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 comparison of routine, opt-out HIV screening with the expected yield from physician-directed HIV testing in the ED.

OBJECTIVES: The Centers for Disease Control and Prevention recommends routine opt-out HIV screening in health care settings. Our goal was to evaluate the feasibility and yield of this strategy in the emergency department (ED) and to compare it to the expected yield of physician-directed testing. METHODS: This is a cross-sectional study in an urban ED during random shifts over 1 year. Patients were ineligible for screening if they were younger than 18 years or older than 64, a prisoner, a victim of sexual assault, in an ED resuscitation room, or had altered mental status. Research associates administered rapid HIV tests and conducted standardized interviews. The patients' ED physician, blinded to the HIV result, was asked if they would have ordered a rapid HIV test if it had been available. RESULTS: Of 7756 ED patients, 3957 (51%) were eligible for HIV screening, and 2811 (71%) of those did not opt out. Routine testing yielded 9 new HIV cases (0.32% of those tested; 95% confidence interval, 0.16%-0.63%). Physician-directed testing would have missed most of these infections: 2 of the 785 patients identified by physicians for testing would have been newly diagnosed with HIV (0.25%; 95% confidence interval, 0.04%-1.0%). Of the 9 new HIV cases, 5 established HIV care, and their median CD4 count was 201 cells/µL (range, 71-429 cells/µL). CONCLUSIONS: Routine opt-out HIV screening was feasible and accepted by a majority of ED patients. The yield of this strategy only modestly exceeded what may have been observed with physician-directed testing.

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.

Randomized clinical trial of propofol versus ketamine for procedural sedation in the emergency department.

OBJECTIVES: The objective was to compare the occurrence of respiratory depression, adverse events, and recovery duration of propofol versus ketamine for use in procedural sedation in the emergency department (ED). METHODS: This was a randomized nonblinded prospective clinical trial of adult patients undergoing procedural sedation for painful procedures in the ED. Patients with pain before the procedure were treated with intravenous (IV) morphine sulfate until their pain was adequately treated at least 20 minutes before starting the procedure. Patients were randomized to receive either propofol 1 mg/kg IV followed by 0.5 mg/kg every 3 minutes as needed or ketamine 1.0 mg/kg IV followed by 0.5 mg/kg every 3 minutes as needed. Doses, vital signs, nasal end-tidal CO(2) (ETCO(2)), and pulse oximetry were recorded. Subclinical respiratory depression was defined as a change in ETCO(2) of >10 mm Hg, an oxygen saturation of <92% at any time, or an absent ETCO(2) waveform at any time. Clinical interventions 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. After the procedure, patients were asked if they experienced pain during the procedure and had recall of the procedure. Physicians were asked to describe any adverse events or the occurrence of recovery agitation. RESULTS: One-hundred patients were enrolled; 97 underwent sedation and were included in the analysis. Fifty patients received propofol and 47 received ketamine. Subclinical respiratory depression was seen in 20 of 50 patients in the propofol group and 30 of 47 patients in the ketamine group (p = 0.019, effect size 22.8%; 95% CI = 4.0% to 43.6%). Clinical interventions related to respiratory depression were used in 26 of 50 propofol patients and 19 of 47 ketamine patients (p = 0.253, effect size = -13.7%; 95% CI = -33.8% to 6.4%). The median times of the procedures were 11 minutes (range = 4 to 33 minutes) for the ketamine group versus 10 minutes (range = 5 to 33 minutes) for the propofol group (p = 0.256). The median time to return to baseline mental status after the procedure was completed was 14 minutes (range = 2 to 47 minutes) for the ketamine group and 5 minutes (range = 1 to 32 minutes) for the propofol group (p < 0.001). Pain during the procedure was reported by 3 of 50 patients in the propofol group and 1 of 47 patients in the ketamine group (effect size = -3.9%, 95% confidence interval [CI] = -11.9 to 4.1). Recall of some part of the procedure was reported by 4 of 50 patients in the propofol group and 6 of 47 patients in the ketamine group (effect size = 4.8%, 95% CI = -7.6% to 17.1%). Forty-eight of 50 procedures were successful in the propofol group and 43 of 47 in the ketamine group (p = 0.357, effect size = 0.3%; 95% CI = -7.8% to 8.4%). Recovery agitation was reported in 4 of 50 in the propofol group and 17 of 47 in the ketamine group (effect size = 28.2%, 95% CI = 12.4% to 43.9%). CONCLUSIONS: This study detected a higher rate of subclinical respiratory depression in patients in the ketamine group than the propofol group. There was no difference in the rate of clinical interventions related to respiratory depression, pain, or recall of the procedure between the groups. Recovery agitation was seen more frequently in patients receiving ketamine than in those receiving propofol. The time to regain baseline mental status was longer in the ketamine group than the propofol group. This study suggests that the use of either ketamine or propofol is safe and effective for procedural sedation in the ED.

Randomized clinical trial of propofol with and without alfentanil for deep procedural sedation in the emergency department.

OBJECTIVES: The objectives were to compare the efficacy, occurrence of adverse events, and recovery duration of propofol with and without alfentanil for use in procedural sedation in the emergency department (ED). METHODS: This was a randomized nonblinded prospective trial of adult patients undergoing procedural sedation for painful procedures in the ED. Patients with pain before the procedure were given intravenous (IV) morphine sulfate until their pain was adequately treated at least 20 minutes before starting the procedure. Patients received 1 mg/kg propofol either with or without a supplemental dose of 10 mug/kg alfentanil for deep procedural sedation. Doses, vital signs, nasal end-tidal CO(2) (ETCO(2)), pulse oximetry, and bispectral electroencephalographic (EEG) analysis scores were recorded. Subclinical respiratory depression was defined as a change in ETCO(2) of >10 mmHg, an oxygen saturation of <92% at any time, or an absent ETCO(2) 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. After the procedure, patients were asked if they experienced pain during the procedure or had recall of the procedure. RESULTS: A total of 150 patients were enrolled; 146 underwent sedation and were included in the analysis. Seventy-four patients received propofol, and 71 received propofol with alfentanil. No clinically significant complications were noted. Subclinical respiratory depression was seen in 24/74 patients in the propofol group and 30/71 patients in the propofol/alfentanil group (effect size = 9.8%, 95% CI = -5.8% to 25.5%). Clinical signs of respiratory depression included an increase in supplemental oxygen use in 25 of the 74 propofol patients and 31 of the 71 propofol/alfentanil patients (effect size 9.9%, 95% CI = -5.9% to 25.7%), the use of bag-valve mask apparatus in seven patients in the propofol group and 12 in the propofol/alfentanil group (effect size = 5.6%, 95% CI = -3.5% to 18.4%), airway repositioning in 13 propofol patients and 20 propofol/alfentanil patients (effect size = 10.6%, 95% CI = -3.0% to 24.2%), and stimulation to induce breathing in 11 propofol patients and 20 propofol/alfentanil patients (effect size = 13.3%, 95% CI = 0.1% to 26.5%). The total time of the procedure was longer for the alfentanil/propofol group (median = 11 minutes, range = 5-22 minutes) than for the propofol group (median = 9 minutes, range = 1 to 43 minutes; effect size = 1.93 minutes, 95% CI = 0.73 to 2.58, p = 0.02). Pain during the procedure was reported by 10 of the 74 patients in the propofol group and 7 of the 71 patients in the propofol/alfentanil group (effect size = 4.5%, 95% CI = -6.8% to 14.1%). Recall of some part of the procedure was reported by 12 patients in the propofol group and 9 in the propofol/alfentanil group (effect size = 3.5%, 95% CI = -7.9% to 15.0%). All procedures were successfully completed. CONCLUSIONS: The use of supplemental alfentanil with propofol for procedural sedation did not result in a difference in reported pain or recall immediately after the procedure. There was an increase in the proportion of patients who required stimulation to induce respiration during the procedure in patients who received propofol with supplemental alfentanil. The addition of supplemental opioid to procedural sedation with propofol does not appear beneficial.

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.