EMS MEd Blog

Article Bites #4: Learning from the Military - Association between Prehospital Blood Product transfusion & survival for Combat Casualties

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Article:

Association of Prehospital Blood Product Transfusion During Medical Evacuation of Combat Casualties in Afghanistan With Acute and 30-Day Survival

Shackelford SA, Del junco DJ, Powell-Dunford N, et al. Association of Prehospital Blood Product Transfusion During Medical Evacuation of Combat Casualties in Afghanistan With Acute and 30-Day Survival. JAMA. 2017;318(16):1581-1591. [PMID: 2906742]

Background & Objectives:

Given that hemorrhage is the leading cause of death in patients suffering from severe traumatic injuries, the utility of prehospital blood product transfusion has been a highly debated topic. Despite the important role of early transfusion in the management of hemorrhagic shock, the majority of published data at this time has shown inconclusive findings with regards to survival benefit from prehospital blood product transfusion, particularly within civilian trauma systems. Many of these studies suffered from significant flaws, and therefore, the verdict is still out on the role of prehospital transfusion. The purpose of this study was to address these deficiencies in the medical literature by studying the effect of prehospital transfusion within the context of the US military experience on MEDEVAC aircraft in Afghanistan. More specifically, the authors of this manuscript wanted to study the following question: Is prehospital blood product transfusion among military combat casualties associated with improved survival at 24 hours and at 30 days?

Methods:

The investigators conducted a retrospective cohort study of US military combat casualties in Afghanistan between April 1, 2012 and August 7, 2015. Patients were recruited from the Department of Defense trauma registry, the prehospital trauma registry, and the Armed Forces Medical Examiner System Database. Inclusion in the study was predicated on the following criteria being met: 

1.     US military service member who survived until MEDEVAC rescue from point of injury AND

2.     At least 1 of the following criteria for prehospital transfusion for severe trauma 

· 1 or more traumatic limb amputations with at least 1 amputation located above the knee or elbow OR 

· Hemorrhagic shock defined by systolic blood pressure <90 mmHg or heart rate >120 beats per minute 

The interventions that were examined were 1) initiation of prehospital transfusion (red blood cells and/or plasma) and 2) minutes from MEDEVAC rescue to initiation of transfusion regardless of setting (i.e. in the field vs surgical hospital). As stated earlier, the key outcomes that were examined were survival at 24 hours and at 30 days. Interestingly, the investigators compared individuals who received prehospital transfusion to nonrecipients of prehospital transfusion. These individuals were frequency matched based on 5 characteristics including mechanism of injury, prehospital shock, type and severity of traumatic limb amputation hemorrhagic torso injury assessed by Abbreviated Injury Scale (AIS) and finally severity of head injury assessed by AIS score. Using Cox regression analysis, further stratification was performed and adjusted for age, injury year, transport team, tourniquet use and time to MEDEVAC rescue. 

Key Results:

During the specified time frame of the study, there were 502 casualties who met inclusion criteria. 55 individuals received prehospital transfusion vs 447 individuals who did not receive transfusion. Of these individuals who did not receive transfusion, 345 were frequency matched to prehospital transfusion recipients based on the characteristics mentioned above. The key findings were as follows:

With respect to the entire study population:

· Within 24 hours of MEDEVAC rescue, 3/55 (5%) of prehospital transfusion recipients died compared to 85/447 (19%) of non-recipients (between group difference -14%; 95% CI -21% to -6%; p=0.01). 

· Within 30 days of MEDEVAC rescue, 6 prehospital transfusion recipients died (11%) compared to 102 non-recipients (23%) (between group difference -12%; 95% CI -21% to -2%; p=0.04)

With respect to matched study cohorts:

· Within 24 hours of MEDEVAC rescue, 3 (5%) prehospital transfusion recipients died compared 69 (20%) matched non-recipients (between group difference -15%; 95% CI -22% to -7%; p=0.007)

· Within 30 days of MEDEVAC rescue, 6 (11%) prehospital transfusion recipients died  compared to 78 (23%) matched non-recipients (Between group difference -12%; 95% CI -21% to -2%; p=0.05)

With respect to survival analysis:

· Among the 386 patients within the matched groups, adjusted hazard ratios were calculated. The investigators reported the adjusted hazard ratio for mortality to be 0.26 (95% CI 0.08 to 0.84; p=0.02) within the first 24 hours. Within the first 30 days, the adjusted hazard ratio for mortality was 0.39 (95% CI 0.16 to 0.92; p=0.03). 

With respect to time to first transfusion:

· The study revealed that time to initial transfusion was associated with reduced mortality within 24 hours only up to the first 15 minutes after MEDEVAC rescue (adjusted hazard ratio 0.17 95% CI 0.04-0.73; p = 0.02)

Takeaways:

· For US military casualties in Afghanistan, prehospital blood transfusion was associated with a statistically significant improvement in survival at 24 hours and 30 days compared with a matched sample that received no prehospital transfusion. 

· Early prehospital transfusion was associated with improved mortality but only within the first 15 minutes of MEDEVAC rescue. 

 

What this means for EMS:

There is no question that civilian trauma care has been greatly influenced by lessons learned on the battlefield. While this study performed on MEDEVAC helicopters in Afghanistan supports the notion that improved mortality can be achieved with prehospital blood transfusion for hemorrhagic shock, the translation of these findings to EMS systems back home may be more challenging. For starters, the logistical implementation of prehospital blood transfusion would require massive utilization of precious resources. Refrigeration, coordination with blood banks and hospitals, and care as to avoid wasting of life saving blood products are few of the many obstacles to ubiquitous implementation of prehospital blood transfusion in the civilian EMS world. Furthermore, the advanced resuscitative capabilities of MEDEVAC aircraft may not always be readily available in civilian systems, which may have accounted for the improved mortality observed in the study. Overall, while the results from the study were extremely encouraging, more research needs to be done to evaluate the precise role of prehospital transfusion in civilian EMS settings. 

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Article Bites #3: Does the Duration and Depth of Out-of-Hospital Hypotension affect mortality in TBI?

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Outcomes related to traumatic brain injury are thought to be related to cerebral perfusion pressure (among other factors). Cerebral perfusion pressure is equal to mean arterial pressure minus the intracranial pressure. Hypotension decreases cerebral perfusion pressure to the brain and is associated with increased mortality in this patient population. This is of particular importance especially in the prehospital arena where prior research has demonstrated that hypotension is associated with increased mortality in patients with traumatic brain injury. However, there have been no studies to date have examined the relationship between both the depth and the duration of hypotension with  mortality in patients with traumatic brain injury. The investigators of this study sought to tackle this very issue.

 

Methods:

The investigators conducted a retrospective observational study of patients with traumatic brain injury within the EPIC (Excellence in Prehospital Injury Care) database as part of the Arizona State Trauma Registry between January 2007 and March 2014. The primary outcome examined was survival to hospital discharge. Patients were determined to have traumatic brain injury based on trauma center diagnoses as a part of either isolated traumatic brain injury or multi system traumatic injury.  More specifically, participants were selected who met the classification for moderate or severe traumatic brain injury based on CDC guidelines, ICD-9 head region severity scores and Abbreviated Injury scores. Patients were excluded from the study if they were younger than 10 years of age, were involved in an interfacility transfer or had any systolic blood pressure greater than 200, or systolic blood pressure of 0 indicating traumatic arrest. Hypotension was defined as SBP <90 mmHg. To calculate the “dose” of hypotension, the investigators looked at the depth of hypotension integrated across exposure time (in minutes) AKA “area under the curve”. The integrated values from all hypotensive segments were added together to obtain a dose (in mmHg-minutes). The relationship between mortality and hypotension dose was examined by logistic regression analysis with adjustment for confounding factors.

 

Key Results:

A total of 16,711 transports for patients with traumatic brain injury were analyzed during the study period, of which 7,521 met inclusion criteria for the study. The key findings were as follows:

· 539 of 7,521 patients (7.2%) were hypotensive during transport

· Among patients with no hypotension (6,982 patients), mortality was 7.8% (95% CI 7.2 to 8.5%). This compared to patients who were hypotensive, where there was 33.4% (95% CI 29.4 to 37.6%) mortality

· Mortality increased in a linear relationship using a log2 hypotension dose and log odds of death (OR =1.19, 95% CI 1.14 to 1.25) per 2 fold increase in hypotension dose increase. In specific quartiles of hypotension dose, the following outcomes were established:

o   16.3% mortality with dose between 0.01 to 14.99 mmHg-minutes

o   28.1% mortality with dose between 15 to 49.99 mmHg-minutes

o   38.8% mortality with dose between 50-141.99 mmHg-minutes

o   50.4% mortality with dose greater than 142 mmHg-minutes

 

Takeaways:

· A dose response exists between prehospital hypotension dosage and mortality. Each 2 fold increase in hypotension dose (depth of hypotension integrated over time) during prehospital transport is associated with a 19% increase in mortality

 

What this means for EMS:

Out-of-hospital hypotension for patients with traumatic brain injury is associated with worse patient outcomes, i.e. decreased survival to hospital discharge. While this study was observational and did not address whether treatment of hypotension improved survival or neurologically intact recovery, it did emphasize an important variable that may serve as the foundation for future EMS research and quality improvement initiatives regarding the management of traumatic brain injury in the field. Going forward, more accurate (and more frequent) acquisition of blood pressure measurements in the prehospital setting may prove to be invaluable in implementing future prehospital resuscitative strategies for patients with traumatic brain injury. 

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Article Bites #2: Identifying factors associated with repeated transports of older adults

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Background & Objectives:

Adults aged 65 and older make up a significant proportion of the population (estimated to be approximately 20% of the total US population by 2030). In addition, this subset of patients has disproportionate utilization of EDs as well as EMS services (estimated at 38% of EMS transports). Little is known regarding the precise characteristics of this population that is associated with higher utilization of EMS. The investigators of the study aimed to investigate the proportion of older adults receiving repeat transport within 30 days and to potentially identify characteristics that were associated with repeat use of EMS. 

Methods:

The investigators conducted a retrospective analysis of EMS transports listed in the North Carolina Prehospital Medical Information Systems (PreMIS) database from 2010 to 2015. In particular, EMS encounters that were associated with 911 calls for adults aged 65 years or older that resulted in transport were examined. The primary outcome that was evaluated was repeated EMS transport within 30 days. Additional secondary outcomes that were examined included stratification of individuals by total number of EMS transports during the study period within 30 days. A multivariable logistic regression model was used to calculate adjusted odds ratios and 95% confidence intervals of repeated EMS transport within 30 days. 

Key Results:

A total of 1,719,998 transports for individuals aged 65 or greater were analyzed during the study period, of which 689,664 were for unique individuals. In this specific population, the key findings were as follows:

  • 17.7% (303,099 transports) had at least one repeated transport within 30 days
  • Odds of repeated transport within 30 days was higher in the following individuals: 

- Those from healthcare/residential facilities (OR 1.42 CI 1.38 to 1.47)

 - Black vs white (OR 1.29 95% CI 1.24 to 1.33)

 - Dispatch complaint of “sick person”, “fall”, “breathing problem”, “abdominal pain”, “diabetic problem”, “unknown person/person down”, “back pain”, “psychiatric problem”, “headache”

  • 15.6% of all repeated transports were related to falls 

Takeaways:

  • Greater than 1 in 6 EMS transports of individuals greater than the age of 65 is followed by a repeated transport within 30 days. 
  • Individuals in healthcare/residential settings and blacks (versus whites) have increased odds of repeated transport within 30 days

What this means for EMS:

Repeat transport of elderly adults is associated with significant healthcare costs and utilization of limited resources both in the hospital and pre-hospital setting. Identification of specific variables that are associated with repeated transport may assist with the development of targeted strategies to both improve patient outcomes and simultaneously decrease the demand for EMS resources that are already stretched very thin. 

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Article Bites #1: Bystander Efforts and 1-Year Outcomes in Out-of-Hospital Cardiac Arrest

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Reference: Kragholm K, Wissenberg M, Mortensen RN, et al. Bystander Efforts and 1-Year Outcomes in Out-of-Hospital Cardiac Arrest. N Engl J Med. 2017;376(18):1737-1747. [PMID: 2846789]

Background & Objectives:

Bystander CPR and defibrillation has been associated with increased survival in patients with out-of-hospital cardiac arrest (OHCA). It is well studied that many patients who survive cardiac arrest have long term neurological deficits secondary to anoxic brain injury. Many of these patients require assistance with activities of daily living in the form of nursing home care. However, there is little known whether there is any improvement in functional outcomes for patients with OHCA in the setting of bystander CPR and defibrillation. The authors of this study hypothesized that bystander CPR in addition to use of an automated external defibrillator would potentially augment cerebral perfusion and reduce the extent of neurological insult by decreasing the amount of time to acquisition of ROSC. The authors sought to examine whether bystander CPR and bystander defibrillation would affect long term risk of anoxic brain damage or nursing home admission among 30 day survivors of OHCA over a 1 year period.  

Methods:

Danish investigators evaluated all 30 day survivors for OHCA aged 18 and older who were listed in the Danish Cardiac Arrest Registry from 2001 to 2012. Using nationwide registries, 1 year risk of anoxic brain injury, nursing home admission and all cause mortality was examined. Survivors of cardiac arrest were divided into four groups: 1) no bystander resuscitation 2) bystander CPR but no bystander defibrillation 3) bystander debrillation (regardless of bystander CPR status) and 4) EMS witnessed cardiac arrest. In addition, temporal changes in bystander interventions were studied (i.e. outcomes in relationship to increasing rates of bystander interventions in Denmark over the study period). 

Key Results:

Of the 34,459 individuals eligible for the study, 2,855 patients were 30 day survivors of OHCA during the 2001-2012 study period. The key findings were as follows:

  • 10.5% of patients had anoxic brain injury or were admitted to a nursing home. 9.7% of patients died within 1 year.  
  • Percentage of 30 day survivors increased from 3.9% to 12.4% over the course of the study
  • Percentage of bystander CPR in OHCA unwitnessed by EMS (n=2084) increased from 66.7% to 80.6% (p<0.001) over the course of the study. Percentage of bystander defibrillation increased from 2.1% to 16.8% (p<0.001). In concert, the rate of brain damage or nursing home admission decreased from 10.0% to 7.6% (p<0.001). All cause mortality decreased from 18.0% to 7.9% (p=0.002). 
  • Bystander CPR was associated with lower risk of brain damage or nursing home admission compared to no bystander resuscitation (adjusted hazard ratio 0.62 95% CI 0.47-0.82). Similar findings were observed with bystander defibrillation compared to no bystander resuscitation (adjusted hazard ratio 0.45 95% CI 0.24-0.84) 

Takeaways:

  • There is lower risk of anoxic brain damage, nursing home admission or death from any cause in 30 day survivors of OHCA who undergo bystander CPR or bystander defibrillation compared to those who do not receive bystander intervention.
  • Increasing rates of bystander interventions in Denmark during the course of the study period was associated with decreased rates of anoxic brain injury, nursing home admission, and all-cause mortality

What this means for EMS:

Denmark has instituted widespread initiatives including mandatory and voluntary CPR training, dissemination of automated external defibrillators throughout the country, health care professionals at emergency dispatch centers and dispatcher-assisted CPR. System wide measures and efforts to educate the lay public on BLS skills including high quality CPR and use of automated external defibrillation, is a critical step in both increasing survival rates from OHCA and improving functional outcomes for patients. 

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