The use of inhaled nitrous oxide for analgesia in adult ED patients: a pilot study.

BACKGROUND: Oligoanalgesia challenges emergency department (ED) health care providers and remains an area of patient dissatisfaction. Nitrous oxide (NO) is a safe, quick-acting, and well-tolerated sedative agent with analgesic and anxiolytic properties that make it ideal for ED use. OBJECTIVES: We seek to test the effectiveness of a self-administered and self-contained NO device as an analgesic agent in the ED and assess patient and staff satisfaction with this method. METHODS: We enrolled 85 patients 18 years and older in a prospective observational study of patients presenting to the ED with moderate to severe pain (≥30 mm on a 100-mm visual analog scale). Subjects received a mixture of 50% NO via a self-administered portable delivery device. Primary outcome was the reduction in baseline pain scores at 20, 40, and 60 minutes. Secondary outcomes were patient, nurse, and physician satisfaction as reported on a brief satisfaction questionnaire. RESULTS: There was a significant reduction in mean pain scores from baseline to 20 minutes that was sustained through the 60-minute period. Most subjects (93%; 95% confidence interval [CI], 85%-97%) and nurses (97%; 95% CI, 90%-99%) reported that the NO delivery system was easy to use and were satisfied with the level of pain relief and would use NO in the future (82%; 95% CI, 73%-89%). Physicians and nurses were also satisfied with the analgesic effects of NO (82%; 95% CI, 73%-89%). CONCLUSIONS: The portable NO device is an effective analgesia adjunct for ED patients presenting with painful conditions, and patients, ED nurses, and emergency physicians are satisfied with its use. Nitrous oxide coupled with a nurse-driven analgesia protocol may provide a novel solution for improvement in ED analgesia rates and overall patient satisfaction with ED pain management.

MicroRNA circulating in the early aftermath of motor vehicle collision predict persistent pain development and suggest a role for microRNA in sex-specific pain differences.

BACKGROUND: Molecular mediators influencing the transition from acute to persistent musculoskeletal pain following common stress exposures such as motor vehicle collision (MVC) remain poorly understood. In this exploratory, proof of concept study, we compared circulating microRNA (miRNA) expression profiles in the early aftermath of MVC among individuals who did and did not subsequently develop persistent pain. Blood RNA samples were obtained from African American individuals (n = 53) who presented to the emergency department after MVC and were discharged to home after evaluation. The presence or absence of severe pain in the axial region, the most common and morbid region in which post-MVC pain occurs, was assessed 6 weeks following MVC via standardized questionnaire. miRNA expression was determined using miRNA-sequencing; nonparametric analyses were used to compare miRNA expression levels among individuals with and without persistent pain. RESULTS: Thirty-two mature miRNA were differentially expressed (p < 0.05) in those with and without severe axial pain at 6 weeks. miR-135a-5p, a regulator of the serotonin receptor that is known to be stress-responsive, differed most significantly between groups (p = 3 × 10(-4)). This miRNA, and miR-3613-3p (p = 0.001) survived correction for multiple testing (FDR = 0.15) in this small sample. Interestingly, differentially expressed miRNA were enriched for X chromosome location. In secondary analyses, the eight X chromosome miRNA were (a) more significantly associated with axial pain in women than men, (b) expressed more highly in the peripheral blood of women than men, and (c) predicted in pathway analyses (DIANA miRPath v 2.0) to regulate neuronal and neuroendocrine pathways previously implicated in various pain pathologies. CONCLUSIONS: These results show that circulating miRNA predict persistent severe axial pain after MVC and suggest that they may be involved in the pathogenesis of post-traumatic musculoskeletal pain. However, further studies are needed to determine if these miRNA play a direct causal role.

MicroRNA 320a Predicts Chronic Axial and Widespread Pain Development Following Motor Vehicle Collision in a Stress-Dependent Manner.

Study Design Prospective human cohort study combined with molecular studies. Background A microRNA is a small, noncoding RNA molecule that can play a role in disease onset. Recent studies found that circulating levels of microRNA 320a (miR-320a) are associated with musculoskeletal pain conditions and that miR-320a is stress responsive. Objectives To investigate whether circulating expression levels of miR-320a in the peritraumatic period predict persistent axial musculoskeletal pain 6 months after motor vehicle collision (MVC). Methods We evaluated whether (1) circulating miR-320a and related members of the miR-320a family predict axial musculoskeletal pain and other musculoskeletal pain outcomes 6 months following MVC, and (2) miR-320a regulates stress system and pain-related transcripts in cell culture. Given the wealth of data suggesting that biological mechanisms influencing pain outcomes are often sex and/or stress dependent, interactions between miR-320a, stress, and sex were evaluated. Results In primary analyses (n = 69), a significant crossover interaction was observed between the influence of circulating miR-320a and peritraumatic distress (ß = -0.01, P = .002) on post-MVC axial musculoskeletal pain. Reduced peritraumatic miR-320a expression levels predicted axial musculoskeletal pain in distressed individuals (ß = -0.12, P = .006) but not nondistressed individuals. In secondary analyses, miR-320a predicted widespread musculoskeletal pain, and related members of the miR-320a family also predicted axial and widespread musculoskeletal pain. In cell culture, miR-320a bound stress and pain-associated 3'UTR transcripts (FKBP5, ADCYAP1, PER2, and NR3C1). Conclusion These data suggest that miR-320a may help mediate regional and widespread changes in pain sensitivity after MVC. J Orthop Sports Phys Ther 2016;46(10):911-919. doi:10.2519/jospt.2016.6944.

Methodology of AA CRASH: a prospective observational study evaluating the incidence and pathogenesis of adverse post-traumatic sequelae in African-Americans experiencing motor vehicle collision.

INTRODUCTION: A motor vehicle collision (MVC) is one of the most common life-threatening events experienced by individuals living in the USA. While most individuals recover following MVC, a significant proportion of individuals develop adverse post-traumatic sequelae such as post-traumatic stress disorder or persistent musculoskeletal pain. Adverse post-traumatic sequelae are common, morbid and costly public health problems in the USA and other industrialised countries. The pathogenesis of these disorders following MVC remains poorly understood. In the USA, available data suggest that African-Americans experience an increased burden of adverse post-traumatic sequelae after MVC compared to European Americans, but to date no studies examining the pathogenesis of these disorders among African-Americans experiencing MVC have been performed. METHODS AND ANALYSIS: The African-American CRASH (AA CRASH) study is an NIH-funded, multicentre, prospective study that enrols African-Americans (n=900) who present to the emergency department (ED) within 24 hours of MVC. Participants are enrolled at 13 ED sites in the USA. Individuals who are admitted to the hospital or who report a fracture or tissue injury are excluded. Participants complete a detailed ED interview that includes an assessment of crash history, current post-traumatic symptoms and health status prior to the MVC. Blood samples are also collected in the ED using PAXgene DNA and PAXgene RNA tubes. Serial mixed-mode assessments 6 weeks, 6 months and 1 year after MVC include an assessment of adverse sequelae, general health status and health service utilisation. The results from this study will provide insights into the incidence and pathogenesis of persistent pain and other post-traumatic sequelae in African-Americans experiencing MVC. ETHICS AND DISSEMINATION: AA CRASH has ethics approval in the USA, and the results will be published in a peer-reviewed journal.

Phencyclidine Intoxication Case Series Study.

BACKGROUND: Phencyclidine (PCP) is a synthetic compound derived from piperidine and used as an anesthetic and hallucinogenic. Little has been recently published regarding the clinical presentation of PCP intoxication. PCP use as a recreational drug is resurging. OBJECTIVE: Our objective was to describe clinical findings in patients presenting to the emergency department (ED) under the influence of PCP. METHODS: This was a case series study conducted at a tertiary care center with an annual census of 100,000 patients/year. Emergency physicians, residents, physician assistants, and research assistants identified patients with possible PCP intoxication. Self-reported PCP use, report by bystanders or Emergency Medical Services (EMS) staff, was used in this process. A structured data collection form was completed, documenting both clinical and behavioral events observed by the treating team during the ED visit. RESULTS: We collected data on 219 patients; 184 were analyzed; two patients were excluded secondary to incomplete data. The mean age of patients was 32.5 years (±7 years) with 65.2 % being males. PCP use was self-reported by 60.3 % of patients. Of the 184 patients, 153 (83.1 %) received a urine drug screen (UDS); 152 (98.7 %) were positive for PCP. On arrival, 78.3 % of patients were awake and alert, and 51.6 % were oriented to self, time/date, and place. Mean physiological parameters were the following: heart rate 101.1 bpm (±24.3), RR 18.9 bpm (±3.4), BP 146.3 (±19.4)/86.3 (±14.0) mmHg, 36.9° C (±0.5), and pulse oximetry 98.2 % (±1.9). Clinical findings were the following: retrograde amnesia in 46 (25 %), horizontal nystagmus in 118 (64.1 %), vertical nystagmus in 90 (48.9 %), hypertension in 87 (47.3 %), and agitation in 71 (38.6 %). Concomitant use of at least one other substance was reported by 99 (53.8 %) patients. The mean length of stay in the ED for all subjects was 261.1 (±172.8) minutes. Final disposition for 152 (82.6 %) patients was to home. Of the 184 patients, 14 (7.6 %) required admission; 12 were referred to Crisis Response Center. CONCLUSION: Patients with PCP intoxication tended to be young males. The prevalent clinical signs and symptoms were the following: retrograde amnesia, nystagmus, hypertension, and psychomotor agitation. Co-use of other substances was the norm. Most patients presenting to the ED with PCP intoxication do well and can be discharged home after a period of observation.

Unrecognized hypoxia and respiratory depression in emergency department patients sedated for psychomotor agitation: pilot study.

INTRODUCTION: The incidence of respiratory depression in patients who are chemically sedated in the emergency department (ED) is not well understood. As the drugs used for chemical restraint are respiratory depressants, improving respiratory monitoring practice in the ED may be warranted. The objective of this study is to describe the incidence of respiratory depression in patients chemically sedated for violent behavior and psychomotor agitation in the ED. METHODS: Adult patients who met eligibility criteria with psychomotor agitation and violent behavior who were chemically sedated were eligible. SpO2 and ETCO2 (end-tidal CO2) was recorded and saved every 5 seconds. Demographic data, history of drug or alcohol abuse, medical and psychiatric history, HR and BP every 5 minutes, any physician intervention for hypoxia or respiratory depression, or adverse events were also recorded. We defined respiratory depression as an ETCO2 of ≥50 mmHg, a change of 10% above or below baseline, or a loss of waveform for ≥15 seconds. Hypoxia was defined as a SpO2 of ≤93% for ≥15 seconds. RESULTS: We enrolled 59 patients, and excluded 9 because of ≥35% data loss. Twenty-eight (28/50) patients developed respiratory depression at least once during their chemical restraint (56%, 95% CI 42-69%); the median number of events was 2 (range 1-6). Twenty-one (21/50) patients had at least one hypoxic event during their chemical restraint (42%, 95% CI 29-55%); the median number of events was 2 (range 1-5). Nineteen (19/21) (90%, 95% CI 71-97%) of the patients that developed hypoxia had a corresponding ETCO2 change. Fifteen (15/19) (79%, 95% CI 56-91%) patients who became hypoxic met criteria for respiratory depression before the onset of hypoxia. The sensitivity of ETCO2 to predict the onset of a hypoxic event was 90.48% (95% CI: 68-98%) and specificity 69% (95% CI: 49-84%). Five patients received respiratory interventions from the healthcare team to improve respiration [Airway repositioning: (2), Verbal stimulation: (3)]. Thirty-seven patients had a history of concurrent drug or alcohol abuse and 24 had a concurrent psychiatric history. None of these patients had a major adverse event. CONCLUSION: About half of the patients in this study exhibited respiratory depression. Many of these patients went on to have a hypoxic event, and most of the incidences of hypoxia were preceded by respiratory depression. Few of these events were recognized by their treating physicians.