Johanna C. Moore

Randomized, Double-Blinded, Clinical Trial of Propofol, 1:1 Propofol/Ketamine, and 4:1 Propofol/Ketamine for Deep Procedural Sedation in the Emergency Department

STUDY OBJECTIVE We compare the frequency of airway and respiratory adverse events leading to an intervention between propofol with 1:1 and 4:1 mixtures of propofol and ketamine (ketofol). METHODS We performed a randomized, double-blinded trial in which emergency department adults undergoing deep sedation received propofol, 1:1 propofol and ketamine, or 4:1 propofol and ketamine. Our primary outcome was the frequency of airway and respiratory adverse events leading to an intervention. Other outcomes included sedation depth, efficacy, procedure and recovery time, patient satisfaction, pain, and procedural recall. RESULTS Two hundred seventy-one subjects completed the trial, 90 receiving propofol, 85 receiving 1:1 propofol and ketamine, and 96 receiving 4:1 propofol and ketamine. Airway or respiratory adverse events leading to an intervention were similar between groups: 29%, 19%, and 32%, respectively (P=.21). There were no serious adverse events in any group. Secondary outcomes were generally similar between groups, with greater recovery agitation observed in the 1:1 ketofol group (8%, 21%, and 10%, respectively). CONCLUSION We found a similar frequency of airway and respiratory adverse events leading to intervention between propofol alone and either 1:1 or 4:1 ketofol.

A prospective study of ketamine versus haloperidol for severe prehospital agitation

Abstract Context: Ketamine is an emerging drug for the treatment of acute undifferentiated agitation in the prehospital environment, however no prospective comparative studies have evaluated its effectiveness or safety in this clinical setting. Objective: We hypothesized 5 mg/kg of intramuscular ketamine would be superior to 10 mg of intramuscular haloperidol for severe prehospital agitation, with time to adequate sedation as the primary outcome measure. Methods: This was a prospective open label study of all patients in an urban EMS system requiring chemical sedation for severe acute undifferentiated agitation that were subsequently transported to the EMS system’s primary Emergency Department. All paramedics were trained in the Altered Mental Status Scale and prospectively recorded agitation scores on all patients. Two 6-month periods where either ketamine or haloperidol was the first-line therapy for severe agitation were prospectively compared primarily for time to adequate sedation. Secondary outcomes included laboratory data and adverse medication events. Results: 146 subjects were enrolled; 64 received ketamine, 82 received haloperidol. Median time to adequate sedation for the ketamine group was 5 minutes (range 0.4–23) vs. 17 minutes (range 2–84) in the haloperidol group (difference 12 minutes, 95% CI 9–15). Complications occurred in 49% (27/55) of patients receiving ketamine vs. 5% (4/82) in the haloperidol group. Complications specific to the ketamine group included hypersalivation (21/56, 38%), emergence reaction (5/52, 10%), vomiting (5/57, 9%), and laryngospasm (3/55, 5%). Intubation was also significantly higher in the ketamine group; 39% of patients receiving ketamine were intubated vs. 4% of patients receiving haloperidol. Conclusions: Ketamine is superior to haloperidol in terms of time to adequate sedation for severe prehospital acute undifferentiated agitation, but is associated with more complications and a higher intubation rate.

Using thrombolytics in frostbite injury

Until recently, the treatment of frostbite injuries has been limited to supportive care only, with mediocre outcomes. The use of thrombolytic therapy has been presented in a limited fashion in the literature since 2005. This case study describes the work-up and treatment of a patient with severe frostbite injury who received tPA. We then discuss thrombolytic therapy in more detail, with particular attention to the two studies outlining different treatment regimens.

Effect of position and weight force on inferior vena cava diameter--implications for arrest-related death.

INTRODUCTION The physiology of many sudden, unexpected arrest-related deaths (ARDs) proximate to restraint has not been elucidated. A sudden decrease in central venous return during restraint procedures could be physiologically detrimental. The impact of body position and applied weight force on central venous return has not been previously studied. In this study, we use ultrasound to measure the size of the inferior vena cava (IVC) as a surrogate of central venous return in the standing position, prone position, and with weight force applied to the thorax in the prone position. METHODS This was a prospective, observational study of volunteer human subjects. The IVC was visualized from the abdomen in both the longitudinal and transverse section in the standing and prone positions without weight force applied, and with 100 lbs (45 kg) and 147 lbs (67 kg) of weight force on the upper back in the prone position. Maximum and minimum measurements were determined in each section to account for possible respiratory variation of the IVC. RESULTS The IVC significantly decreased in size with each successive change: from standing to prone, from prone to prone with 100 lbs (45 kg) weight compression, from prone with 100 lbs (45 kg) weight compression to prone with 147 lbs (67 kg) weight compression (p < 0.0001). The vital sign measurements had no statistical change. CONCLUSIONS The physiology involved in many sudden, unexpected ARDs has not been elucidated. However, in our study, we found a significant decrease in IVC diameter with weight force compression to the upper thorax when the subject was in the prone position. This may have implications for the tactics of restraint to aid in the prevention of sudden, unexpected ARD cases.

An evaluation of two conducted electrical weapons and two probe designs using a swine comparative cardiac safety model

Despite human laboratory and field studies that have demonstrated a reasonable safety profile for TASER brand conducted electrical weapons (CEW), the results of some swine studies and arrest related deaths temporal to the use of the CEWs continue to raise questions regarding cardiac safety. TASER International, Inc., has released a new CEW, the TASER X2, touted to have a better safety profile than its long-standing predecessor, the TASER X26. We have developed a model to assess the relative cardiac safety of CEWs and used it to compare the TASER X2 and the TASER X26. This safety model was also used to assess the relative safety of an experimental probe design as compared to the standard steel probe. Our results suggest that the TASER X2 has an improved safety margin over the TASER X26. The new probe design also has promise for enhanced cardiac safety, although may have some disadvantages when compared to the existing design which would make field use impractical.

Oral versus intravenous opioid dosing for the initial treatment of acute musculoskeletal pain in the emergency department.

OBJECTIVES The objective was to compare the time to medication administration, the side effects, and the analgesic effect at sequential time points after medication administration of an oral treatment strategy using oxycodone solution with an intravenous (IV) treatment strategy using morphine sulfate for the initial treatment of musculoskeletal pain in emergency department (ED) patients. METHODS This was a prospective randomized clinical trial of patients >6 years old who were going to receive IV morphine sulfate for the treatment of musculoskeletal pain but did not yet have an IV. Consenting patients were randomized to have the treating physician order either 0.1 mg/kg morphine sulfate IV or 0.125 mg/kg oxycodone orally in a 5 mg/5 mL suspension as their initial treatment for pain. The time from the placement of the order to the administration of the medication was recorded. Pain was measured using a 100-mm visual analog scale (VAS) and recorded at 0, 10, 20, 30 and 40 minutes after drug administration. RESULTS A total of 405 eligible patients were identified during the study period; 328 (81.0%) patients consented to be in the study. A total of 158 patients were randomized to the IV morphine sulfate treatment group, and 162 were randomized to the oral oxycodone treatment group. Of the patients who were randomized to IV therapy, 34 were withdrawn from the study prior to drug administration; leaving 125 patients in the IV group for analysis. Of the patients who randomized to oral therapy, 22 were withdrawn from the study prior to drug administration, leaving 140 patients for analysis. No serious adverse events were detected. There was a 12-minute difference between the median time of the order and the administration of oral oxycodone (8.5 minutes) and IV morphine (20.5 minutes). The mean percent change in VAS score was larger for patients in the IV therapy group than those in the oral therapy group at 10 and 20 minutes. At 30 and 40 minutes, the authors could no longer detect a difference. The satisfaction scale score was higher after treatment for the morphine group (median = 4; interquartile range [IQR] = 4 to 5) than for the oxycodone group (median = 4; IQR = 2 to 5; p = 0.008). CONCLUSIONS The oral loading strategy was associated with delayed onset of analgesia and decreased patient satisfaction, but a shorter time to administration. The oral loading strategy using an oxycodone solution provided similar pain relief to the IV strategy using morphine 30 minutes after administration of the drug. Oral 0.125 mg/kg oxycodone represents a feasible alternative to 0.1 mg/kg IV morphine in the treatment of severe acute musculoskeletal pain when difficult or delayed IV placement greater than 30 minutes presents a barrier to treatment.

Randomized Clinical Trial of the Effect of Supplemental Opioids in Procedural Sedation with Propofol on Serum Catecholamines

OBJECTIVES The objective was to assess the effect on stress biomarkers of supplemental opioid to a standard propofol dosing protocol for emergency department (ED) procedural sedation (PS). The hypothesis was that there is no difference in the change in serum catecholamines between PS using propofol with or without supplemental alfentanil. METHODS This was a randomized, nonblinded pilot study of adult patients undergoing PS in the ED for the reduction of fractures and dislocations. Patients with pain before the procedure were treated with intravenous (IV) morphine sulfate until their pain was adequately treated for at least 20 minutes before starting the procedure. Patients were randomized to receive either 10 μg/kg alfentanil followed by 1 mg/kg propofol, followed by 0.5 mg/kg every 3 minutes as needed, or propofol only, dosed in similar fashion without supplemental alfentanil. Doses, vital signs, nasal end-tidal CO2 (ETCO2), pulse oximetry, and bispectral electroencephalogram (EEG) analysis scores were recorded. Subclinical respiratory depression was defined as a change in ETCO2 > 10 mm Hg, an oxygen saturation of < 92% at any time, or an absent ETCO2 waveform at any time. Clinical events related to respiratory depression were noted during the procedure, including the addition of or increase in the flow rate of supplemental oxygen, the use of a bag-valve-mask apparatus, airway repositioning, or stimulation to induce breathing. Blood was drawn 1 minute prior to the administration of the medications for PS and again 1 minute after completion of the procedure for which the patient was sedated. Serum was tested for total catecholamines, epinephrine, norepinephrine, and dopamine. Postprocedure, patients were asked to report any pain perceived during the procedure. Data were analyzed using descriptive statistics, Wilcoxon rank sum tests, and chi-square tests, as appropriate. RESULTS Twenty patients were enrolled; 10 received propofol and 10 received propofol with alfentanil. No clinically significant complications were noted. Subclinical respiratory depression was seen in four of 10 (40%) patients in the propofol group and five of 10 (50%) patients in the propofol/alfentanil group (effect size = -10%, 95% confidence interval [CI] = -53% to 33%). There was no difference in the rate of clinical signs of respiratory depression between the two groups. Pain during the procedure was reported by two of 10 (20%) patients in the propofol group and five of 10 (50%) patients in the propofol/alfentanil group (effect size = -30%, 95% CI = -70% to 10%). Recall of some part of the procedure was reported by 0 of 10 (0%) patients in the propofol group and five of 10 (50%) of patients in the propofol/alfentanil group (effect size = -50%, 95% CI = -81% to -19%). There was no difference in the baseline or postprocedure catecholamine levels between the groups. CONCLUSIONS No difference in serum catecholamines was detected immediately after PS between patients who receive propofol with and without supplemental opioid in this small pilot study. PS using propofol only without supplemental opioid did not appear to induce markers of physiologic stress in this small pilot study.

Diagnostic Performance of High Sensitivity Compared with Contemporary Cardiac Troponin I for the Diagnosis of Acute Myocardial Infarction

BACKGROUND We examined the diagnostic performance of high-sensitivity cardiac troponin I (hs-cTnI) vs contemporary cTnI with use of the 99th percentile alone and with a normal electrocardiogram (ECG) to rule out acute myocardial infarction (MI) and serial changes (deltas) to rule in MI. METHODS We included consecutive patients presenting to a US emergency department with serial cTnI onclinical indication. Diagnostic performance for acute MI, including MI subtypes, and 30-day outcomes were examined. RESULTS Among 1631 patients, MI was diagnosed in 12.9% using the contemporary cTnI assay and in 10.4% using the hs-cTnI assay. For ruling out MI, contemporary cTnI ≤99th percentile at 0, 3, and 6 h and a normal ECG had a negative predictive value (NPV) of 99.5% (95% CI, 98.6-100) and a sensitivity of 99.1% (95% CI, 97.4-100) for diagnostic and safety outcomes. Serial hs-cTnI measurements ≤99th percentile at 0 and 3 h and a normal ECG had an NPV and sensitivity of 100% (95% CI, 100-100) for diagnostic and safety outcomes. For ruling in MI, contemporary cTnI measurements had specificities of 84.4% (95% CI, 82.5-86.3) at presentation and 78.7% (95% CI, 75.4-82.0) with serial testing at 0, 3, and 6 h, improving to 89.2% (95% CI, 87.1-91.3) by using serial cTnI changes (delta, 0 and 6 h) >150%. hs-cTnI had specificities of 86.9% (95% CI, 85.1-88.6) at presentation and 85.7% (95% CI, 83.5-87.9) with serial testing at 0 and 3 h, improving to 89.3% (95% CI, 87.3-91.2) using a delta hs-cTnI (0 and 3 h) >5 ng/L. CONCLUSIONS hs-cTnI and contemporary cTnI assays are excellent in ruling out MI following recommendations predicated on serial testing and the 99th percentile with a normal ECG. For ruling in MI, deltas improve the specificity. ClinicalTrials.gov Identifier: NCT02060760.

A Prospective Observational Study of Patients Receiving Intravenous and Intramuscular Olanzapine in the Emergency Department

Study objective: Parenteral olanzapine is an emerging therapy for a variety of conditions in the emergency department (ED). Intramuscular administration is standard; however, intravenous administration has been proposed as a safe alternative route. We investigate the safety and efficacy of both intramuscular and intravenous olanzapine in the ED when used for a variety of indications. Methods: This was a prospective observational study of patients presenting to an urban Level I trauma center ED. Trained research associates screened the ED for patients receiving parenteral olanzapine. The primary outcome of the study was incidence of respiratory depression measured with standard markers. Secondary outcomes included use of additional doses or sedatives, corrected QT interval (QTc) data, time to nadir sedation, adverse events, and physician assessment of efficacy. Results: There were 784 patients included in the final analysis. Intravenous olanzapine was administered to 295 patients; 489 received intramuscular olanzapine. Respiratory depression occurred in 11 of 295 patients (3.7%; 95% confidence interval [CI] 1.6% to 5.9%) receiving intravenous olanzapine and 10 of 489 (2.0%; 95% CI 0.8% to 3.3%) receiving intramuscular olanzapine. Seven patients required intubation, 2 in the intravenous group and 5 in the intramuscular group. Nonrespiratory complications occurred in 8 patients, 6 of 295 (2.0%; 95% CI 0.4% to 3.6%) in the intravenous group and 2 of 489 (0.4%; 95% CI 0% to 0.96%) in the intramuscular group. Dysrhythmias were isolated to 2 episodes of bradycardia requiring only supportive care. Conclusion: These data suggest that, with proper monitoring, administration of olanzapine, both intramuscular and intravenous, is safe for several indications in the ED.

Gender Differences in Patient‐described Pain, Stress, and Anxiety Among Patients Undergoing Treatment for Painful Conditions in the Emergency Department

OBJECTIVES The primary objective of this study was to determine whether patient-described pain correlates with patient-described stress, anxiety, and satisfaction with ongoing treatment and if that correlation differs by gender. METHODS This was a prospective observational study at an urban, Level I trauma center conducted between June 1, 2010, and January 1, 2013. Patients reporting pain rated greater than 3 of 10 were eligible. Patients who qualified and consented for participation completed demographic and pain, anxiety, stress, and satisfaction scales at baseline, every 30 minutes, and at discharge. Data were analyzed using analysis of variance, chi-square tests, t-tests, multiple regression, and the Wilcoxon-Mann-Whitney rank test. RESULTS A total of 7,124 patients were screened for enrollment. Of those, 3,495 (49%) did not qualify at screening for various reasons, including insufficient pain levels (17.5%), elected not to participate (37.7%), did not qualify for other reasons (12.4%), and reason not captured (32.4%). A total of 3,629 (51%) screened patients were eligible and consented. Of those, 620 (16.8%) did not have any data collected past baseline, leaving 3,009 as the final sample size. The patients completing data collection had a median age of 39 years (range = 18 to 90 years), and 50% were male. The mean presenting pain visual analog scale (VAS) score was 71.5 mm. Presenting stress and anxiety VAS scores were significantly higher in females (0.61 and 0.53, respectively) than males (0.56 and 0.50, respectively), whereas presenting pain VAS (0.71 male and 0.72 female) and satisfaction VAS (0.34 male and 0.35 female) did not differ by sex. Ethnicity, education, and income were all statistically different when compared with baseline pain, stress, anxiety, and satisfaction. Male gender was associated with a significant change in pain over time from baseline (coefficient = 0.040, p = 0.037); however, when adjusting for age, ethnicity, education, and income, and for changes in stress, anxiety, and satisfaction VAS scores, changes in pain related to male gender was no longer significant (coefficient = 0.034, p = 0.11). When asked about their satisfaction with the results of the pain treatment that had been provided, patients reported a median of 2 (out of 6, 1 = satisfied, 6 = dissatisfied; interquartile range = 1 to 2). There was no significant difference between sexes (p > 0.90). CONCLUSIONS Patient-reported stress and anxiety were higher among female patients than male patients, but there was no significant difference in reported pain and satisfaction between sexes. Sex alone was not a significant predictor of change in pain for patients presenting to the emergency department with pain-related complaints. Anxiety and stress may potentially influence the pain-gender relationship.