Management of coagulopathies in a non-permissive environment

Author: Dr. Maj. Nadir Rachedi, Anaesthetist and military doctor, Celio Hospital, Rome

Source: Extract of a colloquial presentation during the HEMS Congress, 2019, Massa Airport, Italy

In this pitch presentation given during the HEMS Congress (2019), we summarize the possibilities of massive hemorrhage in a non-permissive environment. The speaker was Major Nadir Rachedi, a physician and major in the Italian Army, deployed at the Military Policlinic del Celio in Rome, an expert in medevac and active in several operational and tactical theaters.

The issues addressed are:

• Damage Control Resuscitation
• Golden Hour and HELI-Blood
• Component Therapy or Whole Blood
• Next Future (lidocaine, walking blood bank, etc.)

The first point of this talk takes its cue from the Lesson Learned during the 2013 Boston bombing, where the massive presence of military veterans meant that many wounded were treated immediately with improvised tourniquets. The skills of military and ex-military personnel were of great benefit in this case in preventing a profoundly serious massacre.

Nevertheless, how is it possible to manage coagulopathies in a non-permissive environment?

First, we need to understand why patients with hemorrhagic trauma continue to die despite stopping the bleeding. Karim Brohi’s study (2019) is fascinating from this point of view. In the pre-hospital setting, mortality is always higher in the first 24 hours. Between 2009 and 2015, however, that mortality dropped drastically, whereas, after 24 hours, it increased. Patients with significant bleeding who received a unit of whole blood saw a 25% drop in mortality. However, patients are admitted to the ER have a 50% higher mortality rate than patients who have already been to the ER for 3 hours. Improved management of coagulopathy reduces mortality tremendously, although associations with 30-day death increase; this data will be explained later in this paper. Brohi was able to compare patients with similar injuries and severity in both timing and characteristics.

Consequently, we know that Acute Traumatic Coagulopathy is one of the factors that allows us to understand the death of patients who arrive with a coagulopathy even if pre-hospital treatment was excellent and the patient was correctly dilated and remained warm. ATC is an independent predictor of mortality, and according to Brohi’s study, hypoxia is indicated as the key driver of this process: the average patient with an ISS between 59 and 64 has a mortality rate four times higher than the patient without coagulopathy. At the moment, there are many suppositions as to why it happens; in particular, we focused on TIC, or multi-organ failure syndrome, since it involves persistent inflammation, immunosuppression, and catabolism.

• 

• 

• 

Is the role of the endothelium important in hemorrhage?

Nevertheless, perhaps the endothelium plays a vital role in ICT (the tissue lines blood vessels, lymphatic vessels, and the heart). These are thousands of square meters of tissue, which have perfusion that has been little studied. For this reason, Brohi himself with Harris and Mai reported that more work is needed to identify how to repair or increase the hemostasis of the endothelium and reduce multi-organ failure. In short, blood should be considered as an organ: the endothelial microcirculation – it is estimated – to represent an area between 4,000 and 7,000 square meters, and the endothelium can be considered one of the most studied points to reduce the danger of trauma and bleeding.

• 

• 

• 

The military bleeding patient: if they are breathing, can they shoot and help you?

As we know, a natural anticoagulant system contributes to hemorrhage from trauma. However, we know this only for the military wounded. The latter is – as Captain Micheletti said – incredibly healthy people until the moment before the trauma. What plays against us is that we are talking about trauma with high impact and severity scores. On the battlefield, the first question we ask the wounded person is, “Are you there? Can you answer me?” If the casualty does not respond, we go ahead and shoot. If they do respond, the second question is, “Can you shoot?”.

Our target is not to determine where to hospitalize but how to arrange for rescue: the objective is not the immediate operating room but to prevent damage within the time frame needed for recovery. Therefore, the latest information on endotheliopathy is noteworthy, and it gives us a way to look at interesting guidelines.

What can we do as clinicians to avoid making an injury worse?

Unfortunately, the physician’s role in these scenarios is not to save a patient but to understand what not to do to worsen an injury. Moreover, hemostatic resuscitation has changed a lot in recent years. Previously, we relied on retrospective studies applied to resuscitations performed on the battlefield, while now we understand that hemostatic balancing to replace whole blood or balance plasma and platelets reduces mortality with added red blood cells. The factors we act on in hemostatic resuscitation are coagulation, hypothermia, and acidosis. From the publication of the fifth edition of the European Guides to the Management of Major Hemorrhagic Trauma and Coagulopathy, we started to intervene on a few factors, namely: coagulation, acidosis, and hypothermia.

We frequently discuss permissive Hypotension, which should be allowed when no blood products are available. However, one can ponder how permissive it is and how we assess how long to use it. There are renal resistivity indices to assess how much this practice is “empathetic” to metabolism. However, it is always an issue of time and duration.

• 

• 

• 

Timing in the management of hemorrhage

Going back to the times (numbers), we have now established an operational pathway. The 10 minutes platinum sees the military member engaged with self-made care or their fellow soldier with buddy care. Between 10 minutes and the first hour from the injury, the patient must receive Damage Control Resuscitation Care from trained personnel and, within 2 hours, must get surgical support. Now, I would like to pause on this topic as there have been different policies in Afghanistan that can offer several data over the last few years. In Afghanistan, all military casualties had to get to the operating table within 1 hour after the incident. This was a massive, incredible effort since Afghanistan comprehends a vast territory, resulting in massive distances to cover briefly. Unlike in the civilian sector, we cannot always get the casualty to the most appropriate hospital. In Afghanistan, we have seen that applying the Golden Hour in an orthodox and methodical way has paid off, despite the increase in the injury severity score: the number of attacks has decreased over time; however, more explosives have become increasingly severe, with injuries considerably more challenging to treat.

The Case Fatality Rate and Transport Time between 2001 and 2013 was published in JAMA. Since 2009, transport to the operating room has increased dramatically, and the mortality rate has inversely declined. Additionally, what is evident from this paper – written by an anesthesiologist who has worked in the field – is how hypotension dramatically increases acidosis when it drops below 100mmHg. There is a mortality step – increasing by 10% – when reaching 90mmHg.

How is it possible to immediately be ready for transfusion?

Thus, if we look at the outcomes of bleeding and the epidemiology of preventable deaths, we can see that 1/3 of the deaths in patients treated before reaching the hospital are preventable deaths. Moreover, almost all of those deaths are of bleeding patients. For this reason, we need to identify massive bleeding and coagulopathy right away, perhaps with the TICCS scale. However, how do we transfuse right away? Based on the studies done on blood product administration, since 2003, there has been a focus on getting blood to advanced settings, geographically speaking. Highly capacitated refrigerators have been created to handle the blood properly, but a considerably massive logistical problem remains since blood arrives from Italy and returns to Italy via Afghanistan or Iraq.

Given the situation, we also evaluated the impact of transfusions aboard helicopters was. One study evaluated the outcomes of transfused versus non-transfused patients at 24 hours and 30 days with equal injury rates and recommended transfusion.

Nevertheless, another study was conducted in Afghanistan: “Once embarked if I transfuse patients within 15 minutes or after 15 minutes does it change anything?”. The answer was positive: the outcome of those transfused was immediately superior. In my opinion, there is no significant difference at 30 days between different between transfused and non-transfused patients, for reasons highlighted earlier. Over the years, we have unfortunately been faced with explosive powers in the highest attacks, and incidents series have had much more severe patients on average.

So, transfusion right away, but how?

If we solve the situation with blood, there are no evident problems, but the situations we have are not numerous, and what if we need plasma? That is where the French, German, and South African teams who invented freeze-dried plasma come in. The latter is a product equal to our liquid plasma but with less fibrinogen, and it can be preserved at room temperature for one year, and the infusion is made by putting 200ml of physiological saline. The French are also thinking of making plastic transport bottles, but they are still in the study phase. For us, plasma is a resuscitation fluid, and we know it provides fluid recovery with immediate benefits. French physicians, in particular, believe that plasma is the primary and only resuscitation fluid to make volume, excluding the presence of crystalloids (in France, they avoid the topic of endotheliopathy). The extra share they give of fibrinogen, according to them, does not harm the patient; in fact, they consider it a bonus, but our patients are always healthy. As the Israelis also wrote: “The key concept of pre-hospital and preoperative hemorrhagic treatment is that you have to balance the response with the “least bad” of the available options. The goal is to give the injured intravascular volume to survive until tissue repair or effective reanimation is achieved.”

In case of penetrating trauma to the chest or abdomen, Israelis always use 2 grams of TXA acid (in the protocol, it is marked 1, but it has been updated). According to CRASH, all trauma patients with severe bleeding at 3 hours after injury should be treated with TXA. After 3 hours, TXA may increase the risks of death. In addition, the time at which TXA should be administered has changed from a time of hospital assessment (1B) to a time of assessment during hospital transport (1C).

• 

• 

• 

The advent of the Walking Blood Bank

Therefore, if these are the best options, how is it possible to have blood always ready? That is why Americans have created the so-called Walking Blood Bank. There is no difference in administration concerning hospital mortality, both for those who received specific types of blood types and in people who received a 0. In fact, only three transfusions out of 10,000 administrations caused deaths. Furthermore, we are talking about 10,000 transfused people who would most likely have died during transport without infusion.

Then, there are several other things to look at, like the REBOA study and abundant others on the adenosine-lidocaine-magnesium combination that should have exceptional brain protection and hemorrhage reduction. However, the above-mentioned study was carried out in Australia and resulted in a 60% reduction in deaths from non-compressible hemorrhage. One of the authors stated that: “ALM appears to give systemic protection by preserving cardiocerebral function and improving endothelial status, and also by reducing inflammation and coagulopathy. The exact operation mechanism is under investigation but appears to involve a high number of evolutionary pathways.”

• 

• 

• 

• 

• 

• 

• 

• 

•