Читать книгу Surgical Critical Care and Emergency Surgery - Группа авторов - Страница 18

Lindsey Karavites, MD and Kazuhide Matsushima, MD

Division of Acute Care Surgery, University of Southern California, LAC+USC Medical Center, Los Angeles, CA, USA

1 57‐year‐old man was brought into the trauma bay after a witnessed fall from his third‐floor apartment onto the sidewalk. He is lethargic but arousable with blood pressure 80/40 mmHg and heart rate 135 beats/min. He is noted to have a scalp laceration and bilateral lower extremity deformities with significant blood loss noted at the scene. What is one advantage of selecting low titer whole blood for his resuscitation over component therapy?24‐hour survival benefit in the severely injured.Decreased 24‐hour total transfusion requirement.Cost effectiveness of prolonged time to product expiration.Decreased transfusion reactions due to standardized safe antibody titer levels.No risk of post‐transfusion hemolysis.Increasing retrospective data from the military medical community for use of whole blood in resuscitation have led to similar efforts in civilian trauma patients. Low titer whole blood may have institution specific definitions; however, it is generally considered unseparated blood collected from a donor with low titers of Ig M and/or IgG anti‐A and anti‐B. Implementation of cold‐stored low‐titer anti‐A and anti‐B group O whole blood (LTOWB) transfusion strategies are in place in civilian trauma centers but further prospective data are necessary to examine discrete comparisons of whole blood without simultaneous use of components, verification of appropriate safety, and determination of cost–benefit analyses. To date, the only randomized controlled pilot trial comparing the use of whole blood to component therapy demonstrated that those receiving whole blood required fewer blood products at 24 hours with no difference in mortality. Another recent study comparing between LTOWB vs. component therapy showed that the use of LTOWB was significantly associated with a reduction in post‐emergency department blood transfusion and improved 30‐day survival. Additional advantages include ease of use with single bag product storage, reduced human error with administration, decreased transfusion reactions, although no standard safe antibody titer levels have been established, as well as avoidance of excessive volume, additives and anticoagulants.Answer: BCotton, B.A, Podbielski, J., Camp, E., et al. (2013) Early Whole Blood Investigators: A randomized controlled pilot trial of modified whole blood versus component therapy in severely injured patients requiring large volume transfusions. Ann Surg ,258 (4), 527–532.Williams, J., Merutka, D., Bai, Y., et al. (2019) Safety profile and impact of low‐titer group O whole blood for emergency use in trauma. J Trauma Acute Care Surg , 88 (1), 87–93.

2 When massive transfusion is indicated, the American College of Surgeons Trauma Quality Improvement Program currently recommends one unit of apheresis platelets to be given following the administration of how many units of packed red blood cells (PRBCs) in the setting of balanced component 1:1–1:2 (Plasma/PRBCs) resuscitation?12468Evidence currently supports a balanced transfusion strategy that targets a plasma:PRBC ratio approaching 1:1. There is no apparent increase in respiratory complications in the 1:1 group, despite prior retrospective associations between increased plasma transfusion and acute respiratory distress syndrome (ARDS). The latest massive transfusion guidelines from American College of Surgeons Trauma Quality Improvement Program (ACS‐TQIP) recommends a 1:1–1:2 (plasma/RBCs) transfusion ratio with one unit of apheresis platelets given for every 6 units of RBCs transfused.Answer: DCryer, H.G., Nathens, A.B., Bulger, E.M. (2014), American College of Surgeons Trauma Quality Improvement Program Massive Transfusion in Trauma Guidelines. facs.org/‐/media/files/quality‐programs/trauma/tqip/transfusion_guildelines.ashx.

3 A 75‐year‐old woman with cirrhosis arrives in the trauma bay after being hit by a car while crossing the street. Her initial work up revealed two left‐sided rib fractures and a grade 3 splenic laceration without evidence active extravasation. She is hemodynamically stable and her initial laboratory tests reveal a hemoglobin of 9.5 g/dL, hematocrit of 29%, platelet count of 125 000/mm 3 , and international normalized ratio of 3.1. While being managed nonoperatively in the intensive care unit, she becomes hypotensive. 1 unit of packed red blood cells (PRBCs) and 1 unit of fresh frozen plasma (FFP) are transfused. Shortly after the transfusions are completed, she develops tachycardia and dyspnea requiring supplement oxygen. Which of the following is the most diagnostic of transfusion‐associated acute lung injury (TRALI) as the source of her new oxygen requirement?Bilateral infiltrate on chest radiographyHeart Rate: 135PaO2/FiO2: 300Systolic Blood Pressure: 90Temperature 37.9The differential diagnosis of respiratory distress is broad in the setting of polytrauma, especially in those with known rib fractures and those requiring transfusions. Transfusion‐related acute lung injury (TRALI) is defined by the documentation of acute hypoxemia with PaO2/FIO2 ratio (P/F) of less than 300 mm Hg, bilateral infiltrates on chest radiograph (in the absence of left atrial hypertension), and the absence of acute injury before transfusion. In addition, onset of transfusion‐related acute lung injury is required to have occurred within 6 hours of the last transfusion. Transfusion‐associated circulatory overload (TACO) was defined as acute onset or worsening respiratory distress during or up to 12 hours after transfusion, plus evidence of acute or worsening pulmonary edema and volume overload. Signs/symptoms include fever, dyspnea, and hypotension. The treatment of TRALI is respiratory support, including measures to avoid worsening of lung injury. Transfusion of all types of blood products can cause TRALI. Pathogenesis is related to donor antibodies in the transfused blood and may also be related to modifications of stored blood. Measures to prevent TRALI include a restrictive transfusion policy, as well as blood bank measures such as predominant use of plasma from male donors.Answer: ASemple, J.W., Rebetz, J., and Kapur, R. (2019) Transfusion‐associated circulatory overload and transfusion‐ related acute lung injury. Blood , 133 (17), 1840–1853.

4 A 45‐year‐old man requires helicopter evacuation following a farming accident in which he was pinned under a peanut trailer experiencing crush injuries to his lower extremities. Transport time to nearest facility is approximately 35 minutes. His heart rate is 145 per minute, systolic blood pressure is 80 mmHg, and he appears confused. Prehospital providers obtained IV access and administered 1 L of crystalloid in the field. Repeat vitals en route demonstrate a heart rate of 125 and systolic blood pressure of 90. What additional resuscitation, if any, would offer the greatest survival benefit while traveling to the nearest hospital?Additional 1 L of crystalloid1 unit packed red blood cell (PRBC)1 unit fresh frozen plasma (FFP)1 unit PRBC + 1 unit FFPNo additional resuscitation requiredMore than one‐third of preventable deaths due to hemorrhage occur in the field. Evidence gathered from the Prehospital Air Medical Plasma Trial and its secondary analysis, patients with signs of shock should receive prehospital blood products whenever available. Crystalloid alone appears to be inferior to blood products and has a dose–response increase in mortality in this setting. If both PRBC and plasma are available, patients should receive both, as reduction in mortality has been demonstrated. If only 1 product can be added, plasma should be favored, as there is level 1 evidence to support it. The additive benefit of PRBC and plasma also suggests that there may be a benefit to the use of whole blood in the prehospital setting. Finding a balance between organ perfusion and hemostasis is critical when resuscitating a severely injured trauma patient. Answer E would allow for permissive hypotension which would not be advisable for this patient given that his mechanism may have also resulted in a traumatic brain and/or spinal cord injury which have yet to be ruled out. Permissive hypotension is not recommended in the setting of central nervous system injury.Answer: DGuette, F.X., Sperry, J.L., Peitzman, A.B., et al. (2019) Prehospital blood product and crystalloid resuscitation in the severely injured patient: A secondary analysis of the prehospital air medical plasma trial. Ann Surg. doi: 10.1097/SLA.0000000000003324.

5 Which of the following patients would receive the most benefit from administration of tranexamic acid (TXA)?25‐year‐old male with massive transfusion protocol activated approximately 9 hours post fall from height.80‐year‐old female with a nondisplaced pelvic fracture and stable vital signs on Warfarin.35‐year‐old male with massive transfusion protocol activated for hemodynamic instability 1‐hour after sustaining gunshot wounds to the chest.8‐year‐old male receiving 1:1 component resuscitation immediately following motor vehicle collision.65‐year‐old female with a history of stroke receiving 1:1 component resuscitation after being struck by a car.TXA is a synthetic derivative of the amino acid lysine that inhibits fibrinolysis by blocking the lysine binding site on plasminogen. In patients undergoing elective procedures, TXA has been shown to reduce the need for blood transfusion. The CRASH‐2 trial, a randomized, placebo‐controlled trial of TXA in trauma patients with significant bleeding, demonstrated a significant reduction in all‐cause mortality, as well as deaths due to hemorrhage, in the patients who received TXA within 3 hours. Trial results have been met with both enthusiasm and controversy regarding the application antifibrinolytics for patients with traumatic bleeding. As a consequence, several high‐quality randomized controlled trials are currently underway to help further elucidate the utility of TXA and other antifibrinolytics in traumatic injury, as well as other conditions with severe bleeding. Based on current evidence, TXA is most beneficial in the setting of trauma when empirically used in massive transfusion situations in those patients presenting within 3 hours of injury. Further trials are needed to refine and optimize TXA dosing regimens due to concern for seizures with higher dosing. There was no increase in vascular occlusive events in patients receiving TXA in the CRASH‐2 trial. However, history of or risk factors predisposing to thromboembolic events is considered a relative contraindication, as is the use of TXA in patients with subarachnoid hemorrhages owing to the association with increased cerebral ischemia. Although TXA has been studied extensively in the adult trauma patient, less evidence exists for children, and its use in the pediatric trauma population is not as widespread.Answer: CRamirez, R.J., Spinella, P.C., and Bochicchio, G.V. (2017) Tranexamic acid update in trauma. Crit Care Clin , 33 (1), 85–99.The CRASH‐2 Collaborators (2010) Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant hemorrhage (CRASH‐2): a randomized, placebo‐controlled trial. Lancet , 376 (9734), 23–32.

6 A 28‐year‐old man is taken emergently to the operating room for abdominal exploration after sustaining a gunshot wound to the right upper quadrant. On arrival, he was found to be in hemorrhagic shock and massive transfusion protocol was initiated. Intraoperatively, the bleeding is difficult to control, and diffuse oozing is noted as the case progresses. Rapid thrombelastography (TEG) is performed and reveals a prolonged R value, K value is slightly prolonged, α‐angle is reduced, a normal maximum amplitude. What component replacement would aid in resuscitative efforts?CryoprecipitatePlateletsTranexamic acidFresh frozen plasma (FFP)Platelets and cryoprecipitateThrombelastography (TEG) has been used as a guide to blood product replacement for acutely bleeding patients and has been studied as an alternative to ratio‐based mass transfusion protocols. TEG offers the advantage of real‐time point of care testing of coagulation function in whole blood. A rapid TEG differs from conventional TEG because tissue factor is added to the whole blood specimen, resulting in accelerated reaction and subsequent analysis. See graphic representation and interpretation below (Figure 11.1 and Table 11.1). The R value, which is recorded as activated clotting time (ACT) in the rapid TEG specimen, reflects clotting factor activation and the time to onset of clot formation. Normal R time ranges from 5–10 minutes. A deficiency of clotting factors will result in a prolonged ACT, which can be treated by FFP transfusion. The K value is the interval from the beginning of clot formation to a fixed level of clot firmness measured at a standard 20 mm amplitude. It reflects the activity of thrombin which cleaves fibrinogen. Normal K time is 1–3 minutes. Similarly, the α angle reflects the rate of clot formation and is another measure of fibrinogen activity. Normal α angle is 53–72°. A prolonged K value and a decreased α angle represent a fibrinogen deficit which can be treated by transfusion of FFP or cryoprecipitate. The maximum amplitude (MA) measures the final clot strength, reflecting the end result of platelet–fibrin interaction. Normal MA is 50–70 mm. If the MA is decreased after transfusion of FFP, then platelet transfusion should be considered. The patient described has a prolonged ACT as well as prolonged K time and decreased α angle. This is best treated by FFP transfusion to replace both the clotting factor deficiency and fibrinogen deficiency. If the K time remains prolonged after correction of the ACT, then cryoprecipitate can be given.Figure 11.1 Normal thromboelastogram tracingTable 11.1 Normal thromboelastogram tracingThromboelastogram (TEG) InterpretationComponentsDefinitionNormal valuesProblemTreatmentR TimeTime to onset of clot formation5–10 minutesCoagulation factorsFFPK TimeTime until fixed strength is reached1–3 minutesFibrinogenCryoprecipitateAlpha angleSpeed of fibrin accumulation53–72°FibrinogenCryoprecipitateMaximum amplitudeHighest vertical amplitude of the TEG50–70 mmPlateletsPlateletsLysis at 30 minutes (LY30)Percentage of amplitude reduction 30 minutes after maximum amplitude0–8%Excess fibrinolysisTranexamic acidAnswer: DInaba, K., Rizoli, S., Veigas, P.V., et al. (2015) 2014 consensus conference on viscoelastic test‐based transfusion guidelines for early trauma resuscitation: report of the panel. J Trauma Acute Care Surg , 78 (6), 1220–1229.Gonzalez, E., Pieracci, F.M., Moore, E.E., et al. (2010) Coagulation abnormalities in the trauma patient: The role of point‐of‐care thromboelastography. Semin Thromb Hemost , 36 (7), 723–737.

7 Which of the following is not an advantage of rapid thrombelastography (TEG) in the setting of trauma?Viscoelastic assays better characterize trauma‐induced coagulopathy when compared to conventional coagulation profiles.TEG can better direct massive transfusion than protocol‐driven balanced ratio component therapy allowing for reduced product administration.TEG is the only clinically available means of detecting fibrinolysis accurately and in a point‐of‐care setting.TEG results are available within minutes.TEG has demonstrated survival benefit in guiding the management of thromboembolic events in the setting of post‐injury hypercoagulability.TEG characterizes the life‐span of a clot; from initial fibrin formation, to incorporation of platelets, to fibrinolysis. With results available within 10 minutes, an initial hemostatic assessment with TEG identifies patients at risk for post‐injury coagulopathy upon arrival. The point‐of‐care variables that result enable the clinician direct management of patients in the trauma bay in real time while allowing for a data‐driven, goal‐directed hemostatic resuscitation. A recent clinical trial demonstrated that the use of TEG to guide massive transfusion in trauma patients, compared with conventional coagulation assays, resulted in a decrease in mortality while using fewer blood products. TEG is also currently used for patient‐personalized administration of antifibrinolytics (e.g., tranexamic acid) based on LY30 parameters rather than administering TXA empirically when massive transfusion is required. Additionally, because TEG characterizes dynamic hypercoagulability and simultaneously reflects the antithrombotic effect of chemoprophylaxis, it may serve as a template for designing tailored thromboprophylaxis regimens; however additional studies are needed, and survival benefit has yet to be demonstrated.Answer: EGonzalez, E., Moore, E.E., Moore, H.B., et al. (2016) Goal‐directed hemostatic resuscitation of trauma‐induced coagulopathy: A pragmatic randomized clinical trial comparing a viscoelastic assay to conventional coagulation assays. Ann Surg , 263 (6), 1051–1059.Gonzalez, E., Pieracci, F.M., Moore, E.E., et al. (2010) Coagulation abnormalities in the trauma patient: The role of point‐of‐care thromboelastography. Semin Thromb Hemost , 36 (7), 723–737.

8 A 29‐year‐old man dropped off by his friend after crashing his all‐terrain vehicle. Upon evaluation, he has altered mental status and a distended abdomen that is diffusely tender. His blood pressure is 80/60 mmHg and heart rate 140 per minute. He does not respond to initial resuscitation and massive transfusion protocol is activated. The time of his injury is unclear at this time and his initial thromboelastography (TEG) results reveal normal R time, normal k time, normal MA and LY30 greater than normal. What is the next best step in management?Give 2 units of fresh frozen plasmaAdminister 1 g of tranexamic acid (TXA)Give 1 unit of plateletsGive 10 units of cryoprecipitateGive cryoprecipitate and plateletsTEG is useful in evaluating trauma‐induced coagulopathy for goal‐directed therapy. In this instance, the patient has massive transfusion requirements and time of injury is unclear. Rather, than empirically administering TXA, the TEG is useful in quickly identifying that this patient would likely benefit from its administration. LY30 greater than 3–5% is representative of hyperfibrinolysis. It seems intuitive that an antifibrinolytic medication should only be administered to those who have demonstrable hyperfibrinolysis; however, advocates for its empiric administration to all trauma patients exist. As evident by the CRASH‐II trial, mortality benefit was seen in all trauma patients receiving TXA; however, this study also found that administration of tranexamic acid greater than 3 hours after injury was associated with increased mortality. Therefore, it is prudent to utilize TEG to ascertain those patients most likely to benefit from TXA.Answer: BGonzalez, E., Moore, E.E., and Moore, H.B. (2017) Management of trauma‐induced coagulopathy with thrombelastography. Crit Care Clin , 33 (1), 119–134.

9 A 35‐year‐old man is recovering in the intensive care unit 1 day after undergoing a damage control laparotomy for hemodynamic instability following a motorcycle crash in which he suffered a severe left pulmonary contusion, pneumothorax, femur fracture, grade 5 splenic laceration requiring splenectomy and destructive colon injury. He required massive transfusion as part of his resuscitation. Currently, his blood pressure is 110/75 mm Hg and heart rate 100. He is awake and breathing spontaneously on the ventilator with minimal support. His laboratory results reveal a hemoglobin of 7.9 g/dL, platelets 40 000/mm 3 , prothrombin time 16 seconds, partial thromboplastin time 38 seconds, and fibrinogen 255 g/dL. He has remained stable and off vasopressors since admission to the ICU.Which product(s) should be transfused at this time?Red blood cells, platelets, and plasmaRed blood cells, platelets, and cryoprecipitateTranexamic AcidNo products at this timeRed blood cellsBased on guidelines for enrollment in the current Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) study, criteria for stopping the massive transfusion protocol should include both anatomic (control of bleeding) and physiologic criteria (normalizing hemodynamic status). In this stable trauma patient without evidence of active bleeding, no blood products are needed at this time. A restrictive transfusion strategy maintaining hemoglobin at 7.0–9.0 g/dL has been shown to be as effective as a liberal transfusion strategy maintaining hemoglobin concentration at 10.0–12.0 g/dL. For those with an APACHE II score ≤ 20, 30‐day mortality is significantly less with a restrictive strategy. In the absence of clinical bleeding, fresh frozen plasma transfusion may be associated with an increased incidence of acute lung injury. Evidence to support prophylactic platelet transfusion in critically ill patients without active bleeding is conflicting. Several authors have recommended avoidance of prophylactic platelet transfusion altogether, while others have recommended thresholds ranging from 10 000/mm3 to 100 000/mm3 for patients at risk of bleeding.Answer: DHolcomb, J.B., Tilley, B.C., Baraniuk, S., et al. (2015) Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: The PROPPR randomized clinical trial. J Am Med Assoc , 313 (5), 471–482.Hébert, P., Wells, B., Blajchman, M., et al. (1999) A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med , 340 (6), 409–417.

10 A 75‐year‐old woman is admitted to the intensive care unit following coronary artery bypass grafting. There were no complications during her surgery, and she is hemodynamically stable. Her postoperative labs reveal a hemoglobin of 8.1 g/dL. Which of the following supports implementing a restrictive transfusion strategy in this patient?Restrictive strategies reduce the risk of transfusion related reactions.Restrictive strategies reduce overall morbidity.Restrictive strategies improve survival.Restrictive strategies reduce the incidence of postoperative myocardial infarction.Restrictive strategies have demonstrated improvement in end‐organ oxygen consumption.In a recent trial involving patients undergoing cardiac surgery, restrictive red‐cell transfusion strategy (hemoglobin threshold of < 7.5 g/dL) was noninferior to a liberal strategy (hemoglobin threshold of < 9.5 g/dL in the operating room or intensive care unit) in regard to death and major disability (including myocardial infarction, stroke, and new‐onset renal failure with dialysis) among postoperative patients who had a moderate to high risk of death. These outcomes were achieved with fewer units of blood being transfused. Contemporary evidence‐based guidelines for all surgical patients also discourage liberally transfusing packed red blood cells (PRBCs) in most cases when bleeding has been controlled. Although transfusion of PRBCs was traditionally used to improve oxygen delivery, multiple studies have failed to demonstrate an improvement in end‐organ oxygen consumption with transfusion. This may be partially explained by the decreased deformability and adverse microcirculatory effects of stored red blood cells. Risks associated with RBC transfusion include fluid overload, fever, acute transfusion reaction, increased rate of multi‐organ failure, increased infection rates, transfusion‐associated immunomodulation, human error with incorrect blood administration, transfusion‐related acute lung injury (TRALI), and viral transmission.Answer: AMazer, C.D., Whitlock, R.P., Fergusson, D.A., et al. (2017) Restrictive or liberal red‐cell transfusion for cardiac surgery. N Engl J Med , 377 (22), 2133–2144.Mirski, M.A., Frank, S.M., Kor, D.J., et al. (2015) Restrictive and liberal red cell transfusion strategies in adult patients: reconciling clinical data with best practice. Crit Care Med , 19 (1), 1–11.

11 Given that mortality is improved with the rapid activation of massive transfusion protocol (MTP), but complications from unnecessary exposure to blood products can be devastating, prediction tools can be used to aid clinicians in the careful decision to initiate massive transfusion. Which of the following is not a metric of the Assessment of Blood Consumption (ABC) score used to trigger MTP?Heart rate > 120 per minuteSystolic blood pressure < 90 mmHgGlasgow Coma Scale < 9Positive FAST (focused assessment with sonography for trauma)Penetrating injury to the torsoThere are no uniformly accepted criteria for activating an MTP. Several clinical factors have been validated as individual predictors of massive transfusion. The ABC score consists of four such factors (pulse > 120, SBP < 90, positive FAST, and penetrating torso injury), each assigned one point. A score of two or more warrants MTP activation. The ABC score overestimates the need for transfusion, with a positive predictive value of 50–55%, meaning that 45–50% of patients in whom MTP is activated will not need a massive transfusion. However, the ABC score is excellent at identifying patients who will not need massive transfusion, with a negative predictive value of less than 5%. Massive transfusion has been variably defined (e.g., ≥10 units packed red blood cells [PRBCs] over 24 hours, ≥3 units PRBCs per hour). Survival is improved by the timely administration of blood products in proper ratios.Answer: CNunez, T.C., Woskresensky, I.V., Dossett, L.A., et al. (2009) Early prediction of massive transfusion in trauma: Simple as ABC (assessment of blood consumption). J Trauma , 66 (2), 346–352.Callcut, R.A., Cotton, B.A., Muskat, P., et al. (2013) Defining when to initiate massive transfusion: a validation study of individual massive transfusion triggers in PROMMTT patients. J Trauma Acute Care Surg , 74 (1), 59–65.

12 A 68‐year‐old intubated woman is being resuscitated in the intensive care unit after presenting in hemorrhagic shock following multiple episodes of hematemesis. She has received 6 units of packed blood cells (PRBCs) over the past 12 hours and her provider decides to administer plasma and platelets to balance her resuscitation efforts. What is the rationale for administering apheresis platelets over pooled platelets in this scenario?Apheresis platelets have reduced risk of bacterial and viral contamination.Mortality is improved with use of apheresis platelets.Apheresis platelets are readily available and cost effective.Apheresis platelets have reduced risk of transfusion‐related acute lung injury.Apheresis platelets have reduced risk of hemolytic transfusion reaction.A high ratio of platelets to PRBCs is defined variably in previous studies as approximately one unit of apheresis platelets for every 6–10 units of PRBCs transfused. Additionally, the PROPPR trial showed faster hemostasis and fewer deaths from hemorrhage in the group treated with a higher ratio of plasma and platelets to PRBCs. When massive transfusion is required, platelets should be transfused in an appropriate ratio without waiting for clinical laboratory results to confirm low platelet counts. No prospective study has demonstrated survival difference between apheresis and pooled donor platelets. One unit of apheresis platelets is obtained from a single donor, while pooled platelets are combined from six to eight donors. As a result, pooled platelets have a higher risk of bacterial contamination as well as viral transmission; however, there is no difference in transfusion‐related lung injury. There is no difference in hemolytic transfusion reactions between the two.Answer: AHolcomb, J.B., Tilley, B.C., Baraniuk, S., et al. (2015) Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: The PROPPR randomized clinical trial. J Am Med Assoc , 313 (5), 471–482.Inaba, K., Lustenberger, T., Rhee, P., et al. (2011) The impact of platelet transfusion in massively transfused trauma patients. J Am Coll Surg , 211, 573–579.

13 An 85‐year‐old man is admitted to the intensive care unit following endovascular repair of a ruptured abdominal aortic aneurysm. He required a total of 12 units packed red blood cells intraoperatively. His postoperative labs reveal a calcium level of 6.1 mg/dL. Which of the following is not a consequence of his hypocalcemia?Muscle tremorsProlonged QTHypotensionArrythmiaT wave inversionHypocalcemia is the most common abnormality associated with massive transfusion, occurring in >90% of patients receiving a massive blood transfusion. Stored blood is anticoagulated with citrate, which binds calcium and causes hypocalcemia after large‐volume blood transfusion. Complications of hypocalcemia include prolonged QT, decreased myocardial contractility, hypotension, muscle tremors, pulseless electrical activity, and ventricular fibrillation. T wave inversion is classically associated with hypokalemia.Answer: ESihler, K. and Napolitano, L. (2010) Complications of massive transfusion. Chest , 137, 209–220.

14 A 56‐year‐old man with a history of chronic atrial fibrillation is brought to the emergency department after being found down. He is unresponsive and promptly intubated. His blood pressure is 75/25 and there are no obvious external signs of trauma. A chest x‐ray is performed for endotracheal tube confirmation and massive free air is noted under the bilateral hemidiaphragms. Stat laboratory results are most notable for white blood cell count of 23, hemoglobin of 12, hematocrit of 30, platelet count of 250, and an international normalized ratio of 3.1. Plans are made for emergent abdominal exploration. What is the fastest way to correct his coagulopathy in preparation for his procedure?Activate the massive transfusion protocol.Administer 4‐factor prothrombin complex concentrate.Transfuse fresh frozen plasma.Transfuse fresh frozen plasma and administer vitamin K.No preoperative reversal is indicated as the case is a surgical emergency.Coagulopathy can delay or complicate surgical diseases that require emergent surgical treatment. Historically, warfarin reversal was achieved with rapid administration of fresh frozen plasma (FFP). In 2013, the US FDA approved a 4‐factor prothrombin complex concentrate (PCC) for urgent warfarin reversal. PCC alone reduces INR and time to surgery effectively and safely in coagulopathic patients without an apparent increased risk of thromboembolic events, when compared to FFP use alone.Answer: BGoldstein, J.N., Refaai, M.A., Milling, T.J., et al. (2015) Four factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open‐label, non‐inferiority, randomized trial. Lancet ,385 (9982), 2077–2087.Younis, M., Ray‐Zack, M., Haddad, N.N., et al. (2018) Prothrombin complex concentrate reversal of coagulopathy in emergency general surgery patients. World J Surg , 42 (8), 2383–2391.

15 A 26‐year‐old man is admitted to the surgical intensive care unit after an automobile struck his motorcycle. He is hemodynamically stable and found to have a grade 3 splenic laceration with no active extravasation and a left, displaced, mid‐shaft fracture of the humerus. The fracture was reduced and leg placed in traction while he is being observed for his splenic laceration. Suddenly he becomes confused with progressive shortness of breath and hypoxia requiring intubation. A chest X‐ray demonstrates diffuse bilateral infiltrates. Labs reveal a platelet count is 75 000/mm 3 , prothrombin time of 19 second, partial thromboplastin time of 50 second, oozing is noted from intravenous access sites, and blood is suctioned from his endotracheal tube. Which of the following test results would be consistent with the diagnosis of disseminated intravascular coagulation?Increased antithrombin levelElevated fibrin degradation productsDecreased bleeding timeElevated fibrinogen levelDecreased D‐dimerDisseminated intravascular coagulation (DIC) is characterized by widespread microvascular thrombosis with activation of the coagulation system and impaired protein synthesis, leading to exhaustion of clotting factors and platelets. The end result is organ failure and profuse bleeding from various sites. DIC is always associated with an underlying condition that triggers diffuse activation of coagulation, most commonly sepsis, trauma with soft tissue injury, head injury, fat embolism, cancer, amniotic fluid embolism, toxins, immunologic disorders, or transfusion reaction. In this case, the patient appears to meet criteria for fat embolism syndrome which likely triggered his DIC. There is no single laboratory test that can confirm or rule out a diagnosis of DIC. A combination of tests in a patient with an appropriate clinical condition can be used to make the diagnosis. Low platelet count, elevated fibrin degradation products or D‐dimer, prolonged prothrombin time, and low fibrinogen level are all consistent with a diagnosis of DIC.Answer: BLevi, M . (2007) Disseminated intravascular coagulation. Crit Care Med , 35 (9), 2191–2195.

16 A 61‐year‐old man is admitted to the surgical intensive care unit with a diagnosis of ischemic colitis. Subcutaneous injection of unfractionated heparin was started for venous thromboembolism prophylaxis, and he is monitored closely with serial abdominal examinations. On hospital day five, he noted acute onset of left lower extremity pain and is found to have absent pedal pulses in the affected limb. His platelet count is noted to have dropped from 250 000/mm 3 to 90 000/mm 3 , and his creatinine has increased from 1.2 mg/dL to 2.8 mg/dL. He is taken to the operating room where he underwent thrombectomy of a white appearing clot in the right superficial femoral artery. He is diagnosed with Heparin Induced Thrombocytopenia (HIT) and started on argatroban postoperatively. What is the mechanism of action of argatroban?Direct factor Xa inhibitorDirect factor IIa inhibitorIndirect factor IIa inhibitorBinds antithrombin IIIIndirect factor Xa inhibitorHIT is a life‐threatening disorder that occurs after exposure to unfractionated, or less commonly, low‐molecular‐weight heparin. HIT usually occurs after 5–10 days of heparin therapy and is caused by antibodies against the heparin‐platelet factor 4 complex. Thrombotic complications occur in 20–50% of patients. The thrombus associated with HIT has been described as “white clot” with predominantly fibrin platelet aggregates and few red blood cells. Thrombocytopenia is common in the critically ill, and diagnosis of HIT can be difficult. Delays in obtaining test results often mean that management decisions must be made on the basis of clinical suspicion. Clinical findings that imply a diagnosis HIT are:Platelet fall of more than 50% from baseline, with platelet nadir > 20 000. Profound thrombocytopenia suggests a cause other than HIT.Onset on day 5–10 of heparin exposure.Thrombosis, skin necrosis, or an anaphylactoid reaction after heparin bolus.No other cause for the thrombocytopenia is present.Treatment of HIT includes discontinuation of all sources of heparin and if anticoagulation is clinically warranted, use of a direct thrombin (factor IIa) inhibitor such as argatroban is recommended.Answer: BGreinacher, A. (2015) Heparin‐induced thrombocytopenia. N Eng J Med , 373 (3), 252–261.17

17 An 18‐year‐old man is undergoing an exploratory laparotomy and right groin exploration for a gunshot wound to the right hip. Injuries to the right common femoral vein, bladder, and sigmoid colon are noted. Massive blood loss was reported at the scene and the patient was found to be in hemorrhagic shock on arrival. He has received 12 units of packed red blood cells, 12 units of fresh frozen plasma, and 2 units of apheresis platelets while in the operating room. His vital signs are: blood pressure 100/60 mm Hg, heart rate 120 beats/min, temperature 34.8 °C. Laboratory studies: hemoglobin 8.5 g/dL, platelets 100 000/mm 3 , prothrombin time 14 second, partial thromboplastin time 40 second. pH 7.1. His femoral vein has been ligated, bladder injuries were repaired, and sigmoid colon was resected. What is the next most appropriate treatment for his ongoing bleeding?Transfuse platelets, create a stoma, and close the abdomen.Transfuse fresh frozen plasma, perform primary anastomosis, and close the abdomen.No transfusion required, create stoma, and close the abdomen.External warming, primary anastomosis, and close the abdomen.Leave in discontinuity, place temporary abdominal closure device, and admit to surgical intensive care unit for external rewarming.This patient is severely hypothermic and acidotic. Following surgical control of bleeding and massive resuscitation, ongoing aggressive resuscitation is required to reverse the “lethal triad” of coagulopathy, acidosis, and hypothermia. Damage control operation should be performed with prompt admission to surgical intensive care unit for resuscitation and rewarming. Clotting factor and platelet deficiencies have been addressed during this resuscitation by maintaining 1:1 component replacement. Hypothermia < 35 °C is a strong independent risk factor for mortality in trauma patients, with more severe hypothermia conveying greater risk of mortality. Hypothermia contributes to coagulopathy through platelet and clotting factor dysfunction. Recommended measures for rewarming a patient with low body temperature include forced air warming, infusion of warmed fluids, under‐body heating pads, radiant warmers, and humidified ventilation. If bleeding continues after aggressive warming and correction of clotting abnormalities, the patient must return to the operating room without further delay.Answer: EInaba, K., Teixeira, P., Rhee, P., et al. (2009) Mortality impact of hypothermia after cavitary explorations in trauma. World J Surg , 33 (4), 864–869.Perlman, R., Callum, J., Laflamme, C., et al. (2016) A recommended early goal‐directed management guideline for the prevention of hypothermia‐related transfusion, morbidity, and mortality in severely injured trauma patients. Crit Care , 20 (1), 1–11.

18 A 22‐year‐old man was involved in a drive by shooting. He is noted to have multiple gunshot wounds to his back, abdomen, and extremities. He has a distended abdomen that is diffusely tender. His blood pressure is 80/60 mm Hg. What fluid should be administered while preparing for emergent laparotomy?Lactated ringersHypertonic salinepositive bloodType‐specific bloodCrossmatched bloodThe described physical exam findings are consistent with hemoperitoneum resulting in hemorrhagic shock; therefore, the patient requires emergent resuscitation and operative hemorrhage control to avoid mortality. Crystalloid solution should be minimized and resuscitation with blood products should be initiated without delay. Type O positive blood is readily available in most centers and can be used for emergent transfusion of male patients and women beyond childbearing age. If uncrossmatched blood resources are limited, type O negative blood may be used but is typically reserved for women of childbearing age to avoid the risk of Rh isoimmunization. Type O positive blood has been shown to be safe for transfusion in hemorrhaging trauma patients, with a very low rate of transfusion reaction. Advantages of using uncrossmatched type O blood include immediate availability before type‐specific blood becomes available and avoidance of errors in multi‐casualty situations. The safety of type O blood has been improved by prescreening donor blood for anti‐A and anti‐B antibodies, which can lead to hemolysis of native red blood cells.Answer: CBall, C.G., Salomone, J.P., Shaz, B., et al. (2010) Uncrossmatched blood transfusions for trauma patients in the emergency department: incidence, outcomes and recommendations. Can J Surg , 54 (2), 111–115.Dutton, R., Shih, D., Edelman, B., et al. (2005) Safety of uncrossmatched type‐O red cells for resuscitation from hemorrhagic shock. J Trauma , 59 (6), 1445–1449.

19 A 90‐year‐old man presents after a ground‐level fall. He is found to have bruising on all extremities and a scalp laceration that requires suture repair for hemostasis. His daughter accompanies him to the emergency department and reports that he took dabigatran for his chronic atrial fibrillation 4 hours prior to the admission. Imaging reveals a moderate subdural hematoma. What is the best option for reversing effects of dabigatran?No reversal is required if the INR is < 2Administer idarucizumabAdminister plateletsAdminister fresh frozen plasmaAdminister cryoprecipitateOral anticoagulants alternative to warfarin for reducing the risk of thromboembolic events in patients with chronic atrial fibrillation include rivaroxaban, apixaban, and dabigatran. Rivaroxaban and apixaban are factor Xa inhibitors. Dabigatran is a direct thrombin inhibitor. A major advantage of these medications is that they do not require routine INR monitoring. In clinical trials, bleeding events on these medications were comparable to, or lower than warfarin for similar indications. The major drawbacks of these agents are (1) their anticoagulation effect is not reliably measured by common laboratory tests, and (2) effects can be difficult to reverse. In 2016, the FDA approved idarucizumab as a specific reversal agent for dabigatran. Fresh frozen plasma (FFP) can be used to resuscitate patients on these medications who suffer low‐ to moderate‐risk bleeding events. However, FFP is not a specific reversal agent. It takes time to infuse and cannot rapidly reverse coagulopathy. Administration of FFP can also lead to volume overload and transfusion reactions. For all of these reasons, FFP is not an ideal therapy. This patient has a life‐threatening intracranial hemorrhage that requires rapid reversal of dabigatran. Idarucizumab is a monoclonal antibody fragment developed to rapidly, durably, and safely reverse the anticoagulant effect of dabigatran in emergency situations. PCC can also be considered to reverse dabigatran if idarucizumab is unavailable.Answer: BPollack, C.V., Reilly, P.A., Van Ryn, J., et al. (2017) Idarucizumab for Dabigatran reversal – full cohort analysis. N Engl J Med , 377 (5), 431–441.Faraoni, D., Levy, J.H., Albaladejo, P., et al. (2015) Updates in the perioperative and emergency management of non‐vitamin K antagonist oral anticoagulants. Crit Care , 19, 1–6.