Introduction: Two protocols were developed to guide the use of subdissociative dose ketamine (SDDK) for analgesia and dissociative sedation ketamine for severe agitation/excited delirium in the emergency department (ED). We sought to evaluate the safety of these protocols implemented in 18 EDs within a large health system. Methods: We conducted a retrospective chart review to evaluate all adult patients who received intravenous (IV) SDDK for analgesia and intramuscular (IM) dissociative sedation ketamine for severe agitation/excited delirium in 12 hospital-based and six freestanding EDs over a one-year period from the protocol implementation. We developed a standardized data collection form and used it to record patient information regarding ketamine use, concomitant medication use, and any comorbidities that could have impacted the incidence of adverse events. Results: Approximately 570,000 ED visits occurred during the study period. SDDK was used in 210 ED encounters, while dissociative sedation ketamine for severe agitation/excited delirium was used in 37 ED encounters. SDDK was used in 83% (15/18) of sites while dissociative sedation ketamine was used in 50% (9/18) of sites. Endotracheal intubation, non-rebreather mask, and nasal cannula ≥ four liters per minute were identified in one, five, and three patients, respectively. Neuropsychiatric adverse events were identified in 4% (9/210) of patients who received SDDK. Conclusion: Patients experienced limited neuropsychiatric adverse events from SDDK. Additionally, dissociative sedation ketamine for severe agitation/excited delirium led to less endotracheal intubation than reported in the prehospital literature. The favorable safety profile of ketamine use in the ED may prompt further increases in usage.

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Early CPWPTs vary significantly in their prioritization factors. These tools partially reflect the scope of clinical pharmacy practice at the sites where they are used.

Introduction: Daratumumab (DARA) is an anti-CD38 human monoclonal antibody FDA-approved for the treatment of multiple myeloma (MM) and has demonstrated efficacy in AL amyloidosis. Infusion-related reactions (IRRs) occur in over 50% of patients treated with DARA, most commonly with the first infusion despite premedication with corticosteroids, antipyretics, antihistamines, and post-infusion corticosteroids. If DARA is tolerated without IRRs, the infusion rate can be escalated in standardized increments to a final infusion rate administered over 90 minutes in patients with MM (Barr et al. Leukemia 2018). Rapid infusions of DARA decrease length of infusion visits, potentially improving patient satisfaction and optimizing healthcare resources. Recent studies showed that DARA is safe and highly effective in treating AL amyloidosis (Khouri et al, Br J Haematol 2018), but no information is available regarding the safety of administering rapid infusions of DARA in patients with AL amyloidosis. We hypothesized that patients with AL amyloidosis, especially those with cardiac involvement, may not tolerate a rapid administration of fluids. Thus, a DARA rapid infusion protocol for patients with AL amyloidosis was implemented at our institution in April 2018. We report findings from the protocol implementation. Methods: A retrospective observational study was conducted to review adult patients with AL amyloidosis who received rapid infusions of DARA from April 2018 to October 2018. Data collected included relevant past medical history, vitals, premedications, infusion rates, and management of IRRs. Patients were eligible for rapid DARA after tolerating two prior doses of DARA at standard infusion rates. Rapid DARA was infused at 200 mL/hr for 30 minutes, then increased to 450 mL/hr for 60 minutes. Protocol premedications included acetaminophen, diphenhydramine, famotidine, and dexamethasone. No post-infusion corticosteroids were required. The first two standard and first four rapid DARA infusions were evaluated for each patient. Results: 27 patients with AL amyloidosis were included in the study with 162 doses of rapid DARA evaluated. Baseline characteristics included age (median 72 years old), gender (55.6% male), diastolic heart failure (59.3%), combined systolic and diastolic heart failures (11.1%), chronic obstructive pulmonary disease (7.4%), asthma (7.4%), and chronic kidney disease (25.9%). 62.9% of patients had cardiac AL involvement and 51.9% had renal AL involvement. 11/27 (40.7%) patients had IRRs to the first infusion of DARA (cycle 1, day 1) requiring hypersensitivity medications. All 27 patients progressed to rapid rate DARA after both initial and subsequent rates were tolerated. 22/27 (81.5%) patients initiated the first rapid DARA with the protocol premedications. Premedication usage decreased by the fourth rapid DARA dose with only 23.1% patients receiving diphenhydramine, 57.7% receiving famotidine, and 38.5% receiving dexamethasone (Figure 1). No patients received post-infusion corticosteroids. There were no clinically significant IRRs with the DARA rapid infusion protocol across all patients, regardless of organ involvement. There were 10 cases of CTCAE grade 2-3 hypertension that did not require intervention. No hypersensitivity medications were required for any rapid DARA doses. 11/11 (100%) patients who experienced IRRs requiring hypersensitivity medications during their first or second standard DARA infusions tolerated rapid DARA administration without recurrence of IRRs. Conclusions: Rapid administration of DARA is safe and well-tolerated in patients with AL amyloidosis, regardless of organ involvement. Patients who experienced an IRR with the initial DARA dose were able to safely transition to the rapid infusion protocol without recurrence of IRRs. Furthermore, decreased premedication usage after tolerance of rapid DARA infusion did not increase IRRs, suggesting premedications can be discontinued to mitigate associated toxicities. Disclosures Anwer: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; In-Cyte: Speakers Bureau. Valent:Celgene corporation: Speakers Bureau; Amgen corporation: Speakers Bureau; Takeda pharmaceuticals: Speakers Bureau. OffLabel Disclosure: Daratumumab for the treatment of AL amyloidosis