TXA in Trauma

Going to take a quick break from the PSA for #traumatuesday

 What is TXA and how does it work?

Tranexamic Acid is a medication used to treat or prevent excessive bleeding.

It works by reversibly binding receptor sites on plasminogen, which reduces conversion of plasminogen to plasmin, further preventing fibrin degradation making up the clot's framework.

Here's a cute animated video showing the mechanism of TXA: https://www.youtube.com/watch?v=emAHFC-Aidg

What role does TXA play in trauma?

CRASH-2 Trial (Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage-2)

• Double-blinded RCT published in 2010

• 20,211 patients with traumatic hemorrhage (SBP < 100 and/or HR > 110) or at risk of significant hemorrhage, within 8 hours of injury

• Dose used was 1g TXA over 10 minutes + 1g over 8 hours

• All-cause mortality significantly reduced with TXA

• Risk of death due to bleeding on day of presentation significantly reduced with TXA

• No significant difference in vascular occlusive events

• No significant reduction in blood transfusion requirements

• Greatest benefit seen with early administration (< 1 hour after injury but also < 3 hours). Increased risk of death due to bleeding if administered after 3 hours.

MATTERs (Military Application of TXA in Trauma Emergent Resuscitation)

• Retrospective observational cohort study published in 2012

• 896 military personnel who received at least 1 Unit of PRBCs within 24 hours of admission following a combat-related injury

• Dose used was 1g TXA IV bolus, repeated as deemed necessary by provider

• All-cause mortality significantly reduced at 48 hours and 30 days especially in patients requiring massive blood transfusion due to their injury

CRASH-3 Trial (Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage-3)

• Double-blinded RCT published in 2019

• 12,639 patients with traumatic brain injury (< 3 hours after injury, GCS < 13 or ICH on CT). Patients excluded had major extracranial bleeding, GCS of 3, bilateral unreactive pupils.

• Dose used was 1g TXA over 10 minutes + 1g over 8 hours

• Death due to head injury significantly reduced at 24 hours but not at 28 days

• No significant difference in disability or vascular occlusive events

Bottom Line (based on the literature above):

• In adult trauma patients in severe hemorrhagic shock for which you are transfusing blood, administer TXA 1g IV over 10 minutes, followed by 1g infused over 8 hours.

• Reasonable to try TXA for TBI patients with GCS 9-15 and ICH on CT within 3 hours of injury but need more evidence

CRASH-2: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60835-5/fulltext

MATTERs: https://jamanetwork.com/journals/jamasurgery/fullarticle/1107351

CRASH-3: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32233-0/fulltext

Reviews from FOAMed sources:

https://emcrit.org/pulmcrit/crash3/

https://www.thebottomline.org.uk/summaries/icm/crash-2/

https://rebelem.com/crash-3-txa-for-ich/

https://first10em.com/the-crash-2-trial/

https://first10em.com/crash-3/

https://emcrit.org/wp-content/uploads/2012/02/TXA-in-trauma-How-should-we-use-it.pdf

Procedural Sedation and Analgesia - Part 2

For those of you following along from PSA Part 1...the answer to the question at the end is ketamine!

For Part 2, we’ll be discussing the most commonly used Procedural Sedation and Analgesia (PSA) agents including their classifications, recommended doses, peak effects, durations, and some comments that I think are noteworthy about each of them as they relate to PSA. And yes there's more than just ketamine!

Remember for our purposes when we discuss PSA, our goal is usually moderate to deep sedation!

Commonly used agents:

 Midazolam (Benzodiazepine)

anxiolytic, sedative, amnestic, muscle relaxant, anticonvulsant

Dose: 0.05 - 0.1 mg/kg IV; 0.1mg/kg IM

Peak effect: 2-3 mins IV; 15-30 mins IM

Duration: 20-30 mins IV; 1-2h IM

Comments: May produce paradoxical excitement.

Can use flumazenil as a reversal agent.

Does not provide analgesia (sometimes given with opioid).

Can cause hypotension and respiratory depression. 

Fentanyl (Opioid)

analgesic

Dose: 1 - 3  mcg/kg IV

Peak effect: 2-3 mins

Duration: 30-60 mins

Comments: Typically used in conjunction with another agent for pain relief.

100 times more potent than morphine but much shorter acting.

Relatively safe hemodynamic profile, rarely causes hypotension.

Can cause respiratory depression.

Can use naloxone as a reversal agent.

Commonly observed reaction is nasal pruritus so patients will try to scratch their nose.

Rare but serious side effect to remember is that it can cause Rigid Chest Syndrome, usually in pediatrics and usually with larger doses. Can attempt rescue ventilation in this case but will likely need to reverse with naloxone or possibly give paralytic and intubate.

Can give intranasally for immediate pain relief prior to a PSA and if applicable, before IV access is established (more commonly done in pediatrics).

Pentobarbital (barbiturate)

sedative, amnestic, anticonvulsant

Dose: 2.5 mg/kg IV

Peak effect: 3-5 mins

Duration: 15 mins

Comments: Can lead to respiratory depression and hypotension.

Apparently the IV sedative of choice for children in many diagnostic imaging centers for its quick onset and short duration of action and considered superior to midazolam.

Ketamine (NMDA receptor antagonist)

dissociative, analgesic, amnestic

Dose: 1mg/kg IV; 4mg/kg IM

Peak effect: 1-3 mins IV; 5-20 mins IM

Duration: 15-30 mins IV; 30-60 mins IM

Comments: Everyone’s favorite in EM and probably deserves its very own post.

Not considered a sedative in the classic sense because of its dissociative properties.

Can cause bronchodilation and bronchorrhea resulting in excessive salivation.

Can cause transient apnea and transient laryngospasm. If suspecting laryngospasm, can try jaw thrust using the laryngospasm notch maneuver. If that doesn’t work can try bagging through. If still unable to ventilate, will need to give paralytic and intubate.

Can cause a profound emergence reaction and is contraindicated in patients with schizophrenia and psychosis. Emergence reaction is less common in pediatric patients. One way to prevent this recovery agitation is by helping the patient go into the “K-Hole” smoothly prior to and during medication administration by helping them think happy thoughts, having them think of their favorite place, or maybe even doing some magic therapy (for more info: www.magic-aid.org). If patient is having a very agitated emergence reaction and calmly talking to them/trying to redirect them does not work, can give a dose of midazolam or propofol to help calm them. Would not recommend magic therapy on a patient with emergence reaction.

Can cause emesis, typically in the recovery phase. Can give ondansetron in recovery phase. No evidence that co-administration of ondansetron with ketamine reduces incidence of nausea in recovery phase.

Can cause muscle rigidity.

Typically pushed slowly but no evidence to show that this reduces incidence of laryngospasm or nausea, contrary to popular belief.

Sympathomimetic properties which cause inhibition of catecholamine reuptake results in increase in blood pressure and heart rate. This means that in a critically ill patient who is on multiple pressors and is out of native catecholamines, ketamine actually causes myocardial depression.

Can give IM before IV access is established and maybe not even start an IV if you don't need one (more commonly done in pediatrics).  

Etomidate (GABA agonist, positive modulator of GABA receptor)

sedative, anxiolytic

Dose: 0.15 mg/kg IV

Peak effect: 15-30 secs

Duration: 3-8 mins

Comments: No analgesic property.

Hemodynamically stable.

Fast-on and fast-off.

Can possibly cause adrenal suppression in septic patients although likely irrelevant for one time dose for PSA.

Can cause respiratory depression, myoclonus, vomiting.

Can lower seizure threshold. Do not give to someone with epilepsy.

Propofol (positive modulator of GABA receptor)

sedative, anxiolytic

Dose: 0.5 - 1 mg/kg IV

Peak effect: 30-60 secs

Duration: 5-6 mins

Comments: No analgesic property.

Hurts going into vein, can pretreat with lidocaine or mix with lidocaine.

Can cause transient apnea, respiratory depression, hypotension.

Fast-on and fast-off.

Can cause muscle relaxation

Common teaching has been to avoid in patients with known or suspected allergy to eggs or soy products but this has been debunked.

“Ketofol” (combination of ketamine and propofol)

Dose: ketamine 0.125-0.5mg/kg + propofol 0.5mg/kg IV

Peak effect: 30-60 secs

Duration: 15 mins

Comments: Can either give 1:1 or give subdissociative dose of ketamine with PSA dose propofol.

These agents supplement each other: ketamine mitigates propofol-induced hypotension and propofol mitigates ketamine-induced vomiting and recovery agitation.

Some commonly encountered procedures requiring PSA and what I like to use (just in general, always take into account specific patient factors):

Cardioversion = etomidate + fentanyl

Complicated pediatric laceration repair: ketamine

Fracture/Joint reduction (recently dislocated): ketamine

Adult Joint reduction (delayed presentation): ketamine + propofol

What are your thoughts? Do you have any favorite go-to procedure-drug pairings?

Stay tuned for PSA Part 3 where we put everything together and discuss the setup and procedure!

Procedural Sedation and Analgesia - Part 1

Procedural sedation and analgesia (PSA) is the use of analgesic, sedative, and/or dissociative agents with the purpose of relieving pain and anxiety associated with a procedure.

It is well within the scope of the emergency physician and the aim of this post is to go over some key points as well as go over some of the most commonly used agents.

First thing to remember is that sedation is a spectrum and our goal state is determined by our indication for PSA including the duration of the procedure, and the level of pain/anxiety associated with the procedure.

We can then achieve our goal by careful selection of the proper agent, route, and dose.

Also take into account the patient’s age and comorbidities, including hepatic, renal, and cardiopulmonary insufficiencies.

For our purposes, PSA will only be referring to moderate sedation.

Our goal for PSA is to induce a state that allows a patient to tolerate unpleasant procedures while maintaining cardiorespiratory function by producing a depressed level of consciousness but allowing the patient to maintain airway control independently and consciously.

Before getting into the different agents, here are some definitions to be familiar with:

Analgesia:  Relief of pain without intentional production of an altered mental state such as sedation. An altered mental state may be a secondary effect of medications administered for this purpose.

Anxiolysis: State of decreased apprehension concerning a particular situation in which there is no change in a patient’s level of awareness

Dissociation: Trancelike cataleptic state in which the cortical centers are prevented from receiving sensory stimuli, but cardiopulmonary activity and responses are preserved.

Can you guess which PSA agent was used on this pediatric patient?

Find out next time in our PSA POTD - Part 2!