Venous thromboembolism (VTE) and stroke carry significant mortality and morbidity in cancer patients. Direct oral anticoagulants (DOACs) have been demonstrated to be effective for the treatment of VTE and prevention of stroke in atrial fibrillation (AF). Bleeding rates are variable and are based on the cancer type and the patient\'s specific risk factors. There are approved specific antidotes for DOAC-associated bleeding. Other strategies are available for bleeding reversal, including the use of prothrombin complex concentrate (PCC). No randomized studies have compared head-to-head the efficacy and safety of reversal agents. We aim to examine the safety and effectiveness of hemostatic agents in cancer patients with DOAC-related major bleeding. A retrospective chart review study of patients at MD Anderson Cancer Center with DOAC-related major bleeding between 2014 and 2019. Bleeding severity and clinical hemostasis were described based on ISTH guidelines and the Sarode criteria, respectively. The rates of thrombotic complications and mortality at 30-day from the index bleeding event were described. We identified 23 patients with DOAC-related major bleeding; 14 patients received PCC and 9 patients received andexanet alfa. The most common sites of bleeding were the gastrointestinal tract and intracranial. Effective hemostasis and 30-day mortality were similar to reported results from other reports of outcomes of reversal agents for DOAC related-bleeding in non-cancer patients. One patient in each treatment group experienced a thrombotic event. Further larger scale studies are needed to confirm our findings in cancer patients.

The administration of intravenous lipid emulsion (ILE) is a proven antidote used to reverse local anesthetic-related systemic toxicity. Although the capacity of ILE to generate blood tissue partitioning of lipophilic drugs has been previously demonstrated, a clear recommendation for its use as an antidote for other lipophilic drugs is still under debate. Venlafaxine (an antidepressant acting as a serotonin-norepinephrine reuptake inhibitor (SNRI)) and quetiapine (a second-generation atypical antipsychotic) are widely used in the treatment of psychotic disorders. Both are lipophilic drugs known to induce cardiotoxicity and central nervous depression. We report the case of a 33-year-old man with a medical history of schizoaffective disorder who was admitted to the emergency department (ED) after having been found unconscious due to a voluntary ingestion of 12 g of quetiapine and 4.5 g of venlafaxine. Initial assessment revealed a cardiorespiratory stable patient but unresponsive with a GCS of 4 (M2 E1 V1). In the ED, he was intubated, and gastric lavage was performed. Immediately after the admission to the intensive care unit (ICU), his condition quickly deteriorated, developing cardiovascular collapse refractory to crystalloids and vasopressor infusion. Junctional bradycardia occurred, followed by spontaneous conversion to sinus rhythm. Subsequently, frequent ventricular extrasystoles, as well as patterns of bigeminy, trigeminy, and even episodes of non-sustained ventricular tachycardia, occurred. Additionally, generalized tonic-clonic seizures were observed. Alongside supportive therapy, antiarrhythmic and anticonvulsant therapy, intravenous lipid emulsion bolus, and continuous infusion were administered. His condition progressively improved over the following hours, and 24 h later, he was tapered off the vasopressor. On day 2, the patient repeated the cardiovascular collapse and a second dose of ILE was administered. Over the next few days, the patient\'s clinical condition improved, and he was successfully weaned off ventilator and vasopressor support. ILE has the potential to become a form of rescue therapy in cases of severe lipophilic drug poisoning and should be considered a viable treatment for severe cardiovascular instability that is refractory to supportive therapy.

Methotrexate is a commonly used agent in the treatment of many malignancies and rheumatologic/inflammatory diseases. Working by inhibiting dihydrofolate reductase and thereby preventing eventual formation of tetrahydrofolate, methotrexate inhibits synthesis of purines and thymidylate, therefore disabling a malignant cell\'s ability to replicate. While it is able to effectively do this, methotrexate also holds potential for significant toxicity. Therefore, serum methotrexate monitoring is of utmost importance when administering the drug, particularly when high doses are used. Although there are several different measurement systems, the immunoassay is a commonly used monitoring system that may be prone to interference when using agents with similar carbon backbone as methotrexate, including folinic acid (leucovorin) at high doses, as well as in the setting of glucarpidase use and consequent methotrexate breakdown. However, adjusting leucovorin dosing policy and being aware of the potential of the immunoassay to be \"confused\" by similar molecules have allowed for the efficient and effective use of the immunoassay while preventing prolonged hospital stays at our institution.

Anticholinergic toxicity is a common cause of delirium in emergency department patients. The standard antidotal treatment for anticholinergic toxicity is physostigmine. Physostigmine functions as a reversible acetylcholinesterase inhibitor that readily crosses the blood-brain barrier. Rivastigmine is another member of this class currently approved for the treatment of Alzheimer\'s disease and Parkinson\'s disease. Rivastigmine also crosses the blood-brain barrier and has been found to be effective in the management of anticholinergic toxicity in limited case reports.
A 61-year-old women presented to the emergency department via emergency medical services with altered mental status and a Glasgow Coma Scale score of 8 out of 15. She was found down near multiple medication bottles, including diphenhydramine and dicyclomine. Her physical examination was consistent with anticholinergic toxicity with mydriasis, obtundation, and warm flushed skin. In addition to standard resuscitation, she received two doses of rivastigmine 3 mg via nasogastric tube. After the second dose she was alert and oriented. She was admitted to the intensive care unit and had a rivastigmine patch applied. She was deemed back to her baseline 27 h after presentation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although the standard antidotal treatment for anticholinergic toxicity is physostigmine, there is a national shortage of this medication. In the absence of this standard antidote, it is reasonable for emergency physicians to use rivastigmine as an alternative treatment. This can be delivered orally or via nasogastric tube with dosing each hour until resolution of symptoms. Alternatively, in consultation with toxicology, it may be reasonable to use transdermal rivastigmine, as it provides consistent drug absorption for 24 h.

Xylazine is a type of sedative commonly used in veterinary medicine. It acts on the central alpha-2 receptor and suppresses norepinephrine release from the peripheral nerve terminal. It is also reported to have action on cholinergic, serotogenic, H2-histamine, dopaminergic, and opioid receptors. Once administered in animals, it causes hypotension, bradycardia, central nervous system depression, and respiratory depression. The effect will start within minutes after absorption and last up to 4 h depending on the dosage given. Till date, it is only exclusively used in animals as approved by the Food and Drug Administration. Human intoxication is uncommon, and no specific antidote is available. Naloxone, a competitive opioid receptor antagonist, was postulated to have an antidotal effect on xylazine. We report two cases of accidental human injection with xylazine. Naloxone was administered in one of the cases. Acute hypertension and mydriasis were observed; however, no apparent reversal of toxidrome was seen. This finding reveals the question regarding the efficacy and benefit of naloxone usage in xylazine intoxication. General management remains supportive of care focusing on ventilation and hemodynamics. Attending physicians should be aware of potential xylazine intoxication incidents in the area of livestock or veterinary activities.

Although glucagon use in beta blocker toxicity has been recommended for many years, evidence for its safety and efficacy in humans is limited. This study aims to determine the magnitude of effect of glucagon on heart rate (HR) and systolic blood pressure (SBP) in patients with suspected beta blocker toxicity and describe potential adverse effects of the medication.
We conducted a retrospective, multi-center case series of patients greater than 12 years of age who received glucagon for suspected beta blocker toxicity. The primary outcome was the mean difference in HR from immediately pre- to 20-minutes post-glucagon administration. Secondary outcomes included the median difference in SBP, and occurrence of nausea, vomiting, and hyperglycemia.
A total of 107 patients met inclusion criteria accounting for 144 glucagon orders. The mean difference in HR from pre- to post-glucagon administration was 4 bpm ± 10.6 (95% CI [2.25-5.76], p < 0.001). The median difference (IQR) in SBP was 4.5 (- 6 to 16) mmHg (p = 0.004). Similar increases were observed when patients receiving concomitant vasopressors were excluded. A total of nine glucagon administrations (6.3%) were associated with nausea and 14 (9.7%) with vomiting; however, 52 doses (36.1%) were administered concomitantly with antiemetic medications. Fifteen administrations (10.4%) were associated with hyperglycemia.
Glucagon administration was associated with a statistically significant increase in HR, but a small absolute difference of uncertain clinical significance. A similar observation was noted for SBP. Few patients experienced adverse events.

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UNASSIGNED: Historically, the first step in treating cyanide (CN-) toxicity utilized antidotes to induce methemoglobinemia. This is concerning in patients who are already hypoxemic or have elevated carboxyhemoglobin. Hydroxocobalamin (OHCbl) is now the first-line antidote for CN- toxicity and is not known to induce methemoglobinemia. We observed elevated methemoglobin (MetHb) levels in several patients treated with OHCbl and sought to investigate the incidence of MetHb formation following administration of OHCbl.
UNASSIGNED: Chart review: A single-center, retrospective case series of patients who received 5 or 10 g of hydroxocobalamin from 01/01/2011 through 04/30/2019. Data was analyzed using descriptive statistics. In-vitro study: Discarded blood was separated into whole blood and plasma samples. OHCbl and normal saline was added to reach 0×, 1×, 2×, and 4× peak therapeutic concentrations and analyzed at times 0, 2, and 4 h after administration.
UNASSIGNED: Chart review: Twenty-seven cases of OHCbl administration were identified. The median age was 53 years (IQR 38 - 64) and 20 (74.1%) were male. Exposure to a house fire or smoke inhalation was the reason for OHCbl administration in 21 (77.8%) patients. Five (18.5%) patients received 10 g of OHCbl while the rest received 5 g. Six (22.2%) patients developed methemoglobinemia, all after 5 g OHCbl administration; four had been exposed to fire and smoke, two received the medication for severe acidosis of unknown etiology not related to fire or smoke. The median peak level was 7.1% (IQR 2.2 - 16.4%) at a median time of 11.4 h post-administration. Two patients received methylene blue (MB), neither responded. Death occurred in 17 (63%) cases. In-vitro study: We observed a dose dependent elevation in total hemoglobin but did not detect any increase in MetHb.
UNASSIGNED: We observed a noteworthy temporal association between the formation of methemoglobinemia and the administration of hydroxocobalamin. This does not appear to be an artifact of the CO-oximeters. This could have profound implications for patients who are already hypoxemic or have impaired oxygen carrying capacity from carboxyhemoglobin.

Calcium channel blocker overdose is usually very fatal and challenging to manage. The patients are usually asymptomatic on admission, but deteriorate very rapidly. Currently, there is no specific antidote, and the treatment is supportive requiring high level of critical care, and may necessitate extracorporeal membrane oxygenation. The use of high-dose insulin is reported to help stabilize the blood pressure and wean off inotropes. The recommendations for supportive treatment in patients with calcium channel blocker overdose are based upon low-quality evidence reports including case series and animal studies. We present the case of a 55-year-old male with a history of atrial fibrillation who was admitted to the hospital 30 min after intentionally ingesting 80 tablets of 180 mg extended release verapamil. On admission, the patient was asymptomatic, but electrocardiogram (ECG) showed a complete heart block which necessitated a transcutaneous pacing, followed by transvenous pacemaker placement. Rapid deterioration of the patient\'s hemodynamic status led to the patient getting intubated and was started on pressors as well as high-dose insulin. Despite all the aggressive measures, the patient died in less than 24 h after being admitted. We report this case to provide a brief review of the treatment options available at this time, because to date, there is no specific antidote for such overdose, and it remains very fatal despite the amount of supportive care provided.

Sugammadex is a novel reversal agent for the neuromuscular blocking agents rocuronium and vecuronium; it has been shown to rapidly and completely reverse neuromuscular blockade for rocuronium and vecuronium, even when the blockade is profound. We present the case of a 2-week-old, 850-g infant born at 25 weeks\' gestation, who presented to the operating room for exploratory laparotomy and repair of ileal atresia. Anesthesia was induced and neuromuscular blockade with 1.2 mg/kg of rocuronium was administered. The neonate experienced rapid oxyhemoglobin desaturation and progressively became very difficult to mask ventilate. Direct laryngoscopy failed to result in successful intubation of the trachea and ventilation became impossible. To reverse the effects of rocuronium, 16 mg/kg of sugammadex was administered. Immediately after, the infant resumed spontaneous ventilation and was able to maintain adequate oxyhemoglobin saturation between 90% and 95% with supplemental oxygen. To our knowledge, this is the first report of successful reversal of neuromuscular blockade, with sugammadex, in an emergent situation after failure to intubate/ventilate an extremely low birth weight infant.