Comparing the cardiorespiratory safety of parenteral olanzapine and benzodiazepines to parenteral haloperidol/droperidol and benzodiazepines in emergency department patients.

INTRODUCTION: This study sought to assess the cardiorespiratory safety of parenteral olanzapine and benzodiazepine combination treatment compared to parenteral droperidol or haloperidol and benzodiazepine combination treatment. MATERIALS AND METHODS: This was a retrospective chart review conducted in adult emergency department patients who received intramuscular (IM) or intravenous (IV) droperidol, haloperidol, or olanzapine within one hour of IM or IV benzodiazepine. Patients were stratified into groups based on whether they received either olanzapine in combination with a benzodiazepine (n = 48) or droperidol or haloperidol in combination with a benzodiazepine (n = 48). RESULTS: Patients in each group had a decrease in their systolic blood pressure (SBP) after IM/IV olanzapine and IM/IV droperidol or haloperidol when used in combination with an IM/IV benzodiazepine ((Olanzapine + benzodiazepine (mmHg), median (IQR): Pre-SBP: 132 (117-151) vs. Post-SBP: 117 (99-131), p < 0.01) (Droperidol or haloperidol + benzodiazepine (mmHg), median (IQR): Pre-SBP: 138 (122-149) vs. Post-SBP: 106 (98-127), p < 0.01)). Both groups had similar percent SBP decreases post-combination treatment (Olanzapine + benzodiazepine (15.6 %) vs. Droperidol or haloperidol + benzodiazepine (15.2 %); p = 0.55). We did not observe any statistically significant between group differences for hypotension (Olanzapine + benzodiazepine: 1/48, 2.1 % vs. Droperidol or haloperidol + benzodiazepine: 3/48, 6.3 %; p = 0.62)), escalation in oxygen requirements (Olanzapine + benzodiazepine: 7/48, 14.6 %) vs. Droperidol or haloperidol + benzodiazepine: 5/48, 10.4 %; p = 0.76)), or intubation due to cardiorespiratory depression (Olanzapine + benzodiazepine: 0/0, 0 % vs. Droperidol or haloperidol + benzodiazepine: 0/0, 0 %; p = 1.00)). CONCLUSION: This study found decreases in SBP after administering parenteral olanzapine and parenteral droperidol or haloperidol in combination with a parenteral benzodiazepine. The percent change in SBP and the frequency of hypotensive episodes post-combination treatment were not different between groups. There were also no differences between groups in need of increased oxygen requirements post-combination treatment or need for intubation due to cardiorespiratory depression. This study suggests parenteral olanzapine in combination with a parenteral benzodiazepine may have comparable cardiorespiratory safety versus parenteral droperidol or haloperidol in combination with a parenteral benzodiazepine when treating agitation in the adult ED.

Preparation/administration of push-dose versus continuous infusion epinephrine and phenylephrine: A simulation.

BACKGROUND: Hypotension is a common problem in the emergency department (ED) and intensive care unit (ICU) and can increase risk for poor outcomes. Many EDs/ICUs utilize epinephrine and phenylephrine to treat hypotension and these medications are most often administered as a continuous infusion (CI). Push-dose (PD) is the administration of small medication doses as intermittent intravenous pushes (IVPs). There is limited information comparing the time required to prepare and administer PD versus CI and errors have been reported when preparing and administering these medications at bedside. This simulation study sought to estimate preparation and administration times and preparation and errors with PD and CI epinephrine and phenylephrine when prepared by an ED/ICU pharmacist. METHODS: This crossover simulation study took place in a simulation center at an academic medical center and utilized a multi-venous intravenous training arm kit equip with an 18-gauge intravenous line, an extension tubing set, and a luer-lock adapter. The primary outcome was total preparation and administration time in seconds. The secondary outcome was major preparation and administration errors, defined as errors causing a five-fold or greater overdose. RESULTS: In total, 16 pharmacists participated, including nine ED and seven ICU pharmacists. PD had faster total preparation and administration time and administration time, but not preparation time; PD showed an approximate 70 s decrease in total preparation and administration time versus CI. PD had more major preparation and administration errors and six PD preparations (18.8%, 6/32) had at least one major preparation and administration error. CI, on the other hand, had no major preparation and administration errors. DISCUSSION: This simulation found faster total preparation and administration time with PD versus CI epinephrine and phenylephrine, but also found that PD had more major preparation and administration errors. Dilutional errors during medication preparation were the cause of 83.3% (5/6) of our overdoses. CONCLUSION: This simulation study showed that ED/ICU pharmacists had faster median total preparation and administration times for PD epinephrine and phenylephrine versus CI, but PD also had more preparation and administration errors.

Retrospective Assessment of Desmopressin Effectiveness and Safety in Patients With Antiplatelet-Associated Intracranial Hemorrhage.

OBJECTIVE: Current international guidelines offer a conditional recommendation to consider a single dose of IV desmopressin (DDAVP) for antiplatelet-associated intracranial hemorrhage based on low-quality evidence. We provide the first comparative assessment analyzing DDAVP effectiveness and safety in antiplatelet-associated intracranial hemorrhage. DESIGN: Retrospective chart review. SETTING: Single tertiary care academic medical center. PATIENTS: Adult patients taking at least one antiplatelet agent based on presenting history and documented evidence of intracranial hemorrhage on cerebral CT scan were included. Patients were excluded for the following reasons: repeat cerebral CT scan not performed within the first 24 hours, noncomparative repeat cerebral CT scan, chronic anticoagulation, administration of fibrinolytic medications, concurrent ischemic stroke, and neurosurgical intervention. In total, 124 patients were included, 55 received DDAVP and 69 did not. INTERVENTIONS: DDAVP treatment at recognition of antiplatelet-associated intracranial hemorrhage versus nontreatment. MEASUREMENTS AND MAIN RESULTS: Primary effectiveness outcome was intracranial hemorrhage expansion greater than or equal to 3 mL during the first 24 hospital hours. Primary safety outcomes were the largest absolute decrease from baseline serum sodium during the first 3 treatment days and new-onset thrombotic events during the first 7 days. DDAVP was associated with 88% decreased likelihood of intracranial hemorrhage expansion during the first 24 hours ([+] DDAVP, 10.9% vs [-] DDAVP, 36.2%; p = 0.002; odds ratio [95% CI], 0.22 [0.08-0.57]). Largest median absolute decrease from baseline serum sodium ([+] DDAVP, 0 mEq/L [0-5 mEq/L] vs [-] DDAVP, 0 mEq/L [0-2 mEq/L]; p = 0.089) and thrombotic events ([+] DDAVP, 7.3% vs [-] DDAVP, 1.4%; p = 0.170; odds ratio [95% CI], 5.33 [0.58-49.16]) were similar between groups. CONCLUSIONS: DDAVP was associated with a decreased likelihood of intracranial hemorrhage expansion during the first 24 hours. DDAVP administration did not significantly affect serum sodium and thrombotic events during the study period.

Impact of premix antimicrobial preparation and time to administration in septic patients.

OBJECTIVE: Strategies that reduce the time to antimicrobial administration, such as the availability of premix antimicrobials (PMAs) in the emergency department (ED), may better align with the goals of the Surviving Sepsis Campaign and improve outcomes in septic patients. The objective of this study was to evaluate the impact of antimicrobial preparation on time to administration in septic patients located in the emergency department (ED). METHODS: This was a retrospective, single-center, cohort study and adult patients with a diagnosis of sepsis who received at least one initial intravenous (IV) antimicrobial in the ED were included. Time to complete an empiric antimicrobial therapy was defined as the time between prescriber order entry and the infusion initiation time of the final antimicrobial agent of a patient's antimicrobial regimen. Appropriate, empiric antimicrobial therapy was based on treatment recommendations by nationally accepted guidelines for the specific indication. RESULTS: The first antimicrobial was initiated earlier when available as a PMA preparation (median (IQR): premix 25 minutes (16.5-42.3) vs. non-premix 46 minutes (20-102), p=0.027). When comparing complete, empiric antimicrobial regimen administration, there was no difference in time to administration between regimens containing one or more non-premix antimicrobials and regimens containing all PMAs (median (IQR): premix 69 minutes (21-115) vs. non-premix 65 minutes (38.5-133.8); p=0.455). CONCLUSIONS: PMA preparations significantly reduced time to administration of the first antimicrobial agent for septic patients treated in the ED, but time to administration of subsequent antimicrobials were not improved.

Impact of a Combination Antibiotic Bag on Compliance With Surviving Sepsis Campaign Goals in Emergency Department Patients With Severe Sepsis and Septic Shock.

BACKGROUND: Severe sepsis and septic shock represent common presentations in the emergency department (ED) and have high rates of mortality. Guideline-recommended goals of care have been shown to benefit these patients, but can be difficult to provide. OBJECTIVE: To determine whether the use of a premixed bag consisting of 2 g cefepime and 1 g vancomycin in 1000 mL of normal saline increases the probability of patients receiving Surviving Sepsis Campaign (SSC) recommendations for the initiation of antimicrobials and fluid challenge. METHODS: This was a 6-month retrospective analysis conducted to determine the impact of an intervention on time to antimicrobials and fluid administration in patients with severe sepsis and septic shock. Patients presenting to the ED who received a diagnosis of severe sepsis or septic shock and were administered 2 antibiotics were eligible for inclusion. The primary outcome assessed was compliance with SSC recommendations for antibiotic and fluid goals within 3 hours of ED arrival. RESULTS: A total of 160 patients were included. In the intervention group, 63.8% of patients met the primary outcome compared with 22.5% in the historical group (odds ratio = 2.32; 95% CI = 1.67-3.23). Time to administration of antibiotics was less with the combination antibiotic bag (CAB: median (IQR) = 72 (48-115) minutes; non-CAB: median (IQR) = 135 (102-244) minutes; P ≤ 0.001). CONCLUSION: This intervention significantly increased the proportion of patients provided with SSC goals of care. Such interventions have not been reported previously and could be meaningful in the management of severe sepsis and septic shock.