The Crashing Abdominal Aortic Aneurysm Patient
- Sep 3rd, 2019
- Drew A. Long
- categories:
Author: Drew Long, MD (@drewlong2232, EM Chief Resident-Research, San Antonio, TX) // Edited by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)
“There is no disease more conducive to clinical humility than aneurysm of the aorta.” ~William Osler
You are working at a small freestanding Emergency Department, and your next patient is a 67-year-old male with flank pain and lower abdominal pain. His heart rate is 105, blood pressure is 106/53, oxygen saturation is 99% on room air, he is breathing 22 times a minute, and he is afebrile. He has a history of hypertension, diabetes, and kidney stones. He looks mildly uncomfortable as he tells you this pain began suddenly this morning and reminds him of a kidney stone he experienced years prior.
Background
The aorta is the largest artery in the human body, carrying blood from the heart through the chest and into the abdomen, where it splits into the common iliac arteries. The aortic wall consists of 3 layers, the tunica externa (outer layer), tunica media (middle layer), and tunica intima (inner layer).1,2 An aneurysm of the aorta is a focal dilation of all three layers of the vessel wall.1,2 For the abdominal aorta, an aneurysm is considered when the size of the aorta is > 3 cm.1 Aneurysms can be divided into fusiform (most common) and saccular. The most common location for an abdominal aortic aneurysm (AAA) is infrarenal.2 Risk factors for the development of AAA include advanced age, male sex, hypertension, smoking, connective tissue disease, and a first degree relative with AAA.3
Ruptured Abdominal Aortic Aneurysm (rAAA) is a surgical emergency, with overall mortality estimated up to 80%.4 Ruptured AAA is defined as blood outside the adventitia of the aortic wall, with rupture either occurring into the peritoneal cavity or into the retroperitoneum.5 Retroperitoneal rupture is more likely to be seen in patients who present alive, as intraperitoneal rupture is usually rapidly fatal.6
History
AAA has a wide range of clinical manifestations. A patient may present asymptomatically with a AAA, with symptoms due to expansion of a AAA, or with symptoms due to rupture of a AAA. Aortic rupture usually occurs rapidly without a specific syndrome or typical presentation.7 The onset of pain may not always be sudden but may occur gradually over the course of hours to days.8 Consider symptomatic AAA or rAAA in elderly patients (>50) with abdominal pain, back pain, flank pain, lightheadedness or syncope, or/and hypotension.8 Symptoms may be caused by rapid expansion of the aneurysm, ischemia or thrombosis of branch vessels from the aorta, or frank aortic rupture.6 AAA leading to back or flank pain in a stable patient may result from simple aneurysmal dilation or rupture into the retroperitoneum with tamponade. On the other hand, peritoneal rupture or free retroperitoneal rupture will likely lead to a patient presenting in extremis with hypotension and shock.5,6
When gathering past medical and surgical history, remember to ask about history of AAA or previous surgical aortic procedures such as grafting or endovascular repair. These patients face many long-term complications such as graft infection, thrombosis, anastomotic aneurysm, dissection, and development of fistulas.9
Exam
The exam is of limited utility in the evaluation of AAA and rAAA. The classic triad of pulsatile abdominal mass, hypotension, and back pain is present in less than 50% of patients with a ruptured AAA.7 In a meta-analysis on the accuracy of abdominal palpation for the detection of AAA, the pooled sensitivity of palpation was based on AAA diameter; 29% for AAAs from 3-4cm, 50% for AAAs from 4-5cm, and 76% for AAAs >5cm.10 The Emergency Physician should not rely on the presence of an abdominal mass for the diagnosis of AAA.11
Differential Diagnosis
Presence and expansion of AAAs is usually a silent disease. When rupture does occur, it usually happens quickly without a typical presentation. The differential diagnosis for a patient presenting with hypotension, abdominal pain, back pain, flank pain, or syncope is broad. It is vital for the Emergency Physician to keep AAA on the differential diagnosis, or it will be missed. A pooled analysis with 9 studies including 1109 patients showed a 42% misdiagnosis of rAAA.12 In a retrospective study of 152 patients with missed AAA, the most common misdiagnoses were renal colic (24%), diverticulitis (13%), and GI bleeding (13%).13 The misdiagnoses as GI bleeding in this retrospective study were partially due to the presence of an aortoenteric fistula. The most common exam findings in misdiagnosed patients were abdominal pain (70%), shock (57%), and back pain (50%).13 AAA may also present with hematuria in addition to flank/abdominal pain, further confounding the diagnosis.14 The high misdiagnosis rate suggests rAAA is a difficult diagnosis to make, and the condition must be considered in elderly (>50 years old) patients presenting with abdominal pain, back pain, flank pain, and/or hypotension.
While you are continuing to gather the history on the 67 y/o male with flank and abdominal pain, you notice he becomes diaphoretic and his pain worsens. His next BP is 88/58. You start to wonder if there is something more than meets the eye…
Diagnostic Modalities
rAAA is rapidly fatal without immediate diagnosis and treatment. Ultrasound is a quick, reliable, and accurate imaging modality for the evaluation of AAAs. A study from 1998 showed decreased time to diagnosis in patients when bedside US was used (5.4 minutes), compared to 83 minutes with other diagnostic modalities (CT scan).15 Additionally, in this study, the time to disposition for patients requiring operative management was decreased from 90 to 12 minutes.15 Dent et al. found that emergency US has a sensitivity of 96.3%, specificity of 100%, negative predictive value of 98.6%, and a positive predictive value of 100% for the diagnosis of AAA.16
While US is vital to a timely diagnosis of AAA, there are several pitfalls. The most common form of rAAA is retroperitoneal, which may result in unreliable ultrasound findings.16,17 FAST exam will be positive in AAA with peritoneal rupture, but negative for retroperitoneal rupture. Also, contained ruptures may be missed due to possible presentation as a hypoechoic mixed density surrounding the aorta.16,17 This underlies the key principle in ultrasonography of the aorta to measure from outer lumen to outer lumen of the vessel wall (see Figure 1). Additionally, obese patients or the presence of bowel gas may result in a challenging and/or unreliable US exam.
A last pitfall to consider is that US measurements of the aorta are usually smaller than those on CT scan, with ultrasound most unreliable with AAAs measuring >5cm.18 To accommodate for this pitfall, discuss with vascular surgery the feasibility of CT prior to OR in stable patients with either rAAA or symptomatic AAA (Figure 2).
In addition to suspected rAAA, ultrasonography should be utilized in any hypotensive patient. An invaluable diagnostic tool in the unstable patient is the Rapid Ultrasound for Shock and Hypotension (RUSH exam). This exam includes ultrasound of the heart, inferior vena cava, focused assessment with sonography in trauma exam (FAST exam), aorta, and lungs. This allows rapid assessment of several of the deadly pathologies of hypotension. For further information on the RUSH exam, go to http://www.emdocs.net/rush-protocol/.
You tell the nurse to insert a 2ndlarge bore IV and grab the ultrasound. You see that the heart is tachycardic with adequate EF, and the IVC is collapsible. The FAST exam is negative, and you move on to the aorta. The aorta around the celiac trunk is difficult to visualize due to bowel gas, but as you move lower in the abdomen you notice a dilation of the aorta with a large amount of hypoechoic material surrounding the aorta inferior to the renal arteries. The aorta measures 6.3 cm from outer lumen to outer lumen. You suspect a retroperitoneal AAA rupture and start to think of your next steps in management of this patient.
Management
Ruptured abdominal aortic aneurysm carries a high mortality, with upward estimates of 80%.4 While every patient with rAAA requires at least 2 large bore IVs and adequate resuscitation in the ED, definitive management of rAAA occurs in the OR. In addition to resuscitation, there are several key tenets of management unique to rAAA to consider. These tenets include permissive hypotension, blood transfusion, reversal of anticoagulation, airway management, and timely transfer.
Permissive Hypotension (Hypotensive Hemostasis)
One of the key principles in management of ruptured AAA is permissive hypotension, or hypotensive hemostasis.19,20 The term permissive hypotension was first coined in management of trauma patients.21,22 This strategy emphasizes a lower blood pressure (SBP 70-100), titrated to end organ perfusion or mental status, in order to prevent “popping the clot” and to counter worsening hemostasis. Much of the literature on resuscitative management of rAAA originated in patients suffering traumatic injuries.5,8,23,24 While resuscitation of trauma patients at first emphasized intravenous crystalloid prior to blood products, the paradigm has shifted over the years, and most trauma centers currently recommend limiting crystalloid and utilizing blood products if available. Similar to patients with traumatic injuries, patients with rAAA are hypotensive due to hemorrhagic shock. Giving large amounts of crystalloid resuscitation worsens the “lethal triad” of acidosis, coagulopathy, and hypothermia. A study in 2013 in Journal of Vascular Surgery found increased risk of perioperative death with aggressive volume resuscitation prior to operative management.23 These authors found each liter of crystalloid prior to surgery increased the relative perioperative risk of death by 60%.23 When positing an explanation for these findings, the authors stated “whereas arterial hypotension facilitates local coagulation and tamponade, increased transmural pressure at the bleeding site may dislodge thrombotic plugs.”23 The 2018 Vascular Surgery Guidelines on the management of AAA recommend restricting aggressive fluid resuscitation as long as the patient has a SBP from 70 to 90mm Hgand is mentating appropriately.24
Blood transfusion
As opposed to crystalloids, blood products may aid both in maintaining systemic perfusion and avoiding coagulopathy. Unfortunately, the optimal hemostatic resuscitation strategy in rAAA has not been determined. Several studies showed increased survival in patients undergoing operative repair for rAAA with early transfusion of plasma and platelets.25 A 2016 study in European Journal of Vascular and Endovascular Surgery found 71% of patients undergoing rAAA repair required massive transfusion, defined as >4 units of PRBCs in 1 hour or 10 units of PRBCs transfused in 24 hours.26 This study found that in rAAA patients undergoing open repair, a transfusion ratio of FFP to RBC closer to 1:1 was associated with lower mortality risk, which corresponded with previous studies.25,27,28
There have not been any large studies examining the use of whole blood transfusion in patients with rAAA. A 2012 study in Western Vascular Society examined intraoperative blood product resuscitation and found greater use of autotransfusion but not FFP was associated with survival in rAAA patients undergoing massive transfusion.29 The strategy has shifted in many large trauma centers from a balanced transfusion ratio of 1:1:1 (of PRBCs, FFP, and Platelets) to a transfusion strategy utilizing whole blood. One of the main disadvantages of component therapy is that it yields a more dilute solution than whole blood. In a 1:1:1 blood component transfusion ratio, the hematocrit is estimated to be 29%, the platelet count is about 90,000/mL, and the coagulation factors are about 62% as concentrated as those in whole blood concentrations.30 As much of the management regarding optimal resuscitation in patients with rAAA came from preceding research conducted on transfusion strategies in patients suffering traumatic injuries, the paradigm may shift towards patients with rAAAs receiving resuscitation with whole blood. Whole blood yields a more physiologic resuscitation medium than component therapy and may avoid both worsening coagulopathy and tissue hypoperfusion, and if available, should be used for resuscitation in patients with rAAA. If not available, a 1:1:1 ratio is recommended.
Anticoagulation Reversal
There are no studies evaluating efficacy of reversal of anticoagulation in patients with rAAA. If a patient with a AAA or rAAA is unstable and on anticoagulation, they should be reversed with the appropriate agent similar to any other patient on an anticoagulant presenting with a life-threatening bleed. While there is a paucity of data regarding tranexamic acid for patients with rAAA, there are multiple studies showing early use of TXA both reduced bleeding and mortality in trauma patients with hemorrhagic shock.31,32 If managing an unstable patient with rAAA, early administration of TXA should be considered as a useful adjunct to resuscitation.
Airway management
There is little data examining the optimal airway management in patients with AAA. However, there is a plethora of evidence on airway management in critically ill patients. One study showed 30% of critically ill patients had cardiovascular collapse after intubation.33 An article in Western Journal of Emergency Medicine examined predictors of cardiovascular collapse from airway management, citing four main factors: hypoxemia, hypotension, metabolic acidosis, and right ventricular failure.34 Preinduction hypotension and shock index > 0.8 (HR/BP) has been shown to predict patients at risk for post-intubation hypotension.35,36
In patients with AAA, the best airway management is to delay a definitive airway until the patient reaches the OR. As one of the key tenets in the management of rAAA is permissive hypotension, maintaining a SBP of 70-100 mm Hg places these patients at high risk for peri-intubation hypotension and cardiac arrest.34-36 If these patients require definitive airway management prior to the OR, use a small dose of induction agent and be prepared to manage worsening hypotension and possible cardiac arrest.
Hypertension
On the other extreme, in the hypertensive AAA patient, blood pressure management may be indicated. Increased blood pressure may increase shearing force on the aorta wall, which may worsen the rupture and decrease potential hemostasis. Beta-blocker therapy may be used to both reduce blood pressure and stress on the arterial wall, with vasodilatory agents such as nitrates added as necessary to achieve normotension. Calcium channel blockers can be used in patients in whom nitrates are contraindicated.8
Transfer
Definitive management of the AAA patient requires a vascular surgeon. If a center does not have vascular surgery, the patient requires rapid transfer to a center that does have a vascular surgery team. Similar to management of patients with STEMI and stroke, establishing a regional protocol for transfer of patients with rAAA is essential. One study showed in the presence of a protocol for transfer and treatment, mortality for patients with rAAA was 18%, compared to 32% in the absence of a protocol.37 With an organized regional transfer system, operative repair can be performed in the majority of patients with rAAA, with one study showing >95% of patients with a ruptured AAA surviving to receive operative management with 67% survival.38
A goal of door-to-intervention, or door-to-OR, time of <90 minutes is recommended by the 2018 Vascular Surgery practice guidelines for patients with rAAA.24 The Vascular Surgery Practice Guidelines suggest a 30-30-30 model for transfer of patients with rAAA. Time zero is defined as the time of first medical contact. During the first 30 minutes the Emergency Physician evaluates, diagnoses, begins resuscitation, and initiates the transfer process. The next 30 minutes entails rapid transfer to a center with vascular surgery team and includes physician-physician phone handoff and EMS transport and management. The last 30 minutes is time from patient arriving to the accepting center, receiving evaluation by in-house vascular surgery, and arrival to the OR for intervention by vascular surgery. A diagram of this protocol is shown in Figure 3.24
While 90 minutes from first medical contact to definitive management (especially if a patient requires transfer) may seem infeasible, this goal underlies the importance of timely management of rAAA. Due to the high rate of misdiagnosis of AAA, this may be challenging in patients presenting with normal blood pressure and vague symptoms such as back pain, flank pain, or abdominal pain. However, in the hypotensive patients with rAAA, 30 minutes should allow ample time for bedside ultrasonography to diagnose AAA, begin initial resuscitation, and arrange for definitive care.
Another issue is which patients with rAAA should be transferred. As previously stated, US cannot distinguish between symptomatic and retroperitoneal ruptured AAA. All symptomatic AAA should be assumed to be retroperitoneal ruptures until proven otherwise. From the Journal of Vascular Surgery, it is recommended that for rAAA, “patients with good functional status and without severe comorbidity should be transferred without delay” (Level 1A recommendation).24 While vascular surgery recommends delayed repair in patients with significant comorbidities and symptomatic AAAs, the decision should be left to the vascular surgery and anesthesia teams to decide which patients should receive immediate intraoperative management vs delayed management. The Emergency Physician should arrange for definitive care for any patient discovered to have a symptomatic AAA or a rAAA. The only contraindication to transfer is patients with rAAAs in cardiac arrest, as outcomes are extremely poor in these patients.
Controversies
An emerging therapy for the treatment of traumatic hemorrhage is resuscitative endovascular balloon occlusion of the aorta (REBOA). This therapy involves use of a balloon catheter in the aorta to prevent blood flow to the site of hemorrhage.39 This is a potential therapy to prevent bleeding and exsanguination from the anatomic site of a rAAA.39 If used in a patient with a rAAA, this is a temporizing measure, designed to help the patient survive until definitive management in the OR. Several studies have evaluated use of REBOA in the ED for AAA. A systematic review and meta-analysis in 2018 included 89 studies and evaluated the use of REBOA in trauma patients and ruptured aortic aneurysm patients.37 Fifty of these studies evaluated patients with hemorrhage arising from rAAA. This study found improvement of hemodynamics (increased mean systolic pressure by 56 mmHg) in patients following REBOA use.39 Unfortunately, REBOA is not without complications. These can include incorrect placement, limb ischemia, and multisystem organ failure. Additionally, placement of a REBOA should not be used if it delays definitive surgical management of a patient with a rAAA.
The 67 y/o male patient with the ruptured AAA continues to mentate at baseline, even though his BP continues to drop to 80/59 and his HR increases to 123. You call for 2 units of O+ whole blood, order 1g of TXA, and contact the nearest medical center with a vascular surgery team. The vascular surgery team accepts the patient, and you start to arrange transfer. The EMS service arrives in the next 15 minutes. At this point the patient has stabilized, with a BP of 98/55 and HR 112 after 1 unit of whole blood. You instruct the EMS crew to give the 2ndunit of whole blood during transport, with a goal SBP of 70-100 and normal mental status. The patient is successfully transferred from your freestanding ED to a larger medical center for more definitive care.
Conclusion
Abdominal aorta aneurysm is defined as a dilation of the abdominal aorta >3 cm. This condition carries high morbidity and mortality, particularly in patients presenting with a ruptured AAA. Symptomatic AAA or rAAA should be considered in patients older than 50 with back pain, flank pain, abdominal pain, syncope, or hypotension. US is an effective and rapid screening test that can be utilized to diagnose AAA. Every patient with AAA should receive 2 large bore IVs for anticipated resuscitation. Other key tenets of management include permissive hypotension, resuscitation with whole blood or balanced blood component therapy, tranexamic acid, and reversal of anticoagulation if necessary. Definitive airway management should be delayed until the patient receives operative management if possible. As soon as the diagnosis of AAA is made, the Emergency Physician should contact vascular surgery for definitive management. Vascular Surgery Guidelines suggest a 30-30-30 timeframe for transfer of patients with ruptured AAA. The first 30 minutes includes initial diagnosis and resuscitation, the second 30 minutes includes transfer, and the last 30 minutes includes time for arrival to a center with vascular surgery to the OR for definitive management. In order for this timeframe to work, the Emergency Physician must maintain a high suspicion for AAA, diagnose AAA rapidly, begin resuscitation promptly, and arrange for definitive management as soon as the diagnosis is made.
Pearls
- Consider symptomatic or ruptured AAA in any patient (especially elderly) with abdominal pain, flank pain, back pain, syncope, especially if he/she is presenting with hypotension.
- The RUSH exam is key in any hypotensive patient and can rapidly diagnose AAA.
- Resuscitation of rAAA includes 2 large bore IVs, early blood products, minimizing crystalloid, permissive hypotension, tranexamic acid, and delayed airway management.
- As soon as a AAA or rAAA is diagnosed or suspected, vascular surgery consultation is recommended. Surgery is required for definitive management.
- Permissive hypotension is maintaining BP as low as possible to maintain end organ perfusion in an attempt to preserve hemostasis.
- Vascular surgery guidelines recommend a 90-minute time from first medical contact to definitive operative management for ruptured AAA, with a 30-minute time from first medical contact to transfer to a center with definitive management.
- REBOA is a potential therapy to attempt in the crashing AAA patient, but should not be used if it delays time to the operating room for definitive management.
References/Further Reading
- Almahameed A, Latif AA, Graham LM. Managing abdominal aortic aneurysms: Treat the aneurysms and the risk factors. Cleve Clin J Med. 2005;72:877-888.
- Mitchell MD, Rutherford RB, Krupski WC. Infrarenal aortic aneurysms. In: Rutherford RB, ed. Vascular Surgery. 4th Philadelphia, PA: WB Saunders; 1995.
- Lederle FA, Johnson GR, Wilson SE, et al. The aneurysm detection and management study screening program: validation cohort and final results. Aneurysm Detection and Management Veterans Affairs Cooperative Study Investigators. Arch Intern Med.2000; 160:1425.
- Taylor LM Jr, Porter JM.Basic data related to clinical decision making in abdominal aortic aneurysms. Ann Vasc Surg.1987;1:502-4.
- Gawenda M, Brunkwall J. Ruptured abdominal aortic aneurysm—the state of play. Dtsch Arztebl Int. 2012;109(43): 727-32.
- Barkin AZ, Rosen CL. Ultrasound detection of abdominal aortic aneurysm. Emerg Med Clin North Am. 2004;22:675-682.
- Tayal VS, Graf CD, Gibbs MA. Prospective study of accuracy and outcome of emergency ultrasound for abdominal aortic aneurysm over 2 years. Acad Emerg Med. 2003 Aug;10(8)867-871.
- Reed, KC, Curtis LA. Aortic Emergencies—Part II: Abdominal Aneurysms and Aortic Trauma. Emergency Medicine Practice. 2006 Mar;8(3):1-24.
- Bhalla S, Menias CO, Heiken JP. CT of acute abdominal disorders. Radiol Clin North Am. 2003;41:1153-1169.
- Lederle FA, Simel DL. The rational clinical examination: Does this patient have an abdominal aortic aneurysm. 1992;281:77-82.
- American College of Emergency Physicians. Clinical policy: critical issues for the initial evaluation and management of patients presenting with a chief complain of nontraumatic acute abdominal pain. Ann Emerg Med. 2000;36:406-415.
- Azhar B, Patel SR, Holt PJ, et al.Misdiagnosis of ruptured abdominal aortic aneurysm: systematic review and meta-analysis. J Endovasc Ther. 2014 Aug;21(4):568-75.
- Marston WA, Ahlquist R, Johnson G, et al. Misdiagnosis of ruptured abdominal aortic aneurysms. J Vasc Surg. 1992;16:17-22.
- Pomper SR, Fiorillo MA, Anderson CW, et al. Hematuria associated with ruptured abdominal aortic aneurysms. Int Surg. 1995;80:261-263.
- Plummer D, Clinton J, Matthew B. Emergency department ultrasound improves time to diagnosis and survival in ruptured abdominal aortic aneurysm [abstract]. Acad Emerg Med. 1998;5:417.
- Dent B, Kendall RJ, Boyle AA, et al. Emergency ultrasound of the abdominal aorta by UK emergency physicians: A prospective cohort study. Emerg Med J. 2007;24(8):547-549.
- Mateer J, Ma O. Emergency Ultrasound. New York, NY: McGraw-Hill; 2002.
- Sprouse LR II, Meier GH III, Lesar CJ, et al. Comparison of abdominal aortic aneurysm diameter measurements obtained with ultrasound the computed tomography: Is there a difference? J Vasc Surg. 2003;38(3):466-471.
- Lachat M, Enzler M. Innovations in the treatment of ruptured AAA may improve future outcome. 2007;36: 227-8.
- Reimerink JJ, van der Laan MJ, Koelemay MJ, et al. Systematic review and meta-analysis of population-based mortality from ruptured abdominal aortic aneurysm. Br J Surg.2013;100:1405-13.
- Rossaint R, Bouillon B, Cerny V, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition. Crit Care. 2016;20:100.
- Shaftan GW, Chiu CJ, Dennis C, Harris B. Fundamentals of physiologic control of arterial hemorrhage. Surgery. 1965;58(5):851–6.
- Dick F, Erdoes G, Opfermann P, et al. Delayed volume resuscitation during initial management of ruptured abdominal aortic aneurysm. J Vasc Surg.2013 Apr;57(4):943-50.
- Chaikof EL, Dalman RL, Eskandari MK, et al.The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm. J Vasc Surg. 2018 Jan;67(1):2-77.e2.
- Mell MW, O’Neil AS, Callcut RA, et al. Effect of early plasma transfusion on mortality in patients with ruptured abdominal aortic aneurysm. 2010;148(5):955e62.
- Montan C, Hammar U, Wikman A, et al.Massive Blood Transfusion in Patients with Ruptured Abdominal Aortic Aneurysm. Eur J Vasc Endovasc Surg. 2016 Nov;52(5):597-603.
- Borgman MA, Spinella PC, Perkins JG, et al. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a com- bat support hospital. J Trauma.2007;63(4):805e13.
- Johansson PI, Stensballe J, Rosenberg I, et al. Proactive administration of platelets and plasma for patients with a ruptured abdominal aortic aneurysm: evaluating a change in transfusion practice. 2007;47(4): 593e8.
- Kauvar DS, Sarfati MR, Kraiss LW.Intraoperative blood product resuscitation and mortality in ruptured abdominal aortic aneurysm. J Vasc Surg. 2012 Mar;55(3):688-92.
- Ponschab M, Schochl H, Gabriel C, et al. Haemostatic profile of reconstituted blood in a proposed 1:1:1 ratio of packed red blood cells, platelet concentrate and four different plasma preparations. 2015; 70: 528–36.
- Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ.Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg. 2012 Feb;147(2):113-9.
- Roberts I, Shakur H, Coats T, et al.The CRASH-2 trial: a randomized controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients.Health Technol Assess. 2013 Mar;17(10):1-79.
- Perbet S, De Jong A, Delmas J, et al. Incidence of and risk factors for severe cardiovascular collapse after endotracheal intubation in the ICU: a multicenter observational study. Crit Care. 2015;19:257.
- Mosier JM, Joshi R, Hypes C, et al. The Physiologically Difficult Airway. West J Emerg Med. 2015;16(7):1109–1117.
- Green RS, Edwards J, Sabri E, et al. Evaluation of the incidence, risk factors, and impact on patient outcomes of postintubation hemodynamic instability. 2012;14:74-82.
- Green R, Hutton B, Lorette J, et al. Incidence of postintubation hemodynamic instability associated with emergent intubations performed outside the operating room: a systematic review. 2014;16:69-79.
- Moore R, Nutley M, Cina CS, et al. Improved survival after introduction of an emergency endovascular therapy protocol for ruptured abdominal aortic aneurysms. J Vasc Surg.2007;45:443-50.
- Haveman JW, Karliczek A, Verhoeven EL, et al. Results of streamlined regional ambulance transport and subsequent treatment of acute abdominal aortic aneurysms. Emerg Med J.2006;23:807-10.
- Borger van der Burg BLS, van Dongen TTCF, Morrison JJ, et al. A systematic review and meta-analysis of the use of resuscitative endovascular balloon occlusion of the aorta in the management of major exsanguination. Eur J Trauma Emerg Surg. 2018;44(4):535–550.