Lauren R. Klein

Evaluation of fixed dose 4-factor prothrombin complex concentrate for emergent warfarin reversal

OBJECTIVES Four-factor prothrombin complex concentrates (4FPCCs) are emerging as the standard of care for emergent warfarin reversal due to their ability to rapidly and effectively achieve hemostasis. The ideal dose of this medication is not known. Recently, our hospital instituted a protocol where all doses of 4FPCC were a fixed dose of 1500 IU. This protocol provides 4FPCC rapidly and precludes delay waiting for international normalized ratio (INR) values. The purpose of this study was to evaluate our experience with this fixed dose protocol. METHODS This is a retrospective review of patients who received 1500 IU of 4FPCC for emergent warfarin reversal between March 2014 and January 2015. Demographic and clinical data regarding administration, efficacy, and safety were collected and analyzed. RESULTS A total of 39 patients met inclusion criteria. The most common indication for treatment was intracranial hemorrhage (28, 71.8%). The median INR at presentation was 3.3, and the median INR after a single dose of 1500 IU was 1.4 (P < .001). A total of 36 patients (92.3%) achieved successful reversal with a target INR of less than 2.0, and 28 patients (71.8%) achieved successful reversal with a target INR of 1.5 or less. There were no thrombotic adverse events within 7 days. CONCLUSIONS Administration of a fixed dose of 1500 IU of 4FPCC leads to high rates of successful INR reversal and no related thrombotic adverse events within 7 days, and there was no need to wait for INR at presentation. These findings suggest good efficacy and safety when using 1500 IU of 4FPCC for emergent warfarin reversal.

Unsuspected Critical Illness Among Emergency Department Patients Presenting for Acute Alcohol Intoxication

Study objective: Emergency department (ED) visits for acute alcohol intoxication are common, but this population is at risk for decompensation and occult critical illness. The purpose of this study is to describe the incidence and predictors of unsuspected critical illness among patients with acute alcohol intoxication. Methods: This was a retrospective observational study of ED patients from 2011 to 2016 with acute alcohol intoxication. The study cohort included patients presenting for alcohol intoxication, whose initial assessment was uncomplicated alcohol intoxication without any other active acute medical or traumatic complaints. The primary outcome was defined as the unanticipated subsequent use of critical care resources during the encounter or admission to an ICU. We investigated potential predictors for this outcome with generalized estimating equations. Results: We identified 31,364 eligible patient encounters (median age 38 years; 71% men; median breath alcohol concentration 234 mg/dL); 325 encounters (1%) used critical care resources. The most common diagnoses per 1,000 ED encounters were acute hypoxic respiratory failure (3.1), alcohol withdrawal (1.7), sepsis or infection (1.1), and intracranial hemorrhage (1.0). Three patients sustained a cardiac arrest. Presence of the following had an increased adjusted odds ratio (aOR) of developing critical illness: hypoglycemia (aOR 9.2), hypotension (aOR 3.8), tachycardia (aOR 1.8), fever (aOR 7.6), hypoxia (aOR 3.8), hypothermia (aOR 4.2), and parenteral sedation (aOR 2.4). The initial blood alcohol concentration aOR was 1.0. Conclusion: Critical care resources were used for 1% of ED patients with alcohol intoxication who were initially assessed by physicians to have low risk. Abnormal vital signs, hypoglycemia, and chemical sedation were associated with increased odds of critical illness.

A prospective study of ketamine as primary therapy for prehospital profound agitation

Objective: We investigated the effectiveness of ketamine as a primary therapy for prehospital profound agitation. Methods: This was a prospective observational study of patients receiving 5 mg/kg of intramuscular ketamine for profound agitation, defined as a score of + 4 on the Altered Mental Status Scale (AMSS), a validated ordinal scale of agitation from − 4 (unresponsive) to + 4 (most agitated). The primary outcome was time to adequate sedation (AMSS < + 1). Secondary outcomes included need for additional sedatives, intubation frequency, complications associated with ketamine, and mortality. Results: Forty‐nine patients were enrolled. Median age was 29 years (range 18–66); 76% (37/49) were male. Median time to adequate sedation was 4.2 min (95% CI: 2.5–5.9, range 1–25 min) and 90% (44/49) had adequate sedation prehospital. Seven patients (14%) received a second sedative prehospital. Intubation occurred in 57% (28/49) of patients. Mechanical ventilation lasted < 24 h in 82% (23/28) of patients, and < 48 h in 96% (27/28) of patients. A single physician intubated 36% (10/28) of the patients. Complications related to ketamine included hypersalivation (n = 9, 18%), vomiting (n = 3, 6%), and emergence reaction (n = 2, 4%). One patient died from complications of septic shock on hospital day 29, likely unrelated to ketamine. Conclusions: In patients with prehospital profound agitation, ketamine provides rapid effective sedation when used as a primary therapy. Intubation was common but accompanied by a short duration of mechanical ventilation and appears to have been subject to individual physician practice variation.

Electrocardiographic criteria to differentiate acute anterior ST-elevation myocardial infarction from left ventricular aneurysm

BACKGROUND ST elevation (STE) on the electrocardiogram (ECG) may be due to acute myocardial infarction (AMI) or other nonischemic pathologies such as left ventricular aneurysm (LVA). The objective of this study was to validate 2 previously derived ECG rules to distinguish AMI from LVA. The first rule states that if the sum of T-wave amplitudes in leads V1 to V4 divided by the sum of QRS amplitudes in leads V1 to V4 is greater than 0.22, then acute ST-segment elevation MI is predicted. The second rule states that if any 1 lead (V1-V4) has a T-wave amplitude to QRS amplitude ratio greater than or equal to 0.36, then acute ST-segment elevation MI is predicted. METHODS This was a retrospective analysis of patients with AMI (n = 59) and LVA (n = 16) who presented with ischemic symptoms and STE on the ECG. For each ECG, the T-wave amplitude and QRS amplitude in leads V1 to V4 were measured. These measurements were applied to the 2 ECG rules; and sensitivity, specificity, and accuracy in predicting AMI vs LVA were calculated. RESULTS For rule 1 (sum of ratios in V1-V4), sensitivity was 91.5%, specificity was 68.8%, and accuracy was 86.7% in predicting AMI. For rule 2 (maximum ratio in V1-V4), sensitivity was 91.5%, specificity was 81.3%, and accuracy was 89.3% in predicting AMI. CONCLUSIONS When patients present to the emergency department with ischemic symptoms and the differential diagnosis for STE on the ECG is AMI vs LVA, these 2 ECG rules may be helpful in differentiating these 2 pathologies. Both rules are highly sensitive and accurate in predicting AMI vs LVA.

Definitive airway management in emergency department patients with a King laryngeal tube™ in place: a simple and safe approach.

To the Editor, We read with interest the article by Subramanian et al. describing their experience with definitive airway management in 48 patients arriving at the emergency department (ED) with a King LT(S)-D laryngeal tube (KingLT) placed by pre-hospital personnel. We agree that there are potential complications associated with removing the KingLT in such patients. We were surprised, however, at the proportion of patients requiring surgical airway management [14 (29%) patients] and airway techniques [i.e., tube exchange catheter or flexible bronchoscopy, 14 (29%)] beyond direct (DL) or video (VL) laryngoscopy. We therefore offer a summary of our own experience with such patients and suggest a simple, non-surgical technique for exchanging the KingLT for an endotracheal tube (ETT). Over a similar five-year period (2010-2015), a total of 454 patients arrived at our Level 1 trauma centre ED with a KingLT in situ. A survey of our faculty revealed that 453 (99.8%) patients had a definitive airway secured by emergency physicians with non-surgical techniques (Table). The most common definitive airway technique for patients with the KingLT in place was VL-guided endotracheal intubation without removing the device. We recently described this technique in detail, and we summarize it here. We believe that the simplest way to intubate with the KingLT (King Systems; Noblesville, IN, USA) in situ is to use VL and a bougie. During the first portion of the procedure, the KingLT balloons remain inflated, and ventilation through the device is ongoing. The first step is to place the VL blade anterior to the KingLT, advancing it along the tongue until the oropharyngeal balloon is well visualized (Figure A). The KingLT balloons are then deflated, allowing visualization of the glottic structures on the VL monitor. A bougie can then be advanced into the trachea followed by an ETT (Figure B-D). Unlike DL, VL consistently allows good visualization of the glottis with the KingLT in situ. Also, in rare cases of failed intubation, the KingLT remains in a functional position, and the balloons can be immediately re-inflated and ventilation resumed. In summary, our experience is that conventional nonsurgical techniques (most often VL) can be used to secure a definitive airway in nearly every patient arriving at the ED with a KingLT in place. We believe that the safest technique for managing such patients is to intubate endotracheally using VL and then place a bougie while the KingLT remains in position. This technique is simple, intuitive, and utilizes airway equipment that is readily available in most EDs and operating suites. This letter is accompanied by a reply. Please see Can J Anesth 2016; 63: this issue.

The Bougie and First-Pass Success in the Emergency Department

Study objective: The bougie may improve first‐pass intubation success in operating room patients. We seek to determine whether bougie use is associated with emergency department (ED) first‐pass intubation success. Methods: We studied consecutive adult ED intubations at an urban, academic medical center during 2013. Intubation events were identified by motion‐activated video recording. We determined the association between bougie use and first‐pass intubation success, adjusting for neuromuscular blockade, video laryngoscopy, abnormal airway anatomy, and whether the patient was placed in the sniffing position or the head was lifted off the bed during intubation. Results: Intubation with a Macintosh blade was attempted in 543 cases; a bougie was used on the majority of initial attempts (80%; n=435). First‐pass success was greater with than without bougie use (95% versus 86%; absolute difference 9% [95% confidence interval {CI} 2% to 16%]). The median first‐attempt duration was higher with than without bougie (40 versus 27 seconds; difference 14 seconds [95% CI 11 to 16 seconds]). Bougie use was independently associated with greater first‐pass success (adjusted odds ratio 2.83 [95% CI 1.35 to 5.92]). Conclusion: Bougie was associated with increased first‐pass intubation success. Bougie use may be helpful in ED intubation.

Effect of Use of a Bougie vs Endotracheal Tube and Stylet on First-Attempt Intubation Success Among Patients With Difficult Airways Undergoing Emergency Intubation: A Randomized Clinical Trial.

Importance The tracheal tube introducer, known as the bougie, is typically used to aid tracheal intubation in poor laryngoscopic views or after intubation attempts fail. The effect of routine bougie use on first-attempt intubation success is unclear. Objective To compare first attempt intubation success facilitated by the bougie vs the endotracheal tube + stylet. Design, Setting, and Patients The Bougie Use in Emergency Airway Management (BEAM) trial was a randomized clinical trial conducted from September 2016 through August 2017 in the emergency department at Hennepin County Medical Center, an urban, academic department in Minneapolis, Minnesota, where emergency physicians perform all endotracheal intubations. Included patients were 18 years and older who were consecutively admitted to the emergency department and underwent emergency orotracheal intubation with a Macintosh laryngoscope blade for respiratory arrest, difficulty breathing, or airway protection. Interventions Patients were randomly assigned to undergo the initial intubation attempt facilitated by bougie (n = 381) or endotracheal tube + stylet (n = 376). Main Outcomes and Measures The primary outcome was first-attempt intubation success in patients with at least 1 difficult airway characteristic (body fluids obscuring the laryngeal view, airway obstruction or edema, obesity, short neck, small mandible, large tongue, facial trauma, or the need for cervical spine immobilization). Secondary outcomes were first-attempt success in all patients, first-attempt intubation success without hypoxemia, first-attempt duration, esophageal intubation, and hypoxemia. Results Among 757 patients who were randomized (mean age, 46 years; women, 230 [30%]), 757 patients (100%) completed the trial. Among the 380 patients with at least 1 difficult airway characteristic, first-attempt intubation success was higher in the bougie group (96%) than in the endotracheal tube + stylet group (82%) (absolute between-group difference, 14% [95% CI, 8% to 20%]). Among all patients, first-attempt intubation success in the bougie group (98%) was higher than the endotracheal tube + stylet group (87%) (absolute difference, 11% [95% CI, 7% to 14%]). The median duration of the first intubation attempt (38 seconds vs 36 seconds) and the incidence of hypoxemia (13% vs 14%) did not differ significantly between the bougie and endotracheal tube + stylet groups. Conclusions and Relevance In this emergency department, use of a bougie compared with an endotracheal tube + stylet resulted in significantly higher first-attempt intubation success among patients undergoing emergency endotracheal intubation. However, these findings should be considered provisional until the generalizability is assessed in other institutions and settings. Trial Registration clinicaltrials.gov Identifier: NCT02902146

A 20‐year Review: The Use of Exception From Informed Consent and Waiver of Informed Consent in Emergency Research

BACKGROUND Due to the acuity and time-sensitive needs of their clinical condition, patients presenting with certain emergent pathologies may lack capacity to provide meaningful prospective informed consent to participate in clinical research. For these reasons, these populations have often been excluded from research investigations. To mitigate this, regulations allowing exception from informed consent (EFIC; 21 CFR 50.24) or waiver of informed consent (WIC; 45 CFR 46.101) were developed in 1996. The purpose of this study was to identify trends in the utilization of EFIC and WIC in emergency research. We also sought to describe the disclosure of necessary prestudy regulatory requirements and justification for the use of EFIC/WIC as reported in completed EFIC/WIC clinical trials. METHODS This study is a review of 20 years of published trials using EFIC or WIC as the primary method of patient consent. Studies were identified using a MEDLINE search; ClinicalTrials.gov; queries to emergency and resuscitation researchers, research directors, department chairs, and principal investigators of acute care research networks; clinical review papers; and a query of the Federal Drug Administration (FDA) docket. All eligible studies were reviewed by three investigators and study data of interest were abstracted. Data are presented descriptively. RESULTS We identified 45 potentially eligible studies; 11 were ongoing (with no data yet available), four were completed (with no publications or data available), and two did not use EFIC or WIC. Of the remaining 28 studies, 24 (86%) used EFIC and four used WIC. The most common pathologies under study were cardiac arrest (10), hemorrhagic shock (six), and traumatic brain injury (five). Completion of the prestudy regulatory requirements was reported as follows: FDA investigational new drug/investigational device exemption application (for FDA regulated studies; 14, 50%), community consultation (13, 46%), public disclosure (10, 36%), and opt-out procedures if requested by the institutional review board (seven, 25%). The justification of the need for the use of EFIC or WIC in the reported clinical trial, as defined as mention of at least one of the eight established criteria, was described in the text of 13 (46%) publications. CONCLUSIONS Since their implementation in 1996, the EFIC/WIC regulations have allowed progress in research aimed at determining optimal care for devastating life-threatening conditions. However, consistent and rigorous report of regulatory prestudy requirements and justification of the use of EFIC/WIC is lacking in clinical trial publications or on websites such as ClinicalTrials.gov. Since research without consent is an ethically sensitive issue and not widely understood, better justification of its needs within the presentation of the research itself may educate the general medical community and also reduce concerns about whether or not the regulations are being properly applied.

Intentional Recreational Abuse of Quetiapine Compared to Other Second-generation Antipsychotics

Introduction Case reports and poison center data have demonstrated that the second-generation antipsychotic quetiapine is being obtained and used for recreational abuse. The purpose of this study was to describe the relative rates of single-substance abuse for different atypical antipsychotics and compare their demographic and clinical features. Methods We conducted a 10-year retrospective analysis of the National Poison Data System (NPDS) database (2003 – 2013). Trained nurses and pharmacists with specialty training in toxicology prospectively collect all NPDS data at poison control centers around the United States. We queried the NPDS for all cases of single-substance second-generation antipsychotic exposures coded as “intentional abuse.” The data provided by the NPDS regarding rates and clinical features of quetiapine abuse and the abuse of all other second-generation antipsychotics were compared and described descriptively. Results During the study period, 2,118 cases of quetiapine abuse and 1,379 cases of other second-generation antipsychotic abuse were identified. Quetiapine abuse was more common than the abuse of other second-generation antipsychotics, compromising 60.6% of all abuse cases during the study period. After quetiapine, the next most frequently abused medications were risperidone (530 cases, 15.2%) and olanzapine (246 cases, 7.0%). For all second-generation antipsychotics including quetiapine, central nervous system clinical effects were most common, including drowsiness, confusion, and agitation. Other serious clinical effects observed with second-generation antipsychotic abuse included hypotension, respiratory depression, and seizures. Conclusion Quetiapine abuse is relatively common, and is abused far more often than any other second-generation antipsychotic. Emergency physicians should be aware of the clinical effects that may occur after second-generation antipsychotic abuse.

The Use, Safety, and Efficacy of Olanzapine in a Level I Pediatric Trauma Center Emergency Department Over a 10-year Period

Objectives Olanzapine is a second-generation antipsychotic increasingly used in emergency medicine for many indications. Literature on its use in children is sparse. Our objectives were to describe the use, safety, and efficacy of olanzapine in pediatric emergency patients. Methods A structured chart review was performed of patients 18 years old or younger receiving olanzapine from 2007 to 2016 in the emergency department of a pediatric level I trauma center. Results A total of 285 children received olanzapine. Mean age was 16.4 years (range, 9–18 years); 121 were male (42.8%). Primary indications for olanzapine included agitation (n = 166, 58.3%), headache (n = 58, 20.4%), nausea/vomiting/abdominal pain (n = 37, 12.5%), unspecified pain (n = 20, 7%), and other (n = 4, 1.4%). Route of olanzapine administration was intramuscular (n = 160, 56%; median dose, 10 mg; range, 2.5–20), intravenous (n = 101, 36%; median dose, 5 mg; range, 1.25–5), and oral (n = 24, 8%; median dose, 10 mg; range, 5–10). For agitated patients, 28 (17%) received another sedative within 1 hour. For headache patients, 5 (8.6%) received another analgesic. For gastrointestinal complaints, 5 patients (13.5%) received another analgesic/antiemetic. Adverse respiratory events were hypoxia (pulse oximetry reading, in percentage, <92%; n = 7, 2.4%), supplemental oxygen placement (n = 9, 3.2%), and intubation (n = 2, 0.7%). No patient died or had a dysrhythmia. One patient experienced dystonia. Conclusions Olanzapine seems safe when used for a variety of conditions in pediatric emergency patients. It may be effective for acute agitation, primary headache, and gastrointestinal complaints.