Empirical antimicrobial prescribing for pyelonephritis in patients discharged from 15 US Emergency Departments: an opportunity for improvement.

BACKGROUND: Urinary tract infections (UTIs) are commonly treated in the emergency department (ED), and unfortunately, resistance to first-line agents is increasing. OBJECTIVES: To characterize treatment of pyelonephritis in a nationally representative sample of ED patients and to identify patient- and treatment-specific factors associated with receiving initial inactive antibiotics. METHODS: We conducted a multicentre, observational cohort study utilizing the Emergency Medicine PHARMacotherapy Research NETwork (EMPHARM-NET), comprising 15 geographically diverse US EDs. All patients ≥18 years of age with a diagnosis of pyelonephritis between 2018 and 2020 were included. The primary endpoint was the proportion of patients who received initial inactive empirical antibiotic therapy and to identify predictive factors of inactive antibiotic therapy. RESULTS: Of the 3714 patients evaluated, 223 had culture-positive pyelonephritis. Median patient age was 50.1 years and patients were mostly female (78.3%). Overall, 40.4% of patients received an IV antibiotic, most commonly ceftriaxone (86.7%). The most frequently prescribed antibiotics were cefalexin (31.8%), ciprofloxacin (14.3%), cefdinir (13.5%) and trimethoprim/sulfamethoxazole (12.6%). Overall, 10.3% of patients received initial inactive therapy. After adjustment in a multivariable analysis, long-acting IV antibiotic was predictive of inactive therapy (OR 0.23, 95% CI 0.07-0.83). CONCLUSIONS: In our prospective, multicentre observational study, we found that only 40.4% of patients with pyelonephritis received empirical IV antibiotics in the ED, contributing to inactive therapy. Receipt of long-acting IV antibiotics was independently associated with a decreased rate of initial inactive therapy. This reinforces guideline recommendations to administer long-acting IV antibiotics empirically in the ED upon suspicion of pyelonephritis.

Safety and Efficacy of Reduced-Dose Versus Full-Dose Alteplase for Acute Pulmonary Embolism: A Multicenter Observational Comparative Effectiveness Study.

OBJECTIVES: Systemic thrombolysis improves outcomes in patients with pulmonary embolism (PE) but is associated with the risk of hemorrhage. The data on efficacy and safety of reduced-dose alteplase are limited. The study objective was to compare the characteristics, outcomes, and complications of patients with PE treated with full- or reduced-dose alteplase regimens. DESIGN: Multicenter retrospective observational study. SETTING: Tertiary care hospital and 15 community and academic centers of a large healthcare system. PATIENTS: Hospitalized patients with PE treated with systemic alteplase. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pre- and post-alteplase hemodynamic and respiratory variables, patient outcomes, and complications were compared. Propensity score (PS) weighting was used to adjust for imbalances of baseline characteristics between reduced- and full-dose patients. Separate analyses were performed using the unweighted and weighted cohorts. Ninety-eight patients were treated with full-dose (100 mg) and 186 with reduced-dose (50 mg) regimens. Following alteplase, significant improvements in shock index, blood pressure, heart rate, respiratory rate, and supplemental oxygen requirements were observed in both groups. Hemorrhagic complications were lower with the reduced-dose compared with the full-dose regimen (13% vs. 24.5%, p = 0.014), and most were minor. Major extracranial hemorrhage occurred in 1.1% versus 6.1%, respectively ( p = 0.022). Complications were associated with supratherapeutic levels of heparin anticoagulation in 37.5% of cases and invasive procedures in 31.3% of cases. The differences in complications persisted after PS weighting (15.4% vs. 24.7%, p = 0.12 and 1.3% vs. 7.1%, p = 0.067), but did not reach statistical significance. There were no significant differences in mortality, discharge destination, ICU or hospital length of stay, or readmission after PS weighting. CONCLUSIONS: In a retrospective, PS-weighted observational study, when compared with the full-dose, reduced-dose alteplase results in similar outcomes but fewer hemorrhagic complications. Avoidance of excessive levels of anticoagulation or invasive procedures should be considered to further reduce complications.

Ketamine for Primary Analgosedation in Critically Ill Surgery and Trauma Patients Requiring Mechanical Ventilation.

OBJECTIVES: Evaluate effectiveness and safety outcomes associated with the use of ketamine for primary analgosedation in the surgical/trauma ICU setting. DESIGN: Retrospective cohort study. SETTING: Academic medical center in Minnesota. PATIENTS: Patients admitted to the surgical ICU between 2015 and 2019 requiring mechanical ventilation and meeting one of three definitions for ketamine primary analgosedation were included: 1) no concomitant opioid infusion, 2) ketamine monotherapy for greater than or equal to 6 hours with subsequent opioid infusion, or 3) ketamine initiated concomitantly or within 4 hours of opioid and total opioid duration less than 4 hours. INTERVENTIONS: None. MEASUREMENTS: Use of ketamine, analgesics, and sedatives were evaluated. Pain, sedation, and delirium assessments immediately before and during ketamine infusion were collected and compared with reported goals. Concomitant analgesics, sedatives, and psychotropics were recorded. Reported failures due to ineffectiveness and toxicity were collected. MAIN RESULTS: Of 164 included patients, 88% never received a concomitant opioid infusion (primary analgosedation definition 1), 12% met alternative criteria for primary analgosedation (definitions 2 and 3). A majority, 68%, were surgical admissions and mean Acute Physiology and Chronic Health Evaluation III score was 90 (± 30). Median mechanical ventilation duration was 2.5 days (1.1-4.5) and ICU length of stay of 4.9 days (3-8). The median ketamine infusion dose and duration were 0.18 mg/kg/hr (0.1-0.3) and 30 hours (15.1-51.8). Concomitant infusions of propofol and dexmedetomidine were administered in 49% and 29% of patients, respectively. During ketamine infusion, the median percent of total pain scores at goal was 62% (33-96%), while 64% (37-91%) of Richmond Agitation Sedation Scale scores were at goal, and 47% of patients were Confusion Assessment Method-ICU positive during the ketamine infusion. Hallucinations were documented in 14% of patients and ketamine failure occurred in 11% of patients. CONCLUSIONS: Ketamine may be an effective primary analgosedation option in intubated surgical ICU patients, but prospective randomized studies are needed to evaluate this strategy.

Implementation of Tenecteplase for Acute Ischemic Stroke Treatment.

INTRODUCTION: Acute ischemic stroke is a neurologic emergency, requiring rapid recognition and treatment with intravenous thrombolysis. Since the publication of the 2019 American Heart Association/American Stroke Association Guidelines that recommend tenecteplase as an alternative agent, several centers across the United States are transitioning from alteplase to tenecteplase as the agent of choice for thrombolysis in acute ischemic stroke. METHODS: Our health system transitioned to tenecteplase for the treatment of acute ischemic stroke in 2021 due to increasing evidence for efficacy and potential for improved door-to-needle time. Herein we describe our experience and provide guidance for other institutions to implement this change. CONCLUSION: Emergency nurses are vital to the care of acute ischemic stroke patients. There are several pharmacologic and logistical differences between alteplase and tenecteplase for this indication. This paper outlines these key differences.

Nonsteroidal Anti-inflammatory Medications in Cranial Neurosurgery: Balancing Opioid-Sparing Analgesia with Bleeding Risk.

Postcraniotomy pain is a common problem frequently encountered by neurosurgeons. This is typically managed with opioids; however, opioids have been shown to increase intracranial pressure by way of hypercapnia and straining from the associated constipation. Additionally, opioids can confound and mask the neurologic examination of postcraniotomy patients, as well as be the nidus for a potential opioid addiction. Thus, alternative solutions for opioids have been a major topic of investigation within the neurosurgical community. Nonsteroidal anti-inflammatory drugs (NSAIDs) present as a potential solution due to their nonaddictive and analgesic properties, but utilization of NSAIDs in neurosurgical patients has been controversial given that NSAIDs alter platelet function. The degree to which NSAIDs alter platelet function and bleeding time to a clinically relevant manner has remained controversial, although several well-designed studies concluded that the utilization of NSAIDs in post-craniotomy patients does not increase the risk of postoperative bleeding. Herein, we review the pharmacology, efficacy, and safety of NSAIDs with a particular emphasis on NSAID use for postintracranial neurosurgical procedure pain management.

Risk of arrhythmia in post-resuscitative shock after out-of-hospital cardiac arrest with epinephrine versus norepinephrine.

OBJECTIVE: To determine the rates of clinically significant tachyarrhythmias and mortality in the management of post-resuscitative shock after return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest (OHCA) who receive a continuous epinephrine versus norepinephrine infusion. DESIGN: Retrospective cohort study. SETTING: A large multi-site health system with hospitals across the United States. PATIENTS: Adult patients admitted for OHCA with post-resuscitative shock managed with either epinephrine or norepinephrine infusions within 6 h of ROSC. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between May 5th, 2018, to January 31st, 2022, there were 221 patients admitted for OHCA who received post-resuscitative epinephrine or norepinephrine infusions. There was no difference in the rate of tachyarrhythmias between epinephrine and norepinephrine infusion in univariate (47.1% vs 41.7%, OR 1.24, 95% CI 0.71-2.20) or multivariable analysis (OR 1.34, 95% CI 0.68-2.62). Patients treated with epinephrine were more likely to die during hospitalization than those treated with norepinephrine (90.0% vs 54.3%, OR 6.21, 95% CI 2.37-16.25, p < 0.001). Epinephrine treated patients were more likely to have re-arrest during hospital admission (55.7% vs 14.6%, OR 5.77, 95% CI 2.74-12.18, p < 0.001). CONCLUSION: There was no statistically significant difference in clinically significant cardiac tachyarrhythmias in post-OHCA patients treated with epinephrine versus norepinephrine infusions after ROSC. Re-arrest rates and in-hospital mortality were higher in patients who received epinephrine infusions in the first 6 h post-ROSC. Results of this study add to the literature suggesting norepinephrine may be the vasopressor of choice in post-OHCA patients with post-resuscitative shock after ROSC.

Norepinephrine versus epinephrine for hemodynamic support in post-cardiac arrest shock: A systematic review.

PURPOSE: The preferred vasopressor in post-cardiac arrest shock has not been established with robust clinical outcomes data. Our goal was to perform a systematic review and meta-analysis comparing rates of in-hospital mortality, refractory shock, and hemodynamic parameters in post-cardiac arrest patients who received either norepinephrine or epinephrine as primary vasopressor support. METHODS: We conducted a search of PubMed, Cochrane Library, and CINAHL from 2000 to 2022. Included studies were prospective, retrospective, or published abstracts comparing norepinephrine and epinephrine in adults with post-cardiac arrest shock or with cardiogenic shock and extractable post-cardiac arrest data. The primary outcome of interest was in-hospital mortality. Other outcomes included incidence of arrhythmias or refractory shock. RESULTS: The database search returned 2646 studies. Two studies involving 853 participants were included in the systematic review. The proposed meta-analysis was deferred due to low yield. Crude incidence of in-hospital mortality was numerically higher in the epinephrine group compared with norepinephrine in both studies, but only statistically significant in one. Risk of bias was moderate to severe for in-hospital mortality. Additional outcomes were reported differently between studies, minimizing direct comparison. CONCLUSION: The vasopressor with the best mortality and hemodynamic outcomes in post-cardiac arrest shock remains unclear. Randomized studies are crucial to remedy this.

Treatment of Factor-Xa Inhibitor-associated Bleeding with Andexanet Alfa or 4 Factor PCC: A Multicenter Feasibility Retrospective Study.

Background: There are no randomized trials comparing andexanet alfa and 4 factor prothrombin complex concentrate (4F-PCC) for the treatment of factor Xa inhibitor (FXa-I)-associated bleeds, and observational studies lack important patient characteristics. We pursued this study to demonstrate the feasibility of acquiring relevant patient characteristics from electronic health records. Secondarily, we explored outcomes in patients with life-threatening FXa-I associated bleeds after adjusting for these variables. Methods: We conducted a multicenter, chart review of 100 consecutive adult patients with FXa-I associated intracerebral hemorrhage (50) or gastrointestinal bleeding (50) treated with andexanet alfa or 4F-PCC. We collected demographic, clinical, laboratory, and imaging data including time from last factor FXa-I dose and bleed onset. Results: Mean (SD) age was 75 (12) years; 34% were female. Estimated time from last FXa-I dose to bleed onset was present in most cases (76%), and patients treated with andexanet alfa and 4F-PCC were similar in baseline characteristics. Hemostatic efficacy was excellent/good in 88% and 76% of patients treated with andexanet alfa and 4F-PCC, respectively (P = 0.29). Rates of thrombotic events within 90 days were 14% and 16% in andexanet alfa and 4F-PCC patients, respectively (P = 0.80). Survival to hospital discharge was 92% and 76% in andexanet alfa and 4F-PCC patients, respectively (P = 0.25). Inclusion of an exploratory propensity score and treatment in a logistic regression model resulted in an odds ratio in favor of andexanet alfa of 2.01 (95% confidence interval 0.67-6.06) for excellent/good hemostatic efficacy, although the difference was not statistically significant. Conclusion: Important patient characteristics are often documented supporting the feasibility of a large observational study comparing real-life outcomes in patients with FXa-I-associated bleeds treated with andexanet alfa or 4F-PCC. The small sample size in the current study precluded definitive conclusions regarding the safety and efficacy of andexanet alfa or 4F-PCC in FXa-I-associated bleeds.

Derivation and Validation of a New Equation for Estimating Free Valproate Concentration in Critically Ill Adult Patients.

IMPORTANCE: Protein binding of valproate varies among ICU patients, altering the biologically active free valproate concentration (VPAC). Free VPAC is measured at few laboratories and is often discordant with total VPAC. Existing equations to predict free VPAC are either not validated or are inaccurate in ICU patients. OBJECTIVES: We designed this study to derive and validate a novel equation to predict free VPAC using data from ICU patients and to compare its performance to published equations. DESIGN: Retrospective cohort study. SETTING: Two academic medical centers. PARTICIPANTS: Patients older than 18 years old with concomitant free and total VPACs measured in the ICU were included in the derivation cohort if admitted from 2014 to 2018, and the validation cohort if admitted from 2019 to 2022. MAIN OUTCOMES AND MEASURES: Multivariable linear regression was used to derive an equation to predict free VPAC. Modified Bland-Altman plots and the rate of therapeutic concordance between the measured and predicted free VPAC were compared. RESULTS: Demographics, median free and total VPACs, and valproate free fractions were similar among 115 patients in the derivation cohort and 147 patients in the validation cohort. The Bland-Altman plots showed the new equation performed better (bias, 0.3 [95% limits of agreement, -13.6 to 14.2]) than the Nasreddine (-9.2 [-26.5 to 8.2]), Kodama (-9.7 [-30.0 to 10.7]), Conde Giner (-7.9 [-24.9 to 9.1]), and Parent (-9.9 [-30.7 to 11.0]) equations, and similar to Doré (-2.0 [-16.0 to 11.9]). The Doré and new equations had the highest therapeutic concordance rate (73%). CONCLUSIONS AND RELEVANCE: For patients at risk of altered protein binding such as ICU patients, existing equations to predict free VPAC are discordant with measured free VPAC. A new equation had low bias but was imprecise. External validation should be performed to improve its precision and generalizability. Until then, monitoring free valproate is recommended during critical illness.

Real world utilization of Andexanet alfa in the management of oral factor Xa inhibitor-associated gastrointestinal bleeding.

BACKGROUND: Andexanet alfa (AA) is approved for reversal of factor Xa inhibitor (FXaI) bleeds; however, there are limited reports of its use for gastrointestinal bleeding (GIB) in real-world populations. The objective of this study was to report real-world utilization and evaluation of the effectiveness of AA for FXaI-associated GIB. METHODS: This retrospective cohort study including consecutive patients receiving AA for FXaI-associated GIB (7/2018-2/2021). Demographics, blood product administration, hemostatic efficacy, rebleeding, thrombosis, and mortality rates were collected. Hemostatic efficacy (HE), based on corrected hemoglobin at 12 h compared to baseline, was categorized as excellent (<10% decrease), good (≤ 20% decrease), or poor (>20% decrease, > 2 units of additional coagulation intervention or death prior to repeat hemoglobin). Comparative transfusion requirements between efficacy groups was assessed by Wilcoxon-Rank test. RESULTS: Twenty-two patients were included (64% male, median (IQR) age 76 years (67, 80). Most patients (59%, n = 13) were on apixaban, and the primary anticoagulation indication was atrial fibrillation (64%, n = 14). Median initial hemoglobin was 7.5 g/dL (IQR 6.4, 8.8) and 50% (n = 11) were upper GIB. Hemostatic efficacy was excellent in 46% (n = 10), good in 23% (n = 5), and poor in 32% (n = 7). There was no statistically significant difference in red blood cells (RBCs) received between those with excellent/good hemostasis (median 2, IQR 1 to 2) and those with poor hemostasis (median 4, IQR 1.5 to 4.5). Two patients (9%) had arterial thrombotic events within 30 days of reversal. CONCLUSION: In this multicenter, single arm, real-world observational analysis of patients with factor Xa inhibitor associated GIB most patients achieved good hemostasis following administration of AA. There was a 9% 30-day thrombotic event rate. The lack of a control group limits the strength of the conclusions that can be drawn from this study.

Pharmacotherapy optimization for rapid sequence intubation in the emergency department.

PURPOSE: Rapid-sequence intubation (RSI) is the process of administering a sedative and neuromuscular blocking agent (NMBA) in rapid succession to facilitate endotracheal intubation. It is the most common and preferred method for intubation of patients presenting to the emergency department (ED). The selection and use of medications to facilitate RSI is critical for success. The purpose of this review is to describe pharmacotherapies used during the RSI process, discuss current clinical controversies in RSI medication selection, and review pharmacotherapy considerations for alternative intubation methods. SUMMARY: There are several steps to the intubation process requiring medication considerations, including pretreatment, induction, paralysis, and post-intubation sedation and analgesia. Pretreatment medications include atropine, lidocaine, and fentanyl; but use of these agents in clinical practice has fallen out of favor as there is limited evidence for their use outside of select clinical scenarios. There are several options for induction agents, though etomidate and ketamine are the most used due to their more favorable hemodynamic profiles. Currently there is retrospective evidence that etomidate may produce less hypotension than ketamine in patients presenting with shock or sepsis. Succinylcholine and rocuronium are the preferred neuromuscular blocking agents, and the literature suggests minimal differences between succinylcholine and high dose rocuronium in first-pass success rates. Selection between the two is based on patient specific factors, half-life and adverse effect profiles. Finally, medication-assisted preoxygenation and awake intubation are less common methods for intubation in the ED but require different considerations for medication use. AREAS FOR FUTURE RESEARCH: The optimal selection, dosing, and administration of RSI medications is complicated, and further research is needed in several areas. Additional prospective studies are needed to determine optimal induction agent selection and dosing in patients presenting with shock or sepsis. Controversy exists over optimal medication administration order (paralytic first vs induction first) and medication dosing in obese patients, but there is insufficient evidence to significantly alter current practices regarding medication dosing and administration. Further research examining awareness with paralysis during RSI is needed before definitive and widespread practice changes to medication use during RSI can be made.

CLinician and patient characteristics effect on Antimicrobial Stewardship Interventions (CLASI) study.

OBJECTIVE: To determine whether the gender of clinicians making antimicrobial stewardship recommendations has an impact on intervention acceptance rate. DESIGN: A retrospective, multivariable analysis of antimicrobial stewardship prospective audit and feedback outcomes. SETTING: A multisite healthcare system including Mayo Clinic Rochester (MN), Mayo Clinic Arizona, Mayo Clinic Florida and 17 health-system hospital sites, where prospective audit and feedback is performed and documented within an electronic tool embedded in the medical record. PARTICIPANTS: The study included 143 Mayo Clinic clinicians (84 cisfemales and 59 cismales). METHODS: Outcomes were analyzed from July 1, 2017, to June 30, 2022, for intervention rates, communication methods, and intervention acceptance by clinician gender, profession, patient age, and intensive care unit (ICU) status of patient. RESULTS: Of 81,927 rules, 71,729 rules met study inclusion. There were 18,175 (25%) rules associated with an intervention. Most of the rules were reviewed by pharmacists (86.2%) and stewardship staff (85.5%). Of 10,363 interventions with an outcome documented, 8,829 (85.2%) were accepted and 1,534 (14.8%) were rejected. Female clinicians had 6,782 (86.5%) of 7,843 interventions accepted, and male clinicians had 2,047 (81.2%) of 2,520 interventions accepted (P = .19). Female patients had more interventions than male patients (female vs male: 25.9% vs 24.9%; OR, 1.04; 95% CI, 1.02-1.08; P = .001). Patients in the ICU had a significantly lower intervention acceptance rate (ICU vs non-ICU: 78.2% vs 86.7%; OR, 0.56; 95% CI, 0.45-0.7; P < .001). CONCLUSIONS: Female and male clinicians were equally effective at prospective audit and feedback in a multisite antimicrobial stewardship program. Patients in the ICU were less likely to have stewardship interventions accepted.

Extracorporeal cardiopulmonary resuscitation: A primer for pharmacists.

PURPOSE: To describe the use of mechanical circulatory support in the setting of cardiac arrest and summarize pharmacists' role in extracorporeal cardiopulmonary resuscitation (ECPR). SUMMARY: ECPR is increasingly used to reduce morbidity and improve mortality after cardiac arrest. ECPR employs venoarterial ECMO, which provides full circulatory perfusion and gas exchange in both adult and pediatric patients in cardiac arrest. After the emergency medicine team identifies potential candidates for ECPR, the ECMO team is consulted. If deemed a candidate for ECPR by the ECMO team, the patient is cannulated during ongoing standard cardiopulmonary resuscitation. A multidisciplinary team of physicians, nurses, perfusionists, pharmacists, and support staff is needed for successful ECPR. Pharmacists play a vital role in advanced cardiac life support (ACLS) prior to cannulation. Pharmacists intervene to make pharmacotherapy recommendations during ACLS, prepare medications, and administer medications as allowed by institutional and state regulations. Pharmacists also provide pharmacotherapy support in the selection of anticoagulation agents, ongoing vasopressor administration during ECMO cannulation, and the optimization of medication selection in the peri-ECPR period. CONCLUSION: With the growing use of ECPR, pharmacists should be aware of their role in medication optimization during ECPR.

UpdatED: The emergency medicine pharmacotherapy literature of 2022.

The purpose of this article is to summarize pharmacotherapy related emergency medicine (EM) literature indexed in 2022. Articles were selected utilizing a modified Delphi approach. The table of contents from pre-determined journals were reviewed and independently evaluated via the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system by paired authors, with disagreements adjudicated by a third author. Pharmacotherapy-related publications deemed to be GRADE 1A and 1B were reviewed by the group for inclusion in the review. In all, this article summarizes and provides commentary on the potential clinical impact of 13 articles, 4 guidelines, and 3 meta-analyses covering topics including anticoagulant reversal, tenecteplase in acute ischemic stroke, guideline updates for heart failure and aortic aneurysm, magnesium in atrial fibrillation, sedation in mechanically ventilated patients and pain management strategies in the Emergency Department (ED), and tranexamic acid use in epistaxis and GI bleed.

Safety of peripheral 3% hypertonic saline bolus administration for neurologic emergency.

BACKGROUND/OBJECTIVE: Hypertonic sodium chloride (HTS) is used for emergent treatment of acute cerebral edema and other neurologic emergencies. Central access is not commonly available in emergent situations and 3% HTS is utilized peripherally. Many studies have shown the safety of its administration at rates up to 75 mL/h, but there is a lack of data to establish the safety of peripherally administered, rapid bolus dosing in emergent situations. The objective of this study is to describe the safety of rapid, peripherally administered (≥ 250 mL/h) 3% HTS for neurologic emergencies. METHODS: This is a retrospective, cohort study including adult patients receiving 3% HTS via a peripheral IV site for elevated intracranial pressure, cerebral edema, or other neurological emergencies at a rate of at least 250 m/h between May 5, 2018 - September 30, 2021. Patients were excluded if they simultaneously received another hypertonic saline fluid. Baseline characteristics collected included HTS dose, rate and site of administration, indication for use and patient demographics. The primary safety outcome was incidence of extravasation and phlebitis within one hour of HTS administration. RESULTS: There were 206 patients receiving 3% HTS who were screened, and 37 patients met inclusion criteria. The most common reason for exclusion was administration at a rate < 250 m/h. The median age was 60 (IQR 45, 72) with 51.4% being male. The most common indications for HTS were traumatic brain injury (45.9%) and intracranial hemorrhage (37.8%). The most common administration location was the emergency department (78.4%). The median IV-gauge (n = 29) was 18 (IQR 18, 20), with the most common placement site being antecubital (48.6%). The median dose of HTS was 250 mL (IQR 250, 350), with a median administration rate of 760 mL/h (IQR 500, 999). There were no episodes of extravasation or phlebitis noted. CONCLUSIONS: Rapid, peripheral administration of 3% HTS boluses is a safe alternative for treatment of neurologic emergencies. Administration at rates up to 999 mL/h did not result in extravasation or phlebitis.

Comparison of nimodipine formulations and administration techniques via enteral feeding tubes in patients with aneurysmal subarachnoid hemorrhage: A multicenter retrospective cohort study.

BACKGROUND: Nimodipine improves outcomes following aneurysmal subarachnoid hemorrhage (aSAH) and current guidelines suggest that patients with aSAH receive nimodipine for 21 days. Patients with no difficulty swallowing will swallow the whole capsules or tablets; otherwise, nimodipine liquid must be drawn from capsules, tablets need to be crushed, or the commercially available liquid product be used to facilitate administration through an enteral feeding tube (FT). It is not clear whether these techniques are equivalent. The goal of the study was to determine if different nimodipine formulations and administration techniques were associated with the safety and effectiveness of nimodipine in aSAH. METHODS: This was a retrospective multicenter observational cohort study conducted in 21 hospitals across North America. Patients admitted with aSAH and received nimodipine by FT for ≥3 days were included. Patient demographics, disease severity, nimodipine administration, and study outcomes were collected. Safety end points included the prevalence of diarrhea and nimodipine dose reduction or discontinuation secondary to blood pressure reduction. Predictors of the study outcomes were analyzed using regression modeling. RESULTS: A total of 727 patients were included. Administration of nimodipine liquid product was independently associated with higher prevalence of diarrhea compared to other administration techniques/formulations (Odds ratio [OR] 2.28, 95% confidence interval [CI] 1.41-3.67, p-value = 0.001, OR 2.76, 95% CI 1.37-5.55, p-value = 0.005, for old and new commercially available formulations, respectively). Bedside withdrawal of liquid from nimodipine capsules prior to administration was significantly associated with higher prevalence of nimodipine dose reduction or discontinuation secondary to hypotension (OR 2.82, 95% CI 1.57-5.06, p-value = 0.001). Tablet crushing and bedside withdrawal of liquid from capsules prior to administration were associated with increased odds of delayed cerebral ischemia (OR 6.66, 95% CI 3.48-12.74, p-value <0.0001 and OR 3.92, 95% CI 2.05-7.52, p-value <0.0001, respectively). CONCLUSIONS: Our findings suggest that enteral nimodipine formulations and administration techniques might not be equivalent. This could be attributed to excipient differences, inconsistency and inaccuracy in medication administration, and altered nimodipine bioavailability. Further studies are needed.

Safety and effectiveness of benzodiazepines and antipsychotics for agitation in older adults in the emergency department.

PURPOSE: To examine the safety and effectiveness of benzodiazepines (BZD) as compared to antipsychotics for the management of acute agitation in older adults in the emergency department (ED). BASIC PROCEDURES: Retrospective observational cohort study of 21 EDs across four states in the US, including adults ≥60 years old who received either BZD or antipsychotics for acute agitation in the ED and subsequently were admitted to the hospital. Safety was measured as presence of adverse events: respiratory depression, cardiovascular effects, extrapyramidal side effects, or a fall during hospitalization. Effectiveness was measured as indicators of treatment failure: need for additional medication, one-to-one observation, or physical restraints following initial medication administration. Proportions and odds ratios with 95% confidence intervals (CI) were calculated. Univariable and multivariable logistic regression were used to assess the association between potential risk factors and for efficacy and safety endpoints. MAIN FINDINGS: A total of 684 patients were included (63.9% received a BZD and 36.1% an antipsychotic). There was no difference in the incidence of adverse events between groups (20.6% vs 14.6%, difference 6.0%, 95% CI -0.2% to 11.8%), but there was a higher intubation rate in the BZD group (2.7% vs 0.4%, difference 2.3%). There were more treatment failures in the antipsychotic group for the composite primary efficacy endpoint (94.3% vs 87.6%, difference 6.7%, 95% CI 2.5% to 10.9%). This appears to have been driven by the need for 1:1 observation; sensitivity analysis excluding 1:1 observation in the composite outcome demonstrated no significant difference with a failure rate of 38.5% in the antipsychotic group and 35.2% in the benzodiazepine group. PRINCIPAL CONCLUSIONS: Overall there are high rates of treatment failure among agitated older adults receiving pharmacological treatment for agitation in the emergency department. The optimal selection of pharmacological treatment for agitation in older adults should be made considering patient-specific factors that could increase the risk of adverse effects or treatment failure.

The incidence of cardiovascular instability in patients receiving various vasopressor strategies for peri-intubation hypotension.

INTRODUCTION: Patients frequently experience hypotension in the peri-intubation period. This can be due to the underlying disease process, physiologic response to the intervention, or adverse effect from medications. With the heterogeneity in cause for hypotension, the duration can also be short or prolonged. Initiation of vasopressors for peri-intubation hypotension includes various strategies using continuous infusion norepinephrine (NE) or push-dose phenylephrine (PDPE) to obtain goal mean arterial pressure. There is a paucity of data describing cardiovascular stability outcomes in patients receiving vasopressors for peri-intubation hypotension. METHODS: This is a retrospective cohort study including emergency department patients across three academic medical centers and smaller health system sites who received vasopressors for hypotension within 30 min of intubation. Patients were matched based on factors likely to influence vasopressor selection and were divided into groups if they received PDPE alone, continuous infusion NE alone, or PDPE followed by continuous infusion NE. The primary outcome was a composite of the incidence of hypotension (systolic blood pressure < 90 mmHg), bradycardia (HR < 60 beats per minute), and cardiac arrest within 2 h following initiation of vasopressors. RESULTS: Screening occurred for 2518 patients, with 105 patients undergoing matching. Mean time to vasopressor initiation was 10 min following intubation. The composite primary outcome was not statistically different between groups and occurred 88.6%, 80.0%, and 88.6% in the NE, PDPE, and PDPE+NE groups, respectively. A subgroup analysis of patients with an ED diagnosis of sepsis or septic shock were more likely to receive PDPE before starting continuous infusion NE (41.3% vs. 27.1%, p = 0.075) and more frequently experienced the primary composite outcome (p = 0.045) but was not correlated with vasopressor strategy (p = 0.55). DISCUSSION: Cardiovascular instability following vasopressor initiation for peri-intubation hypotension was no different depending on the selected vasopressor strategy. This held true in patients with a sepsis or septic shock diagnosis. Selection of vasopressors should continue to include patient specific factors and product availability.