Lack of Association of Initial Vasopressor Dosing with Survival and Cardiac Re-Arrest Likelihood After Return of Spontaneous Circulation.

BACKGROUND: Cardiac arrest occurs in approximately 350,000 patients outside the hospital and approximately 30,000 patients in the emergency department (ED) annually in the United States. When return of spontaneous circulation (ROSC) is achieved, hypotension is a common complication. However, optimal dosing of vasopressors is not clear. OBJECTIVE: The objective of this study was to determine if initial vasopressor dosing was associated with cardiac re-arrest in patients after ROSC. METHODS: This was a retrospective, single-center analysis of adult patients experiencing cardiac arrest prior to arrival or within the ED. Patients were assigned to one of four groups based on starting dose of vasopressor: low dose (LD; < 0.25 µg/kg/min), medium dose (MD; 0.25-0.49 µg/kg/min), high dose (HD; 0.5-0.99 µg/kg/min), and very high dose (VHD; ≥ 1 µg/kg/min). Data collection was performed primarily via manual chart review of medical records. The primary outcome was incidence of cardiac re-arrest within 1 h of vasopressor initiation. Multivariate logistic regression analysis was conducted to identify any covariates strongly associated with the primary outcome. RESULTS: No difference in cardiac re-arrest incidence was noted between groups. The VHD group was significantly more likely to require a second vasopressor (p = 0.003). The HD group had lower survival rates to hospital discharge compared with the LD and MD groups (p = 0.0033 and p = 0.0147). In the multivariate regression, longer duration of pre-vasopressor re-arrests and hyperkalemic cardiac arrest etiology were significant predictors of cardiac re-arrest after vasopressor initiation. CONCLUSIONS: Initial vasopressor dosing was not found to be associated with risk of cardiac re-arrest or, conversely, risk of adverse events.

Impact of timing and dosing of four-factor prothrombin complex concentrate administration on outcomes in warfarin-associated intracranial hemorrhage.

STUDY OBJECTIVE: The objective of this study was to evaluate clinical outcomes associated with time to administration and dose of four-factor prothrombin complex concentrate (4F-PCC) in patients with ICH on warfarin. DESIGN: This was a single-center retrospective analysis of patients with ICH on warfarin who received 4F-PCC. SETTING: The site of the study was a large, Level I trauma, academic medical center with a dedicated neurologic intensive care unit and an emergency department (ED) that has approximately 72,000 visits annually. PATIENTS: Patients were included if they were ≥18 years of age, diagnosed with ICH, had an INR >1 due to warfarin use, and received both 4F-PCC and IV vitamin K for anticoagulation reversal. Exclusion criteria included patients who were less than 18 years of age, were not currently taking warfarin, had a bleeding site other than ICH, were pregnant or incarcerated, had an inadequate medical record, had a left ventricular assist device, had known liver disease with Child-Pugh Class C, received anticoagulation with heparin therapy within 24 h of anticoagulation reversal, or did not receive vitamin K within 24 h of hospital admission. INTERVENTION: Our primary outcome was a composite of hematoma expansion or death due to neurologic injury. Treatment groups were defined as receipt of 4F-PCC within 0-30, 31-60, 61-90, 91-120 min, or greater than 120 min. Hematoma expansion was defined as any increase in hematoma size as assessed by a radiologist via standard 6-h CT. Death due to neurologic injury was defined as death prior to a repeat CT being performed or documentation of a neurologic cause of death. Adequate INR reversal (INR ≤1.3 on repeat INR) vs. inadequate INR reversal and weight-based vs. fixed-dose 4F-PCC were also assessed. MEASUREMENTS AND MAIN RESULTS: A total of 94 patients met the inclusion criteria. Forty-one patients (43.6%) met the composite endpoint, including 60% of the 31-60 min group, 47.6% of the 61-90 min group, 71.4% of the 91-120 min group, and 30.6% of the >120-min group. A significant difference in primary outcome occurred between the 91-120 min and >120-min groups (71.4% vs. 30.6%; p= 0.005), but this difference was not observed when accounting for disparities in Glasgow Coma Scale (GCS). Patients with adequate INR reversal were less likely to meet the primary endpoint than those with inadequate INR reversal (28.1% vs. 58.6%; p= 0.0059). There was less failure of anticoagulation reversal with weight-based dosing compared with fixed dosing (24.2% vs. 65.0%; p< 0.001). CONCLUSIONS: No difference in clinical outcomes among 4F-PCC dosing strategies or time windows to administration was observed in patients with GCS <15. Rates of repeat INR ≤1.3 were higher with weight-based dosing, suggesting investigation of populations in which fixed dosing may be inappropriate is warranted.

Comparison of Clinical Outcomes with Initial Norepinephrine or Epinephrine for Hemodynamic Support After Return of Spontaneous Circulation.

BACKGROUND: The optimal vasoactive agent for management of patients with return of spontaneous circulation (ROSC) after cardiac arrest has not yet been identified. The Advanced Cardiac Life Support guidelines recommend initiation of either norepinephrine (NE), epinephrine (EPI), or dopamine (DA) to maintain adequate hemodynamics after ROSC is achieved. The goal of this study is to retrospectively assess the impact of initial vasopressor agent on incidence rate of rearrest, death, or need for additional vasopressor in post-cardiac arrest emergency department (ED) patients. METHODS: A retrospective review of electronic medical records was conducted at a tertiary care, academic medical center over a 32-month period. Inclusion criteria were any patient who received vasopressors in the ED after achieving ROSC from out-of-hospital cardiac arrest, or in ED cardiac arrest. The incidence of the primary outcome was assessed during care within the ED, at 6 h regardless of location (early resuscitation period), and throughout the entire hospitalization. Secondary outcomes included incidence of tachyarrhythmia while on vasopressor, type of additional therapy needed for refractory shock, and functional status at discharge as determined by discharge location (discharged home without assistance, or discharged to long-term care facility, subacute rehabilitation, or assisted living). RESULTS: A total of 93 patients were included for analysis; 45 received NE, 42 EPI, and six DA. Due to small sample size, DA was excluded from reporting post hoc. Significantly more EPI patients met the primary outcome of refractory hypotension, rearrest, or death in the emergency department (EPI 21/42, 50% vs. NE 10/45, 22.2%; P = 0.008). The incidence was no longer significantly different during the early resuscitation period of 6 h (EPI 30/42, 71.4% vs. NE 25/45, 55.6%; P = 0.182), or during the entire hospitalization (EPI 40/42, 95.2% vs. NE 36/45, 80.0%; P = 0.051). Notably, the EPI group had higher rates of rearrest prior to vasopressor initiation, potentially signaling more severe illness despite other prognostic variables being similarly distributed. In an adjusted regression model, which included adjustment for rearrest prior to vasopressor initiation, the odds of reaching the primary outcome in the ED were 3.94 [95%CI 1.38-12.2] (P = 0.013) times higher in the EPI group compared to NE treated patients. No difference in tachyarrhythmia or functional status at discharge was detected between groups. CONCLUSION: These data suggest prospective study of initial vasopressors used for hemodynamic support after ROSC may be warranted. Rates of intra-emergency department refractory shock, rearrest, or death were higher among epinephrine treated patients compared to norepinephrine treated patients in this population. However, inability to control for potential confounding variables in retrospective studies limits the findings. These results are hypothesis generating and further study is warranted.

Involvement of pharmacist-reviewed urine cultures and sexually transmitted infections in the emergency department reduces time to antimicrobial optimization.

PURPOSE: To streamline workflow of the culture review process in the emergency department (ED), a transition from a nurse-driven to a pharmacist-initiated process was implemented. METHODS: This was a single-center retrospective study conducted at an adult urban level 1 trauma academic medical center. The pharmacist-initiated culture review process was compared to the previous nurse-initiated process. The primary objective was time from final culture result to patient contact by an advanced practice provider. Secondary objectives included incidence of treatment failure and hospital admission within 30 days of ED visit. RESULTS: A total of 283 patients met inclusion criteria: 144 patients in the pre-intervention group and 139 patients in the postintervention group. Patients were contacted a median time of 15.7 hours (95% confidence interval [CI], 9.88-18.83) earlier for definitive urinary tract infection antibiotic therapy and 46.7 hours (95% CI, 33.34-61.62) earlier for definitive sexually transmitted infection therapy in the pharmacist-initiated workflow compared to the nurse-initiated workflow (P < 0.001). Treatment failure occurred in 0.01% of patients in the postintervention group and 6.3% in the pre-intervention group (P = 0.01). Hospital admission within 30 days of the ED visit occurred in 0% of patients in the postintervention group and 4.2% in the pre-intervention group (P = 0.03). CONCLUSION: Pharmacist-initiated culture review in the ED at an academic medical center reduced time from final culture to patient contact for optimal antibiotic therapy and decreased hospital admission and treatment failure rates. A change in the culture review workflow involving pharmacists appears to have a positive impact on clinical outcomes.

Pharmacist Impact on Ischemic Stroke Care in the Emergency Department.

BACKGROUND: The Froedtert Acute Stroke Team (FAST) is composed of various health professionals who respond to stroke calls, but it does not formally include a pharmacist at this time. However, emergency department (ED) pharmacists have been actively involved in patient evaluation and facilitation of i.v. recombinant tissue plasminogen activator (rtPA) preparation and administration in the ED. ED pharmacists are qualified to dose and prepare rtPA, as well as screen for contraindications to therapy. OBJECTIVE: The primary objective was to compare the accuracy of rtPA dosing, mean door-to-rtPA time, and identification of contraindications to rtPA therapy when a pharmacist was present vs. absent in the ED. METHODS: This is a retrospective study of 105 patients who received rtPA for acute ischemic stroke in the ED at a comprehensive stroke center from January 1, 2008 to October 1, 2012. RESULTS: A total of 105 patients were included in this study. Dosing accuracy was similar when a pharmacist was present vs. absent (96.6% vs. 95.6%; p = 0.8953). The median door-to-rtPA time when a pharmacist was present was statistically significantly shorter than when a pharmacist was absent (69.5 vs. 89.5 min; p = 0.0027). When a pharmacist was present, a door-to-rtPA time of < 60 min was achieved 29.9% of the time, as compared with 15.8% in the pharmacist-absent group (p = 0.1087). CONCLUSIONS: Pharmacist involvement on stroke teams may have a beneficial effect on door-to-rtPA time and patient care in the ED.

Evaluation of treatment with direct thrombin inhibitors in patients with heparin-induced thrombocytopenia.

STUDY OBJECTIVE: To evaluate the efficacy, safety, and associated costs of anticoagulation with argatroban, bivalirudin, and lepirudin for managing patients with heparin-induced thrombocytopenia (HIT) or presumed HIT. DESIGN: Retrospective medical record review. SETTING: University-affiliated teaching hospital. PATIENTS: Forty-two patients who were hospitalized between January 1 and December 31, 2004, and who were treated with bivalirudin, argatroban, or lepirudin for at least 24 hours. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the time to reach the desired goal for activated partial thromboplastin time (aPTT). Secondary outcomes were the number of aPTT measurements within the therapeutic range, costs, treatment duration, clinical outcomes, and adverse events. Of the 42 patients who met the inclusion criteria, 24 received bivalirudin, 13 received argatroban, and 5 received lepirudin. Patients receiving bivalirudin who reached therapeutic aPTTs attained them sooner than those receiving either argatroban or lepirudin (8.5 vs 14 and 24 hrs, respectively, p=0.124). Average percentage of therapeutic aPTTs/patient was greatest in the argatroban group (62%), followed by the bivalirudin (57%) and lepirudin (29%) groups (p=0.062). Average drug cost/day/patient was greater in the lepirudin group than the other groups, whereas average laboratory costs were similar among groups. Treatment duration was longer with argatroban than with bivalirudin or lepirudin. Bleeding rates were similar in the argatroban and bivalirudin groups, but higher than in the lepirudin group. A composite of clinical outcomes (deep vein thrombosis, nonfatal myocardial infarction, nonfatal stroke, limb amputation, and all-cause mortality) were similar among the three groups. CONCLUSION: All three drugs were effective as anticoagulants for patients with HIT or presumed HIT. Based on average use and average wholesale price, bivalirudin cost less per day than the other two agents. Although not yet approved by the United States Food and Drug Administration for management of HIT, bivalirudin appears to be a viable treatment alternative for anticoagulation therapy.