Impact of a calcium replacement protocol during massive transfusion in trauma patients at a level 2 trauma center.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Hypocalcemia is associated with increased mortality in trauma patients with hemorrhagic shock who require massive transfusion protocols (MTPs). Despite known risks of potentiating hypocalcemia with blood product administration, there is little research discussing appropriate calcium replacement. The purpose of this study was to evaluate the ability of a standardized calcium replacement protocol to reduce the incidence of hypocalcemia in trauma patients undergoing MTP. METHODS: This retrospective, single-center, pre-post study evaluated the use of a calcium replacement protocol during MTP. Adult trauma patients with MTP orders who received at least one "round" of product transfusion were included. Patients were excluded if their ionized calcium (iCa) levels were unavailable or they were transferred to a higher level of care within 4 hours of presentation. The primary outcome was incidence of hypocalcemia (iCa of <1.1 mg/dL) within 24 hours of MTP initiation. Secondary endpoints included the incidence of severe hypocalcemia (iCa of <0.9 mg/dL), time to first calcium dose, total calcium dose administered (mEq), resolution of hypocalcemia within 24 hours, hypercalcemia, adherence to the calcium replacement protocol, and mortality. RESULTS: The incidence of hypocalcemia within 24 hours was significantly lower in the postprotocol group (63% vs 95.2%; P = 0.006). There was not a significant difference in the incidence of severe hypocalcemia between the groups (39.1% vs 69.1%; P = 0.083). Time to first calcium dose was significantly shorter in postprotocol patients compared to preprotocol patients (median [interquartile range], 5.5 [0-21] minutes vs 43 [22.8-73] minutes; P < 0.0001), and postprotocol patients were administered more calcium during MTP (40.8 [27.2-54.4] mEq vs 27.2 [14-32.2] mEq; P = 0.005). Adherence to the protocol was seen in only 37% of patients in the postprotocol group. There was no difference in the rate of adverse events or overall mortality. CONCLUSION: Trauma patients who received massive transfusion of blood products had a significantly lower incidence of hypocalcemia after a calcium replacement protocol was implemented.

Adverse events of undiluted intravenous push levetiracetam.

BACKGROUND: In patients who experience a seizure, the seizure duration is a strong indicator of prognosis. Thus, reducing time to antiepileptic medications in patients who are actively seizing is critical. While findings from retrospective studies suggest that the rapid administration of undiluted intravenous (IV) levetiracetam may be safe, some gaps in the literature remain. OBJECTIVE: The purpose of this research study was to prospectively assess adverse events associated with the rapid administration of undiluted IV levetiracetam. METHODS: This was a prospective, observational cohort study of adult patients who received rapid administration of undiluted IV levetiracetam at doses up to 4500 mg in the emergency department (ED) of a large community, teaching hospital. The primary endpoint was the incidence of any pre-defined adverse event. Secondary endpoints included the incidence of each type of adverse event, the incidence of seizure termination, and the time to completion of drug administration in patients actively seizing at the time of study inclusion. RESULTS: A total of 321 doses of IV push levetiracetam were ordered for 318 patients and 250 patients were subsequently included. Fourteen (5.6%) patients experienced an adverse event, most commonly due to injection site reactions (9/14). Clinically relevant hypotension, tachycardia, and hypertension occurred in five patients. For actively seizing patients, 79% (15/19) achieved seizure termination and the median time from medication order to completion of therapy was 12 min. CONCLUSION: This study found that the rapid administration of undiluted IV levetiracetam in ED patients was associated with few adverse events.

Esmolol, vector change, and dose-capped epinephrine for prehospital ventricular fibrillation or pulseless ventricular tachycardia.

BACKGROUND: Refractory ventricular fibrillation (VF) and pulseless ventricular tachycardia (pVT) cardiac arrest describes a subset of patients who do not respond to standard Advanced Cardiac Life Support (ACLS) interventions and are associated with poor outcomes. Esmolol administration and vector change defibrillation have shown promise in improving outcomes in these patients, however evidence is limited. OBJECTIVES: This study compares clinical outcomes between patients with prehospital refractory VF/pVT who received an Emergency Medical Service (EMS) bundle, comprised of esmolol administration, vector change defibrillation, and dose-capped epinephrine at 3 mg, to patients who received standard ACLS interventions. METHODS: This multicenter, retrospective, cohort study evaluated medical records between October 18, 2017 and March 15, 2022. Patients were enrolled if they experienced a prehospital cardiac arrest with the rhythm VF or pVT, had received at least three standard defibrillations, at least 3 mg of epinephrine, and 300 mg of amiodarone. Patients who received the EMS bundle after its implementation were compared to patients who received standard ACLS interventions prior to its implementation. The primary outcome was sustained return of spontaneous circulation (ROSC), defined as ROSC lasting 20 min without recurrence of cardiac arrest. Secondary outcomes included the incidence of any ROSC, survival to hospital arrival, survival at hospital discharge, and neurologically intact survival at hospital discharge. RESULTS: Eighty-three patients were included in the study. Thirty-six were included in the pre-EMS bundle group and 47 patients were included in the post-EMS bundle group. Patients in the pre-EMS bundle group achieved significantly higher rates of sustained ROSC (58.3% vs 17%, p < 0.001), any ROSC (66.7% vs 19.1%, p < 0.001), and survival to hospital arrival (55.6% vs 17%, p < 0.001). The rates of survival to hospital discharge (16.7% vs 6.4%, p = 0.17) and neurologically intact survival at hospital discharge (5.9% vs 4.3%, p = 1.00) were not significantly different between groups. CONCLUSIONS: Patients who received the EMS bundle achieved sustained ROSC significantly less often and were less likely to have pulses at hospital arrival. The incidence of neurologically intact survival was low and similar between groups.

Current and investigational therapies for the treatment of refractory ventricular fibrillation.

PURPOSE: Esmolol, dual sequential defibrillation, vector change defibrillation, and left stellate ganglion block are presented and reviewed for the treatment of refractory ventricular fibrillation. SUMMARY: Although no formal definition has been established for refractory ventricular fibrillation, the literature describes it as a pulseless ventricular arrhythmia that persists despite 3 standard defibrillation attempts, administration of amiodarone 300 mg intravenously, and provision of three 1-mg intravenous doses of epinephrine. Evolving literature surrounding resuscitation in this particular subset of cardiac arrest challenges the efficacy of traditional therapies, such as epinephrine, and suggests that other treatment modalities may improve outcomes. Case reports, case series, and small retrospective studies have pointed to benefit when utilizing a variety of therapies, namely, esmolol, dual sequential defibrillation, vector change defibrillation, or left stellate ganglion block, in patients with refractory ventricular fibrillation arrest. CONCLUSION: A mounting, although limited, body of evidence suggests that esmolol, dual sequential defibrillation, vector change defibrillation, or left stellate ganglion block may be effective at terminating refractory ventricular fibrillation and improving patient outcomes. Further evidence is required before these therapies can be adopted as standard practice; however, as key members of the code response team, it is imperative for pharmacists to be familiar with the supporting evidence, safety considerations, and logistical challenges of utilizing these treatments during arrest.

Idarucizumab (PRAXBIND®) as a sole reversal agent in an unstable hemorrhagic shock patient on an unknown anticoagulant with elevated protime/international normalized ratio (PT/INR).

Dabigatran is a direct oral anticoagulant thrombin inhibitor approved for stroke prophylaxis in patients with non-valvular atrial fibrillation and prophylaxis or treatment of venous thromboembolism. Since approval, there has been increasing concern regarding bleeding risk, predominantly in the elderly population and those with renal disease. We present a case of an 85-year-old female with an unknown medication history, shortness of breath and severe anemia due to an upper gastrointestinal bleed. Laboratory abnormalities were significant for INR 6.43 and serum creatinine 2.21 mg/dL. While in the emergency department the patient decompensated requiring intubation, aggressive crystalloid resuscitation, blood products and initiation of vasopressors. The inability to distinguish between warfarin- and dabigatran-induced coagulopathies paired with the lack of medical information complicated selection of the appropriate anticoagulation reversal agent. In an attempt to prevent a prothrombotic state, prothrombin complex concentrates (PCC) were held and reversal was accomplished with idarucizumab alone, although warfarin-induced coagulopathy remained a possibility. 30 min after administration, repeat PT/INR was 16.1 s and 1.55, respectively. It was later confirmed that the patient was on sole dabigatran therapy. This case highlights the potential for dabigatran to cause extreme elevation in PT/INR in patients with acute renal failure, which may mimic warfarin-induced coagulopathy. Further, it demonstrates significant, rapid correction of abnormal coagulation assays following administration of idarucizumab in a patient with severe INR elevation and suspected dabigatran use.