparent (2%). More than one-half of the exposures involved methadone (64%). Naloxone was administered in 28% of cases. Approximately one-fourth of the children did not experience any effect after the reported exposure, one-half (51%) experienced some effect (minor, moderate, or major), and there was 1 death (1%). More than one-half of the children were admitted to the hospital, with 40% admitted to critical care and 13% to noncritical care. Approximately 23% were treated and released from the hospital, and 20% were lost to follow-up or never arrived to the hospital. The remaining 4% were managed on site without a visit to the hospital. CONCLUSION: Exposures to methadone and buprenorphine are dangerous with some leading to serious health effects. Safe storage and disposal instructions are needed for homes where children may be present.

Endogenous digoxin-like factors (EDLF) are compounds that promote natriuresis, inhibit sodium-potasium-ATPase, and cross-react with antibodies raised against cardiac glycosides. Although EDLF are well described in experimental animal models and a variety of clinical conditions in humans, no investigation previously evaluated an association between EDLF and hypothermia. We used two separate models to examine the presence of EDLF in hypothermic humans. The first study consisted of a case-controlled comparison of patients with unintentional environmental hypothermia. All patients with environmental hypothermia were prospectively enrolled if they were not taking cardiac glycosides and had no conditions previously associated with EDLF. A digoxin concentration obtained at presentation was compared to one obtained from presentation on patients from a demographically matched control group of normothermic patients. The second study enrolled a convenience sample of patients undergoing controlled cold cardioplegia for surgery. Once again, patients were excluded for conditions previously associated with EDLF, and were required to have a non-detectable preoperative digoxin concentration. Digoxin concentrations were subsequently compared in the pre- and post-operative periods. In addition to serving as their own controls, a comparison group of normothermic patients were added to help control for confounding factors associated with surgery under general anesthesia. Twenty-two patients with environmental hypothermia (mean temperature 91° Fahrenheit, range, 83.8-93.8° Fahrenheit) and 22 controls were included in the first study. Ten hypothermic patients had measurable digoxin concentrations, 6 of which were above 0.15 ng/mL. All control patients had digoxin concentrations of 0.00 ng/mL (p = 0.03, Fisher's exact test). The second study enrolled ten patients undergoing surgery with cold cardioplegia and ten control patients undergoing normothermic surgery under general anesthesia. None of the ten control patients had measurable digoxin concentrations on either pre or postoperative testing. Although all of the cold cardioplegia hypothermic patients had negative preoperative digoxin concentrations, one developed a postoperative concentration of 0.44 ng/mL. We conclude that hypothermia is associated with the presence of EDLF. An animal model and further human testing will be required to establish causation

BACKGROUND: Since intentional overdose with rivaroxaban is expected to lead to significant coagulopathy and bleeding, prophylactic reversal has been suggested. We report a single massive ingestion confirmed by a blood concentration that was managed with expectant therapy alone. CASE REPORT: A 71-year-old man with atrial fibrillation, aortic valve replacement, and congestive heart failure presented to the emergency department after an intentional ingestion of 97 (1940 mg total) rivaroxaban tablets in a suicide attempt. Initial laboratories revealed: PT, 60.2 s; INR 7.2; aPTT, 55.7 s; BUN 28 mg/dL; and creatinine 1.2 mg/dL. A whole-blood rivaroxaban concentration obtained on hospital-day three was 160 ng/mL. The patient was admitted for continued observation and the coagulation markers trended downward with no major bleeding events. No reversal agents or blood products were given during his hospitalization. CONCLUSION: In the setting of a single, acute rivaroxaban overdose, with normal renal function, and no active bleeding, conservative therapy alone may be sufficient.