Welcome to Current Concepts in Adult Critical Care 2024. My name is Nassim Motaier. I'm an assistant professor of critical care medicine, and I'm very excited to talk to you about hemostatic resuscitation for traumatic and non-traumatic hemorrhage. I believe that this is an important topic, whether or not you're at a trauma center, because bleeding can happen anywhere. It can happen anytime during or before admission. Additionally, COVID-19 pandemic was a great example of what happens in times of capacity issues, where patients had delayed transfer times to higher level of care centers and had to be managed at smaller community hospitals. We believe that in 2024, no one should die of bleeding, and every intensivist should know the basics of resuscitating these bleeding patients. That is why we have developed a comprehensive chapter that is designed to give every clinician the tools that they need to manage these patients. I also wanted to mention Dr. Morali. Him and I co-authored this chapter together, and we believe that hemorrhagic shock resuscitation requires a multidisciplinary team to save a critically ill patient. And we hope that this presentation will demonstrate the steps and the importance of that. I have no financial disclosures or conflict of interest. The objectives for this presentation will be to, one, describe the pathophysiology of hemorrhagic shock and how to recognize this condition, illustrate the steps involved in evaluation and resuscitation of these patients, as well as provide an overview of the tools that are available to every intensivist for treating these patients, both in terms of traumatic and non-traumatic hemorrhage. I'm going to start by giving you an introduction to hemorrhagic shock, and then I will talk to you about evaluation and management, and then I will talk about complications of resuscitation, as well as the importance of de-resuscitation. Let's first start by understanding what hemorrhagic shock means. Hemorrhagic shock is a state of hypovolemia that is a direct result of acute blood loss, which leads to tissue hyperperfusion, impaired oxygen delivery, and organ failure, and if not treated promptly and adequately, it can result in death. If you look at the bar graph on the left side, you can see that the most common cause of death from bleeding is in the trauma population, and then on the left side of that graph, we have the most common causes in the medical population. The leading cause of death from hemorrhage in non-trauma patients is from a ruptured abdominal aortic aneurysm, followed by peptic ulcer disease, followed by maternal hemorrhage. If you look on the right side, you can see that 61,000 people die of bleeding in the U.S. every year, and if you look at that number globally, it's closer to 1.9 million. If you look at the number of years of life lost, that's closer to 86 million, and a majority of that is accounted for by the young trauma patients that are dying of hemorrhage. So you can see that it's a major cause of both morbidity and mortality, and hence, this is why it's important for all of us to know how to manage these patients adequately and promptly. As mentioned previously, this is a time-sensitive process. If not addressed quickly, it will lead to end organ failure and death. So how do we fix it? Well, the goals of therapy are to, one, restore blood plasma volume, two, reverse coagulopathy, and then number three is to identify and stop the source of bleeding. Let us review the physiology of hemorrhagic shock. If you recall, mean arterial pressure, or MAP, is a product of cardiac output and resistance of the vasculature. Cardiac output is then a product of heart rate and stroke volume. What happens in hemorrhagic shock is this is a type of hypovolemic shock because of acute blood loss resulting in a decrease in stroke volume. There are compensatory mechanisms that aim to maintain MAP. Heart rate increases and the resistance of the vessels also increase, and this is a result of release of catecholamines. Unfortunately, when the tank is empty and stroke volume is low, despite these mechanisms, MAP cannot be maintained, which results in hypoperfusion, impaired oxygen delivery, and all the consequences of that. If you look at the bottom, you can see that hemorrhagic shock is a type of hypovolemic shock. Central venous pressure is low because stroke volume is decreased. Cardiac output is low, again, because of the stroke volume. Systemic vascular resistance is increased because of release of catecholamines, and the venous oxygen saturation is also low. So what determines the outcome in these patients? The estimated probability of survival is based on the type of anatomic injury, physiologic injury, patient reserve, and error-slash-experience. Anatomic injury refers to the severity and degree of injury. Some injuries are non-survivable. Minor injuries are more likely to be fixable. Physiologic injury refers to what happens at the tissue level. Hypovolemia and vasoconstriction cause hyperperfusion and an organ damage in the kidneys, liver, intestines, and other organs, which can lead to multi-organ failure in survivors and non-survivors. Severe internal or external blood loss results in inadequate oxygen delivery. At the molecular level, what happens is the mitochondria are unable to sustain aerobic metabolism, and as a result, switch to anaerobic metabolism to produce ATP, which results in lactate production. The sympathetic nervous system activation tries to divert blood from non-vital organs to vital organs through vasoconstriction. However, you end up with worsening acidosis as a result of both lactic acid production and a mismatch of oxygen delivery, and ultimately lose the ability to maintain vasoconstriction, again, in setting of severe acidosis. Patient reserve refers to characteristics of your patient. So this can be, or some examples of this could be the age of your patient or comorbidities. So a younger patient generally has a higher reserve than an older patient, and they have a higher tolerance for blood loss. A person that has heart failure or other comorbidities, or for example, somebody that's on beta blockers, may be unable to increase their heart rate in response to losing their stroke volume because of blood loss, and so their ability to compensate is much lower than a young person. The other factor would be errors, which refers to delayed identification, inappropriate resuscitation, delayed therapy, and or procedural inexperience. So all of these together determine your patient's outcome, and some of them are out of our control or not modifiable, and some of them are modifiable. For example, minimizing errors and providing prompt delivery and learning to identify signs and symptoms of hemorrhagic shock can truly decrease the time to therapy and improve outcomes, and again, that is the goal of this class. Now let's talk about overview of management. The first step in approaching these patients is recognition of hemorrhagic shock, followed by stabilization, which requires a multidisciplinary team approach, localization and stopping the source of bleeding, monitoring both for response to therapy and complications, and lastly, focusing on de-resuscitation. The graph below is showing you phases of care, and it is truly my favorite way of explaining resuscitation of a wide spectrum of critically ill patients. It has been described in many different ways in the literature. Phase one is generally referring to the disease phase. In our case, it would be the bleeding phase, where your goal is to resuscitate, optimize, and stabilize. So resuscitation refers to restoring blood volume. Optimization refers to reversing coagulopathy, finding and fixing source of bleeding, and then once you've reached the stabilization phase, your focus becomes on more goal-directed therapy and giving time to heal and continue to monitor closely. Once the patients have stabilized and are in the recovery phase, you're focusing more on de-resuscitation. For example, if they're volume overloaded, you start to diurese them. If they're deconditioned, you focus on physical therapy and rehab. If you've started medications in the intensive care unit, you come up with a weaning plan and so forth. Now let's talk about evaluation and management, starting by talking about how to recognize this condition, emergent stabilization, source identification, correction of coagulopathy, and monitoring. Principles of a diagnosis. Rapid identification can lead to prompt hemostasis, correction of coagulopathy, and restoration of blood volume. So you want to start with taking a history and a physical exam. Unfortunately, a lot of the times, these patients are too ill for you to be able to take a history. But if you have a patient that is stable and you can take a history, that would be very helpful in trying to identify, one, a source of bleeding, and two, try to quantify how much blood they have lost prior to arrival. The next thing is your physical exam, like I mentioned, and you're looking for any bruising, any pain, or signs of active bleeding. Again, that can direct you to the source of bleeding. The advanced trauma life support has a four-stage classification system that's been used for many decades to try to estimate the amount of blood loss. So class one is basically a patient that has suspected bleeding without any changes in their vital signs or a change in their base deficit. These patients have an estimated blood loss of less than 15%, and based on this classification system, they fall into class one, and the recommendation is to monitor them. Class two refers to patients that are starting to show vital sign abnormalities. So you might see an elevation in their heart rate, decrease in their pulse pressure, and a mild elevation in their base deficit of two to six. These patients have an estimated blood loss 15% to 30%, and at this stage it is recommended to prepare blood but not transfuse. Class three is referring to patients with more vital sign abnormalities. So these patients have an elevated heart rate. They may have a drop decrease in their blood pressure. Their pulse pressure is also decreased. Respiratory rate can be increased. Urine output is decreased, which is a sign of hypoperfusion, and their GCS score may also be decreased, again as a result of hypoperfusion, and they have a larger base deficit of six to ten milliequivalents per liter. And so these patients have an estimated blood loss of 30% to 40%, and this falls under class three, as I mentioned before, and at this stage it is recommended to transfuse them. Class four refers to a patient that has a severely elevated heart rate, a decreased blood pressure, a pulse pressure that is also decreased, respiratory rate that is increased, urine output that is more decreased than the class three, and the GCS score that is decreased. So you definitely have evidence of end organ damage here, and your base deficit is really increased, so greater than ten milliequivalents per liter, and these patients have an estimated blood loss that's greater than 40%, and at this stage it is recommended to activate a massive transfusion protocol. So let's now go to a case. This is a case of a 28-year-old G1P1 at 28 weeks pregnant who was shot in the leg at the park. She has visible injury on her left leg. EMS arrive and stabilize her bleeding and bring her to the hospital. On arrival to the emergency department, her vital signs are as follows. Temperature is 37.5 degrees Celsius, blood pressure is 90 over 53 with a heart rate of 70, and respirations are at 16. Creatinine is one, bicarb is 18, sodium is 145, chloride is 109, and her white blood cell count is 11, H and H is 8 and 24, platelet count is slightly decreased at 135, and the lactic acid is mildly up at 4.3. So what is the next best step in management? Do you monitor? Do you prepare blood? Do you transfuse? Or do you activate the massive transfusion protocol? And the point of this question is to try to apply the ATLS classification system. I'm going to give you a minute to think about this question. And hopefully everybody has had a chance to think about the question. I would say that the correct answer here would be C or D. And actually the point of this question was to demonstrate the limitations of this classification system. The relevance of this classification system has been called into question in the last few decades. Not all patients can mount the same response. So for example, in the case of an OB patient, their physiology at baseline is different. So their plasma volume is increased. Their cardiac output is increased. And they're also anemic at baseline. So these patients are younger and with the increase in their plasma volume and cardiac output, they may be able to tolerate up to two liters of blood loss before they start to show any signs and symptoms. And that might actually be too late. So if you don't resuscitate them early, they can actually go from looking okay to crashing and possibly dying. So what this is trying to demonstrate is that the ATLS classification system is somewhat flawed because not all patients can mount the same response. If somebody is on a beta blocker or an antihypertensive, their blood pressure might be low. If somebody has a really high blood pressure at baseline, they might come in with normal looking vital signs, but it might be relatively low for them. Intensity of compensatory mechanisms may be different for different patients. We already talked about pregnant patients. And then elderly patients may also have a lower reserve. So if you wait for them to mount the vital sign response that you're seeing in class three or four, it might already be too late. So this classification system is limited and you really want to customize the care of your patient to the patient that's in front of you. Now let's look at another case. So you're here on the left side on your on-call ICU shift. And then they call you and tell you there is a female that's bleeding in the ER. You walk down to evaluate the patient in the trauma bay. You look at the monitor when you arrive. The patient's tachycardic at 110. Their SpO2 is a little bit low at 90% on two liters of nasal cannula. She's tachypneic breathing 30 times a minute and her blood pressure is low at 85 over 50 with a MAP of 62. And her temperature is also a little bit decreased at 36.5 degrees Celsius. You go to examine the patient and you look at her mucous membranes and it's clearly very dry. You go to check her capillary refill and it's delayed. And then you go to listen to her lungs. She's tachypneic with clear lung sounds and she did have some hypoxia and which was easily fixed with only two liters of nasal cannula. Her x-ray is normal so there's no abnormalities there. She is confused so she has some encephalopathy and you know when you're looking again you want to look for bruising, you want to look for pain, you want to see any signs of visible bleeding. So these are the signs and symptoms that you're going to look for when you're examining a patient. Then you decide to do an ultrasound. So on your ultrasound you can look at the IVC collapsibility index using M mode to see if the IVC is dilated or if it's collapsed. If it's collapsed then you know that suggests that the patient may be hypovolemic. And then you can also look at the diameter of the IVC and you know if it's narrow then you know that you need to volume resuscitate the patient. You can also look at the stroke volume variation which I have not demonstrated here. The next thing you can do when you're evaluating these patients is an eFAST exam and I know that it was already discussed in detail so I'm not going to discuss it again but you know if you look at image A on the left and image B we have demonstrated the liver and the kidney and here you can see some free fluid so that tells you that you know that's the site of injury. And then you can also use the same view to demonstrate fluid in the thorax. So this is the diaphragm and then there is some fluid there so that's probably a hemothorax and you know that again helps you identify a source of bleeding. Here we have the spleen sorry we have the spleen and we have the kidney and then again you have some free fluid here. So then here we're looking at the bladder and you have some suprapubic fluid there that suggests that you have injury in the pelvis. Then you can look at the heart in the subxiphoid view and this is normal so RV LV RA LA and here you can see a pericardial effusion so again that directs you to try to figure out where your site of injury is. So vital signs you know I demonstrated in the case previously what you should look for so again cardiovascular you're generally seeing tachycardia, hypotension, decreased pulse pressure, although these are late signs and symptoms so hopefully you've already prevented that from happening. Pulmonary you can have tachypnea, you can have hypoxia, we talked about mismatch of oxygen delivery and then CNS you can have hypothermia, you can have confusion and then your physical exam you're gonna have signs of volume depletion so you have or poor perfusion so you have poor skin turgor, delayed capillary refill, decreased temperature, absence of diaphoresis and then looking at the head and neck they're gonna be paled because they're anemic and they have dry mucous membranes and then CNS we already talked about both under vital signs and on also under physical exam and then renal they can have a low urine output. In terms of your labs we talked about how you can have increased lactic acid there's two different mechanisms for that and that results in an increased base deficit, you can have end organ damage such as AKI so your creatinine can be elevated, your urine specific gravity can be elevated again because this is a type of hypovolemic shock so you end up with like a pre renal situation. In terms of point-of-care ultrasound which has been an asset to all of us in the ICU you can do your eFAST exam so you can look for intra-abdominal fluid and then you can also look at the heart and look for pericardial fluid, you can look at the IVC diameter and the collapsibility index and you can also look to see if there is increased stroke volume variation which again is suggestive of hypovolemic shock and generally these patients have hyperdynamic cardiac function. Like other critically ill patients those presenting with hemorrhagic shock should have emergent stabilization of their circulation, airway and breathing. The priority in treating hemorrhagic shock is to restore and maintain perfusion to vital organs. The first step is to obtain multiple points of large-bore venous vascular access. Now for those patients that are severely ill and hypovolemic obtaining intravenous access may be difficult, hence intraosseous access can be considered and in fact this has become popular on the field and in emergent situations. Airway management requires a thoughtful approach. Frequently these patients will have threatened or compromised airways due to blood or vomitus in the airway, severe alteration of mental status and so forth. However rapid sequence induction and positive pressure ventilation can be risky in these patients who are often severely hypovolemic and hypotensive. So the consideration should be given to temporizing the airway with oropharyngeal, nasopharyngeal, supraglottic airways as well as bagged mast ventilation until a more definite airway can be obtained after the patient is resuscitated. Let's try another case. So you are the intensivist on call and the emergency room nurse in the critical care bay runs up to you and asks if you can quickly put in a femoral central venous catheter to gain additional access points for the bleeding patient in hemorrhagic shock. What will you advise? A, intraosseous access, B, 18-gauge standard IV, 14-gauge standard IV and D, 6-french sheath introducer. Standard IV and this is a good chart that we obtained from the ETM course blog and basically what they have done is they have put in how long it takes to transfuse one liter of fluids into a patient using the different methods, so the different points of vascular access. And if you look the fastest is through an eight and a half rake line which you have generally in the operating rooms. Anesthesia uses them a lot and all the places that deliver transplant generally have them. They're not as commonly stocked in the medical ICUs but trauma ICUs generally also stock them. But just know that those are the fastest way to get blood or fluids into a patient. So you can give a liter in less than a minute, so half a minute. And then the slowest is through a 20-gauge IV. So if you're using a 20-gauge IV, it takes about six and a half minutes. And if you're using an 18-gauge standard IV, that's four minutes and 23 seconds, so it's relatively slow. I'm gonna skip over this and allow you to come back to it if you feel like you need to spend. Once the optimal access point is obtained, and again we recommend shortening length and widening diameter, you can also use intraosseous devices. But keeping in mind that because they are in the bone, trabeculae of the bone can impede with your flow rate. So if you do use them, you should use a pressure bag or a rapid transfuser to make sure that you are you're getting optimal flow rates. Which actually brings me to my next point. In order to transfuse as fast as possible, such as is needed in patients with hemorrhagic shock or those with active visible bleeding, you can use rapid transfusers which can deliver great volumes within seconds to minutes. They also have a heating unit that keeps the products warm and they are great to utilize. If you are not at a trauma center or a center that has access to such devices, then we recommend using a pressure bag or even manual pressure. Basically what you want to do is you want to squeeze the bag as much as you can to deliver volume as fast as you can. And to begin resuscitation, it is okay to use small amounts of fluids. However, ideally you would be repleting and switching to blood products as soon as you can and we will talk about why that is in the next few slides. Principles of resuscitation. So damage control resuscitation is a very well-established principle, especially in the trauma literature. So they're talking about restoring circulation, stopping bleeding, avoiding hypothermia, hypocalcemia, acidosis, and hemodilution. Because all of these things can lead to bleeding. So hypothermia can worsen coagulopathy, hypocalcemia can worsen hypotension and coagulopathy, acidosis can also worsen hypotension and coagulopathy, and hemodilution is obviously bad both in terms of coagulopathy and oxygen delivery. So damage control resuscitation is really paying attention to avoiding these things. The key to resuscitation of a patient that truly has a hemorrhagic shock from massive bleeding is to avoid hemodilution. The experience with transfusion and transfusion ratios initially came from the battlefield. So World War I, World War II, the Korean War, and some animal studies. And so what they saw was that anytime they used whole blood, plasma plus blood, plus early surgery, their patients had better outcomes. When they aggressively resuscitated with saline and delayed surgery, their patients had worse outcomes. So this kind of shed light into our need to try to define what is a good transfusion or what is the optimal transfusion ratio, which resulted in two randomized control trials that evaluated the impact of component therapy. So first was the prompt trial and the second was the proper trial, and we'll talk about what that is. The first study was the Prospective Observational Multi-Center Major Trauma Transfusion Study, and basically what they did was they looked at trauma patients at 10 different level one trauma centers in the U.S. This was a prospective cohort study. They included patients that required at least one unit of packed red blood cells within six hours, or at least three units of PRBC, FFP, or platelets in 24 hours. There were 1,245 patients in the first group, and 905 patients in the second group. The primary outcome was mortality, and what they saw was that there was a reduction in mortality in those that a more balanced resuscitation strategy was utilized. So these patients were three to four times less likely to die versus those that did not receive balanced resuscitation. So the one to one ratio. They also saw significant variation in clinician transfusion strategies. And so this led to the conclusion that higher plasma and platelet ratios early on are associated with decreased mortality. Which brought us to the next trial in 2015, which was a much needed randomized control trial. The transfusion of plasma platelets and red blood cells in a one to one to one versus a one to one to two ratio and mortality in patients with severe trauma, also known as the proper trial. And so this study's aim was to evaluate the efficacy and safety of different resuscitation ratios. And basically what they did was they looked at the one to one to one versus one to one to two strategy. Again, this was conducted in 12 centers, and it was a randomized control trial of 680 patients. And the one to one to one or one to one to two plasma platelets to PACS RBC ratios was evaluated. What they found was the overall 24 hour and 30 day mortalities were similar in both groups, but more patients in the one to one to one achieved hemostasis and fewer patients in that group died of exsanguination. So this study actually led to most trauma centers changing their massive transfusion protocols to use a more balanced ratio, especially for severely injured bleeding patients. So again, the goal is to avoid hemodilution. So whole blood versus component therapy is another question that has come up. And then in the trauma population, there's actually some data to show that if you use low titer whole blood, it can reduce overall transfusions and increase survival compared to component therapy. And the idea is that whole blood has physiologic ratios of RBC coagulation factors and functioning platelets, so it may be actually more beneficial. And if you look on the right, you can see that 500 cc's of volume, you're getting a hematocrit of 38 to 44%, platelets of 150 to 400, and coags are 100% functional, fibrinogen is one gram, so it's very balanced and in a small amount of volume. The medical population actual data is lacking. However, the same idea from trauma is used in medical patients that are truly hemorrhaging to death. I mean, if there is a patient that's actively bleeding out in front of me, and I have access to whole blood, which it can be more difficult to get whole blood, then I'm gonna use it. So the need for a massive transfusion protocol, I know that this is something that was discussed previously, so I'm not gonna get into it in detail, but a lot of the times, especially in the medical setting, clinician judgment is what is used to activate those protocols. In the trauma population, there is some more data and guidelines and the injury severity scores and things that were previously discussed by the speaker before me. So basically, active bleeding can be a criteria to activate massive transfusion protocol. So if I have a patient that is hemorrhaging to death in front of me and I can see active bleeding, then I'm definitely going to activate massive transfusion protocol. Another way that, again, varies from institution to institution is the number of packed red blood cells that are transfused in what duration of time. And again, that duration of time and the number can vary from place to place, but it's more of a customized approach. Scoring systems and trauma, some places use the ABC score. There's shock index score, injury severity score, so it can vary, but I do believe that the East Society has some guidelines to help guide clinicians for the trauma population. And then type and screen generally takes 15 to 30 minutes, and when you have a patient that's in hemorrhagic shock, you don't have 15 to 30 minutes to wait. So generally what happens is you are gonna initiate resuscitation with using some IV fluids. You are going to limit the amount of IV fluids that you're using to 1.5 to maybe two liters at the maximum. And if they're not responding, then you know that you're gonna have to go to your balanced transfusion resuscitation approach. And so if you decide to activate massive transfusion protocol, this is the one thing that I believe is consistent across all institutions. So you identify and you activate, and this takes direct communication from the clinician to the lab to get them to prepare and deliver. Generally, there is a person assigned from the unit that's in charge of communicating with the blood bank and making sure deliveries are happening in a timely manner. So if you don't know the patient's blood type and the type and screen is not available, then you're gonna start with O negative blood. If you don't have O negative blood, and it's a patient that is not of childbearing age, or if it's an older patient or a male, then you can also use O positive, and then generally AB plasma is used. And so that's how you start your resuscitation. If you've given somebody nine units of mismatched blood, then you continue with that because you've pretty much repleted their whole blood volume, so you don't worry about their type and cross at that point. You just continue with what you have been giving them. So lethal triad of trauma is referring to acidosis, which we talked about, acidosis can worsen coagulopathy. Hemodilution, so if you give too much IV fluids, it can cause hemodilution, hemodilution leads to coagulopathy. Hypocalcemia, we talked about, that can lead to coagulopathy as well. And hypothermia, which can also lead to coagulopathy. So you try to do everything you can and guide your resuscitation or center it around these major principles, and you focus on avoiding them. So massive transfuser or the rapid transfuser generally has a heating device or a heating unit in it. So it warms the blood that you're giving. If you have a patient that has open injury and they have organs that are exposed, they're gonna lose more body heat. And so the focus should be to make sure you keep the room temperature hot and you use active warming as needed to make sure their temperature stays normal. Optimal blood pressure, avoidance of over-resuscitation is crucial in these patients. Large volumes of crystalloid fluids can cause dilutional coagulopathy. We already talked about that. Permissive hypotension is another principle in damage control resuscitation, where the idea is that if you're using a normal or low systolic blood pressure, then you are allowing the clot to stabilize. And if you're using a higher blood pressure, potentially you can dislodge the clot. And so the general recommended systolic blood pressure is around 100. Some studies have evaluated a systolic blood pressure of 70 millimeters of mercury, but generally I believe that 100 is the number that is used. And so again, the idea is if you're using a lower blood pressure, you're gonna allow the blood clot to stabilize. The benefit is less clear in non-trauma, especially elderly patients that have what is known as homeostenosis. They're older, they have vessels that are calcified, and they might have hypertension at baseline and actually operate at a higher blood pressure. So their auto-regulation set point is at a higher level. So if you go too low for these patients, you might end up with more damage and organ damage. This is definitely an area that is an area for future investigation. In terms of sources of bleeding, inspection. So we talked about looking to see if there is any evidence of bruising or active bleeding. Palpation, so you're looking for pain. History and physical, if somebody can tell you what happened to them, obviously that is the gold standard. And then we talked about ultrasound. So when it comes to trauma patients, you wanna look at blood on the floor and four more. So a lot of the times, they have had a good quantity of blood that ends up on the floor. So it's really important to get that history from the first responders on scene to kind of get an idea of how much blood was at the scene. And then if you're in the ER or in the OR, again, you wanna pay attention to how much blood ended up on the floor because that can help guide your resuscitation and help you not fall behind. So the four major sources of bleeding in trauma are the abdomen, pelvis and peritoneum, long bone and the thorax. So those are the major areas where you are going to end up bleeding and end up with massive bleeding and hemorrhagic shock. When it comes to, again, sources of bleeding in non-trauma patients, you're gonna see a lot of abdominal, aortic aneurysm ruptures. Tracheoanonymous fistula bleeding is another one that we see commonly in our patients that have a fresh tracheostomy. Post-operative bleeding is another one that you can see depending on the procedure they've done. Pulmonary hemorrhage. This doesn't generally result in hemorrhagic shock. I've seen somebody drop their blood pressure once from having really bad pulmonary hemorrhage, and they were able to control that pretty quickly. Generally, these patients die of asphyxiation before they die of their hemorrhagic shock, so it's less common to see that. Post-partum hemorrhage is another big one that we see both in trauma and in the MICU. In addition to identifying the source of bleeding, it's really important to identify and correct coagulopathy. Coagulopathy is a principle that's extensively studied in the trauma population, and in fact, there is a principle known as acute coagulopathy of trauma shock, which is basically driven by tissue trauma, so what happens is at the site of the injury, vascular endothelium promotes thrombus formation with simultaneous activation of fibrinolytic enzymes, and then you get destruction of the glycocalyx, and you end up with shedding releasing heparin sulfate and protein C, and you end up with a hyperfibrinolysis situation with diffused coagulopathy, and in fact, trauma patients that arrive with signs of this type of coagulopathy have had a worse prognosis than patients that don't have coagulopathy on presentation. So in terms of identifying coagulopathy and monitoring it, we have our conventional coagulation tests, so we have the PTI and RAPTT, and then we have the TAG, so in terms of advantages, the conventional tests are reproducible, there's no operator error, it's pretty standard. Disadvantages are it's not able to reliably predict bleeding risk, so for example, clot firmness, thickness, and the turnaround time is very slow, so it's often not helpful in that acute situation where you're really trying to guide your therapy and resuscitate. Also, it can't look at hypercoagulable and hypofibrinolytic phenotypes, where it can be beneficial to know that, especially in the trauma population. So then the other test that we use is the TAG, and the turnaround on the TAG is very quick, it takes about 15 minutes at the most to get it done at most institutions, and then the data has shown that using a TAG to guide your resuscitation has reduced the need for transfusions and reduced the number of complications. In terms of disadvantages, it's not readily available, some hospitals don't have it, and it can be subject to operator error, so that's something to keep in mind. A TAG can be very helpful, and it's actually a dynamic measure rather than a static measure so it's very helpful. It tells you about clot formation quality and breakdown so it's giving you multiple points that can help aid guide your resuscitation. It can be informative especially in the bleeding patient, commonly used in the liver transplant population, in the operating room, cardiac surgery, trauma, and ECMO. It can also be helpful in detecting early dilutional coagulopathy. So starting on the left side of this slide, the R time is the reaction time and that's the time that it takes for the initial clot to form and it really depends on clotting factors. The K time is the time it takes to reach a certain level of clot strength and it depends on fibrinogen. Alpha angle is the slope between R and K and it measures the speed at which cross-linking occurs and again it depends on fibrinogen. The maximum amplitude is the strength of the fibrin clot and it depends on your platelets, mostly on your platelets. The fibrinolysis phase is the next stage and basically it measures the percentage of decrease in amplitude at 30 minutes so you're looking at how much the maximum amplitude drops at 30 minutes and that's your lyse 30 time. How do you interpret the tag? Well we talked about how to do that but now we want to talk about what do you do if the numbers are abnormal. So R time, reaction time, remember we said it depends on clotting factors and that's like how long it takes for your clot to actually form depending on clotting factors. So if it's abnormal then you want to give fresh frozen plasma. The alpha angle, again we're talking about clot strength and it's dependent on fibrin and so if it's abnormal then you want to replete that with cryoprecipitate. The maximum amplitude depends on platelets so it's looking at clot stability and the way the platelets are functioning with the clot that's formed. So if your maximum amplitude is abnormal then you want to transfuse platelets or give DDAVP or whatever may fit your clinical scenario. The lysis 30 time, we talked about how fast your clot is breaking down at 30 minutes and if that's abnormal then you want to fix that by giving tranexamic acid or TXA. I'm not gonna go over this in detail but we did feel that it would be important to put reversal agents for anticoagulants into one chart just to give all of our readers and listeners a place to go to if they quickly need to see what agent they need for reversal. So we tried to put all the information that we felt was relevant into one place to make it easier for everybody. So in terms of warfarin, the elimination half-life is one to three days and in the case of severe bleeding you want to use prothrombin complex concentrate and then if it's not severe bleeding but you have bleeding then you can consider fresh frozen plasma and vitamin K. Now one thing that I have seen happen is people give PCC or four-factor PCC without vitamin K and you're not supposed to do that because the half-life of prothrombin complex concentrate is not long enough to last so it's really important to make sure that the two are given at the same time. Vitamin K by itself is not enough because it takes about 24 hours to reach its peak effect and if you have somebody that's actively bleeding and they're coagulopathic because they're on warfarin then you know you don't have 24 hours so you really want to fix it as quickly as you can. In terms of DOACs, again the reversal agents are listed there so I'm not going to mention it. The one thing that we didn't put in that chart is adnexin alpha and that is a direct reversal for apexaban or you know for some factor 10a inhibitors but the quality of data supporting its use over PCC is limited so especially in the general trauma and medical patient population I do think that there is some better data for patients with CNS bleeding so as a result of that we decided to leave that out of the table. Alteplase is another one where you know as we see more and more alteplase used you do get some bleeding and you know if you do get bleeding TXA is one way to reverse that if you don't have TXA then aminocarburic acid is another agent that you could use. In terms of platelets the data isn't that great in terms of how much. The transfusion of platelets is really guided by clinician experience when it comes to active bleeding especially in the medical population. The data that we have is for CNS patients or those with active bleeding and needing major surgery then you know the goal of platelets for those patients is greater than 100,000. For patients with active bleeding the goal is greater than 50,000 and for just prophylaxis of spontaneous bleeding it's less than 10,000. In terms of interventions for those with low platelets or at risk for platelet dysfunction you can use platelet transfusion obviously that would be the gold standard. You can give desmopressin especially if you are suspecting platelet dysfunction with uremia. Tranexamic acid can be used as well as aminocarburic acid. What do we know about TXA? It is an antiferbinolytic medication which inhibits plasminogen thereby preventing the breakdown of clots. There are three main trials in the hospitalized patients and more in the pre-hospital setting but our focus today will be in the hospitalized patient. The three main trials that we are going to discuss are the CRASH-2 trial, the HALT-IT trial and the WOMEN trial. The CRASH-2 trial looked at giving TXA in trauma patients within three hours of injury and saw that if it was given within that time frame there was a reduction in mortality. The HALT-IT trial looked at TXA in patients with GI bleeding and did not actually see a reduction in mortality and there was actually a signal for harm in terms of VTEs. The WOMEN trial looked at giving TXA in women with postpartum hemorrhage and actually saw a reduction in mortality so it is very common to see TXA being used in this patient population. When it comes to traumatic hemorrhage, Stop the Bleed campaign was launched by the American College of Surgeons Committee on Trauma and supported nationally to try to train more bystanders and first responders to intervene during bleeding emergencies. Stopping bleeding can include applying direct pressure, extremity tourniquet, using a pelvic binder, resuscitative endovascular balloon occlusion of the aorta, which is performed by vascular and trauma surgeons, as well as utilizing interventional radiology and other interventional subspecialties to intervene where applicable, as well as surgery. And you know to read more details I would like to refer you to our chapters. In terms of non-traumatic hemorrhage, there is a wide spectrum of different sources such as gastrointestinal bleeding, postpartum hemorrhage, massive hemoptysis, ruptured abdominal aortic aneurysm, tracheo- anonymous fistula, and then AV fistulas. So these are just some of the main ones that we really do see in the intensive care unit. And for the sake of time I don't want to get into details of how to manage each of these as they can be different and I'd like to refer you to our book chapter, table 3 in our book chapter, details you know how these patients present and what exactly and how exactly you can obtain hemorrhage control. And so I'd like to refer you to that for more information. Let's now talk about complications and de-resuscitation. Once the patient has stabilized and the source of bleeding is identified and controlled, it is very important to switch focus to monitoring and managing any complications. So at this stage the transfusion strategy should be more of a restrictive transfusion strategy, so focusing more on thresholds of 7 and 21 and managing any complications. So if the patient's hypothermic, you can apply a bear hugger. If they have electrolyte abnormality such as hyperkalemia or hypocalcemia, you want to look out for it and make sure you are treating appropriately. And so a good source to look at is the ABG where you are you know checking your lactate or ionized calcium. A lot of the times there is electrolytes on there and that might be the first sign that something might be abnormal. These patients are also at risk for transfusion related alveolar injury or TRALI, transfusion associated circulation overload or TACO. And so if any of these more life-threatening complications occur, you need to make sure that you're providing adequate supportive care as soon as any signs are evident. So this is one of my favorite graphs when talking about fluid balance. And so here you have fluid balance on the x-axis and you have complications on the y-axis and you have a u-shaped graph. So if you are too restrictive, you're gonna have increased rate of complications. If you're too liberal, then you're gonna have a lot of complications. So ideally you want to be right in the middle where your volume status is optimal. So if you're too restrictive, the tank is gonna be empty, you don't have enough stroke volume, you're gonna end up with a lower blood pressure, a lower mean arterial pressure, and so you are not going to be able to maintain perfusion to your organs. You're gonna end up with end organ damage and multi-system organ failure. If you're too liberal, then you're gonna end up with a lot of edema and you're gonna get all the risk associated with that. So you can get compartment syndrome, you can end up with volume overload and end organ damage from the pressure and so you can end up with having complications with both approaches. In terms of take-home points, we talked about management of a patient with hemorrhagic shock requiring a multidisciplinary team approach that is prompt, systematic, and appropriate and you want to make sure you're focusing on early resuscitation, avoiding coagulopathy, avoiding acidosis, avoiding hypothermia and hypocalcemia. You want to make sure you obtain IV access as promptly as you can because the goal is to restore circulation and you need to have a means of giving blood products into your patients. We talked about optimal preference for intravenous access, so we talked about having a short diameter and a wide radius and then using rapid transfusers to resuscitate patients as quickly as we can. We talked about intraosseous devices being used for patients that are hypovolemic that you can't really get venous access in and then we also talked about the flow rates potentially being slower so if you're using an IO device it's really important to use a rapid transfuser or a pressure bag to make sure you're resuscitating quickly because again time to resuscitation really does determine your outcome so you want to stay on top of resuscitating quickly and not fall behind. Then we talked about using a balanced transfusion ratio so we talked about two studies and the 1 to 1 to 1 ratio as well as the 1 to 1 to 2 ratio were similar in terms of mortality but there was faster hemostasis on the 1 to 1 to 1 ratio so if you have a patient that is truly hemorrhaging that's something that you might want to consider. We talked about the benefit of whole blood it's very balanced it's very physiologic if you have a patient the data is better in the trauma population than the medical patients but again this is an area for future investigation and if you truly have a patient that's bleeding out then you might want to consider whole blood especially if it's accessible to you. Rapid identification we talked about ways of approaching these patients and identifying their sources of bleeding so you can take a history physical exam we talked about belt bedside ultrasound imaging and surgical consultation for exploration. Complications of resuscitation we talked about taco trolley hyperkalemia hypokalemia so you really want to keep an eye out as you're resuscitating. Then we talked about de-resuscitating as soon as the patient is stabilized and getting better. So for more information and more detailed discussion please be sure to read our chapter our references are also provided at the end we have an extensive list so we could not provide it in this presentation but I want to thank you for your time and again refer you to our chapter for more information.

Hemostatic resuscitation

Traumatic hemorrhage

Non-traumatic hemorrhage

Critical care medicine

Bleeding management

COVID-19 pandemic challenges

Multidisciplinary team approach

Resuscitation strategies

De-resuscitation strategies