Bruce Barnhart

The Effect of Combined Out-of-Hospital Hypotension and Hypoxia on Mortality in Major Traumatic Brain Injury

Study objective: Survival is significantly reduced by either hypotension or hypoxia during the out‐of‐hospital management of major traumatic brain injury. However, only a handful of small studies have investigated the influence of the combination of both hypotension and hypoxia occurring together. In patients with major traumatic brain injury, we evaluate the associations between mortality and out‐of‐hospital hypotension and hypoxia separately and in combination. Methods: All moderate or severe traumatic brain injury cases in the preimplementation cohort of the Excellence in Prehospital Injury Care study (a statewide, before/after, controlled study of the effect of implementing the out‐of‐hospital traumatic brain injury treatment guidelines) from January 1, 2007, to March 31, 2014, were evaluated (exclusions: <10 years, out‐of‐hospital oxygen saturation ≤10%, and out‐of‐hospital systolic blood pressure <40 or >200 mm Hg). The relationship between mortality and hypotension (systolic blood pressure <90 mm Hg) or hypoxia (saturation <90%) was assessed with multivariable logistic regression, controlling for Injury Severity Score, head region severity, injury type (blunt versus penetrating), age, sex, race, ethnicity, payer, interhospital transfer, and trauma center. Results: Among the 13,151 patients who met inclusion criteria (median age 45 years; 68.6% men), 11,545 (87.8%) had neither hypotension nor hypoxia, 604 (4.6%) had hypotension only, 790 (6.0%) had hypoxia only, and 212 (1.6%) had both hypotension and hypoxia. Mortality for the 4 study cohorts was 5.6%, 20.7%, 28.1%, and 43.9%, respectively. The crude and adjusted odds ratios for death within the cohorts, using the patients with neither hypotension nor hypoxia as the reference, were 4.4 and 2.5, 6.6 and 3.0, and 13.2 and 6.1, respectively. Evaluation for an interaction between hypotension and hypoxia revealed that the effects were additive on the log odds of death. Conclusion: In this statewide analysis of major traumatic brain injury, combined out‐of‐hospital hypotension and hypoxia were associated with significantly increased mortality. This effect on survival persisted even after controlling for multiple potential confounders. In fact, the adjusted odds of death for patients with both hypotension and hypoxia were more than 2 times greater than for those with either hypotension or hypoxia alone. These findings seem supportive of the emphasis on aggressive prevention and treatment of hypotension and hypoxia reflected in the current emergency medical services traumatic brain injury treatment guidelines but clearly reveal the need for further study to determine their influence on outcome.

Mortality and prehospital blood pressure in patients with major traumatic brain injury: Implications for the hypotension threshold

Importance Current prehospital traumatic brain injury guidelines use a systolic blood pressure threshold of less than 90 mm Hg for treating hypotension for individuals 10 years and older based on studies showing higher mortality when blood pressure drops below this level. However, the guidelines also acknowledge the weakness of the supporting evidence. Objective To evaluate whether any statistically supportable threshold between systolic pressure and mortality emerges from the data a priori, without assuming that a cut point exists. Design, Setting, and Participants Observational evaluation of a large prehospital database established as a part of the Excellence in Prehospital Injury Care Traumatic Brain Injury Study. Patients from the preimplementation cohort (January 2007 to March 2014) 10 years and older with moderate or severe traumatic brain injury (Barell Matrix Type 1 classification, International Classification of Diseases, Ninth Revision head region severity score of 3 or greater, and/or Abbreviated Injury Scale head-region severity score of 3 or greater) and a prehospital systolic pressure between 40 and 119 mm Hg were included. The generalized additive model and logistic regression were used to determine the association between systolic pressure and probability of death, adjusting for significant/important confounders. Main Outcomes and Measures The main outcome measure was in-hospital mortality. Results Among the 3844 included patients, 2565 (66.7%) were male, and the median (range) age was 35 (10-99) years. The model revealed a monotonically decreasing association between systolic pressure and adjusted probability of death across the entire range (ie, from 40 to 119 mm Hg). Each 10-point increase of systolic pressure was associated with a decrease in the adjusted odds of death of 18.8% (adjusted odds ratio, 0.812; 95% CI, 0.748-0.883). Thus, the adjusted odds of mortality increased as much for a drop from 110 to 100 mm Hg as for a drop from 90 to 80 mm Hg, and so on throughout the range. Conclusions and Relevance We found a linear association between lowest prehospital systolic blood pressure and severity-adjusted probability of mortality across an exceptionally wide range. There is no identifiable threshold or inflection point between 40 and 119 mm Hg. Thus, in patients with traumatic brain injury, the concept that 90 mm Hg represents a unique or important physiological cut point may be wrong. Furthermore, clinically meaningful hypotension may not be as low as current guidelines suggest. Randomized trials evaluating treatment levels significantly above 90 mm Hg are needed.

Degradation of benzodiazepines after 120 days of EMS deployment.

Abstract Introduction. EMS treatment of status epilepticus improves outcomes, but the benzodiazepine best suited for EMS use is unclear, given potential high environmental temperature exposures. Objective. To describe the degradation of diazepam, lorazepam, and midazolam as a function of temperature exposure and time over 120 days of storage on active EMS units. Methods. Study boxes containing vials of diazepam, lorazepam, and midazolam were distributed to 4 active EMS units in each of 2 EMS systems in the southwestern United States during May–August 2011. The boxes logged temperature every minute and were stored in EMS units per local agency policy. Two vials of each drug were removed from each box at 30-day intervals and underwent high-performance liquid chromatography to determine drug concentration. Concentration was analyzed as mean (and 95%CI) percent of initial labeled concentration as a function of time and mean kinetic temperature (MKT). Results. 192 samples were collected (2 samples of each drug from each of 4 units per city at 4 time-points). After 120 days, the mean relative concentration (95%CI) of diazepam was 97.0% (95.7–98.2%) and of midazolam was 99.0% (97.7–100.2%). Lorazepam experienced modest degradation by 60 days (95.6% [91.6–99.5%]) and substantial degradation at 90 days (90.3% [85.2-95.4%]) and 120 days (86.5% [80.7–92.3%]). Mean MKT was 31.6°C (95%CI 27.1–36.1). Increasing MKT was associated with greater degradation of lorazepam, but not midazolam or diazepam. Conclusions. Midazolam and diazepam experienced minimal degradation throughout 120 days of EMS deployment in high-heat environments. Lorazepam experienced significant degradation over 120 days and appeared especially sensitive to higher MKT exposure.AbstractIntroduction. EMS treatment of status epilepticus improves outcomes, but the benzodiazepine best suited for EMS use is unclear, given potential high environmental temperature exposures. Objective. To describe the degradation of diazepam, lorazepam, and midazolam as a function of temperature exposure and time over 120 days of storage on active EMS units. Methods. Study boxes containing vials of diazepam, lorazepam, and midazolam were distributed to 4 active EMS units in each of 2 EMS systems in the southwestern United States during May–August 2011. The boxes logged temperature every minute and were stored in EMS units per local agency policy. Two vials of each drug were removed from each box at 30-day intervals and underwent high-performance liquid chromatography to determine drug concentration. Concentration was analyzed as mean (and 95%CI) percent of initial labeled concentration as a function of time and mean kinetic temperature (MKT). Results. 192 samples were collected (2 samples of each drug ...

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

Abstract 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.