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The objective of this article is to summarize the state of the literature surrounding the use of ketamine as a neuroprotective agent following cardiac arrest.Five electronic databases were used to search for studies related to the use of ketamine for neuroprotection following cardiac arrest. This search was performed once in May 2020, and an updated search was conducted in May 2021 and March 2022.All searches combined retrieved 181 results; no clinical trials were identified. As such, the authors were limited to writing a scoping review of the literature rather than a systematic review.The current state of the literature describes the mechanism of action of ketamine as a neuroprotective agent through its action as an NMDA antagonist. There is evidence of its efficacy as a neuroprotective agent in preclinical models of cardiac arrest. Current published clinical work supports the use of ketamine ameliorating neurologic outcomes in other conditions such as epilepsy, traumatic brain injury, and depression. The current state of the literature is reflective of the notion that the use of ketamine following cardiac arrest may result in improved neurologic outcomes. Future research directions should focus on the use of ketamine as a possible clinical intervention following cardiac arrest.

Study objective We hypothesized that the use of intramuscular ketamine would result in a clinically relevant shorter time to target sedation. Methods We conducted a randomized clinical trial comparing the rapidity of onset, level of sedation, and adverse effect profile of ketamine compared to a combination of midazolam and haloperidol for behavioral control of emergency department patients with severe psychomotor agitation. We included patients with severe psychomotor agitation measured by a Richmond Agitation Score (RASS) ≥+3. Patients in the ketamine group were treated with a 5 mg/kg intramuscular injection. Patients in the midazolam and haloperidol group were treated with a single intramuscular injection of 5 mg midazolam and 5 mg haloperidol. The primary outcome was the time, in minutes, from study medication administration to adequate sedation, defined as RASS ≤-1. Secondary outcomes included the need for rescue medications and serious adverse events. Results Between June 30, 2018, and March 13, 2020, we screened 308 patients and enrolled 80. The median time to sedation was 14.7 minutes for midazolam and haloperidol versus 5.8 minutes for ketamine (difference 8.8 minutes [95% confidence interval (CI) 3.0 to 14.5]). Adjusted Cox proportional model analysis favored the ketamine arm (hazard ratio 2.43, 95% CI 1.43 to 4.12). Five (12.5%) patients in the ketamine arm and 2 (5.0%) patients in the midazolam and haloperidol arm experienced serious adverse events (difference 7.5% [95% CI -4.8% to 19.8%]). Conclusion In ED patients with severe agitation, intramuscular ketamine provided significantly shorter time to adequate sedation than a combination of intramuscular midazolam and haloperidol.

Background Buprenorphine-naloxone (BUP) initiation in emergency departments improves follow-up and survival among patients with opioid use disorder. We aimed to assess self-reported BUP-related practices and attitudes among emergency physicians. Methods We designed a cross-sectional physician survey by adapting a validated questionnaire on opioid harm reduction practices, attitudes and barriers. We recruited physician leads from 6 Canadian provinces to administer surveys to the staff physicians in their emergency department groups between December 2018 and November 2019. We included academic and community non-locum emergency department staff physicians. We excluded responses from emergency department groups with response rates less than 50% to minimize nonresponse bias. Primary (BUP prescribing practices) and secondary (willingness and attitudes) outcomes were analyzed using descriptive statistics. Results After excluding 1 group for low response (9/26 physicians), 652 of 798 (81.7%) physicians responded from 22 groups serving 34 emergency departments. Among respondents, 64.1% (95% confidence interval [CI] 60.4%-67.8%, emergency department group range 7.1%-100.0%) had prescribed BUP at least once in their career, 38.4% had prescribed it for home initiation and 24.8% prescribed it at least once a month. Overall, 68.9% (95% CI 65.3%-72.4%, emergency department group range 24.1%-97.6%) were willing to administer BUP, 64.2% felt it was a major responsibility and 37.1% felt they understood people who use drugs. Respondents most frequently rated lack of adequate training (58.2%) and lack of time (55.2%) as very important barriers to BUP initiation. Interpretation Two-thirds of the emergency physicians surveyed prescribed BUP, although only one-quarter did so regularly and one-third prescribed it for home initiation; wide variation between emergency department groups existed. Strategies to increase BUP initiation must address physicians' lack of time and training for BUP initiation and improve their understanding of people who use drugs.

Summary The multidisciplinary International Committee for the Advancement of Procedural Sedation presents the first fasting and aspiration prevention recommendations specific to procedural sedation, based on an extensive review of the literature. These were developed using Delphi methodology and assessment of the robustness of the available evidence. The literature evidence is clear that fasting, as currently practiced, often substantially exceeds recommended time thresholds and has known adverse consequences, for example, irritability, dehydration and hypoglycaemia. Fasting does not guarantee an empty stomach, and there is no observed association between aspiration and compliance with common fasting guidelines. The probability of clinically important aspiration during procedural sedation is negligible. In the post‐1984 literature there are no published reports of aspiration‐associated mortality in children, no reports of death in healthy adults (ASA physical status 1 or 2) and just nine reported deaths in adults of ASA physical status 3 or above. Current concerns about aspiration are out of proportion to the actual risk. Given the lower observed frequency of aspiration and mortality than during general anaesthesia, and the theoretical basis for assuming a lesser risk, fasting strategies in procedural sedation can reasonably be less restrictive. We present a consensus‐derived algorithm in which each patient is first risk‐stratified during their pre‐sedation assessment, using evidence‐based factors relating to patient characteristics, comorbidities, the nature of the procedure and the nature of the anticipated sedation technique. Graded fasting precautions for liquids and solids are then recommended for elective procedures based upon this categorisation of negligible, mild or moderate aspiration risk. This consensus statement can serve as a resource to practitioners and policymakers who perform and oversee procedural sedation in patients of all ages, worldwide.

Buprenorphine-naloxone (BUP) initiation in emergency departments improves follow-up and survival among patients with opioid use disorder. We aimed to assess self-reported BUP-related practices and attitudes among emergency physicians.We designed a cross-sectional physician survey by adapting a validated questionnaire on opioid harm reduction practices, attitudes and barriers. We recruited physician leads from 6 Canadian provinces to administer surveys to the staff physicians in their emergency department groups between December 2018 and November 2019. We included academic and community non-locum emergency department staff physicians. We excluded responses from emergency department groups with response rates less than 50% to minimize nonresponse bias. Primary (BUP prescribing practices) and secondary (willingness and attitudes) outcomes were analyzed using descriptive statistics.After excluding 1 group for low response (9/26 physicians), 652 of 798 (81.7%) physicians responded from 22 groups serving 34 emergency departments. Among respondents, 64.1% (95% confidence interval [CI] 60.4%-67.8%, emergency department group range 7.1%-100.0%) had prescribed BUP at least once in their career, 38.4% had prescribed it for home initiation and 24.8% prescribed it at least once a month. Overall, 68.9% (95% CI 65.3%-72.4%, emergency department group range 24.1%-97.6%) were willing to administer BUP, 64.2% felt it was a major responsibility and 37.1% felt they understood people who use drugs. Respondents most frequently rated lack of adequate training (58.2%) and lack of time (55.2%) as very important barriers to BUP initiation.Two-thirds of the emergency physicians surveyed prescribed BUP, although only one-quarter did so regularly and one-third prescribed it for home initiation; wide variation between emergency department groups existed. Strategies to increase BUP initiation must address physicians' lack of time and training for BUP initiation and improve their understanding of people who use drugs.

BACKGROUND Emergency department (ED) patients with uncomplicated atrial fibrillation (AF) of less than 48 hours may be safely managed with rhythm control. Although both chemical-first and electrical-first strategies have been advocated, there are no comparative effectiveness data to guide clinicians. METHODS At six urban Canadian centers, ED patients ages 18 to 75 with uncomplicated symptomatic AF of less than 48 hours and CHADS2 score of 0 or 1 were randomized using concealed allocation in a 1:1 ratio to one of the following strategies: 1) chemical cardioversion with procainamide infusion, followed by electrical countershock if unsuccessful; or 2) electrical cardioversion, followed by procainamide infusion if unsuccessful. The primary outcome was the proportion of patients discharged within 4 hours of arrival. Secondary outcomes included ED length-of-stay (LOS); prespecified ED-based adverse events; and 30-day ED revisits, hospitalizations, strokes, deaths, and quality of life (QoL). RESULTS Eighty-four patients were analyzed: 41 in the chemical-first group and 43 in the electrical-first group. Groups were balanced in terms of age, sex, vital signs, and CHADS2 scores. All patients were discharged home, with 83 (99%) in sinus rhythm. In the chemical-first group, 13 of 41 patients (32%) were discharged within 4 hours compared to 29 of 43 patients (67%) in the electrical-first group (p = 0.001). In the chemical-first group, the median ED LOS was 5.1 hours (interquartile range [IQR] = 3.5 to 5.9 hours) compared to 3.5 hours (IQR = 2.4 to 4.6 hours) in the electrical-first group, for a median difference of 1.2 hours (95% confidence interval = 0.4 to 2.0 hours, p

We update an evidence-based clinical practice guideline for the administration of propofol for emergency department procedural sedation. Both the unique considerations of using this drug in the pediatric population and the substantial new research warrant revision of the 2007 advisory. We discuss the indications, contraindications, personnel requirements, monitoring, dosing, coadministered medications, and adverse events for propofol sedation.

BACKGROUND: Emergency physicians lack high-quality evidence for many diagnostic and treatment decisions made for patients with suspected or confirmed coronavirus disease 2019 (COVID-19). Our objective is to describe the methods used to collect and ensure the data quality of a multicentre registry of patients presenting to the emergency department with suspected or confirmed COVID-19. METHODS: This methodology study describes a population-based registry that has been enrolling consecutive patients presenting to the emergency department with suspected or confirmed COVID-19 since Mar. 1, 2020. Most data are collected from retrospective chart review. Phone follow-up with patients at 30 days captures the World Health Organization clinical improvement scale and contextual, social and cultural variables. Phone follow-up also captures patient-reported quality of life using the Veterans Rand 12-Item Health Survey at 30 days, 60 days, 6 months and 12 months. Fifty participating emergency departments from 8 provinces in Canada currently enrol patients into the registry. INTERPRETATION: Data from the registry of the Canadian COVID-19 Emergency Department Rapid Response Network will be used to derive and validate clinical decision rules to inform clinical decision-making, describe the natural history of the disease, evaluate COVID-19 diagnostic tests and establish the real-world effectiveness of treatments and vaccines, including in populations that are excluded or underrepresented in clinical trials. This registry has the potential to generate scientific evidence to inform our pandemic response, and to serve as a model for the rapid implementation of population-based data collection protocols for future public health emergencies. TRIAL REGISTRATION: Clinicaltrials.gov, no. NCT04702945.

This article corrects the Guidelines by Green SM, Leroy PL, Roback MG, Irwin MG, Andolfatto G, Babl FE, Barbi E, Costa LR, Absalom A, Carlson DW, Krauss BS, Roelofse J, Yuen VM, Alcaino E, Costa PS, Mason KP on behalf of the International Committee for the Advancement of Procedural Sedation, ‘An international multidisciplinary consensus statement on fasting before procedural sedation in adults and children’ [1]. The authors thank a careful reader who identified that a study from this table by Rajasekaran et al should have been excluded, as it included fewer than 5000 patients. The corrected table without this study is shown below, and this change does not alter our other findings and conclusions. An author and corresponding affiliation were omitted and is now revised as follows: 1 Table Literature estimates of aspiration risk during procedural sedation* (Table presented.) * To include just the largest studies we display those with 5,000 or more patients. We also exclude studies which report duplicate sub-sets of patients.

Background: The rapid control of patients presenting to the emergency department (ED) with psychomotor agitation and violent behavior is paramount for the safety of patients and ED staff. The use of intramuscular (IM) ketamine in the pre-hospital and ED settings has demonstrated promising preliminary results to provide rapid and safe behavioral control. A prospective, randomized controlled trial is required to measure the potential superiority of IM ketamine compared to current standard care (IM benzodiazepines plus antipsychotics). Methods: This will be a parallel, prospective, randomized, controlled trial of 5 mg/kg IM ketamine compared to a combination of 5 mg IM midazolam and 5 mg IM haloperidol. The study will enroll approximately 184 patients, randomized equally to two study arms. There will be one study visit during which study medication will be administered and assessments will be completed. A follow-up safety visit will occur on day 3. The primary objective of this study is to compare IM ketamine to a combination of IM midazolam and haloperidol with regards to the time required for adequate behavioral control, in minutes, in patients presenting to the ED with psychomotor agitation and violent behavior, as measured by the Richmond Agitation-Sedation Scale (RASS). Discussion: We present a novel study to determine whether ketamine is a rapid and safe option, compared to a combination of midazolam and haloperidol for the sedation of patients presenting to the ED with psychomotor agitation and violent behavior. To our knowledge, this study is the first randomized controlled trial to compare ketamine to current standard care for this indication. We have attempted to address numerous logistical issues with the design of this study including a waiver of consent, ensuring adequate blinding of outcome assessors, patient enrolment, and data monitoring. Trial registration: Clinicaltrials.gov, NCT03375671 . Registered on 18 December 2017.

Study objective We describe the characteristics of and predictors for apnea and clinical interventions during emergency department (ED) procedural sedation. Methods High-resolution data were collected prospectively, using a convenience sample of ED patients undergoing propofol or ketofol sedation. End tidal CO 2 (etco 2 ), respiratory rate, pulse rate, and SpO 2 were electronically recorded in 1-second intervals. Procedure times, drug delivery, and interventions were electronically annotated. Kaplan-Meier curves were used to describe the onset of clinical interventions as a function of sedation time. The onset of apnea (15 consecutive seconds with carbon dioxide ≤10 mm Hg) and clinical interventions were estimated with a series of Cox proportional hazards survival models, with time to first apnea or clinical intervention as the dependent variable. Finally, we tested the association between apnea and clinical intervention. Results Three hundred twelve patients were analyzed (53% male patients). Apnea was preceded by etco 2 less than 30 mm Hg or greater than 50 mm Hg at 30, 60, and 90 seconds before its onset. Clinical interventions were predicted by apnea, SpO 2 , and propofol use. Increasing age predicted both apnea and interventions. Apnea was not predicted by respiratory rate or SpO 2 . Apnea occurred in half of the patients and clinical interventions in a quarter of them. Clinical intervention was not predicted by abnormal respiratory rate or abnormal etco 2 level. The majority of clinical interventions (85%) were minor, with no cases of assisted ventilation, intubation, or complications. Conclusion Alterations in etco 2 predicted apnea along a specific time course. Alterations in SpO 2 , apnea, and propofol use predicted clinical interventions. Increasing age predicted both apnea and clinical intervention.

Study objective We compare intranasal ketamine with intranasal placebo in providing pain reduction at 30 minutes when added to usual paramedic care with nitrous oxide. Methods This was a randomized double-blind study of out-of-hospital patients with acute pain who reported a verbal numeric rating scale (VNRS) pain score greater than or equal to 5. Exclusion criteria were younger than 18 years, known ketamine intolerance, nontraumatic chest pain, altered mental status, pregnancy, and nasal occlusion. Patients received usual paramedic care and were randomized to receive either intranasal ketamine or intranasal saline solution at 0.75 mg/kg. The primary outcome was the proportion of patients with VNRS score reduction greater than or equal to 2 at 30 minutes. Secondary outcomes were pain reduction at 15 minutes, patient-reported comfort, satisfaction scores, nitrous oxide consumption, and incidence of adverse events. Results One hundred twenty subjects were enrolled. Seventy-six percent of intranasal ketamine patients versus 41% of placebo patients reported a greater than or equal to 2-point VNRS reduction at 30 minutes (difference 35%; 95% confidence interval 17% to 51%). Median VNRS reduction at 15 minutes was 2.0 and 1.0 and at 30 minutes was 3.0 and 1.0 for ketamine and placebo, respectively. Improved comfort at 15 and 30 minutes was reported for 75% versus 57% and 61% versus 46% of ketamine and placebo patients, respectively. Sixty-two percent of patients (95% confidence interval 49% to 73%) versus 20% (95% confidence interval 12% to 32%) reported adverse events with ketamine and placebo, respectively. Adverse events were minor, with no patients requiring physical or medical intervention. Conclusion Added to nitrous oxide, intranasal ketamine provides clinically significant pain reduction and improved comfort compared with intranasal placebo, with more minor adverse events.

Study objective Lack of oral anticoagulation prescription in the emergency department (ED) has been identified as a care gap in atrial fibrillation patients. This study seeks to determine whether the use of a tool kit for emergency physicians with a follow-up community-based atrial fibrillation clinic resulted in greater oral anticoagulation prescription at ED discharge than usual care. Methods This was a before-after study in 5 Canadian EDs in 3 cities. Patients who presented to the ED with atrial fibrillation were eligible for inclusion. The before phase (1) was retrospective; 2 after phases (2 and 3) were prospective: phase 2 used an oral anticoagulation prescription tool for emergency physicians and patient education materials, whereas phase 3 used the same prescription tool, patient materials, atrial fibrillation educational session, and follow-up in an atrial fibrillation clinic. Each phase was 1 year long. The primary outcome was the rate of new oral anticoagulation prescription at ED discharge for patients who were oral anticoagulation eligible and not receiving oral anticoagulation at presentation. Results A total of 631 patients were included. Mean age was 69 years (SD 14 years), 47.4% were women, and 69.6% of patients had a CHADS 2 score greater than or equal to 1. The rate of new oral anticoagulation prescription in phase 1 was 15.8% compared with 54.1% and 47.2%, in phases 2 and 3, respectively. After multivariable adjustment, the odds ratio for new oral anticoagulation prescription was 8.03 (95% confidence interval 3.52 to 18.29) for phase 3 versus 1. The 6-month rate of oral anticoagulation use was numerically but not significantly higher in phase 3 compared with phase 2 (71.6% versus 79.4%; adjusted odds ratio 2.30; 95% confidence interval 0.89 to 5.96). The rate of major bleeding at 6 months was 0%, 0.8%, and 1% in phases 1, 2, and 3, respectively. Conclusion An oral anticoagulation prescription tool was associated with an increase in new oral anticoagulation prescription in the ED, irrespective of whether an atrial fibrillation clinic follow-up was scheduled. The use of an atrial fibrillation clinic was associated with a trend to a higher rate of oral anticoagulation at 6-month follow-up.

Objectives:Injection drug users (IDUs) often undergo procedural sedation and analgesia (PSA) as part of emergency department (ED) treatment. We compared adverse events (AEs) using a variety of sedation regimens.Methods:This was a retrospective analysis of a PSA safety audit in two urban EDs. Consecutive self-reported IDUs were identified, and structured data describing comorbidities, vital signs, sedation regimens (propofol [P], propofol-fentanyl [PF], fentanyl-midazolam [FM], ketofol [1:1 ketamine:propofol, KF], and ketamine-propofol [KP]) and AEs were collected. The primary outcome was the proportion of patients in each sedation group having an AE; the secondary outcome was the proportion of patients having a cardiovascular or respiratory AE.Results:Data were collected on 276 IDUs (78 P, 82 PF, 65 FM, 25 KF, and 26 KP), and 18 patients had AEs (6.5%, 95% CI 4.0–10.3). The AE rates were 0.0%, 8.5%, 9.2%, 12.0%, and 7.6%, respectively, with propofol having a significantly lower rate (Pearson coefficient 14.9,p= 0.007). The cardiovascular/respiratory AE rates were significantly different as well, with P, KP, and KF having the lowest rates (Pearson coefficient 13.3,p= 0.01).Conclusions:For IDU PSA, the overall AE rate was 6.5%, and propofol appeared to have a significantly lower rate.

ACADEMIC EMERGENCY MEDICINE 2011; 18:237–245 © 2011 by the Society for Academic Emergency Medicine Abstract Objectives: The objective was to evaluate the effectiveness, recovery time, and adverse event profile of intravenous (IV) mixed 1:1 ketamine–propofol (ketofol) for adult procedural sedation and analgesia (PSA) in the emergency department (ED). Methods: Prospective data were collected on all PSA events over a 4.5-year period in a trauma-receiving suburban teaching hospital. PSAs using a 1:1 single-syringe mixture of 10 mg/mL ketamine and 10 mg/mL propofol in patients over 21 years of age were analyzed. Physiologic data, drug doses, adverse events, recovery time, patient satisfaction, and staff satisfaction were recorded. Results: Ketofol PSA was used in 728 patients for primarily orthopedic procedures. Median patient age was 53 years (range = 21 to 99 years, interquartile range [IQR] = 36–70 years). The median dose of ketamine and propofol was 0.7 mg/kg each (range = 0.2 to 2.7 mg/kg, IQR = 0.5–0.9 mg/kg), and median recovery time was 14 minutes (range = 3 to 50 minutes, IQR = 10–17 minutes). PSA was effective in 717 cases (98%). Bag–mask ventilation occurred in 15 patients (2.1%; 95% confidence interval [CI] = 1.0% to 3.1%). Recovery agitation occurred in 26 patients (3.6%; 95% CI = 2.2% to 4.9%), of whom 13 (1.8%; 95% CI = 0.8% to 2.7%) required treatment. One patient experienced vomiting and one patient was admitted to the hospital for monitoring of transient dysrhythmia and hypotension. No sequelae were identified. The median staff satisfaction scores were 10 (IQR = 9–10) on a scale of 1 to 10, and 97% of patients would have chosen the same method of PSA in the future. Conclusions: Ketofol is an effective PSA agent in adult ED patients. Recovery times are short and adverse events are few. Patients and ED staff were highly satisfied.

Introduction: Primary care paramedics (PCPs) have limited options to provide analgesia during transport thus timely pain relief is often significantly delayed. Inhaled nitrous oxide is considered usual care for PCPs, but is limited in effectiveness. Intranasal (IN) ketamine has been shown to provide effective analgesia with no deleterious effects on cardiorespiratory function thus may provide rapid, easily-administered and well-tolerated analgesia in prehospital transports. Methods: This was a randomized double-blind pilot series. Patients with an acute painful condition reporting a pain score of 5 or more on an 11-point verbal numeric rating scale (VNRS) were included. Exclusion criteria were age under 18 years, known intolerance to ketamine, non-traumatic chest pain, altered mental status, pregnancy and nasal occlusion. Patients were randomized to 0.75 mg/kg of IN ketamine or IN saline. All patents received inhaled nitrous oxide. The primary outcome was the proportion of patients experiencing a reduction in VNRS pain score of two points or more (clinically significant pain reduction) at 30 minutes. Secondary outcomes were patient-reported comfort, patient and provider satisfaction, and incidence of adverse events. Results: 40 patients were enrolled, 20 in each group. 80% of IN ketamine patients compared to 60% of placebo patients reported a 2-point reduction in VNRS pain score by 30 minutes. 50% of ketamine vs 25% of placebo patients reported feeling moderately or much better. 85% of ketamine vs 75% of placebo patients reported any improvement in subjective comfort. 80% of ketamine patients reported minor adverse effects compared to 52% of placebo patients. No serious adverse effects were reported. Conclusion: The addition of IN ketamine to usual care with nitrous oxide appears to result in a greater proportion of patients reporting a clinically significant reduction in VNRS pain score and improved subjective comfort, with a greater incidence of minor adverse effects. These findings will be used to power a definitive randomized double-blind trial.

Objectives: This study evaluated the effectiveness, recovery time, and adverse event profile of intravenous (IV) ketofol (mixed 1:1 ketamine–propofol) for emergency department (ED) procedural sedation and analgesia (PSA) in children. Methods: Prospective data were collected on all PSA events in a trauma-receiving, community teaching hospital over a 3.5-year period, from which data on all patients under 21 years of age were studied. Patients receiving a single-syringe 1:1 mixture of 10 mg/mL ketamine and 10 mg/mL propofol (ketofol) were analyzed. Patients received ketofol in titrated aliquots at the discretion of the treating physician. Effectiveness, recovery time, caregiver and patient satisfaction, drug doses, physiologic data, and adverse events were recorded. Results: Ketofol PSA was performed in 219 patients with a median age of 13 years (range = 1 to 20 years; interquartile range [IQR] = 8 to 16 years) for primarily orthopedic procedures. The median dose of medication administered was 0.8 mg/kg each of ketamine and propofol (range = 0.2 to 3.0 mg/kg; IQR = 0.7 to 1.0 mg/kg). Sedation was effective in all patients. Three patients (1.4%; 95% confidence interval [CI] = 0.0% to 3.0%) had airway events requiring intervention, of which one (0.4%; 95% CI = 0.0% to 1.2%) required positive pressure ventilation. Two patients (0.9%; 95% CI = 0.0% to 2.2%) had unpleasant emergence requiring treatment. All other adverse events were minor. Median recovery time was 14 minutes (range = 3 to 41 minutes; IQR = 11 to 18 minutes). Median staff satisfaction was 10 on a 1-to-10 scale. Conclusions: Pediatric PSA using ketofol is highly effective. Recovery times were short; adverse events were few; and patients, caregivers, and staff were highly satisfied. ACADEMIC EMERGENCY MEDICINE 2010; 17:194–201 © 2010 by the Society for Academic Emergency Medicine

Study objective We evaluate the effectiveness and consider the safety of intravenous ketamine/propofol combination ("ketofol") in the same syringe for procedural sedation and analgesia in the emergency department (ED). Methods A prospective case series of consecutive ketofol procedural sedation and analgesia events in the ED of a trauma-receiving community teaching hospital from July 2005 to February 2006 was studied. Patients of all ages, with any comorbid conditions, were included. Ketofol (1:1 mixture of ketamine 10 mg/mL and propofol 10 mg/mL) was administered intravenously at the discretion of the treating physician by using titrated aliquots. The presence or absence of adverse events was documented, as were procedural success, recovery time, and physician, nurse, and patient satisfaction. Physiologic data were recorded with established hospital procedural sedation and analgesia guidelines. Results One hundred fourteen procedural sedation and analgesia events using ketofol were performed for primarily orthopedic procedures. The median dose of medication administered was ketamine at 0.75 mg/kg and propofol at 0.75 mg/kg (range 0.2 to 2.05 mg/kg each of propofol and ketamine; interquartile range [IQR] 0.6 to 1.0 mg/kg). Procedures were successfully performed without adjunctive sedatives in 110 (96.5%) patients. Three patients (2.6%; 95% confidence interval [CI] 0.6% to 7.5%) had transient hypoxia; of these, 1 (0.9%; 95% CI 0.02% to 4.8%) required bag-valve-mask ventilation. Four patients (3.5%; 95% CI 1.0% to 8.7%) required repositioning for airway malalignment, 4 patients (3.5%; 95% CI 1.0% to 8.7%) required adjunctive medication for sedation, and 3 patients (2.6%; 95% CI 0.6% to 7.5%) had mild unpleasant emergence, of whom 1 (0.9%; 95% CI 0.02% to 4.8%) received midazolam. No patient had hypotension or vomiting or received endotracheal intubation. Median recovery time was 15 minutes (range 5 to 45 minutes; IQR 12 to 19 minutes). Median physician, nurse, and patient satisfaction scores were 10 on a 1-to-10 scale. Conclusion Ketofol procedural sedation and analgesia is effective and appears to be safe for painful procedures in the ED. Few adverse events occurred and were either self-limited or responded to minimal interventions. Recoveries were rapid, and staff and patients were highly satisfied.

Procedural sedation has allowed many painful interventions to be conducted outside the operating room. During such procedures, it is important to maintain an appropriate level of sedation to minimize the risk of respiratory depression if patients are over-sedated and added pain or anxiety if under-sedated. However, there is currently no objective way to measure the patient's evolving level of sedation during a procedure. We investigated the use of capnography-derived features as an objective measure of sedation level. Time-based capnograms were recorded from 30 patients during sedation for cardioversion. Through causal k-means clustering of selected features, we sequentially assigned each exhalation to one of three distinct clusters, or states. Transitions between these states correlated to events during sedation (drug administration, procedure start and end, and clinical interventions). Similar clustering of capnogram recordings from 26 healthy, non-sedated subjects did not reveal distinctly separated states.

Introduction: Atrial fibrillation (AF) is the most common sustained arrhythmia affecting 1-2% of the population. Oral anticoagulation (OAC) reduces stroke risk by 60-80% in AF patients, but only 50% of indicated patients receive OAC. Many patients present to the ED with AF due to arrhythmia symptoms, however; lack of OAC prescription in the ED has been identified as a significant gap in the care of AF patients. Methods: This was a multi-center, pragmatic, three-phase before-after study, in three Canadian sites. Patients who presented to the ED with electrocardiographically (ECG) documented, nonvalvular AF and were discharged home were included. Phase 1 was a retrospective chart review to determine OAC prescription of AF patients in each ED; Phase 2 was a low-intensity knowledge translation intervention where a simple OAC-prescription tool for ED physicians with subsequent short-term OAC prescription was used, as well as an AF patient education package and a letter to family physicians; phase 3 incorporated Phase 2 interventions, but added immediate follow-up in a community AF clinic. The primary outcome of the study was the rate of new OAC prescriptions at ED discharge in AF patients who were OAC eligible and were not on OAC at presentation. Results: A total of 632 patients were included from June, 2015-November, 2016. ED census ranged from 30000-68000 annual visits. Mean age was 71±15, 67±12, 67±13 years, respectively. 47.5% were women, most responsible ED diagnosis was AF in 75.8%. The mean CHA2DS2-VASc score was 2.6±1.8, with no difference amongst groups. There were 266 patients eligible for OAC and were not on this at presentation. In this group, the prescription of new OAC was 15.8% in Phase 1 as compared to 54% and 47%, in Phases 2 and 3, respectively. After adjustment for center, components of the CHA2DS2-VASc score, prior risk of bleeding and most responsible ED diagnosis, the odds ratio for new OAC prescription was 8.0 (95%CI (3.5,18.3) pConclusion: Use of a simple OAC-prescription tool was associated with an increase in new OAC prescription in the ED for eligible patients with AF. Further testing in a rigorous study design to assess the effect of this practice on stroke prevention in the AF patients who present to the ED is indicated.

Objectives The objective was to examine the feasibility, effectiveness, and adverse effect profile of intranasal ketamine for analgesia in emergency department (ED) patients. Methods This was a prospective observational study examining a convenience sample of patients aged older than 6 years experiencing moderate or severe pain, defined as a visual analog scale (VAS) score of 50 mm or greater. Patients received 0.5 to 0.75 mg/kg intranasal ketamine. Pain scores were recorded on a standard 100-mm VAS by trained investigators at baseline, then every 5 minutes for 30 minutes, and then every 10 minutes for an additional 30 minutes. The primary outcome was the number and proportion of patients experiencing clinically significant reductions in VAS pain scores, defined as VAS reductions of 13 mm or more, within 30 minutes. Secondary outcomes included the median reduction in VAS, the median time required to achieve a 13 mm reduction in VAS, vital sign changes, and adverse events. Continuous data are reported with medians and interquartile ranges (IQRs). The Wilcoxon signed-ranks test was used to assess changes in VAS scores. Adverse effects are reported with proportions and 95% confidence intervals (CIs). Results Forty patients were enrolled with a median age of 47 years (IQR = 36 to 57 years; range = 11 to 79 years) for primarily orthopedic injuries. A reduction in VAS of 13 mm or more within 30 minutes was achieved in 35 patients (88%). The median change in VAS at 30 minutes was 34 mm (44%). Median time required to achieve a 13 mm VAS reduction was 9.5 minutes (IQR = 5 to 13 minutes; range = 5 to 25 minutes). No serious adverse effects occurred. Minor adverse effects included dizziness (21 patients, 53%; 95% CI = 38% to 67%), feeling of unreality (14 patients, 35%; 95% CI = 22% to 50%), nausea (four patients, 10%; 95% CI = 4% to 23%), mood change (three patients, 8%; 95% CI = 3% to 20%), and changes in hearing (one patient, 3%; 95% CI = 0% to 13%). All adverse effects were transient and none required intervention. There were no changes in vital signs requiring clinical intervention. Conclusions Intranasal ketamine reduced VAS pain scores to a clinically significant degree in 88% of ED patients in this series. Adverse effects were minor and transient. Intranasal ketamine may have a role in the provision of effective, expeditious analgesia to ED patients. Resumen Objetivos Examinar la viabilidad, la efectividad y el perfil de efectos adversos de la ketamina intranasal para la analgesia de pacientes en el servicio de urgencias (SU). Metodologia Estudio observacional prospectivo que examino una muestra de conveniencia de pacientes mayores de 6 anos que experimentaron dolor moderado o grave, definido como una puntuacion en la escala visual analogica (EVA) de 50 mm o mas. Los pacientes recibieron de 0,5 a 0,75 mg/kg de ketamina intranasal. Las puntuaciones de dolor se recogieron en una EVA estandar de 100 mm por investigadores entrenados, en el momento inicial: despues cada 5 minutos durante 30 minutos y finalmente cada 10 minutos durante 30 minutos adicionales. El resultado principal fue el numero y la proporcion de pacientes que experimentaron una reduccion significativa en la puntuacion del dolor en la EVA, definida como una reduccion de 13 mm o mas, en los primeros 30 minutos. Los resultados secundarios incluyeron la reduccion mediana en la EVA, la mediana de tiempo requerido para alcanzar una reduccion de 13 mm en la EVA, los cambios en las costantes vitales y los efectos adversos. Los datos continuos se documentaron con medianas y rangos intercuartilicos (RIC). El test de Wilcoxon se utilizo para evaluar los cambios de puntuaciones en la EVA. Los efectos adversos se documentaron con proporciones y sus intervalos de confianza (IC) al 95%. Resultados Se incluyeron 40 pacientes con una mediana de edad de 47 anos (RIC 36 a 57 anos; rango 11 a 79 anos) fundamentalmente con lesiones traumatologicas. Una reduccion en la EVA de 13 mm o mas en los primeros 30 minutos se alcanzo en 35 pacientes (88%). La mediana de cambio en la EVA a los 30 minutos fue de 34 mm (44%). La mediana de tiempo requerido para alcanzar una reduccion en la EVA de 13 mm fue de 9,5 minutos (RIC 5 a 13 minutos; rango 5 a 25 min.). No ocurrieron efectos adversos graves. Los efectos adversos menores incluyeron mareo (21 pacientes, 53%; IC 95% = 38% a 67%), sensacion de irrealidad (14 pacientes, 35%; IC 95% = 22% a 50%), nauseas (4 pacientes, 10%; IC 95% = 4% a 23%), cambios de humor (3 pacientes, 8%; IC 95% = 3% a 20%) y cambios en la audicion (1 paciente, 3%; IC 95% = 0% a 13%). Todos los efectos adversos fueron transitorios y ninguno requirio intervencion. No hubo cambios en las constantes vitales que requirieran intervencion clinica. Conclusiones La ketamina intranasal redujo las puntuaciones del dolor segun la EVA a un grado clinicamente significativo en un 88% en esta seria de pacientes del SU. Los eventos adversos fueron menores y transitorios. La ketamina intranasal puede tener utilidad para proporcionar analgesia efectiva y rapida a los pacientes en el SU.

The role of ketamine anesthesia in the prehospital, emergency department and operating theater settings is not well defined. A nonsystematic review of ketamine was performed by authors from Australia, Europe, and North America. Results were discussed among authors and the final manuscript accepted. Ketamine is a useful agent for induction of anesthesia, procedural sedation, and analgesia. Its properties are appealing in many awkward clinical scenarios. Practitioners need to be cognizant of its side effects and limitations.

Objective:Injection drug users (IDUs) often undergo procedural sedation and analgesia (PSA) in the emergency department (ED). We compared adverse events (AEs) for IDUs to those for non-IDUs receiving PSA for incision and drainage of cutaneous abscesses.Methods:This was a retrospective analysis of a PSA safety audit. IDU status was prospectively documented among consecutive patients undergoing PSA at two urban EDs. Structured data describing comorbidities, vital signs, sedation regimens, and adverse events were collected. Primary outcome was the proportion of patients in each group experiencing an AE, whereas the secondary outcomes included recovery times.Results:Of 525 consecutive patients receiving PSA for incision and drainage of an abscess, 244 were deemed IDUs and 281 non-IDUs. IDUs received higher doses of sedatives and analgesics, and 14 experienced AEs (5.7%), whereas 10 non-IDUs had AEs (3.6%), for a risk difference of 2.1% (95% CI -1.8, 6.5). Median recovery times were 18 minutes (interquartile range [IQR] 10-36) for IDUs and 12 minutes (IQR 7-19) for non-IDUs, for a difference of 6 minutes (95% CI 2-9 minutes). Median sedation times were also longer in IDUs, for a difference of 6 minutes (95% CI 5-10 minutes). Of 20 IDU patients and 1 non-IDU patient admitted to hospital, none had experienced an AE related to PSA.Conclusions:For ED patients requiring PSA for incision and drainage, IDUs had an AE rate similar to that of non-IDUs but longer sedation and recovery times. In experienced hands, PSA may be as safe in IDUs as in patients who do not use injection drugs.

Objectives Determine the prevalence of drug use in injured drivers and identify associated demographic factors and crash characteristics. Design Prospective cross-sectional study. Setting Seven trauma centres in British Columbia, Canada (2010–2012). Participants Automobile drivers who had blood obtained within 6 h of a crash. Main outcome measures We analysed blood for cannabis, alcohol and other impairing drugs using liquid chromatography/mass spectrometry (LCMS). Results 1097 drivers met inclusion criteria. 60% were aged 20–50 years, 63.2% were male and 29.0% were admitted to hospital. We found alcohol in 17.8% (15.6% to 20.1%) of drivers. Cannabis was the second most common recreational drug: cannabis metabolites were present in 12.6% (10.7% to 14.7%) of drivers and we detected Δ-9-tetrahydrocannabinol (Δ-9-THC) in 7.3% (5.9% to 9.0%), indicating recent use. Males and drivers aged under 30 years were most likely to use cannabis. We detected cocaine in 2.8% (2.0% to 4.0%) of drivers and amphetamines in 1.2% (0.7% to 2.0%). We also found medications including benzodiazepines (4.0% (2.9% to 5.3%)), antidepressants (6.5% (5.2% to 8.1%)) and diphenhydramine (4.7% (3.5% to 6.2%)). Drivers aged over 50 years and those requiring hospital admission were most likely to have used medications. Overall, 40.1% (37.2% to 43.0%) of drivers tested positive for alcohol or at least one impairing drug and 12.7% (10.7% to 14.7%) tested positive for more than one substance. Conclusions Alcohol, cannabis and a broad range of other impairing drugs are commonly detected in injured drivers. Alcohol is well known to cause crashes, but further research is needed to determine the impact of other drug use, including drug–alcohol and drug–drug combinations, on crash risk. In particular, more work is needed to understand the role of medications in causing crashes to guide driver education programmes and improve public safety.

The objective was to evaluate the effectiveness, recovery time, and adverse event profile of intravenous (IV) mixed 1:1 ketamine-propofol (ketofol) for adult procedural sedation and analgesia (PSA) in the emergency department (ED). Prospective data were collected on all PSA events over a 4.5-year period in a trauma-receiving suburban teaching hospital. PSAs using a 1:1 single-syringe mixture of 10 mg/mL ketamine and 10 mg/mL propofol in patients over 21 years of age were analyzed. Physiologic data, drug doses, adverse events, recovery time, patient satisfaction, and staff satisfaction were recorded.Ketofol PSA was used in 728 patients for primarily orthopedic procedures. Median patient age was 53 years (range = 21 to 99 years, interquartile range [IQR] = 36-70 years). The median dose of ketamine and propofol was 0.7 mg/kg each (range =0.2 to 2.7 mg/kg, IQR = 0.5-0.9 mg/kg), and median recovery time was 14 minutes (range = 3 to 50 minutes, IQR = 10-17 minutes). PSA was effective in 717 cases (98%). Bag-mask ventilation occurred in 15 patients (2.1%; 95% confidence interval [CI] = 1.0% to 3.1%). Recovery agitation occurred in 26 patients (3.6%; 95% CI = 2.2% to 4.9%), of whom 13 (1.8%; 95% CI = 0.8% to 2.7%) required treatment. One patient experienced vomiting and one patient was admitted to the hospital for monitoring of transient dysrhythmia and hypotension. No sequelae were identified. The median staff satisfaction scores were 10 (IQR = 9-10) on a scale of 1 to 10, and 97% of patients would have chosen the same method of PSA in the future. Ketofol is an effective PSA agent in adult ED patients. Recovery times are short and adverse events are few. Patients and ED staff were highly satisfied.

In an old Reese’s Peanut Butter Cups television commercial, 2 snacking pedestrians collide and their respective treats—peanut butter and chocolate—inadvertently mix. Both parties sample the blend with unexpected pleasure, and the narrator then pitches the slogan, “Two great tastes that taste great together.” Ketamine and propofol are 2 extremely common agents used for emergency department (ED) procedural sedation, with each having well-documented safety and efficacy. But do these 2 drugs work better together? The combination of ketamine and propofol, referred to by the portmanteau “ketofol,” is currently all the rage. According to Internet and physician buzz, a large number of EDs in North America have adopted this combination as their primary sedation regimen. Much of this popularity has been fueled by anecdote rather than solid research. This is reminiscent of the dramatic entry of propofol a decade ago into emergency medicine, in which clinical application surged far ahead of the science. Ultimately, the original enthusiasm for propofol was properly validated, but will ketofol enjoy the same outcome? Other popular anecdotal therapies were later discredited, eg, aminophylline for asthma, antishock trousers for traumatic hypotension, highdose epinephrine in cardiac arrest. The concept of ketofol has immediate allure because of its intriguing synergistic premise. These 2 completely different sedatives exhibit clinical features that appear to balance each other’s deficits. Propofol is a superb sedative but lacks the analgesia that ketamine can amply provide. Respiratory depression and hypotension are the principal adverse events of propofol; perhaps the sympathomimetic ketamine mitigates them. Vomiting and hallucinatory recovery reactions are the principal adverse events of ketamine; perhaps the antiemetic and hypnotic properties of propofol mitigate them. In this editorial, we debate the pros and cons of ketofol, with our preexisting biases against (S.M.G.), for (G.A.), and neutral (B.K.). Summary arguments are show in the Figure. h

Results: A total of 284 patients were enrolled, 142 per group. Forty-three (30%) patients experienced an adverse respiratory event in the ketofol group compared with 46 (32%) in the propofol group (difference 2%; 95% confidence interval 9% to 13%; P.80). Three ketofol patients and 1 propofol patient received bag-valvemask ventilation. Sixty-five (46%) patients receiving ketofol and 93 (65%) patients receiving propofol required repeated medication dosing or progressed to a Ramsay Sedation Score of 4 or less during their procedure (difference 19%; 95% confidence interval 8% to 31%; P.001). Six patients receiving ketofol were treated for recovery agitation. Other secondary outcomes were similar between the groups. Patients and staff were highly satisfied with both agents. Conclusion: Ketofol for ED procedural sedation does not result in a reduced incidence of adverse respiratory events compared with propofol alone. Induction time, efficacy, and sedation time were similar; however, sedation depth appeared to be more consistent with ketofol. [Ann Emerg Med. 2012;59:504-512.] Please see page 505 for the Editor’s Capsule Summary of this article.

Respiratory muscle weakness occurs commonly at presentation in patients with botulism. Although clinical improvement occurs over several months, symptoms such as fatigue and dyspnea persist in many patients in the long term. To determine whether continued respiratory muscle weakness might contribute to these symptoms, we compared lung function tests, respiratory muscle strength, and exercise performance in 13 patients 2 years after type B botulism. We found that residual symptoms including dyspnea and fatigue were common in botulism patients at 2 years postintoxication. Lung function tests had returned to normal in all patients. Maximal inspiratory and expiratory pressures were similar between botulism patients and control subjects. Evaluation of individual results showed evidence of inspiratory muscle weakness in four of 13 patients with botulism (Plmax less than 65% predicted). Maximal oxygen consumption and maximal workload during exercise were reduced in botulism patients in comparison to control subjects. During exercise, botulism patients had a more rapid and shallow breathing pattern and a higher dyspnea score at a given minute ventilation in comparison to control subjects. Reasons for premature exercise termination in botulism patients were multifactorial. Although respiratory muscle weakness may have been contributory in some patients, most appeared to be limited by reduced cardiovascular fitness, leg fatigue, or reduced motivation.

Obtention de [Mo(PF 3 ) 4 (dppe)], [Mo(Me 2 NPF 2 ) 6 ] et [Mo(CO) 2 (dppe)(MeN(PF 2 ) 2 )]. Mecanismes. Etude comparative des reactions de PO(Me) 3 et dppe avec [Mo(Co) 4 (dppe)] en vue de preciser la nature d'intermediaires de la reaction