Evidence-based EMS: Permissive Hypotension in Trauma

It’s another busy Friday night for your medic unit when you are dispatched to a motorcycle collision on the highway.

You arrive on scene to find a 32-year-old male lying on the highway moaning in pain. He has a significant amount of road rash on his right side and an obvious open right lower extremity deformity. The patient does not believe he lost consciousness, but cannot precisely recall the events surrounding the crash. He was helmeted and has no obvious external signs of head trauma.

You splint his leg and get him into the ambulance for a secondary assessment. His initial vital signs are: heart rate of 115, blood pressure of 95/65, a respiratory rate of 24 and an oxygen saturation of 97% on room air. He appears anxious and has diffuse abdominal pain on palpation.

While en route, you place a 16-gauge IV, hang a liter of normal saline and run it wide open. A repeat blood pressure taken five minutes later is 80/60 and the patient has become slightly confused. You are concerned he is in hemorrhagic shock and you grab another liter of normal saline. While starting your second bag, you remember hearing about “permissive hypotension,” but are unsure what blood pressure parameters are considered safe for this patient or whether this patient is even a candidate for this treatment.

Introduction

The theory behind permissive hypotension in the actively hemorrhaging trauma patient is not new. The idea dates back to the early 20th century when a group of captains in the Army Medical Corps described their experience managing injuries during World War I, noting, “Injection of a fluid that will increase blood pressure has dangers in itself. If the pressure is raised before the surgeon is ready to check the bleeding that may take place, blood that is sorely needed may be lost.” ¹

Unfortunately, these recommendations were largely forgotten for most of the 20th century despite several animal studies performed in the 1950s and 1960s.²

The most current debate regarding hypotensive versus normotensive resuscitation strategies for trauma patients was sparked by a landmark randomized controlled trial (RCT) in 1994, which demonstrated a significantly lower mortality rate in hypotensive patients with penetrating torso trauma who received no or very little fluid resuscitation prior to the operating room.³

The theory behind permissive hypotension is that overly aggressive crystalloid administration leads to worsened outcomes via clot disruption (“popping the clot”), dilutional coagulopathy, dilutional anemia and hypothermia, all of which contribute to the “lethal triad” of coagulopathy, acidosis and hypothermia.

In theory, permissive hypotension maintains a careful balance between organ perfusion and the risk of bleeding or rebleeding. It should be understood that permissive hypotension is neither a treatment nor a substitute for surgery or definitive hemorrhage control, and it currently only applies to trauma patients who are actively exsanguinating in the prehospital or ED setting while awaiting resuscitation with blood products and emergent damage control surgery. Per the permissive hypotension theory, only once the bleeding is controlled should aggressive attempts be made to restore normal physiology.

Animal Studies

In the early 1990s numerous animal studies using rats, swine and sheep were performed to compare techniques for fluid resuscitation in uncontrolled hemorrhage.

In 2003, a systematic review of 52 RCTs in animal models included nine trials that compared a normotensive (mean arterial pressure >80 mmgHg) versus hypotensive resuscitation strategy.⁴ Five of these trials used rat models, while four used a porcine model. Uncontrolled hemorrhage was induced under anesthesia. When compared to normotensive resuscitation, animals who received hypotensive resuscitation had a 67% lower risk of mortality. The obvious limitation of this study was the use of animal subjects, as well as the use of a wide variety of anesthetics with different hemodynamic properties.

A more recent animal study in 2011 attempted to determine an ideal target mean arterial pressure (MAP) and maximal tolerable duration of hypotension during uncontrolled hemorrhagic shock in rats.⁵ After splenic parenchyma and splenic artery transection, uncontrolled hemorrhage continued for 20–30 minutes. Afterward, rats (who, coincidentally, have the same MAPs as humans) were fluid resuscitated with different target MAPs for one hour. Hemostasis was then achieved by splenic artery ligation. Animal survival and survival time in the 50- and 60-mmHg target MAP groups were higher than in all other groups, including the no-treatment group. This was statistically significant. Therefore, researchers concluded that 50–60 mmHg may be the ideal hypotensive resuscitation target MAP in uncontrolled hemorrhage.

Using a new target MAP of 50 mmHg, they found that when comparing a 60-, 90- or 120-minute duration of permissive hypotension, rats subjected to 120 minutes of hypotension had significantly lower survival times, as well as worsened renal and hepatic mitochondrial function. Additionally, they concluded that more than 90 minutes of hypotensive resuscitation could cause severe organ damage and should be avoided. Obviously, the most fundamental limitation of these studies is that the applicability of animal models to human injury remains unclear.

Human Studies

While the previously mentioned landmark prospective RCT in 1994 compared fluid resuscitation strategies in hypotensive patients with penetrating torso injuries,³ an RCT from the United Kingdom in 2002 looked at the effect of two different prehospital fluid protocols on overall mortality for 1,309 trauma patients, of whom more than 90% suffered blunt trauma.⁶

Paramedics in two ambulance services were randomly allocated to one of two treatment protocols. Protocol A required that IV fluids be administered on scene to all adult trauma patients who, under current procedures, would have had fluids started. Protocol B required that fluid be withheld until arrival to the hospital, unless time of transport was greater than one hour.

Overall there was no difference in six-month mortality between the groups. However, this study has been criticized for its questionable randomization technique, poor protocol compliance and poor allocation concealment.

An additional—albeit retrospective—study evaluating resuscitation strategies in patients with blunt trauma compared 150 hypotensive (SBP < 90 mmHg) patients who received either more than 500 mL fluid or no fluid at all in the prehospital setting.⁷ They were matched by Injury Severity Score (ISS) and SBP on scene, with primary outcome being SBP on arrival to the ED. While the group who received fluids had a significantly higher SBP on arrival, there was no difference in survival to hospital discharge after adjusting for age, SBP and ISS.

Another prehospital study sought to determine if there was an association between mortality and the act of simply initiating on-site intravenous fluid replacement in prehospital trauma patients suffering from blunt or penetrating trauma.⁸ It compared 217 patients who had on-site intravenous fluid replacement (IV group) with an equal number of matched patients without IVs (no-IV group) and found significantly higher seven-day mortality in the IV group (23% vs 6%, p < 0.001).

After adjusting for variables including age, gender, ISS, mechanism of injury and prehospital time, the use of on-site IV fluid replacement was associated with a significant increase in mortality. Additionally, when evaluating the association between prehospital transport times and mortality, researchers found that for prehospital times of less than 30 minutes, the use of IV fluid replacement provided no benefit. For prehospital times exceeding 30 minutes, it was associated with an increased risk of mortality.

Regardless, a Cochrane Review in 2003 (with a most recent search run in 2014) found insufficient evidence for or against the use of early or larger volumes of IV fluid administration in uncontrolled hemorrhage.⁹ The review evaluated six trials including two discussed above^3,6 in order to examine the effect of early versus delayed fluid administration, as well as larger versus smaller volume of fluid for the treatment of uncontrolled hemorrhage. It is important to note that this review was not restricted to trauma patients.

Traumatic Brain Injury

Discussion of permissive hypotension in actively hemorrhaging trauma patients usually excludes patients with traumatic brain injury (TBI) due to concern for the risk of inadequate cerebral perfusion pressure. Unfortunately, the diagnosis of TBI can be a difficult distinction to make in the prehospital setting, as altered levels of consciousness are often seen in polytrauma patients suffering hemorrhagic shock from major extracranial injuries, the administration of opioid analgesia or the ingestion of alcohol or illicit drugs.

Most but not all studies on permissive hypotension in trauma patients exclude those with TBI. Interestingly, animal models looking at effects of fluid resuscitation in rats and swine with both head injury and active exsanguination found that rats who underwent low-volume resuscitation had better neurologic outcomes and that pigs who were aggressively resuscitated had increased intracranial pressure and worse cerebral oxygen delivery, presumably secondary to cerebral edema.^10,11

This being said, a retrospective observational study in 1993 showed that a single episode of hypotension (SBP < 90 mmHg) in severely brain-injured patients was associated with a doubling of mortality and a parallel increase in morbidity rates among survivors.¹² Furthermore, patients whose hypotension was not corrected in the field had a worse outcome than those whose hypotension was corrected by time of ED arrival. Guidelines published by the Brain Trauma Foundation in 2007 advocate maintaining SBP above 90 mmHg in severe TBI, but do not specifically state whether this applies to actively hemorrhaging patients.¹³ A more recent retrospective review actually recommended that the threshold for hypotension in TBI be redefined as SBP < 110 mmHg.¹⁴ Regardless, the Brain Trauma Foundation guidelines ultimately conclude, “Clinical intuition suggests that correcting hypotension and hypoxia improves outcomes; however, clinical studies have failed to provide the supporting data.”

Current Guidelines

Trauma guidelines in the United States are largely influenced by the Eastern Association for the Surgery of Trauma (EAST) Practice Management Guideline Committee. Its most recent set of guidelines for prehospital fluid administration from 2009 conclude: “There is insufficient data to suggest that blunt or penetrating trauma patients benefit from prehospital fluid resuscitation. In patients with penetrating injuries and short transport times (less than 30 minutes), fluids should be withheld in the prehospital setting in patients who are alert or have a palpable radial pulse. Fluids (in the form of small boluses, i.e., 250 mL) should be given to return the patient to a coherent mental status or palpable radial pulse. In the setting of traumatic brain injury, however, fluids should be titrated to maintain systolic blood pressure greater than 90 mmHg (or mean pressure greater than 60 mmHg).”¹⁵ The most current Advanced Trauma Life Support (ATLS) guidelines now recommend limiting initial resuscitation to 1 liter of crystalloid, which is an update from their prior recommendation of 2 liters.¹⁶ However, these guidelines do not provide blood pressure goals.

The Europeans have been advocating permissive hypotension for over a decade. As early as 2002, expert consensus guidelines from the United Kingdom stated: “Fluid should not be administered to trauma victims before haemorrhage control if a radial pulse can be felt. Judicious aliquots of 250 mL should be titrated for other patients. If the radial pulse returns, fluid resuscitation can be suspended for the present and the situation monitored. In penetrating torso trauma the presence of a central pulse should be considered adequate.”¹⁷ Additionally, it was recommended that transfer never be delayed due to attempts to obtain IV access. These guidelines were reinforced two years later by the National Institute for Health and Clinical Excellence (NICE).¹⁸

Finally, the most updated European consensus guidelines published in 2010 recommend “a target systolic blood pressure of 80 to 100 mmHg until major bleeding has been stopped in the initial phase following trauma without brain injury (Grade 1C).”¹⁹ The guidelines also state, “A controlled hypotensive fluid resuscitation should aim to achieve a mean arterial pressure of 65 mmHg or more.”

Bottom Line

Permissive hypotension for uncontrolled hemorrhage is the first major component of damage control resuscitation that seeks to avoid excessive fluid administration in the actively exsanguinating trauma patient. Potential benefits include the prevention of clot disruption, hemodilution, hypothermia, and metabolic acidosis. However, it is important to recognize that permissive hypotension is neither a treatment nor a substitute for definitive hemorrhage control.

As there is significant heterogeneity among trauma patients with regard to mechanism (blunt vs. penetrating) and injury severity, this strategy must be carefully selected for and is often presented as a contraindication in certain patient populations, such as those with traumatic brain injury or long transport times. Regardless, it is imperative that the prehospital provider not miss non-hemorrhagic causes of hypotension such as tension pneumothorax.

While there is a paucity of well-conducted RCTs comparing hypotensive with normotensive resuscitation strategies, all studies have demonstrated either improved or, worst-case scenario, unchanged outcomes for blunt or penetrating trauma patients who have been managed with permissive hypotension in the prehospital setting. The question remains if we should be titrating to blood pressure at all (as opposed to mental status or strength of peripheral pulses), and if so, what the optimal blood pressure should be. Current guidelines have trended toward recommending small fluid boluses with minimum MAP goals cited anywhere between 50–65 mmHg, SBP between 70–90 mmHg, or titration to return of a radial pulse or cerebration.

Until future RCTs demonstrate that this approach is truly harmful to the actively exsanguinating trauma patient, permissive hypotension can be an appropriate strategy in the prehospital setting when used in the right patient, setting, and if an option in your protocols.

Case Conclusion

After administering 500 mL of normal saline, you are able to palpate a radial pulse on your motorcycle collision patient. You decide to hold on further fluid administration and pull into the ambulance bay within five minutes. On arrival, your patient’s blood pressure remains 80/60, and resuscitation with blood products is initiated. The patient ultimately goes to the operating room with orthopedic surgery for fixation of pelvic fractures and a femur fracture. He does well post-operatively and leaves the hospital three days later.

References

1. Cannon WB, Fraser J, Cowell EM. The preventive treatment of wound shock. JAMA, 1918; 70:618–21.

2. Wiles MD. Blood pressure management in trauma: from feast to famine? Anaesthesia, 2013; May;68(5):445–9

3. Bickell WH, et al. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med, 1994; 331:1105–1109.

4. Mapstone J, Roberts I, Evans P. Fluid resuscitation strategies: a systematic review of animal trials. J Trauma, 2003; Sep;55(3):571–89.

5.Li T, Zhu Y, Hu Y, et al. Ideal permissive hypotension to resuscitate uncontrolled hemorrhagic shock and the tolerance time in rats. Anesthesiology, 2011; 114(1):111–119.

6. Turner J, Nicholl J, Webber L, Cox H, Dixon S, Yates D. A randomised controlled trial of prehospital intravenous fluid replacement therapy in serious trauma. Health Technol Assess, 2000; 4:1–57.

7. Dula DJ, et al. Use of prehospital fluids in hypotensive blunt trauma patients. Prehosp Emerg Care, 2002; 6(4):417–420.

8. Sampalis JS, et al. Ineffectiveness of on-site intravenous lines: is prehospital time the culprit? J Trauma, 1997; 43(4):608–615.

9. Kwan I, Bunn F, Roberts I. Timing and volume of fluid administration for patients with bleeding. Cochrane Database Syst Rev 2003, CD002245.

10. Talmor D, et al. Treatment to support blood pressure increases bleeding and/or decreases survival in a rat model of closed head trauma combined with uncontrolled hemorrhage. Anesth Analg, 1999; 89:950–956.

11. Bourguignon PR, Shackford SR, Shiffer C, Nichols P, Nees AV. Delayed fluid resuscitation of head injury and uncontrolled hemorrhagic shock. Arch Surg, 1998; 133:390–8.

12. Chesnut RM, et al. The role of secondary brain injury in determining outcome from severe head injury. Journal of Trauma, 1993; 34: 216–22

13. Bratton SL, et al. Guidelines for the management of severe traumatic brain injury. I. Blood pressure and oxygenation. J Neurotrauma, 2007; 24(Suppl 1):S7–13.

14. Berry C, et al. Redefining hypotension in traumatic brain injury. Injury, 2012; 43: 1833–7.

15. Cotton BA, et. al. Guidelines for prehospital fluid resuscitation in the injured patient. Eastern Association for the Surgery of Trauma (EAST) practice management guideline. J Trauma, 2009; 67(2):389–402.

16. American College of Surgeons, Committee on Trauma. ATLS: Advanced Trauma Life Support Student Course Manual 9th ed. Chicago, IL: American College of Surgeons, 2012.

17. Revell M, Porter K, Greaves I. Fluid resuscitation in prehospital trauma care: a consensus view. Emerg Med J, 2002; 19:494–498.

18. National Institute for Health and Clinical Excellence. Pre-hospital initiation of fluid replacement therapy in trauma. Technology appraisal 74. January 2004.

19. Rossaint R, et al. Management of bleeding following major trauma: an updated European guideline. Critical Care, 2010; 14: R52.

Hawnwan Philip Moy, MD, is an assistant medical director of the St. Louis City Fire Department, emergency medicine clinical instructor and core faculty of the EMS Section of the Division of Emergency Medicine at Washington University in Saint Louis, MO. He completed his emergency medicine residency at Barnes Jewish Hospital/Washington University in St. Louis and his EMS fellowship at the University of North Carolina in Chapel Hill.