EMS Treatment Guidelines in Major Traumatic Brain Injury With Positive Pressure Ventilation.

Importance: The Excellence in Prehospital Injury Care (EPIC) study demonstrated improved survival in patients with severe traumatic brain injury (TBI) following implementation of the prehospital treatment guidelines. The impact of implementing these guidelines in the subgroup of patients who received positive pressure ventilation (PPV) is unknown. Objective: To evaluate the association of implementation of prehospital TBI evidence-based guidelines with survival among patients with prehospital PPV. Design, Setting, and Participants: The EPIC study was a multisystem, intention-to-treat study using a before/after controlled design. Evidence-based guidelines were implemented by emergency medical service agencies across Arizona. This subanalysis was planned a priori and included participants who received prehospital PPV. Outcomes were compared between the preimplementation and postimplementation cohorts using logistic regression, stratified by predetermined TBI severity categories (moderate, severe, or critical). Data were collected from January 2007 to June 2017, and data were analyzed from January to February 2023. Exposure: Implementation of the evidence-based guidelines for the prehospital care of patient with TBI. Main Outcomes and Measures: The primary outcome was survival to hospital discharge, and the secondary outcome was survival to admission. Results: Among the 21 852 participants in the main study, 5022 received prehospital PPV (preimplementation, 3531 participants; postimplementation, 1491 participants). Of 5022 included participants, 3720 (74.1%) were male, and the median (IQR) age was 36 (22-54) years. Across all severities combined, survival to admission improved (adjusted odds ratio [aOR], 1.59; 95% CI, 1.28-1.97), while survival to discharge did not (aOR, 0.94; 95% CI, 0.78-1.13). Within the cohort with severe TBI but not in the moderate or critical subgroups, survival to hospital admission increased (aOR, 6.44; 95% CI, 2.39-22.00), as did survival to discharge (aOR, 3.52; 95% CI, 1.96-6.34). Conclusions and Relevance: Among patients with severe TBI who received active airway interventions in the field, guideline implementation was independently associated with improved survival to hospital admission and discharge. This was true whether they received basic airway interventions or advanced airways. These findings support the current guideline recommendations for aggressive prevention/correction of hypoxia and hyperventilation in patients with severe TBI, regardless of which airway type is used.

Correlation between prehospital and in-hospital hypotension and outcomes after traumatic brain injury.

BACKGROUND AND OBJECTIVE: Hypotension has a powerful effect on patient outcome after traumatic brain injury (TBI). The relative impact of hypotension occurring in the field versus during early hospital resuscitation is unknown. We evaluated the association between hypotension and mortality and non-mortality outcomes in four cohorts defined by where the hypotension occurred [neither prehospital nor hospital, prehospital only, hospital only, both prehospital and hospital]. METHODS: Subjects ≥10 years with major TBI were included. Standard statistics were used for unadjusted analyses. We used logistic regression, controlling for significant confounders, to determine the adjusted odds (aOR) for outcomes in each of the three cohorts. RESULTS: Included were 12,582 subjects (69.8% male; median age 44 (IQR 26-61). Mortality by hypotension status: No hypotension: 9.2% (95%CI: 8.7-9.8%); EMS hypotension only: 27.8% (24.6-31.2%); hospital hypotension only: 45.6% (39.1-52.1%); combined EMS/hospital hypotension 57.6% (50.0-65.0%); (p < 0.0001). The aOR for death reflected the same progression: 1.0 (reference-no hypotension), 1.8 (1.39-2.33), 2.61 (1.73-3.94), and 4.36 (2.78-6.84), respectively. The proportion of subjects having hospital hypotension was 19.0% (16.5-21.7%) in those with EMS hypotension compared to 2.0% (1.8-2.3%) for those without (p < 0.0001). Additionally, the proportion of patients with TC hypotension was increased even with EMS "near hypotension" up to an SBP of 120 mmHg [(aOR 3.78 (2.97, 4.82)]. CONCLUSION: While patients with hypotension in the field or on arrival at the trauma center had markedly increased risk of death compared to those with no hypotension, those with prehospital hypotension that was not resolved before hospital arrival had, by far, the highest odds of death. Furthermore, TBI patients who had prehospital hypotension were five times more likely to arrive hypotensive at the trauma center than those who did not. Finally, even "near-hypotension" in the field was strongly and independently associated the risk of a hypotensive hospital arrival (<90 mmHg). These findings are supportive of the prehospital guidelines that recommend aggressive prevention and treatment of hypotension in major TBI.

Impact of in-Station Medication Automated Dispensing Systems on Prehospital Pain Medication Administration.

INTRODUCTION: Medication automatic dispensing systems (ADS) have been implemented in many settings, including fire-based EMS stations. The aim of this study was to evaluate the impact of in-station ADSs on controlled substance administration rates and EMS response intervals. METHODS: This study was a retrospective review of data from a single fire-based EMS agency. Medication administration rates and EMS response intervals were compared before ADS implementation (P1; 6/1/15 to 5/31/16) and after ADS implementation (P3; 6/1/17-5/31/19). Cases with missing data and during a one-year implementation period were excluded. RESULTS: 4045 cases were identified in P1 and 8168 in P3. The odds of morphine or versed administration increased following ADS implementation: OR = 1.77 (95% CI: 1.53, 2.03) and OR = 1.53 (95%CI: 1.18, 2.00) respectively. There were statistically, but likely not operationally significant increases in median response interval and transport interval from P1 to P3 of 14 seconds, (p < 0.001) and 39 seconds (p < 0.001) respectively. Time at hospital for all calls decreased by more than 11 minutes for all transports, from a median of 34 minutes (IQR; 23.7, 45.5) to 22.7 minutes (IQR:18.5, 27.6) in P3, p < 0.001 and by 27.9 minutes for calls in which a controlled substance was given: P1 = 50.6 minutes (IQR: 34.6, 63.2), P3 = 22.7 minutes (IQR: 18.3, 27.4), p < 0.001. CONCLUSION: In this system, medication ADS implementation was associated with an increase in the rates of controlled substance administration and a decrease in the time units were at hospitals.

Optimal Out-of-Hospital Blood Pressure in Major Traumatic Brain Injury: A Challenge to the Current Understanding of Hypotension.

STUDY OBJECTIVE: Little is known about the out-of-hospital blood pressure ranges associated with optimal outcomes in traumatic brain injuries (TBI). Our objective was to evaluate the associations between out-of-hospital systolic blood pressure (SBP) and multiple hospital outcomes without assuming any predefined thresholds for hypotension, normotension, or hypertension. METHODS: This was a preplanned secondary analysis from the Excellence in Prehospital Injury Care (EPIC) TBI study. Among patients (age ≥10 years) with major TBIs (Barell Matrix type 1 and/or Abbreviated Injury Scale-head severity ≥3) and lowest out-of-hospital SBPs of 40 to 299 mmHg, we utilized generalized additive models to summarize the distributions of various outcomes as smoothed functions of SBP, adjusting for important and significant confounders. The subjects who were enrolled in the study phase after the out-of-hospital TBI guideline implementation were used to validate the models developed from the preimplementation cohort. RESULTS: Among 12,169 included cases, the mortality model revealed 3 distinct ranges: (1) a monotonically decreasing relationship between SBP and the adjusted probability of death from 40 to 130 mmHg, (2) lowest adjusted mortality from 130 to 180 mmHg, and (3) rapidly increasing mortality above 180 mmHg. A subanalysis of the cohorts with isolated TBIs and multisystem injuries with TBIs revealed SBP mortality patterns that were similar to each other and to that of the main analysis. While the specific SBP ranges varied somewhat for the nonmortality outcomes (hospital length of stay, ICU length of stay, discharge to skilled nursing/inpatient rehabilitation, and hospital charges), the patterns were very similar to that of mortality. In each model, validation was confirmed utilizing the postimplementation cohort. CONCLUSION: Optimal adjusted mortality was associated with a surprisingly high SBP range (130 to 180 mmHg). Below this level, there was no point or range of inflection that would indicate a physiologically meaningful threshold for defining hypotension. Nonmortality outcomes showed very similar patterns. These findings highlight how sensitive the injured brain is to compromised perfusion at SBP levels that, heretofore, have been considered adequate or even normal. While the study design does did not allow us to conclude that the currently recommended treatment threshold (<90 mmHg) should be increased, the findings imply that the definition of hypotension in the setting of TBI is too low. Randomized trials evaluating treatment levels significantly higher than 90 mmHg are needed.

Availability and use of medications by prehospital providers trained to manage medical complications of patients in hazardous materials incidents.

INTRODUCTION: Little is known about prehospital availability and use of medications to treat patients from hazardous materials (hazmat) medical emergencies. The aim of this study was to identify the availability and frequency of use of medications for patients in hazmat incidents by paramedics with advanced training to care for these patients. METHODS: A prospectively validated survey was distributed to United States paramedics with advanced training in the medical management of patients from hazmat incidents who successfully completed a 16-hour Advanced Hazmat Life Support (AHLS) Provider Course from 1999 to 2017. The survey questioned hazmat medication availability, storage, and frequency of use. Hazmat medications were considered to have been used if administered anytime within the past 5 years. For analyses, medications were grouped into those with hazmat indications only and those with multiple indications. RESULTS: The survey email was opened by 911 course participants and 784 of these completed the survey (86.1 percent). Of these 784 respondents, 279 (35.6 percent) reported carrying dedicated hazmat medication kits, ie, tox-boxes, and 505 (64.4 percent) did not carry tox-boxes. For those medications specifically for hazmat use, hydroxocobalamin was most commonly available, either within or not within a dedicated tox-box. Of the 784 respondents, 313 (39.9 percent) reported carrying hydroxocobalamin and 69 (8.8 percent) reported administering it within the past 5 years. For medications with multiple indications, availability and use varied: for example, of the 784 respondents, albuterol was available to 699 (89.2 percent) and used by 572 (73.0 percent), while calcium gluconate was available to 247 (31.5 percent) and used by 80 (10.2 percent) within the last 5 years. CONCLUSION: Paramedics with advanced training in the medical management of patients in hazmat incidents reported limited availability and use of medications to treat patients in hazmat incidents.

Refusals After Prehospital Administration of Naloxone during the COVID-19 Pandemic.

OBJECTIVE: To determine if COVID-19 was associated with a change in patient refusals after Emergency Medical Services (EMS) administration of naloxone. METHODS: This is a retrospective cohort study in which the incidence of refusals after naloxone administration in a single EMS system was evaluated. The number of refusals after naloxone administration was compared across the before-pandemic interval (01/01/20 to 02/15/20) and the during-pandemic interval (03/16/20 to 04/30/20). For comparison the incidence of all other patient refusals before and during COVID-19 as well as the incidences of naloxone administration before and during COVID-19 were also reported. RESULTS: Prior to the widespread knowledge of the COVID-19 pandemic, 24 of 164 (14.6%) patients who received naloxone via EMS refused transport. During the pandemic, 55 of 153 (35.9%) patients who received naloxone via EMS refused transport. Subjects receiving naloxone during the COVID-19 pandemic were at greater risk of refusal of transport than those receiving naloxone prior to the pandemic (RR = 2.45; 95% CI 1.6-3.76). Among those who did not receive naloxone, 2067 of 6956 (29.7%) patients were not transported prior to the COVID-19 pandemic and 2483 of 6016 (41.3%) were not transported during the pandemic. Subjects who did not receive naloxone with EMS were at greater risk of refusal of transport during the COVID-19 pandemic than prior to it (RR = 1.39; 95% CI 1.32-1.46). CONCLUSION: In this single EMS system, more than a two-fold increase in the rate of refusal after non-fatal opioid overdose was observed following the COVID-19 outbreak.

Can Emergency Medical Services Utilization Rates Be Used to Measure the Success of An Alcohol Amnesty Policy?

INTRODUCTION: Medical Amnesty/Good Samaritan (MAGS) policies, which eliminate legal charges when students call 9-1-1 for excessive drinking, have been implemented with the goal of reducing barriers to accessing Emergency Medical Services (EMS). This study investigated the impact of MAGS policy implementation on EMS calls on campus and if that EMS call volume could be used to measure policy success. The aim of this study was to compare the prevalence of alcohol-related EMS calls before and after MAGS implementation at a single large public university campus. Methods: A retrospective review of all 9-1-1 calls to on-campus locations was conducted using patient care records (PCRs) from a collegiate EMS agency responding exclusively to on-campus 9-1-1 calls. Calls were excluded if the PCR was marked "incomplete", were outside the 2015 CBEMS response zone boundaries, or if patient age was <15 or >25 years old to ensure analysis was targeting the on-campus student population. The incidence of alcohol-related 9-1-1 calls was compared between one academic year (AY) prior to (pre-MAGS, AY2015) and two years after MAGS implementation (post-MAGS, AY2016/17). An alcohol-related 9-1-1 call was defined as an EMS provider primary or secondary impression of "Alcohol, Alcohol Intoxication, or Alcohol Ingestion" or a call in which the patient explicitly admitted to alcohol use. Relative risk (RR) with 95% confidence intervals (CI) were used to describe the results. Results: Over the three-year study period, the collegiate EMS agency responded to 2440 calls of which 1283 met inclusion criteria. 58 calls were excluded for being incomplete, 227 were outside the original boundaries and 872 were outside the defined age range. Of those calls, 351 were pre-MAGS and 932 were post-MAGS. Of the total 9-1-1 calls, 127 (36.2%) were related to alcohol pre-MAGS and 327 (35.1%) were related to alcohol post-MAGS policy implementation. The relative risk of a 9-1-1 call being made for alcohol-related issues after MAGS implementation was RR = 0.97 (95% CI 0.83-1.14; P = 0.713). Conclusion: Implementation of a MAGS policy was not associated with a significant change in the number of alcohol-related EMS responses. It is unclear if these results reflect ineffective policy implementation or a general reduction in on-campus alcohol consumption. However, using EMS call volume as a marker for policy success and quality improvement offers an innovative tool through which EMS agencies can provide valuable feedback to other system stakeholders.

Effect of Implementing the Out-of-Hospital Traumatic Brain Injury Treatment Guidelines: The Excellence in Prehospital Injury Care for Children Study (EPIC4Kids).

STUDY OBJECTIVE: We evaluate the effect of implementing the out-of-hospital pediatric traumatic brain injury guidelines on outcomes in children with major traumatic brain injury. METHODS: The Excellence in Prehospital Injury Care for Children study is the preplanned secondary analysis of the Excellence in Prehospital Injury Care study, a multisystem, intention-to-treat study using a before-after controlled design. This subanalysis included children younger than 18 years who were transported to Level I trauma centers by participating out-of-hospital agencies between January 1, 2007, and June 30, 2015, throughout Arizona. The primary and secondary outcomes were survival to hospital discharge or admission for children with major traumatic brain injury and in 3 subgroups, defined a priori as those with moderate, severe, and critical traumatic brain injury. Outcomes in the preimplementation and postimplementation cohorts were compared with logistic regression, adjusting for risk factors and confounders. RESULTS: There were 2,801 subjects, 2,041 in preimplementation and 760 in postimplementation. The primary analysis (postimplementation versus preimplementation) yielded an adjusted odds ratio of 1.16 (95% confidence interval 0.70 to 1.92) for survival to hospital discharge and 2.41 (95% confidence interval 1.17 to 5.21) for survival to hospital admission. In the severe traumatic brain injury cohort (Regional Severity Score-Head 3 or 4), but not the moderate or critical subgroups, survival to discharge significantly improved after guideline implementation (adjusted odds ratio = 8.42; 95% confidence interval 1.01 to 100+). The improvement in survival to discharge among patients with severe traumatic brain injury who received positive-pressure ventilation did not reach significance (adjusted odds ratio = 9.13; 95% confidence interval 0.79 to 100+). CONCLUSION: Implementation of the pediatric out-of-hospital traumatic brain injury guidelines was not associated with improved survival when the entire spectrum of severity was analyzed as a whole (moderate, severe, and critical). However, both adjusted survival to hospital admission and discharge improved in children with severe traumatic brain injury, indicating a potential severity-based interventional opportunity for guideline effectiveness. These findings support the widespread implementation of the out-of-hospital pediatric traumatic brain injury guidelines.

Prehospital Protocols Reducing Long Spinal Board Use Are Not Associated with a Change in Incidence of Spinal Cord Injury.

Introduction: Many emergency medical services (EMS) agencies have de-emphasized or eliminated the use of long spinal boards (LSB) for patients with possible spinal injury. We sought to determine if implementation of spinal motion restriction (SMR) protocols, which reduce LSB use, was associated with an increase in spinal cord injury (SCI). Methods: This retrospective observational study includes EMS encounters from January 1, 2013 to December 31, 2015 submitted by SMR-adopting ground-based agencies to a state EMS database with hospital discharge data. Encounters were excluded if SMR implementation date was unknown, occurred during a 3-month run-in period, or were duplicates. Study samples include patients with traumatic injury (TI), possible spinal trauma (P-ST), and verified spinal trauma (V-ST) using hospital discharge ICD-9/10 diagnosis codes. The incidence of SCI before and after implementation of SMR was compared using Chi-squared and logistic regression. Results: From 1,005,978 linked encounters, 104,315 unique encounters with traumatic injury and known SMR implementation date were identified with 51,199 cases of P-ST and 5,178 V-ST cases. The incidence of SCI in the pre-SMR and post-SMR interval for each group was: TI, 0.20% vs. 0.22% (p = 0.390); P-ST, 0.40% vs. 0.45% (p = 0.436); and V-ST, 4.04% vs. 4.37% (p = 0.561). Age and injury severity adjusted odds ratio of SCI in the highest risk cohort of patients with V-ST was 1.097 after SMR implementation (95% CI 0.818-1.472). Conclusion: In this limited study, no change in the incidence of SCI was identified following implementation of SMR protocols. Prospective evaluation of this question is necessary to evaluate the safety of SMR protocols.

Association of Statewide Implementation of the Prehospital Traumatic Brain Injury Treatment Guidelines With Patient Survival Following Traumatic Brain Injury: The Excellence in Prehospital Injury Care (EPIC) Study.

Importance: Traumatic brain injury (TBI) is a massive public health problem. While evidence-based guidelines directing the prehospital treatment of TBI have been promulgated, to our knowledge, no studies have assessed their association with survival. Objective: To evaluate the association of implementing the nationally vetted, evidence-based, prehospital treatment guidelines with outcomes in moderate, severe, and critical TBI. Design, Setting, and Participants: The Excellence in Prehospital Injury Care (EPIC) Study included more than 130 emergency medical services systems/agencies throughout Arizona. This was a statewide, multisystem, intention-to-treat study using a before/after controlled design with patients with moderate to critically severe TBI (US Centers for Disease Control and Prevention Barell Matrix-Type 1 and/or Abbreviated Injury Scale Head region severity ≥3) transported to trauma centers between January 1, 2007, and June 30, 2015. Data were analyzed between October 25, 2017, and February 22, 2019. Interventions: Implementation of the prehospital TBI guidelines emphasizing avoidance/treatment of hypoxia, prevention/correction of hyperventilation, and avoidance/treatment of hypotension. Main Outcomes and Measures: Primary: survival to hospital discharge; secondary: survival to hospital admission. Results: Of the included patients, the median age was 45 years, 14 666 (67.1%) were men, 7181 (32.9%) were women; 16 408 (75.1% ) were white, 1400 (6.4%) were Native American, 743 (3.4% ) were Black, 237 (1.1%) were Asian, and 2791 (12.8%) were other race/ethnicity. Of the included patients, 21 852 met inclusion criteria for analysis (preimplementation phase [P1]: 15 228; postimplementation [P3]: 6624). The primary analysis (P3 vs P1) revealed an adjusted odds ratio (aOR) of 1.06 (95% CI, 0.93-1.21; P = .40) for survival to hospital discharge. The aOR was 1.70 (95% CI, 1.38-2.09; P < .001) for survival to hospital admission. Among the severe injury cohorts (but not moderate or critical), guideline implementation was significantly associated with survival to discharge (Regional Severity Score-Head 3-4: aOR, 2.03; 95% CI, 1.52-2.72; P < .001; Injury Severity Score 16-24: aOR, 1.61; 95% CI, 1.07-2.48; P = .02). This was also true for survival to discharge among the severe, intubated subgroups (Regional Severity Score-Head 3-4: aOR, 3.14; 95% CI, 1.65-5.98; P < .001; Injury Severity Score 16-24: aOR, 3.28; 95% CI, 1.19-11.34; P = .02). Conclusions and Relevance: Statewide implementation of the prehospital TBI guidelines was not associated with significant improvement in overall survival to hospital discharge (across the entire, combined moderate to critical injury spectrum). However, adjusted survival doubled among patients with severe TBI and tripled in the severe, intubated cohort. Furthermore, guideline implementation was significantly associated with survival to hospital admission. These findings support the widespread implementation of the prehospital TBI treatment guidelines. Trial Registration: ClinicalTrials.gov identifier: NCT01339702.

Association of Out-of-Hospital Hypotension Depth and Duration With Traumatic Brain Injury Mortality.

STUDY OBJECTIVE: Out-of-hospital hypotension has been associated with increased mortality in traumatic brain injury. The association of traumatic brain injury mortality with the depth or duration of out-of-hospital hypotension is unknown. We evaluated the relationship between the depth and duration of out-of-hospital hypotension and mortality in major traumatic brain injury. METHODS: We evaluated adults and older children with moderate or severe traumatic brain injury in the preimplementation cohort of Arizona's statewide Excellence in Prehospital Injury Care study. We used logistic regression to determine the association between the depth-duration dose of hypotension (depth of systolic blood pressure <90 mm Hg integrated over duration [minutes] of hypotension) and odds of inhospital death, controlling for significant confounders. RESULTS: There were 7,521 traumatic brain injury cases included (70.6% male patients; median age 40 years [interquartile range 24 to 58]). Mortality was 7.8% (95% confidence interval [CI] 7.2% to 8.5%) among the 6,982 patients without hypotension (systolic blood pressure ≥90 mm Hg) and 33.4% (95% CI 29.4% to 37.6%) among the 539 hypotensive patients (systolic blood pressure <90 mm Hg). Mortality was higher with increased hypotension dose: 0.01 to 14.99 mm Hg-minutes 16.3%; 15 to 49.99 mm Hg-minutes 28.1%; 50 to 141.99 mm Hg-minutes 38.8%; and greater than or equal to 142 mm Hg-minutes 50.4%. Log2 (the logarithm in base 2) of hypotension dose was associated with traumatic brain injury mortality (adjusted odds ratio 1.19 [95% CI 1.14 to 1.25] per 2-fold increase of dose). CONCLUSION: In this study, the depth and duration of out-of-hospital hypotension were associated with increased traumatic brain injury mortality. Assessments linking out-of-hospital blood pressure with traumatic brain injury outcomes should consider both depth and duration of hypotension.

Body Temperature after EMS Transport: Association with Traumatic Brain Injury Outcomes.

INTRODUCTION: Low body temperatures following prehospital transport are associated with poor outcomes in patients with traumatic brain injury (TBI). However, a minimal amount is known about potential associations across a range of temperatures obtained immediately after prehospital transport. Furthermore, a minimal amount is known about the influence of body temperature on non-mortality outcomes. The purpose of this study was to assess the correlation between temperatures obtained immediately following prehospital transport and TBI outcomes across the entire range of temperatures. METHODS: This retrospective observational study included all moderate/severe TBI cases (CDC Barell Matrix Type 1) in the pre-implementation cohort of the Excellence in Prehospital Injury Care (EPIC) TBI Study (NIH/NINDS: 1R01NS071049). Cases were compared across four cohorts of initial trauma center temperature (ITCT): <35.0°C [Very Low Temperature (VLT)]; 35.0-35.9°C [Low Temperature (LT)]; 36.0-37.9°C [Normal Temperature (NT)]; and ≥38.0°C [Elevated Temperature (ET)]. Multivariable analysis was performed adjusting for injury severity score, age, sex, race, ethnicity, blunt/penetrating trauma, and payment source. Adjusted odds ratios (aORs) with 95% confidence intervals (CI) for mortality were calculated. To evaluate non-mortality outcomes, deaths were excluded and the adjusted median increase in hospital length of stay (LOS), ICU LOS and total hospital charges were calculated for each ITCT group and compared to the NT group. RESULTS: 22,925 cases were identified and cases with interfacility transfer (7361, 32%), no EMS transport (1213, 5%), missing ITCT (2083, 9%), or missing demographic data (391, 2%) were excluded. Within this study cohort the aORs for death (compared to the NT group) were 2.41 (CI: 1.83-3.17) for VLT, 1.62 (CI: 1.37-1.93) for LT, and 1.86 (CI: 1.52-3.00) for ET. Similarly, trauma center (TC) LOS, ICU LOS, and total TC charges increased in all temperature groups when compared to NT. CONCLUSION: In this large, statewide study of major TBI, both ETs and LTs immediately following prehospital transport were independently associated with higher mortality and with increased TC LOS, ICU LOS, and total TC charges. Further study is needed to identify the causes of abnormal body temperature during the prehospital interval and if in-field measures to prevent temperature variations might improve outcomes.

Sleep/wake firing patterns of human genioglossus motor units.

Although studies of the principal tongue protrudor muscle genioglossus (GG) suggest that whole muscle GG electromyographic (EMG) activities are preserved in nonrapid eye movement (NREM) sleep, it is unclear what influence sleep exerts on individual GG motor unit (MU) activities. We characterized the firing patterns of human GG MUs in wakefulness and NREM sleep with the aim of determining 1) whether the range of MU discharge patterns evident in wakefulness is preserved in sleep and 2) what effect the removal of the "wakefulness" input has on the magnitude of the respiratory modulation of MU activities. Microelectrodes inserted into the extrinsic tongue protrudor muscle, the genioglossus, were used to follow the discharge of single MUs. We categorized MU activities on the basis of the temporal relationship between the spike train and the respiration cycle and quantified the magnitude of the respiratory modulation of each MU using the eta (eta(2)) index, in wakefulness and sleep. The majority of MUs exhibited subtle increases or decreases in respiratory modulation but were otherwise unaffected by NREM sleep. In contrast, 30% of MUs exhibited marked sleep-associated changes in discharge frequency and respiratory modulation. We suggest that GG MUs should not be considered exclusively tonic or phasic; rather, the discharge pattern appears to be a flexible feature of GG activities in healthy young adults. Whether such flexibility is important in the response to changes in the chemical and/or mechanical environment and whether it is preserved as a function of aging or in individuals with obstructive sleep apnea are critical questions for future research.

Firing patterns of human genioglossus motor units during voluntary tongue movement.

The tongue participates in a range of complex oromotor behaviors, including mastication, swallowing, respiration, and speech. Previous electromyographic studies of the human tongue have focused on respiratory-related tongue muscle activities and their role in maintaining upper airway patency. Remarkably, the activities of human hypoglossal motor units have not been studied during the execution of voluntary maneuvers. We recorded single motor unit activity using tungsten microelectrodes in the genioglossus muscle of 10 healthy human subjects performing both slow tongue protrusions and a static holding maneuver. Displacement of the tongue was detected by an isotonic transducer coupled to the lingual surface through a customized lever arm. For protrusion trials, the firing rate at recruitment was 13.1 +/- 3 Hz and increased steeply to an average of 24 +/- 6 Hz, often with very modest increases in tongue protrusion. For the static holding task, the average firing rate was 16.1 +/- 4 Hz, which is surprisingly high relative to limb motor units. The average coefficient of variation of interspike intervals was approximately 20% (range, 10-28%). These are the first recordings of their type obtained in human subjects and provide an initial glimpse into the voluntary control of hypoglossal motoneurons during tongue movements presumably instigated by activity in the motor cortex.

Modulation of articular chondrocyte activity by pirfenidone.

Pirfenidone is under investigation as an anti-inflammatory and anti-fibrotic agent in several organs including lung. Since important features of arthritic conditions include inflammation and long-term damage to articular cartilage, we have investigated whether PD can suppress chondrocyte responses to bacterial lipopolysaccharide (LPS) and interleukin 1 (IL-1); modulators that induce a cascade of inflammatory responses that lead to articular joint tissue damage. PD (0 - 5microM) showed no effect on cell number or viability when incubated with high density primary equine chondrocyte cultures for a 24 hr period. PD did not stimulate nitric oxide (NO) release by chondrocytes when added alone but LPS and IL-1-induced NO release was inhibited by PD, in a dose-dependent manner. PD did not significantly influence GAG release from cartilage matrix nor did it stimulate or suppress the GAG releasing actions of LPS or IL-1. We conclude that PD is capable of attenuating the cytokine-induced production of the inflammatory mediator, NO by chondrocytes, without stimulating matrix glycosaminoglycan loss from cartilage. PD may have potential as an anti-inflammatory agent in the joint.