New Advances in the Care of the Hemorrhaging Patient

Abstract

Thirty-three percent of early traumatic deaths are secondary to hemorrhage. In addition to timing to source control, the literature has seen a surge of research on adjuncts in hemorrhage control. This review focuses on three of the latest interventions in the management of the bleeding patient; an endovascular aortic occlusive balloon, tranexamic acid (TXA), and updates to the massive transfusion protocol.

Introduction

Timely hemorrhage control is the sine qua non of a successful traumatic resuscitation. Traditional methods of hemorrhage control remain a mainstay of treatment, however several advances have been made in recent years allowing for immediate cessation of hemorrhage via less invasive means. One of these methods, an aortic balloon catheter first used in the 1950s, has made a resurgence in the last few years as a temporizing adjunct to initial resuscitation in the emergency department. Recent research in acute trauma-induced coagulopathy has revealed multiple therapeutic targets within the complexities of coagulation cascade, opening the door to novel pharmacologic agents to restore homeostasis. In practice for over a decade, the balanced resuscitation massive transfusion protocol is also evolving with civilian research into the proper ratios of component therapy and consideration of whole blood transfusion. This review article will briefly summarize recent developments in these areas of resuscitation.

Resuscitative Endovascular Balloon Occlusion of the Aorta

Occlusion of the aorta to facilitate improved cardiac and cerebral perfusion in the setting of severe hemorrhagic shock has been utilized for many decades. Traditionally, this has been performed through a thoracotomy, often performed in the emergency department, to gain proximal control of the aorta. Resuscitative thoracotomy is associated with overall poor outcomes, with the highest mortality rates seen in blunt traumatic arrests. The dismal prognosis of patients requiring and undergoing resuscitative thoracotomy has remained static despite advances in resuscitation and surgical technique.¹ Efforts to decrease time and morbidity associated with thoracic aortic control, along with improvements in endovascular technology has resulted in rekindled interest in balloon aortic occlusion for immediate hemorrhage control. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) was originally described in 1954, in which aortic balloon occlusion was utilized in three soldiers with intra-abdominal hemorrhage during the Korean War.² However, commercially available kits have not been available until recently, and as a result multiple studies have shown benefits to its use. The main advantage of balloon aortic occlusion, compared with resuscitative thoracotomy, is rapid deployment without the need for a large incision, via a familiar percutaneous Seldinger technique. Additional benefits include decreased morbidity and infectious complications.³ Of course, potential complications of this new modality include arterial access complications, balloon positioning issues, complications from balloon inflation, and sheath complications.⁴ Patient selection is a key component of success, with patients presenting with intraabdominal or pelvic hemorrhage showing the greatest benefit. Penetrating thoracic trauma is a clear contraindication as balloon occlusion may exacerbate blood loss and delay source control.⁵

Evolution in technique has been well-described and continues to be validated.^6–9 The latest iteration of the catheter uses a 7Fr sheath placed percutaneously into the femoral artery via a Seldinger technique. It is designed for deployment into two of three aortic zones; Zones 1 and 3. Zone 1 extends from the takeoff of the left subclavian artery to the celiac artery, allowing for proximal thoracic aortic control, similar to clamping through a thoracotomy incision. Zone 2 extends from the celiac artery to the lowest renal artery and is traditionally not utilized. Zone 3 extends from the lowest renal artery to the aortic bifurcation, providing control of pelvic hemorrhage, with sparing of renal vasculature. Prior to placement and deployment, the catheter is connected to an arterial waveform transducer which lies at the tip. Proper balloon positioning is suggested by a rapid spike in the systolic blood pressure read by the arterial transducer after the balloon is gently inflated. Thereafter, rapid transport to the operating or endovascular suite is necessary to gain definitive hemorrhage control and to address intraabdominal and pelvic injuries. The catheter should be removed in the operating room once surgical hemorrhage has been addressed.

The less invasive, rapid nature of the REBOA catheter has led to multiple studies showing its benefit in non-compressible truncal hemorrhage. ^3,9,10 Improved survival rates of up to 30% have been shown in patients in extremis upon arrival. This represents a marked improvement from resuscitative thoracotomy, which at best has a less than 10 percent survival in penetrating trauma, and less than 1 percent survival in blunt trauma. Questions arise however, regarding the role of selection bias in many of these studies. The REBOA catheter is less-invasive, and relatively easy to deploy, leading to earlier use in the resuscitation bay. Contrasted with thoracotomy, which many physicians are reluctant to employ prior to full cardiovascular arrest. Ongoing studies aim to directly, and prospectively compare the outcomes of REBOA and resuscitative thoractomy.³

There remain questions regarding use of the catheter, including placement in the emergency department versus the operating room, open versus percutaneous approach, and physician specialty required for placement – emergency medicine versus surgeon. In the future, we may expect to see more data emerge regarding catheter use not only in arterial hemorrhage, but also in the setting of venous injury.^11,12 Despite these questions, it appears endovascular balloon occlusion is a viable alternative to resuscitative thoracotomy, though exactly how, when and where to use the catheter will continue to be defined with emerging studies.

Tranexamic Acid

Since its discovery in 1962, tranexamic acid (TXA) has been widely recognized for its use as an antifibrinolytic.¹³ TXA is a synthetic lysine analog, most commonly intravenously administered, that acts to prevent plasmin degradation of fibrin, thereby preserving the fibrin clot matrix. Its antifibrinolytic action is currently approved for treatment in hemophilia but has seen widespread use as an adjunct to trauma resuscitation.

Prior to the CRASH-2 study in 2010, the use of TXA in bleeding trauma patients was relatively unexplored. The CRASH-2 trial was the first of its kind to assess the prehospital use of TXA in civilian trauma patients with significant hemorrhage. Findings from the trial, including over 20,000 patients, indicated a 1.5% decrease in all-cause mortality as well as a 0.8% decrease in mortality risk due to hemorrhage in patients given TXA. These findings were noted in the setting of no significant differences in quality/quantity of blood products used or number of thromboembolic complications.¹⁴ Several years later, the MATTERs study was undertaken as the first military examination of TXA. This retrospective study included severely injured combat patients requiring at least 1 unit of blood transfusion.¹⁵ Outcomes of the study showed an increased survival benefit in the TXA group, despite the fact that these patients had higher Injury Severity Scores and greater incidence of hypotension. Multiple other studies have shown survival benefit to TXA use in trauma.^16–18

The timing of administration and identification of appropriate patient subtypes are important factors to consider when deciding whom is appropriate for TXA administration. Data suggests a significant decrease in mortality due to bleeding when TXA is administered within 3 hours of injury, and an increase in mortality beyond that 3-hour mark.¹⁹ Further, there appears to be a subset of patients with fibrinolytic shutdown, that are predisposed to increased mortality risk with empiric TXA administration. This has led to more in-depth physiologic studies to determine markers for patients who may benefit from TXA, and those who should not receive it.^20,21 Prehospital TXA administration is currently being studied, and at present there is insufficient evidence to support or refute prehospital TXA use.²²

Massive Transfusion Protocols

Volume resuscitation continues to be a point of study in trauma research. Crystalloid resuscitation modalities have largely fallen out of favor, as multiple studies show increased mortality with crystalloid-based strategies. Whole blood resuscitation, as done more frequently in the military setting, has shown improvements in physiologic parameters and survival. However, it is impractical in the civilian setting governed by cost, storage, and logistical issues. Fixed-ratio blood component therapy has thus emerged as the mainstay of volume resuscitation in trauma.

Nomenclature has moved from “massive transfusion protocol” to “goal directed resuscitation” to “damage control resuscitation.” Traditionally, massive transfusion protocols (MTP) have been utilized for patients in hemorrhagic shock. Massive transfusion has most commonly been defined as the use of 10 units of blood products given within 24 hours. Goal directed resuscitation, in comparison, is driven by tailoring blood products to physiologic deficits. The newer term of “damage control resuscitation” originated in the U.S. military and was applied to resuscitation in patients suffering from hemorrhagic shock in Iraq and Afghanistan. This manner of resuscitation typically follows a fixed transfusion pattern of packed red blood cells, fresh frozen plasma and platelets, with minimization of crystalloid and permissive hypotension.^23,24

The PROMMT study, published in 2013, sought to better validate this new manner of resuscitation in the civilian setting, noting improved outcomes when the ratio to blood and platelets neared 1:1.²⁴ Expanding on these results, the PROPPR trial noted earlier hemostasis, fewer complications and lower mortality in patients receiving a 1:1:1 ratio of blood, plasma and platelets.²⁵ Success of these studies was believed to be, in-part, to earlier initiation of fixed ratio protocols, with an emphasis on early platelet transfusion. Early activation of fixed ratio transfusion modalities has spawned concern over appropriate usage of the limited supply of blood products, although these concerns have yet to be proven in the literature.

Rapid scoring systems based upon physical parameters present on admission have emerged to aid in the decision to initiate massive transfusion protocols. The Assessment of Blood Consumption score utilizes four easily attainable parameters and has demonstrated the ability to correctly identify patients in need for massive transfusion approximately 85% of the time.

As we move toward more targeted blood component resuscitation, it appears that early administration of platelets and plasma portend survival benefit in severely-injured trauma patients. Accurate and timely assessment for the need of massive transfusion is paramount, and institutions are urged to develop evidence-based protocols to drive its use.

Conclusion

While limitations exist for smaller health care institutions in caring for severely-injured trauma patients, developing technological and pharmacological therapies present opportunities to improve care for patients, including at rural critical access hospitals. The REBOA catheter, with proper training and understanding may allow for early, temporary hemorrhage control prior to definitive hemorrhage control. Early administration of TXA has the ability to stop hyperfibrinolysis and result in decreased hemorrhage related to trauma-induced coagulopathy. Development of massive transfusion protocols that include the early administration of plasma and platelets may lead to less physiologic derangement with improved mortality.