Impact of Continuous Infusion Ketamine Compared to Continuous Infusion Benzodiazepines on Delirium in the Intensive Care Unit.

Purpose: The purpose of this study was to evaluate rates of delirium or coma-free days between continuous infusion sedative-dose ketamine and continuous infusion benzodiazepines in critically ill patients. Materials and Methods: In this single-center, retrospective cohort adult patients were screened for inclusion if they received continuous infusions of either sedative-dose ketamine or benzodiazepines (lorazepam or midazolam) for at least 24 h, were mechanically ventilated for at least 48 h and admitted to the intensive care unit of a large quaternary academic center between 5/5/2018 and 12/1/2021. Results: A total of 165 patients were included with 64 patients in the ketamine group and 101 patients in the benzodiazepine group (lorazepam n = 35, midazolam n = 78). The primary outcome of median (IQR) delirium or coma-free days within the first 28 days of hospitalization was 1.2 (0.0, 3.7) for ketamine and 1.8 (0.7, 4.6) for benzodiazepines (p = 0.13). Patients in the ketamine arm spent a significantly lower proportion of time with RASS -3 to +4, received significantly higher doses and longer durations of propofol and fentanyl infusions, and had a significantly longer intensive care unit length of stay. Conclusions: The use of sedative-dose ketamine had no difference in delirium or coma-free days compared to benzodiazepines.

Inhaled volatile anesthetics in the intensive care unit.

The discovery and utilization of volatile anesthetics has significantly transformed surgical practices since their inception in the mid-19th century. Recently, a paradigm shift is observed as volatile anesthetics extend beyond traditional confines of the operating theatres, finding diverse applications in intensive care settings. In the dynamic landscape of intensive care, volatile anesthetics emerge as a promising avenue for addressing complex sedation requirements, managing refractory lung pathologies including acute respiratory distress syndrome and status asthmaticus, conditions of high sedative requirements including burns, high opioid or alcohol use and neurological conditions such as status epilepticus. Volatile anesthetics can be administered through either inhaled route via anesthetic machines/devices or through extracorporeal membrane oxygenation circuitry, providing intensivists with multiple options to tailor therapy. Furthermore, their unique pharmacokinetic profiles render them titratable and empower clinicians to individualize management with heightened accuracy, mitigating risks associated with conventional sedation modalities. Despite the amounting enthusiasm for the use of these therapies, barriers to widespread utilization include expanding equipment availability, staff familiarity and training of safe use. This article delves into the realm of applying inhaled volatile anesthetics in the intensive care unit through discussing their pharmacology, administration considerations in intensive care settings, complication considerations, and listing indications and evidence of the use of volatile anesthetics in the critically ill patient population.

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.

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.

Efficacy of analgesic and sub-dissociative dose ketamine for acute pain in the emergency department.

BACKGROUND: Acute pain accounts for over 70% of Emergency Department (ED) visits. Sub-dissociative dose ketamine (0.1-0.6 mg/kg) is safe and effective for the management of acute pain in the ED. However, the optimal dose of intravenous ketamine that provides effective analgesia and minimizes the risk of adverse effects has yet to be identified. The objective of this study was to describe an effective analgesia dose range of IV ketamine for acute pain in the ED. METHODS: This multi-center, retrospective cohort study evaluated adult patients who received analgesic and sub-dissociative dose ketamine for the management of acute pain between May 5, 2018, and August 30, 2021, in 21 emergency departments at academic, community, and critical access hospitals across four states. Patients were excluded if they received ketamine for an indication other than pain, such as procedural sedation or intubation, or for whom there was incomplete documentation for the primary outcome. Patients who received a ketamine dose <0.3 mg/kg were stratified into the low-dose group, and those who received a dose of 0.3 mg/kg or higher to the high-dose group. The primary outcome was change in pain scores within 60 min using a standard 11-point numeric rating scale (NRS). Secondary outcomes included incidence of adverse effects and use of rescue analgesics. Continuous variables were compared between dose groups using student t-test or Wilcoxon Rank-Sum test. Linear regression was used to assess the association between the change in NRS pain scores within 60 min and dose after adjusting for baseline pain, requiring an additional dose of ketamine, and receiving an opioid. RESULTS: From 3796 patient encounters screened for receipt of ketamine, 384 patients met inclusion criteria including 258 in the low-dose group, and 126 in the high-dose group. The primary reason for exclusion was incomplete documentation of pain scores, or ketamine used for sedation. Median baseline pain scores were 8.2 in the low-dose group and 7.8 in the high-dose group (difference 0.5; 95% CI 0 to 1, p = 0.04). Both groups demonstrated significant reductions in their mean NRS pain scores within 60 min following the first administration of IV ketamine. There were no differences in the change in pain scores between both groups (-2.2 vs -2.6, mean difference 0.4, 95% CI -0.4 to 1.1, p = 0.34). Use of rescue analgesics (40.7% vs 36.5%, p = 0.43) and adverse effects were similar between groups, including early discontinuation of the ketamine infusion (37.2% vs. 37.3%, p = 0.99). Overall, the most common adverse effects were agitation (7.3%) and nausea (7.0%). CONCLUSION: The analgesic efficacy and safety of high-dose sub-dissociative ketamine (≥0.3 mg/kg) was not superior to low-dose (< 0.3 mg/kg) for the management of acute pain in the ED. Low-dose ketamine <0.3 mg/kg is an effective and safe pain management strategy in this population.

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.

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.

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.

Evaluation of Direct Oral Anticoagulant Reversal Agents in Intracranial Hemorrhage: A Systematic Review and Meta-analysis.

Importance: Direct oral anticoagulant (DOAC)-associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH are limited. Objective: To evaluate the safety and outcomes of DOAC reversal agents among patients with ICH. Data Sources: PubMed, MEDLINE, The Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL databases were searched from inception through April 29, 2022. Study Selection: The eligibility criteria were (1) adult patients (age ≥18 years) with ICH receiving treatment with a DOAC, (2) reversal of DOAC, and (3) reported safety and anticoagulation reversal outcomes. All nonhuman studies and case reports, studies evaluating patients with ischemic stroke requiring anticoagulation reversal or different dosing regimens of DOAC reversal agents, and mixed study groups with DOAC and warfarin were excluded. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for abstracting data and assessing data quality and validity. Two reviewers independently selected the studies and abstracted data. Data were pooled using the random-effects model. Main Outcomes and Measures: The primary outcome was proportion with anticoagulation reversed. The primary safety end points were all-cause mortality and thromboembolic events after the reversal agent. Results: A total of 36 studies met criteria for inclusion, with a total of 1832 patients (967 receiving 4-factor prothrombin complex concentrate [4F-PCC]; 525, andexanet alfa [AA]; 340, idarucizumab). The mean age was 76 (range, 68-83) years, and 57% were men. For 4F-PCC, anticoagulation reversal was 77% (95% CI, 72%-82%; I2 = 55%); all-cause mortality, 26% (95% CI, 20%-32%; I2 = 68%), and thromboembolic events, 8% (95% CI, 5%-12%; I2 = 41%). For AA, anticoagulation reversal was 75% (95% CI, 67%-81%; I2 = 48%); all-cause mortality, 24% (95% CI, 16%-34%; I2 = 73%), and thromboembolic events, 14% (95% CI, 10%-19%; I2 = 16%). Idarucizumab for reversal of dabigatran had an anticoagulation reversal rate of 82% (95% CI, 55%-95%; I2 = 41%), all-cause mortality, 11% (95% CI, 8%-15%, I2 = 0%), and thromboembolic events, 5% (95% CI, 3%-8%; I2 = 0%). A direct retrospective comparison of 4F-PCC and AA showed no differences in anticoagulation reversal, proportional mortality, or thromboembolic events. Conclusions and Relevance: In the absence of randomized clinical comparison trials, the overall anticoagulation reversal, mortality, and thromboembolic event rates in this systematic review and meta-analysis appeared similar among available DOAC reversal agents for managing ICH. Cost, institutional formulary status, and availability may restrict reversal agent choice, particularly in small community hospitals.

Hemostatic Management in Extracorporeal Membrane Oxygenation.

The use of extracorporeal membrane oxygenation (ECMO) for acute cardiac and/or respiratory failure has grown exponentially in the past several decades. Systemic anticoagulation is a fundamental element of caring for ECMO patients. Hemostatic management during ECMO walks a fine line to balance the risk of safe and effective anticoagulant delivery to mitigate thromboembolic complications and minimizing hemorrhagic sequelae. This review discusses the pharmacology, monitoring parameters, and special considerations for anticoagulation in patients requiring ECMO.

Description of telepharmacy services by emergency medicine pharmacists.

PURPOSE: Utilization of telemedicine and telepharmacy services has become increasingly popular, as specifically noted during the coronavirus disease 2019 (COVID-19) pandemic. This article describes the implementation of and services provided by emergency medicine pharmacists (EMPs) as part of a telemedicine team in the emergency department (ED). SUMMARY: This report describes the telemedicine and telepharmacy services provided to EDs in the Mayo Clinic Health System from the Mayo Clinic Rochester ED. Telepharmacy services provided by EMPs started in 2018. EMPs cover telepharmacy calls as part of their shift within the ED in Rochester. Recommendations and interventions are documented in the electronic medical record. A retrospective review evaluated interventions provided from November 18, 2018, through November 10, 2020. Baseline patient demographics, as well as the type and number of interventions provided by EMPs, hospital site, and time spent on the interventions, were collected. Telepharmacy consults could include multiple interventions and be classified as more than one type of intervention. During this time period, 24 pharmacists worked in the ED and were able to provide telepharmacy services. There were 279 consults included in this study, with 435 interventions. Most of the calls came from critical access hospitals (48.7%). The most common types of interventions documented were medication selection and dosing (n = 238), antimicrobials (n = 141), monitoring and follow-up (n = 65), discharge (n = 56), drug information (n = 55), and allergy review (n = 50). CONCLUSION: Telepharmacy services can provide increased access to emergency medicine specialty pharmacists in areas that would not otherwise have these services.

Predictors of dysrhythmias with norepinephrine use in septic shock.

PURPOSE: Norepinephrine (NE) is recommended first-line for treatment of septic shock, partly due to its intrinsically low effect on heart rate. While dysrhythmias secondary to NE are still reported, factors associated with development of this adverse effect have not been described. Our study sought to investigate factors associated with dysrhythmias in patients receiving NE for septic shock. MATERIALS AND METHODS: We conducted a retrospective cohort study of adults receiving NE for septic shock if NE was initiated as the first vasopressor and continued for at least 6 h. The primary objective was to determine the rate of dysrhythmias among this patient population. Secondary objectives included determining the effect of dysrhythmia development on patient outcomes and elucidating predictors for dysrhythmia development. RESULTS: Of the 250 patients included, 34.4% (n = 86) developed a dysrhythmia. These patients had higher mortality (30.5% vs. 63.9%; p < 0.001) with decreased ICU-free days (2 vs. 4; p = 0.04) and ventilator-free days (7 vs. 4; p = 0.048). Duration of NE infusion and maximum NE dose were found to be independently associated with increased rates of dysrhythmia (p < 0.005). CONCLUSION: Development of dysrhythmia is associated with increased mortality and is independently associated with longer duration of NE infusion and higher NE doses.