Adverse events following emergent prehospital sedation of patients with behavioral emergencies: A retrospective cohort study.

Background: Patients presenting to emergency medical services (EMS) with behavioral emergencies may require emergent sedation to facilitate care, but concerns about sedation-related adverse events (AEs) exist. This study aimed to describe the frequency of AEs following emergent prehospital sedation with three types of sedative agents: ketamine, benzodiazepines and antipsychotics. Methods: This retrospective cohort study included patients ≥ 15 years who presented to 1031U.S. EMS agencies in calendar year 2019 with behavioral emergencies necessitating emergent prehospital sedation. Serious AEs (SAE) included cardiac arrest, invasive airway placement, and severe oxygen desaturation (<75%). Less-serious AEs included positive pressure ventilation, any oxygen desaturation (<90%), oropharyngeal or nasopharyngeal airway placement, and suctioning. The need for additional sedation was also assessed. Findings: Of 7973 patients, 1996 received ketamine; 4137 received a benzodiazepine; 1532 received an antipsychotic agent; and 308 received an indeterminant agent. Cardiac arrest occurred in 11 patients (0·1%) and any SAE occurred in 165 patients (2·1%). Invasive airway placement was more frequent with ketamine (40, 2·0%) compared with benzodiazepines (17, 0·4%) or antipsychotics (3, 0·2%). Oxygen desaturation below 75% also occurred more frequently with ketamine (51, 2·6%) than with benzodiazepines (52, 1·3%) or antipsychotics (14, 0·9%). Patients sedated with ketamine were less likely to require additional sedation. Propensity-matching to minimize potential confounding between patient condition, sedative choice and AEs did not meaningfully alter the results. Interpretation: Although SAEs were rare among patients receiving emergent prehospital sedation, prehospital clinicians should remain mindful of the potential risks and monitor patients closely. Funding: None.

A Pilot Study to Assess Urban, Fire-Based Paramedic Accuracy in Identification of Anatomical Landmarks Necessary for Cricothyrotomy and Needle Chest Decompression Using Live Patient Models.

BACKGROUND: Cricothyrotomy and chest needle decompression (NDC) have a high failure and complication rate. This article sought to determine whether paramedics can correctly identify the anatomical landmarks for cricothyrotomy and chest NDC. METHODS: A prospective study using human models was performed. Paramedics were partnered and requested to identify the location for cricothyrotomy and chest NDC (both mid-clavicular and anterior axillary sites) on each other. A board-certified or board-eligible emergency medicine physician timed the process and confirmed location accuracy. All data were collected de-identified. Descriptive analysis was performed on continuous data; chi-square was used for categorical data. RESULTS: A total of 69 participants were recruited, with one excluded for incomplete data. The paramedics had a range of six to 38 (median 14) years of experience. There were 28 medical training officers (MTOs) and 41 field paramedics. Cricothyroidotomy location was correctly identified in 56 of 68 participants with a time to identification range of 2.0 to 38.2 (median 8.6) seconds. Chest NDC (mid-clavicular) location was correctly identified in 54 of 68 participants with a time to identification range of 3.4 to 25.0 (median 9.5) seconds. Chest NDC (anterior axillary) location was correctly identified in 43 of 68 participants with a time to identification range of 1.9 to 37.9 (median 9.6) seconds. Chi-square (2-tail) showed no difference between MTO and field paramedic in cricothyroidotomy site (P = .62), mid-clavicular chest NDC site (P = .21), or anterior axillary chest NDC site (P = .11). There was no difference in time to identification for any procedure between MTO and field paramedic. CONCLUSION: Both MTOs and field paramedics were quick in identifying correct placement of cricothyroidotomy and chest NDC location sites. While time to identification was clinically acceptable, there was also a significant proportion that did not identify the correct landmarks.

Dispatcher Identification of Out-of-Hospital Cardiac Arrest and Neurologically Intact Survival: A Retrospective Cohort Study.

INTRODUCTION: To date, there are no published data on the association of patient-centered outcomes and accurate public-safety answering point (PSAP) dispatch in an American population. The goal of this study is to determine if PSAP dispatcher recognition of out-of-hospital cardiac arrest (OHCA) is associated with neurologically intact survival to hospital discharge. METHODS: This retrospective cohort study is an analysis of prospectively collected Quality Assurance/Quality Improvement (QA/QI) data from the San Antonio Fire Department (SAFD; San Antonio, Texas USA) OHCA registry from January 2013 through December 2015. Exclusion criteria were: Emergency Medical Services (EMS)-witnessed arrest, traumatic arrest, age <18 years old, no dispatch type recorded, and missing outcome data. The primary exposure was dispatcher recognition of cardiac arrest. The primary outcome was neurologically intact survival (defined as Cerebral Performance Category [CPC] 1 or 2) to hospital discharge. The secondary outcomes were: bystander cardiopulmonary resuscitation (CPR), automated external defibrillator (AED) use, and prehospital return of spontaneous return of circulation (ROSC). RESULTS: Of 3,469 consecutive OHCA cases, 2,569 cases were included in this analysis. The PSAP dispatched 1,964/2,569 (76.4%) of confirmed OHCA cases correctly. The PSAP dispatched 605/2,569 (23.6%) of confirmed OHCA cases as another chief complaint. Neurologically intact survival to hospital discharge occurred in 99/1,964 (5.0%) of the recognized cardiac arrest group and 28/605 (4.6%) of the unrecognized cardiac arrest group (OR = 1.09; 95% CI, 0.71-1.70). Bystander CPR occurred in 975/1,964 (49.6%) of the recognized cardiac arrest group versus 138/605 (22.8%) of the unrecognized cardiac arrest group (OR = 3.34; 95% CI, 2.70-4.11). CONCLUSION: This study found no association between PSAP dispatcher identification of OHCA and neurologically intact survival to hospital discharge. Dispatcher identification of OHCA remains an important, but not singularly decisive link in the OHCA chain of survival.

Prehospital Double Sequential Defibrillation: A Matched Case-Control Study.

OBJECTIVES: The goal of our study was to determine whether prehospital double sequential defibrillation (DSD) is associated with improved survival to hospital admission in the setting of refractory ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT). METHODS: This project is a matched case-control study derived from prospectively collected quality assurance/quality improvement data obtained from the San Antonio Fire Department out-of-hospital cardiac arrest (OHCA) database between January 2013 and December 2015. The cases were defined as OHCA patients with refractory VF/pVT who survived to hospital admission. The control group was defined as OHCA patients with refractory VF/pVT who did not survive to hospital admission. The primary variable in our study was prehospital DSD. The primary outcome of our study was survival to hospital admission. RESULTS: Of 3,469 consecutive OHCA patients during the study period, 205 OHCA patients met the inclusion criterion of refractory VF/pVT. Using a predefined algorithm, two blinded researchers identified 64 unique cases and matched them with 64 unique controls. Survival to hospital admission occurred in 48.0% of DSD patients and 50.5% of the conventional therapy patients (p > 0.99; odds ratio = 0.91, 95% confidence interval = 0.40-2.1). CONCLUSION: Our matched case-control study on the prehospital use of DSD for refractory VF/pVT found no evidence of associated improvement in survival to hospital admission. Our current protocol of considering prehospital DSD after the third conventional defibrillation in OHCA is ineffective.

Stop the Bleed: The Effect of Hemorrhage Control Education on Laypersons' Willingness to Respond During a Traumatic Medical Emergency.

BACKGROUND: The "Stop the Bleed" campaign advocates for non-medical personnel to be trained in basic hemorrhage control. However, it is not clear what type of education or the duration of instruction needed to meet that requirement. The objective of this study was to determine the impact of a brief hemorrhage control educational curriculum on the willingness of laypersons to respond during a traumatic emergency. METHODS: This "Stop the Bleed" education initiative was conducted by the University of Texas Health San Antonio Office of the Medical Director (San Antonio, Texas USA) between September 2016 and March 2017. Individuals with formal medical certification were excluded from this analysis. Trainers used a pre-event questionnaire to assess participants knowledge and attitudes about tourniquets and responding to traumatic emergencies. Each training course included an individual evaluation of tourniquet placement, 20 minutes of didactic instruction on hemorrhage control techniques, and hands-on instruction with tourniquet application on both adult and child mannequins. The primary outcome in this study was the willingness to use a tourniquet in response to a traumatic medical emergency. RESULTS: Of 236 participants, 218 met the eligibility criteria. When initially asked if they would use a tourniquet in real life, 64.2% (140/218) responded "Yes." Following training, 95.6% (194/203) of participants responded that they would use a tourniquet in real life. When participants were asked about their comfort level with using a tourniquet in real life, there was a statistically significant improvement between their initial response and their response post training (2.5 versus 4.0, based on 5-point Likert scale; P<.001). CONCLUSION: In this hemorrhage control education study, it was found that a short educational intervention can improve laypersons' self-efficacy and reported willingness to use a tourniquet in an emergency. Identified barriers to act should be addressed when designing future hemorrhage control public health education campaigns. Community education should continue to be a priority of the "Stop the Bleed" campaign. Ross EM , Redman TT , Mapp JG , Brown DJ , Tanaka K , Cooley CW , Kharod CU , Wampler DA . Stop the bleed: the effect of hemorrhage control education on laypersons' willingness to respond during a traumatic medical emergency. Prehosp Disaster Med. 2018;33(2):127-132.

The Tourniquet Gap: A Pilot Study of the Intuitive Placement of Three Tourniquet Types by Laypersons.

BACKGROUND: The "Stop the Bleed" campaign in the United States advocates for nonmedical personnel to be trained in basic hemorrhage control and that "bleeding control kits" be available in high-risk areas. However, it is not clear which tourniquets are most effective in the hands of laypersons. OBJECTIVES: The objective of this pilot study was to determine which tourniquet type was the most intuitive for a layperson to apply correctly. METHODS: This project is a randomized study derived from a "Stop the Bleed" education initiative conducted between September 2016 and March 2017. Novice tourniquet users were randomized to apply one of three commercially available tourniquets (Combat Action Tourniquet [CAT; North American Rescue, LLC, Greer, SC], Ratcheting Medical Tourniquet [RMT; m2 Inc., Winooski, VT], or Stretch Wrap and Tuck Tourniquet [SWAT-T; TEMS Solutions, LLC, Salida, CO]) in a controlled setting. Individuals with formal medical certification, prior military service, or prior training with tourniquets were excluded. The primary outcome of this study was successful tourniquet placement. RESULTS: Of 236 possible participants, 198 met the eligibility criteria. Demographics were similar across groups. The rates of successful tourniquet application for the CAT, RMT, and SWAT-T were 16.9%, 23.4%, and 10.6%, respectively (p = 0.149). The most common causes of application failure were: inadequate tightness (74.1%), improper placement technique (44.4%), and incorrect positioning (16.7%). CONCLUSION: Our pilot study on the intuitive nature of applying commercially available tourniquets found unacceptably high rates of failure. Large-scale community education efforts and manufacturer improvements of tourniquet usability by the lay public must be made before the widespread dissemination of tourniquets will have a significant public health effect.

Use of intrathoracic pressure regulation therapy in breathing patients for the treatment of hypotension secondary to trauma.

BACKGROUND: Intrathoracic pressure regulation (IPR) therapy has been shown to increase blood pressure in hypotensive patients. The potential value of this therapy in patients with hypotension secondary to trauma with bleeding is not well understood. We hypothesized that IPR would non-invasively and safely enhance blood pressure in spontaneously breathing patients with trauma-induced hypotension. METHODS: This prospective observational cohort study assessed vital signs from hypotensive patients with a systolic blood pressure (SBP) ≤90 mmHg secondary to trauma treated with IPR (ResQGARD™, ZOLL Medical) by pre-hospital emergency medical personnel in three large US metropolitan areas. Upon determination of hypotension, facemask-based IPR was initiated as long as bleeding was controlled. Vital signs were recorded before, during, and after IPR. An increased SBP with IPR use was the primary study endpoint. Device tolerance and ease of use were also reported. RESULTS: A total of 54 patients with hypotension secondary to trauma were treated from 2009 to 2016. The mean ± SD SBP increased from 80.9 ± 12.2 mmHg to 106.6 ± 19.2 mmHg with IPR (p < 0.001) and mean arterial pressures (MAP) increased from 62.2 ± 10.5 mmHg to 81.9 ± 16.6 mmHg (p < 0.001). There were no significant changes in mean heart rate or oxygen saturation. Approximately 75% of patients reported moderate to easy tolerance of the device. There were no safety concerns or reported adverse events. CONCLUSIONS: These findings support the use of IPR to treat trauma-induced hypotension as long as bleeding has been controlled.

Dual defibrillation in out-of-hospital cardiac arrest: A retrospective cohort analysis.

STUDY OBJECTIVES: The goal of our study is to determine if prehospital dual defibrillation (DD) is associated with better neurologically intact survival in out-of-hospital cardiac arrest. METHODS: This study is a retrospective cohort analysis of prospectively collected Quality Assurance/Quality Improvement data from a large urban fire based EMS system out-of-hospital cardiac arrest (OHCA) database between Jan 2013 and Dec 2015. Our inclusion criteria were administration of DD or at least four conventional 200J defibrillations for cases of recurrent and refractory ventricular fibrillation (VF). We excluded any case with incomplete data. The primary outcome for our study was neurologically intact survival (defined as Cerebral Performance Category 1 and 2). RESULTS: A total of 3470 cases of OHCA were treated during the time period of Jan 2013 to Dec 2015. There were 302 cases of recurrent and refractory VF identified. Twenty-three cases had incomplete data. Of the remaining 279 cases, 50 were treated with DD and 229 received standard single shock 200J defibrillations. There was no statistically significant difference in the primary outcome of neurologically intact survival between the DD group (6%) and the standard defibrillation group (11.4%) (p=0.317) (OR 0.50, 95% CI 0.15-1.72). CONCLUSION: Our retrospective cohort analysis on the prehospital use of DD in OHCA found no association with neurologically intact survival. Case-control studies are needed to further evaluate the efficacy of DD in the prehospital setting.

The long spine board does not reduce lateral motion during transport--a randomized healthy volunteer crossover trial.

OBJECTIVE: For thirty years, emergency medical services agencies have emphasized limiting spinal motion during transport of the trauma patient to the emergency department. The long spine board (LSB) has been the mainstay of spinal motion restriction practices, despite the paucity of data to support its use. The purpose of this study was to determine reduction in lateral motion afforded by the LSB in comparison to the stretcher mattress alone. METHODS: This was a randomized controlled crossover trial where healthy volunteer subjects were randomly assigned to either LSB or stretcher mattress only. All subjects were fitted with a rigid cervical collar, secured to the assigned device (including foam head blocks), and driven on a closed course with prescribed turns at a low speed (<20 mph). Upon completion, the subjects were then secured to the other device and the course was repeated. Each subject was fitted with 3 graduated-paper disks (head, chest, hip). Lasers were affixed to a scaffold attached to the stretcher bridging over the patient and aimed at the center of the concentric graduations on the disks. During transport, the degree of lateral movement was recorded during each turn. Significance was determined by t test. RESULTS: In both groups, the head demonstrated the least motion with 0.46±0.4-cm mattress and 0.97±0.7-cm LSB (P≤ .0001). The chest and hip had lateral movement with chest 1.22±0.9-cm mattress and 2.22±1.4-cm LSB (P≤ .0001), and the hip 1.20±0.9-cm mattress and 1.88±1.2-cm LSB (P≤ .0001), respectively. In addition, lateral movement had a significant direct correlation with body mass index. CONCLUSION: The stretcher mattress significantly reduced lateral movement during transport.

Time to epinephrine in out-of-hospital cardiac arrest: A retrospective analysis of intraosseous versus intravenous access.

INTRODUCTION: The 2015 advanced cardiac life support update continues to advocate administering epinephrine during cardiac arrest. The goal of our study is to determine if prehospital intraosseous (IO) access results in shorter time to epinephrine than prehospital peripheral intravenous (PIV) access. METHODS: The out-of-hospital cardiac arrest (OHCA) database of a large, urban, fire-based emergency medical services system was searched for consecutive cases of OHCA between January 2013 and December 2015. The time to the first dose of epinephrine was calculated and compared by vascular access technique utilized (PIV or IO). Descriptive statistics were used to report first pass success and IO complications. RESULTS: A total of 3,470 OHCA cases were treated during the study period. Of those cases, 2,656 met our inclusion criteria. There were 2,601 cases of IO usage and 55 cases of PIV usage. The mean time from arrival at the patient's side to administration of the first dose of epinephrine was 5.0 minutes (95% CI: 4.7 minutes, 5.4 minutes) for the IO group and 8.8 minutes (95% CI: 6.6 minutes, 10.9 minutes) for the PIV group (p<0.001). There were a total of 2,879 IO attempts with 2,753 IOs successfully placed in 2,601 patients. The first pass IO success rate was 95.6 percent (2,753/2,879). CONCLUSION: In the setting of OHCA, the time to administer the first dose of epinephrine was faster in the IO access group when compared to PIV access group. The prehospital use of IO vascular access for time-dependent medical conditions is recommended.

Capnography for the nonintubated patient in the emergency setting.

BACKGROUND: Multiple studies illustrate the benefits of waveform capnography in the nonintubated patient. This type of monitoring is routinely used by anesthesia providers to recognize ventilation issues. Its role in the administration of deep sedation is well defined. Prehospital providers embrace the ease and benefit of monitoring capnography. Currently, few community-based emergency physicians utilize capnography with the nonintubated patient. OBJECTIVE: This article will identify clinical areas where monitoring end-tidal carbon dioxide is beneficial to the emergency provider and patient. DISCUSSION: Capnography provides real-time data to aid in the diagnosis and patient monitoring for patient states beyond procedural sedation and bronchospasm. Capnographic changes provide valuable information in such processes as diabetic ketoacidosis, seizures, pulmonary embolism, and malignant hyperthermia. CONCLUSIONS: Capnography is a quick, low-cost method of enhancing patient safety with the potential to improve the clinician's diagnostic power.

Promoting early diagnosis of hemodynamic instability during simulated hemorrhage with the use of a real-time decision-assist algorithm.

BACKGROUND: This study aimed to test the hypothesis that the addition of a real-time decision-assist machine learning algorithm by emergency medical system personnel could shorten the time needed to identify an unstable patient during a hemorrhage profile as compared with vital sign information alone. METHODS: Fifty emergency medical team-paramedics from a large, urban fire department participated as subjects. Subjects viewed a monitor screen on two occasions as follows: (1) display of standard vital signs alone and (2) with the addition of an index (Compensatory Reserve Index) associated with estimated central blood volume status. The subjects were asked to push a computer key at any point in the sequence they believed the patient had become unstable based on information provided by the monitor screen. The average difference in time to identify hemodynamic instability between experimental and control groups was assessed by paired, two-tailed t test and reported with 95% confidence intervals (95% CI). RESULTS: The mean (SD) amount of time required to identify an unstable patient was 18.3 (4.1) minutes (95% CI, 17.2-19.4 minutes) without the algorithm and 10.7 (4.2) minutes (95% CI, 9.5-11.9 minutes) with the algorithm (p < 0.001). CONCLUSION: In a simulated patient encounter involving uncontrolled hemorrhage, the use of a monitor that estimates central blood volume loss was associated with early identification of impending hemodynamic instability. Physiologic monitors capable of early identification and estimation of the physiologic capacity to compensate for blood loss during hemorrhage may enable optimal guidance for hypotensive resuscitation. They may also help identify casualties benefitting from forward administration of plasma, antifibrinolytics and procoagulants in a remote damage-control resuscitation model.

Programmable bio-nanochip technology for the diagnosis of cardiovascular disease at the point-of-care.

Cardiovascular disease remains the leading cause of death in the world and continues to serve as the major contributor to healthcare costs. Likewise, there is an ever-increasing need and demand for novel and more efficient diagnostic tools for the early detection of cardiovascular disease, especially at the point-of-care (POC). This article reviews the programmable bio-nanochip (P-BNC) system, a new medical microdevice approach with the capacity to deliver both high performance and reduced cost. This fully integrated, total analysis system leverages microelectronic components, microfabrication techniques, and nanotechnology to noninvasively measure multiple cardiac biomarkers in complex fluids, such as saliva, while offering diagnostic accuracy equal to laboratory-confined reference methods. This article profiles the P-BNC approach, describes its performance in real-world testing of clinical samples, and summarizes new opportunities for medical microdevices in the field of cardiac diagnostics.

Cardiac arrest survival is rare without prehospital return of spontaneous circulation.

BACKGROUND: Emergency medical services (EMS) are crucial in the management of out-of-hospital cardiac arrest (OHCA). Despite accepted termination-of-resuscitation criteria, many patients are transported to the hospital without achieving field return of spontaneous circulation (ROSC). OBJECTIVE: We examine field ROSC influence on OHCA survival to hospital discharge in two large urban EMS systems. METHODS: A retrospective analysis of prospectively collected data was conducted. Data collection is a component of San Antonio Fire Department's comprehensive quality assurance/quality improvement program and Cincinnati Fire Department's participation in the Cardiac Arrest Registry to Enhance Survival (CARES) project. Attempted resuscitations of medical OHCA and cardiac OHCA for San Antonio and Cincinnati, respectively, from 2008 to 2010 were analyzed by city and in aggregate. RESULTS: A total of 2,483 resuscitation attempts were evaluated. Age and gender distributions were similar between cities, but ethnic profiles differed. Cincinnati had 17% (p = 0.002) more patients with an initial shockable rhythm and was more likely to initiate transport before field ROSC. Overall survival to hospital discharge was 165 of 2,483 (6.6%). More than one-third (894 of 2,483, 36%) achieved field ROSC. Survival with field ROSC was 17.2% (154 of 894) and without field ROSC was 0.69% (11 of 1,589). Of the 11 survivors transported prior to field ROSC, nine received defibrillation by EMS. No asystolic patient survived to hospital discharge without field ROSC. CONCLUSION: Survival to hospital discharge after OHCA is rare without field ROSC. Resuscitation efforts should focus on achieving field ROSC. Transport should be reserved for patients with field ROSC or a shockable rhythm.

Roles of the redox-active disulfide and histidine residues forming a catalytic dyad in reactions catalyzed by 2-ketopropyl coenzyme M oxidoreductase/carboxylase.

NADPH:2-ketopropyl-coenzyme M oxidoreductase/carboxylase (2-KPCC), an atypical member of the disulfide oxidoreductase (DSOR) family of enzymes, catalyzes the reductive cleavage and carboxylation of 2-ketopropyl-coenzyme M [2-(2-ketopropylthio)ethanesulfonate; 2-KPC] to form acetoacetate and coenzyme M (CoM) in the bacterial pathway of propylene metabolism. Structural studies of 2-KPCC from Xanthobacter autotrophicus strain Py2 have revealed a distinctive active-site architecture that includes a putative catalytic triad consisting of two histidine residues that are hydrogen bonded to an ordered water molecule proposed to stabilize enolacetone formed from dithiol-mediated 2-KPC thioether bond cleavage. Site-directed mutants of 2-KPCC were constructed to test the tenets of the mechanism proposed from studies of the native enzyme. Mutagenesis of the interchange thiol of 2-KPCC (C82A) abolished all redox-dependent reactions of 2-KPCC (2-KPC carboxylation or protonation). The air-oxidized C82A mutant, as well as wild-type 2-KPCC, exhibited the characteristic charge transfer absorbance seen in site-directed variants of other DSOR enzymes but with a pK(a) value for C87 (8.8) four units higher (i.e., four orders of magnitude less acidic) than that for the flavin thiol of canonical DSOR enzymes. The same higher pK(a) value was observed in native 2-KPCC when the interchange thiol was alkylated by the CoM analog 2-bromoethanesulfonate. Mutagenesis of the flavin thiol (C87A) also resulted in an inactive enzyme for steady-state redox-dependent reactions, but this variant catalyzed a single-turnover reaction producing a 0.8:1 ratio of product to enzyme. Mutagenesis of the histidine proximal to the ordered water (H137A) led to nearly complete loss of redox-dependent 2-KPCC reactions, while mutagenesis of the distal histidine (H84A) reduced these activities by 58 to 76%. A redox-independent reaction of 2-KPCC (acetoacetate decarboxylation) was not decreased for any of the aforementioned site-directed mutants. We interpreted and rationalized these results in terms of a mechanism of catalysis for 2-KPCC employing a unique hydrophobic active-site architecture promoting thioether bond cleavage and enolacetone formation not seen for other DSOR enzymes.

No deaths associated with patient refusal of transport after naloxone-reversed opioid overdose.

INTRODUCTION: Naloxone is widely used in the treatment and reversal of opioid overdose. Most emergency medical services (EMS) systems administer naloxone by standing order, and titrate only to reverse respiratory depression without fully reversing sedation. Some EMS systems routinely administer sufficient naloxone to fully reverse the effects of opioid overdose. Frequently patients refuse further medical evaluation or intervention, including transport. OBJECTIVES: The purpose of this study was to evaluate the safety of this practice and determine whether increased mortality is associated with full reversal of opioids. As a component of a comprehensive quality assurance initiative, we assessed mortality during the 48 hours after patients received naloxone to reverse opioid overdose followed by patient-initiated refusal of transportation. METHODS: The setting was a large urban fire-based EMS system. Investigators provided the Bexar County Medical Examiner's Office (MEO) with a list of patients who were treated by the San Antonio Fire Department with naloxone, and not transported. Inclusion criteria were administration of naloxone and patient-initiated refusal. Patient dispositions also included aid only, referral to the MEO, or referral to law enforcement. The list was then compared with the MEO database. A chart review was completed on all patients treated and subsequently presented to the MEO within two days. A secondary time period of 30 days was also assessed. RESULTS: The list identified 592 patients treated with naloxone and not transported to the emergency department. Five-hundred fifty-two patients received naloxone and refused transport or were not transported. The remaining 40 patients all presented to EMS in cardiac arrest, naloxone was administered during the course of resuscitation, and subsequent efforts were terminated in the field. None of the patients receiving naloxone with a subsequent patient-initiated refusal were examined at the MEO within the two-day end point. The 30-day assessment revealed that nine individuals were treated with naloxone and subsequently died, but the shortest time interval between date of service and date of death was four days. CONCLUSION: The primary outcome was that no patients who were treated with naloxone for opioid overdose and then refused care were examined by the MEO within a 48-hour time frame.

Insights into the nitric oxide reductase mechanism of flavodiiron proteins from a flavin-free enzyme.

Flavodiiron proteins (FDPs) catalyze reductive scavenging of dioxygen and nitric oxide in air-sensitive microorganisms. FDPs contain a distinctive non-heme diiron/flavin mononucleotide (FMN) active site. Alternative mechanisms for the nitric oxide reductase (NOR) activity consisting of either protonation of a diiron-bridging hyponitrite or "super-reduction" of a diferrous-dinitrosyl by the proximal FMNH(2) in the rate-determining step have been proposed. To test these alternative mechanisms, we examined a deflavinated FDP (deflavo-FDP) from Thermotoga maritima. The deflavo-FDP retains an intact diiron site but does not exhibit multiturnover NOR or O(2) reductase (O(2)R) activity. Reactions of the reduced (diferrous) deflavo-FDP with nitric oxide were examined by UV-vis absorption, EPR, resonance Raman, and FTIR spectroscopies. Anaerobic addition of nitric oxide up to one NO per diferrous deflavo-FDP results in formation of a diiron-mononitrosyl complex characterized by a broad S = (1)/(2 )EPR signal arising from antiferromagnetic coupling of an S = (3)/(2) {FeNO}(7) with an S = 2 Fe(II). Further addition of NO results in two reaction pathways, one of which produces N(2)O and the diferric site and the other of which produces a stable diiron-dinitrosyl complex. Both NO-treated and as-isolated deflavo-FDPs regain full NOR and O(2)R activities upon simple addition of FMN. The production of N(2)O upon addition of NO to the mononitrosyl deflavo-FDP supports the hyponitrite mechanism, but the concomitant formation of a stable diiron-dinitrosyl complex in the deflavo-FDP is consistent with a super-reduction pathway in the flavinated enzyme. We conclude that a diiron-mononitrosyl complex is an intermediate in the NOR catalytic cycle of FDPs.

Pathway for H2O2 and O2 detoxification in Clostridium acetobutylicum.

An unusual non-haem diiron protein, reverse rubrerythrin (revRbr), is known to be massively upregulated in response to oxidative stress in the strictly anaerobic bacterium Clostridium acetobutylicum. In the present study both in vivo and in vitro results demonstrate an H2O2 and O2 detoxification pathway in C. acetobutylicum involving revRbr, rubredoxin (Rd) and NADH : rubredoxin oxidoreductase (NROR). RevRbr exhibited both NADH peroxidase (NADH : H2O2 oxidoreductase) and NADH oxidase (NADH : O2 oxidoreductase) activities in in vitro assays using NROR as the electron-transfer intermediary from NADH to revRbr. Rd increased the NADH consumption rate by serving as an intermediary electron-transfer shuttle between NROR and revRbr. While H2O2 was found to be the preferred substrate for revRbr, its relative oxidase activity was found to be significantly higher than that reported for other Rbrs. A revRbr-overexpressing strain of C. acetobutylicum showed significantly increased tolerance to H2O2 and O2 exposure. RevRbr thus appears to protect C. acetobutylicum against oxidative stress by functioning as the terminal component of an NADH peroxidase and NADH oxidase.