What do paramedics really need to know about cannabis?

The recent legalization of cannabis in Canada has changed the landscape for us. Claims of the beneficial effects of cannabis increase every day. It has been used with chemotherapy to reduce nausea, and it may actually be a cure for cancer. It has been used to treat pediatric seizures and it may eventually be used to treat brain damage from strokes. But those unfamiliar with the toxic effects of this drug are ending up in the emergency ward at ever increasing rates.

Is this drug the next best thing, or a dangerous and lethal chemical?

In this article, I will share with you what I have learned. It is a fascinating drug that works on many of our bodies most vital systems. To help you navigate the complexities of this class of drug, I’ll present some of the more important information in the following manner:

Pharmacodynamics (the effect of the drug and mechanism of action)

Therapeutic effects
Common uses
Side effects
Overdose symptoms
Interactions with other drugs


Why do substances from the cannabis plant such as THC and CBD have such a profound effect on the human body? The surprising answer is that our body produces a group of ‘cannabis-like’ chemicals called endogenous cannabinoids, or endocannabinoids. Together, the endocannabinoids regulate many bodily functions, such as sleep, blood pressure, thermoregulation, immune responses, bone growth, and even female reproduction. When endocannabinoids work the way they are supposed to, they promote health. However, it is becoming increasingly clear that an unbalance in endocannabinoid activity is involved in many disease processes.

Dozens of substances in the cannabis plant mimic these naturally occurring cannabinoids but the two that have been most studied are TCH and CBD. These chemicals interact with two important receptors in the endocannabinoid system, CB1 and CB2. CB1 receptors are primarily in the brain but they are also located in smaller amounts throughout the body. CB1 receptors can be found in our endocrine glands, leukocytes, spleen, heart and parts of the reproductive, urinary and gastrointestinal tracts. CB2 receptors are found in the peripheral nervous system and are present in high numbers on immune cells. THC, which is the psychoactive ingredient in cannabis, stimulates both CB1 and CB2 receptors in much the same way as the naturally occurring cannabinoids do but in a more intense fashion.

CBD works a little bit differently. Technically, CBD does not bind directly to cannabinoid receptors. Instead, CBD works by inhibiting an enzyme that degrades something called anandamide. When this enzyme is inhibited, it cannot break down anandamide normally and this leads to increased levels of anandamide in the body. Anandamide is the most important endocannabinoid (or naturally occurring) cannaboid in the body. Slightly elevated levels of anandamide are associated with feelings of well being and may even be responsible for increased health.

When a person ingests marijuana, THC overwhelms the endocannabinoid or ‘EC’ system, quickly attaching to cannabinoid receptors throughout the brain and body. This interferes with the ability of natural cannabinoids to do their job of fine-tuning communication between neurons, and can throw the entire system off balance.

Because cannabinoid receptors are in so many parts of the brain and body, the effects of THC are wide-ranging: It can slow down a person’s reaction time (which can impair driving or athletic skills), disrupt the ability to remember things that just happened, cause anxiety, and affect judgment. THC also affects parts of the brain that make a person feel euphoric—this is what gives people the feeling of being “high.” But over time THC can change how the EC system works in these areas of the brain, which can lead to problems with memory, addiction, and mental health.

Cannabinoids are pretty amazing and interact with many important neurotransmitters and neuromodulators. Here is a short list of them and how the function inside us:

  • Acetylcholine, the chief neurotransmitter of the parasympathetic nervous system
  • Dopamine, the neurotransmitter associated with pleasure
  • GABA, the neurotransmitter associated with calming and preventing seizures
  • Histamine, a compound which is released by cells in response to injury and in allergic and anaphylactic reactions.
  • Serotonin, which is a neurotransmitter involved in a variety of bodily functions. These include; mood, sexual desire and sexual function, appetite, sleep, memory and learning, and even temperature regulation.
  • Glutamate, the most abundant excitatory neurotransmitter in our body. It is involved in learning and memory. High levels of glutamate are actually responsible for cellular death.
  • Norepinephrine, which increases heart rate, blood pressure, arousal and alertness. It also enhances formation and retrieval of memory.
  • Prostaglandins, which are powerful locally acting vasodilators. Prostaglandins are also involved in inflammation. They are synthesized in the walls of blood vessels and prevent needless clot formation. They even regulate the contraction of smooth muscle such as the uterus during labour.
  • Opioid peptides, there is increasing evidence that the reward pathways related to opioid actions are also influenced by the endocannabinoid system.

A number of the pharmacological effects of cannabis can be explained by how they interact with these neurotransmitters. For example, tachycardia and hyposalivation (or dry mouth) are mediated by the effect of THC on acetylcholine. Antiemetic (or anti-vomiting) properties of cannabinoids may be based on interactions with serotonin. The therapeutic effects that are seen in treating seizure or spastic disorders are probably mediated by the GABA, glutamine and dopamine systems. Cannabinoids influence the activity of most neurotransmitters in a complex manner, which sometimes may result in contradictory effects. In other words, external cannabinoids may either suppress or intensify symptoms such as pain, hunger or nausea. Interactions of cannabinoids with other neurotransmitter systems may cause unexpected effects. THC interacting with the Circulatory System can induce tachycardia and increase cardiac output with increased myocardial oxygen demand. It can also produce peripheral vasodilation and orthostatic hypotension. (1)

Therapeutic Effects

One important physiological role of endocannabinoids is neuroprotection. Ischemia and hypoxia in the CNS induce abnormal glutamate hyperactivity and other processes that cause neuronal damage. These processes also play a role in chronic neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease and multiple sclerosis. Clinical studies are under way to investigate the therapeutic potential of a derivative of THC to treat brain injuries. So far, these trials have shown positive results. (1)

Cannabinoids also seem to help with pain relief, muscle relaxation, immunosuppression, inflammation, allergies, sedation, improvement of mood, stimulation of appetite, anti-emesis, lowering of intraocular pressure, seizure control and bronchodilation.

But the list is even longer:

  • Preliminary observations show that endocannabinoids seem to stimulate bone formation
  • Cannabinoid agonists inhibited human breast cancer cell proliferation
  • THC was shown to modulate the immune response in a complex manner. In seems that THC is effective in treating inflammation caused by multiple sclerosis and Crohn’s disease.
  • THC also possesses anxiolytic (anti-anxiety) and anti-psychotic properties. (1)

Common Uses

  • Marinol (dronabinol, ∆9-THC) is approved for medical use in refractory nausea and vomiting caused by cancer drugs and for appetite loss in anorexia and HIV/AIDS patients.
  • Cesamet (nabilone) is also used to treat nausea and vomiting associated with cancer chemotherapy.

There is also increasing evidence for therapeutic effects of THC and cannabis extracts in:

  • Spasticity due to multiple sclerosis and spinal cord injury
  • Chronic pain
  • Tourette‘s syndrome
  • Dystonia (abnormal muscle contractions) and abnormal, uncontrolled, involuntary movements that result in the treatment of Parkinson’s disease

There are also some conditions where the evidence suggests that endocannabinoids are helpful, but the evidence is not yet conclusive:

  • Asthma
  • Glaucoma
  • Inflammation from arthritis
  • Epilepsy
  • Depression,
  • Bipolar disorders and anxiety disorders
  • Dependency to opiates and alcohol and treatment of withdrawal symptoms
  • Agitation in Alzheimer‘s disease.

Side effects

So here is where it starts to get really interesting. Although cannabinoids may be effective in treating many disorders, these drugs are complicated. For example, anandamide, which you may recall is one of the most important naturally occurring cannabinoids, not only binds to cannabinoid receptors but also stimulates vanilloid receptors. Vanilloid receptors are associated with ‘hyperalgesia’ or an abnormally heightened sensitivity to pain.

Also, some antagonists (drugs that block the action of a receptor) may behave as inverse agonists. This means that they not only block the effects of naturally occurring cannabinoids but they actually produce effects that are opposite from those produced by cannabinoid receptor stimulation. Translation – if you take a synthetic cannabinoid type drug that should reduce pain, it may actually cause increased pain.

Another potential problem with using synthetic cannabinoids is finding the correct dose for each person. In studies with mice, low doses of anandamide stimulated immune function while high doses decreased immune functions.

Overdose symptoms

The median lethal dose of oral THC in rats was 800–1900 mg/kg. There were no cases of death due to toxicity following the maximum oral THC dose in dogs (up to 3000 mg/ kg THC) and monkeys (up to 9000 mg/kg THC.

Acute fatal cases in humans have not been substantiated. However, myocardial infarction may be triggered by THC due to effects on circulation. Marijuana can induce a schizophrenic psychosis in vulnerable persons and there is increasing evidence that there is a distinct cannabis psychosis. (1)

Between 2009 and 2015, Colorado’s Regional Poison Control Center studied the effects of legalized cannabis and while the number of accidental poisonings in children increased five-fold, there was only one reported death in an 11-month-old. The patient presented to the hospital unresponsive and in a wide complex tachycardia with a severe metabolic acidosis (pH of 6.7). The patient underwent cardiopulmonary resuscitation for 20 minutes without return of spontaneous circulation. Urine drug screen results were positive for THC and confirmed on post-mortem analysis. The cause of death after autopsy was myocarditis. (2)

Results from a study on admissions to the Colorado Children’s Hospital revealed the following useful facts:

  • The median age of patients was 2.4 years
  • Between 2009 and 2015, 21 of 62 exposures (34%) were from medical marijuana
  • Known marijuana products involved in the exposure included infused edible products (48%)
  • Of those 17 where baked goods (cookies, brownies, and cake),10 where candies, and 2 popcorn products.
  • Forty patients (65%) were observed in the ED, and 13 patients (21%) were admitted to an inpatient ward unit.
  • An additional 9 patients (15%) were admitted to the intensive care unit.
  • Two of these required respiratory supports, a 3-year-old who was intubated for apnea and an 8-month-old who received continuous positive pressure for respiratory insufficiency. (2)

Interactions with other drugs

Other medicines may enhance or reduce certain actions of THC. And certain actions of these medicines may be enhanced or depressed by THC.

The most important interactions may be between cannabinoids and sedatives like alcohol and benzodiazepines. This is because cannabinoids can increase sedation and cause a further decrease in impairment and the level of consciousness.

Other dangerous interactions are between cannabinoids and substances that act on the cardiovascular system. Drugs found on the following list can be seriously influenced by THC:

  • Amphetamines
  • Adrenaline
  • Atropine
  • Beta-blockers
  • Diuretics
  • Tricyclic antidepressants

Most of the cardiovascular effects of cannabinoids are caused by activation of the sympathetic nervous system and inhibition of the parasympathetic nervous system. Smoking cannabis results in an immediate increase in heart rate that may last more than 1 h after exposure. This is followed by a substantial rise in serum norepinephrine level at 30 minutes. Acute exposure to cannabis may also result in elevation of supine systolic blood pressure and may induce atrial fibrillation. Despite the overwhelming public perception of the safety of these substances, an increasing number of serious cardiovascular adverse events have been reported in relation to recreational cannabis use. These have included sudden cardiac death; coronary, cerebral and peripheral vascular events; arrhythmias and stress cardiomyopathy among others. Under controlled experimental conditions, cannabis is believed to cause an acute vasodilatory response. However, this arteriolar vasodilation is not universal to all vascular beds as vasoconstriction has been seen in the coronary, cerebral and peripheral arterial systems and has been directly responsible for many instances of acute myocardial infarction (AMI), stroke and peripheral artery issues. (3)

In patients with ischaemic heart disease, cannabis increases the frequency of anginal symptoms at low levels of exercise, owing to an increase in heart rate and myocardial contractility, and a reduction in the oxygen carrying capacity of blood due to the formation of carboxyhaemoglobin. These adverse haemodynamic changes may trigger plaque rupture in vulnerable individuals culminating in myocardial infarction. Myocardial infarction has also been reported in the presence of normal coronary arteries, suggesting coronary vasospasm. Other reported cardiovascular effects associated with cannabis consumption include transient ischaemic attacks and strokes. (3)

But there are also a number of positive interactions, where cannaboid consumption may beneficially increase the desired effect of the drug. These include:

  • The enhancement of muscle relaxants, bronchodilators and anti-glaucoma medication
  • The increased analgesia by opiates
  • The antiemetic effect of phenothiazines (medications used to treat schizophrenia and manifestations of psychotic disorders)
  • The antiepileptic action of benzodiazepines

The cyclooxygenase inhibitors indomethacin, acetylsalicylic acid, and other non steroidal anti-inflammatory drugs antagonize or block THC effects. Indomethacin significantly reduced the subjective “high” and tachycardia in the heart. (1)


So, there you have it. Cannabis is complex, and we are just beginning to understand how it affects us. And there are clearly things that we need to understand as paramedics to provide optimal care.

We are all on a long and strange trip. Where it leads is debatable. But it seems certain that very soon, research will lead to a greater understanding of the endocannabinoid system. Hopefully, there will be frequent updates.


  1. Pharmacology of Cannabinoids, Franjo Grotenhermen, in Neuro endocrinology letters 25(1-2):14-23 · February 2004. Available from https://www.researchgate.net/publication/8546102_Pharmacology_of_cannabinoids
  • Unintentional Pediatric Exposures to Marijuana in Colorado, 2009-2015;  George Sam Wang, MD1,2; Marie-Claire Le Lait, MS2; Sara J. Deakyne, MPH3; et al. JAMA Pediatrics. 2016;170(9):e160971. doi:10.1001/jamapediatrics.2016.0971

Rural and Remote Paramedicine – Our Dirty Little Secret

I would like to thank Lyle Blumhagen, my publisher at Canadian Paramedicine Magazine, for asking me to write this article

Most of us just want to go through life without causing ourselves any extra work, worry or grief.

So why on earth would smart people volunteer to work in Emergency Services in their own home town?

Recent findings suggest rural ambulance paramedics are at particular risk for increased levels of fatigue, stress, anxiety and depression.

The Issues

Despite a large chunk of my career doing nothing but high risk neonatal, pediatric and maternity calls, a call from my ‘rural and remote’ career has stuck with me as the worst call I ever did. And as bad as calls go, nothing can prepare you for telling your friend’s mother that her son is never coming home again. Especially after you had been sent to save him.

Previous to my posting as a Unit Chief for Burns Lake British Columbia, I worked in Vancouver as an Emergency Medical Assistant ll or EMA ll, and this really did little to prepare me for what I was about to experience. Back in the city we just called in extra cars when we faced multiple patients. We called in higher trained crews when the situation warranted it, and a hospital was always 10 minutes away. I soon learned that working in the country was an entirely different kettle of fish.

We did the best we could with what we had. The crews and I spent many hours attending weekly training sessions on our own time. We took every course that was offered, we practiced and we read. But we could never overcome the sense of hopelessness that envelops you when people die. During the 3 years that I worked in the rural/remote environment we lost friends and neighbours and people too young to die. Some of the more horrific calls led to depletion of our numbers as those attending never came back. It was at times frustrating because there didn’t seem to be any workable solutions.

I saw marriages strained or broken because of the requirement to always carry the pager. Although we were always recruiting, we never seemed to have enough staff.

Maintaining emotional health was and still is a big problem in this setting. Being on call leads to a disruption of a healthy work and life balance. It is almost impossible to exercise, go away for the weekend or attend family events. When crews are exposed to critical incidents and require professional counselling, geography complicates matters as most therapists live in major centers.

All of these factors cause significant hardship for those involved, but that’s not even the worst part. Here’s the dirty little secret that no one wants to talk about.

Being in a small town means that everyone knows everyone. Even worse, everyone knows everyone’s business as well. So imagine how you would feel if you made a mistake while looking after your neighbours child. It happens, everyone makes mistakes. But the scrutiny in a small town can be overwhelming. The deck is stacked against you. Response times are longer as in many towns, there just isn’t sufficient call volume to pay people to be at the station. Skills decline when they aren’t used and a low call volume makes it nearly impossible to stay sharp. And you need to stay sharp because you are looking after your family and friends. There are great expectations that are not reasonably met within the existing structure. It’s a virtual certainty that things will not go well.

A great deal of research has been done on other health care professionals in rural and remote environments, and workable solutions have been discovered. Unfortunately, there are few studies that have looked at the unique set of stressors that affect paramedics in isolated practice and change has been slower.

A few studies show that rural paramedics have significantly higher levels of fatigue, depression, anxiety, and stress, and significantly poorer sleep quality than reference samples. Paramedics also reported less physical activity than community samples. … Consistent with an earlier study of metropolitan paramedics based on the same methodology, findings suggest rural ambulance paramedic shift workers are at particular risk for increased levels of fatigue and depression (regardless of age or gender) and poor quality sleep. Organisational intervention was suggested[1].

To further understand how these stresses are generated, it might be helpful to see how others analyze our behavior.

In 2004, Jonsson and Segesten investigated the prevalence of post-traumatic stress symptoms among professional ambulance personnel in Sweden. They discovered that ambulance paramedics experience stress at different stages of each event that they attend.

The risk of failing

The risk of making mistakes is expressed by ambulance personnel in terms of fear of misjudging or of failing in their desire to help the patient. The feelings of not doing enough for the patient and their family’s makes the worker feel helpless and useless. This feeling can arise even if they have done everything they can.

Participants described how they attempted to raise an emotional shield between themselves and the patient. They stated that they approached the scene by concentrating and focusing on the victim alone, in an attempt to distance themselves from impressions which may distract them from performing their duty. They stated that they can be concentrating so hard on the tasks at hand that afterwards it is not uncommon for ambulance personnel to be unsure how many patients and or vehicles were involved.

To be caught in turmoil

According to Jonsson and Segesten ambulance paramedics go through many emotions after they have left the patient in the emergency room or at the scene of an accident. They have begun to identify with the patient and relate to them. They begin to worry about whether they will be able to help the patient. Numerous participants in the study stated during this time, paramedics can attempt to distance themselves from many variables, but feel more and more enmeshed in the situation. A feeling of anxiety can begin at this stage and workers can get overwhelmed with emotion. At this time ambulance personnel can feel confused, upset, exhausted, sad and distressed, and that the world is chaotic… All participants in their study showed a variety of post-traumatic stress disorder symptoms including; re-experiencing trauma, numbing of compassion and distortion in social or professional performance, and symptoms of increased arousal. However, when they were asked by fellow workers if they felt comfortable, they always tried to hide their feelings. It is clear then that if paramedics are going through all of these things, it is bound to have an impact on their work and personal/family lives.

 Guilt and shame

This theme involved feelings of guilt, shame and self-loathing reported by participants. They expressed that the traumatic event was accompanied by guilt-related memories of the event, which triggered a negative response. The cohort of participants in the study said that they felt guilty when they thought they had failed in their attempt to save the life of a victim, especially if they had given a promise to the patient or relatives that the outcome would be positive. The feelings of guilt appear even if they know they did everything possible to help and support the patient. Questions such as ‘could I have done anything different?’ And ‘had it been possible to do more?’ are always there.

The most shameful thing according to some of the participants was not that they failed in caring or giving attention to the patient, but that they were also overwhelmed by all the impressions from the scene of the incident. The image that they had built up of themselves and for others ….was that nothing could shake them. Afterwards they discovered that they had been terrified and still are, and they suffer from sleeping disturbance, nightmares and intrusive memories. They express their feelings of shame in terms of uselessness, shortcomings and powerlessness as well as in relation to how others see them.

Participants in Jonsson and Segesten’s study further stated that they never talked to anyone about their feelings of shame and failure since. Instead they did everything to hide these feelings. The participants expressed feelings of shame in association with negative self-perceptions and see themselves as inferior to others as a result. It takes a great effort to conceal feelings of shame, when you have failed to be someone you wanted to be[2].

It seems pretty obvious to me that the rural and remote paramedic is exposed to these themes more often than those in major metropolitan areas. While we all feel the pressure of high acuity low volume calls, those without proper resources will be most affected.

Another useful study has led to increased understanding of the issues and hopefully has provided a road map to address the issues.

It revealed stressors peculiar to Australian rural paramedics that were not necessarily reported by their metropolitan counterparts. Key themes revealed stress was associated with:

  • Forced rural posting
  • Isolation, and a lack clinical support
  • Work patterns
  • Deskilling and reskilling
  • Knowing patients

It concludes that ‘Triggers that produce stress for Australian rural paramedics need to be acknowledged and addressed in a positive and constructive manner. Workforce redesign and strategies to enhance interdisciplinary support and professional education are potential mechanisms for the retention of a highly skilled paramedic workforce in rural areas of Australia[3].

The way forward

The Australian study has led to some important changes as some of the recommendations listed below have already been adopted.

Useful strategies to be considered include an expanded scope of practice for rural … paramedics with senior clinical and medical staff playing a mentoring role. … Expanded scope of practice may also pave the way for shared training and professional development programs across all rural healthcare staff. This would be more cost efficient, enhance skills, increase interaction across all health professionals and build teamwork that is so vital in rural health care practice. Expanded scope of practice has already been adopted in the United Kingdom, Canada and some Australian states and has proven as an effective workforce retention strategy.

Many rural healthcare staff share common stressors that are linked to a lack of social and organizational support, and the need for a better work-life balance. Organizational strategies that could assist staff in these areas include flexible work hours, better communication, and career mentoring. Psychological support for staff could be enhanced by using a combination of phone, internet (Skype) and face-to-face debriefing and counseling services. Stress management programs should be proactive rather than reactive and target the rural sector, educating staff about common stressors and how to overcome these and attain a better work-life balance in more remote work locations.

Final Thoughts

Clearly important work has started and support for rural and remote paramedics is increasing. While increased training is required, it will be important to ensure that the training is effective. This training needs to be specific and adequately prepare our staff for high acuity low volume calls that can inflict so much psychological harm.

Sitting in a classroom clearly won’t do. Our rural and remote colleges need to be exposed to high fidelity simulations involving critical interventions and complex team based decision making.

There is an emerging concept of ‘community preparedness’ that may be harnessed as well. Rural and remote paramedics should be supported in their efforts to train the lay public in CPR, basic first aid and critical interventions. This further enhances a team based approach and is the only real strategy to deal with long response times.

During the Jonsson and Segesten interviews, participants were asked to describe their job in 3 words. Some of most common adjectives received back were ‘Fantastic, challenging, rewarding, unpredictable, enjoyable, stressful, frustrating’. Most of the descriptors were relatively positive, despite the fact that they all discussed how stressful the job could be at times. Ambulance paramedics are amazing individuals. The work they do is courageous, mind blowing and challenging. They should be supported, well-resourced and acknowledged for the work they do for our communities[4].

There will be many important ideas generated by the people who serve in small towns and they need to be heard. Their ideas need to be discussed with an open mind, and where appropriate, addressed and adopted. Clearly these are special people who put themselves in harm’s way and take on and accept significant compromises to their own mental health in the service of others.


[1] Journal of Community Health; February 2013, Volume 38, Issue 1, pp 178–186 | Cite as

Caring for the Country: Fatigue, Sleep and Mental Health in Australian Rural Paramedic Shiftworkers

[2] An exploration of the support needs of Ambulance Paramedics, Sandra Porter Doctor of Philosophy 2013 College of Health and Biomedicine Victoria University

[3] Stress in Australian rural ambulance paramedics: It’s more about the ‘rural’ than the ‘paramedic’.

L Hamilton¹, L Stockhausen², J Grootjans³ ¹Charles Sturt University, Bathurst, New South Wales, Australia

²University of Ballarat, Victoria, Australia ³Sydney University, Sydney, Australia

[4] An exploration of the support needs of Ambulance Paramedics, Sandra Porter Doctor of Philosophy 2013 College of Health and Biomedicine Victoria University

How 10mL of fluid and a blanket can save your life

(and a few interesting facts about clotting mechanisms)

First of all, the 10mL of fluid is not saline. In fact, two decades of research tells us that aggressive crystalloid resuscitation is harmful.[1]

Saline presents many challenges when used to resuscitate hypotensive patients:

  • It’s acidic nature causes the body to use and deplete its natural buffers which leads to increased acidosis
  • It is pro-inflammatory and is associated with poor outcomes
  • It dilutes clotting factors
  • It is often cold and contributes to hypothermia

All of this increases mortality by exposing the patient all three aspects of the Trauma Triad of Death:

  • Hypothermia
  • Coagulopathy
  • Metabolic Acidosis

This triad of factors refers to the conditions which increase mortality in the trauma patient. Uncontrolled bleeding causes hypothermia which leads to reduced clotting or ‘Coagulopathy’. Uncontrolled bleeding also leads to hypoxia in tissues which causes metabolic acidosis and decreased myocardial pumping, this leads to further acidosis and increased hypothermia and reduced clotting. This condition continues to spiral out of control unless blood pressure is stabilized, hypothermia is corrected and acidosis reversed.

Early control of bleeding and avoiding hypothermia are the most important aspects of trauma management.

Hypothermia is easily correctable but paramedics often under-appreciate how harmful it is. Clotting is three times longer at +22 degrees C than at +37 degrees C.[2]

But there is a relatively new therapy that can save lives

Tranexamic Acid or TXA is gaining popularity worldwide for its effectiveness in controlling internal bleeding.

Most of the evidence comes from two major studies. The Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage or ‘CRASH 2’[3] study and the ‘Matters’[4] study. The CRASH 2 Study predicted a 32 percent reduction in death due to uncontrolled hemorrhage if TXA was given within one hour. The Journal of Intensive Care had this to say about the CRASH 2 study results:

After the launch of its sensational results, the mainstream treatment protocol in trauma changed worldwide to include TXA administration.[5]

So how does it work?

Drug action

When the body is subjected to hypotensive episodes, changes to the inner lining of our blood vessels secrete substances that break down clots and promote bleeding. This is referred to as ‘Acute Traumatic Coagulopathy’. Acute Traumatic Coagulopathy is present on admission in 25% of trauma patients and associated with a 5-fold increase in mortality.[6]

Tissue and endothelial blood vessel damage lead to release of tissue plasminogen activator (t-PA). tPA combines with plasminogen to make plasmin. Plasmin breaks down clots. This is the body’s way of re-establishing circulation after the occlusion of a blood vessel as seen in myocardial infarction.

Clearly, tPA is helpful if you suffer from vessel occlusion due to clotting. But In cases of traumatic coagulopathy, the situation is reversed and tPA secretion works against survival.

Bleeding due to trauma is one of those situations where paramedics can help the body to adapt to abnormal situations. In this case TXA is helpful because TXA binds to the same receptor as tPA but instead of stimulating clot breakdown, TXA occupies the receptor and effectively blocks other molecules from breaking down the clot. This results in clot formation and reduction of life threatening hemorrhage.

So…to summarize, if I’m having a heart attack, clot breakdown is as welcome as a cold beverage on a sunny day.

But if I’m bleeding out because my spleen has ruptured, clot breakdown is as welcome as a Donald Trump Tweet during the Cuban Missile Crisis. Therefore, I want my paramedic to give me TXA and a blanket!

Interesting Facts

An intriguing feature is the circadian variation in t-PA that has been observed. Free t-PA levels are lowest in the morning and increase during the day to reach their peak activity level in the late afternoon.  It has been suggested that the high incidence of myocardial infarction and cerebral thrombosis in the morning hours, may be connected to the circadian rhythm of fibrinolytic activity.

Mortality statistics in Greenland show that Eskimos have a low prevalence of myocardial infarction. This has been related to their diet, although it may also be due to the observation that Eskimos have a rapid increase in t-PA activity in the morning compared to Caucasians.[7]


Most reports on alcohol and fibrinolysis show an increase in plasma PAI-1 levels following alcohol consumption. PAI causes an acute decrease in t-PA activity. In a recent study of moderate alcohol consumption in a group of healthy men, it was observed that t-PA activity falls sharply after alcohol intake for the first 5 hours, although it then rises and becomes significantly higher after 13 hours. Moderate alcohol consumption may therefore be associated with a lower risk of coronary heart disease ‘the day after’.


A rise in the fibrinolytic activity after exercise has been reported by many authors and attributed mainly to the acute release of t-PA from the vascular endothelium. The increase in t-PA activity is related to both the intensity and the duration of exercise and may reach 30 times the normal after a marathon race. When comparing physically active and inactive men, it was found that t-PA activity increases more in active men.

Insect venom

The release of t-PA from the endothelium may be involved in the pathogenesis of anaphylactic shock induced by insect venom. Levels have been found to increase about 10-fold following a controlled insect-sting challenge in subjects with a previous history of insect-sting induced anaphylactic reaction.

Venous occlusion

The venous occlusion test is often used to test subjects for their capacity to release t-PA from the occluded venous segment. A test takes 5-20 minutes and involves a blood pressure cuff on the upper arm, inflated midway between the systolic and diastolic blood pressure. The t-PA activity rises 3-12 times.


Chronic smoking induces higher baseline levels of t-PA and PAI-1 antigen and lower t-PA activity. In addition, the release of t-PA after a venous occlusion is impaired in chronic smokers.[8]

1. ROC Hypotensive Resuscitation Field Trial of Hypotensive versus Standard Resuscitation in Patients with Hypotension after Trauma. 2014
2. Crit Care Med. 1995 Apr;23(4):698-704. Effects of temperature on bleeding time and clotting time in normal male and female volunteers. Valeri CR1, MacGregor H, Cassidy G, Tinney R, Pompei F.
3. 32 % reduction in bleeding related death if given within 1 hour of trauma event CRASH 2 study, March 2011 (the Lancet) http://www.thelancet.com/crash-2
4. MATTERS, Morrison et all. October 2011 http://www.medschool.lsuhsc.edu/emergency_medicine/docs/archsurg.tranexemic%20acid.pdf
5. Tranexamic acid and trauma-induced coagulopathy Takeshi Nishida, Takahiro Kinoshita and Kazuma YamakawaEmail authorView ORCID ID profile Journal of Intensive Care20175:5 https://doi.org/10.1186/s40560-016-0201-0
6. Brohi K, Singh J, Heron M et al. Acute traumatic coagulopathy. J Trauma 2003; 54:1127–1130.
7. https://diapharma.com/tissue-plasminogen-activator-tpa/
8. https://diapharma.com/tissue-plasminogen-activator-tpa/