All About Salbutamol
In this episode, Marc discusses everything you need to know about salbutamol.
Colbeck, Marc A. (Author). (2018, November 27). All About Salbutamol. [Audio Podcast]. Retrieved from
Beta 2 adrenergic agonist with Respiratory & Antidote effects
Bronchospasm and adjunct agent in treating hyperkalaemia
Mechanism of Action
Selectively activates beta-2 adrenoreceptors to produce relaxation of smooth muscle in the lungs for bronchodilation, minor inotropic and chronotropic effects in the heart, enhanced the activity of sodium/potassium ATPase pumps, increasing the movement of potassium into all cells, relaxation of the smooth muscles of the uterus.
Onset: 2-5 minutes
Peak Effects: Variable
Duration: 1-4 hours
Hypersensitivity, healthy labour, low seizure threshold
Tachycardia, palpitations, tremors, hypokalaemia, anxiety, nausea, vomiting, dry mouth, hypertension, nervousness, headache, sore throat, arrhythmias, tocolytic, bronchospasm (rarely)
Precautions & Facts
May cause paradoxical bronchospasm and beta blockers may blunt effects
Caution required with cardiac patients or patients with limited air movement
Caution required with women in labour as salbutamol can halt contractions
Various preparations between nebules, ampoules and MDI
Adult: 2.5 to 5 to 10 mg nebulised aerosol with 6 to 8 LPM of oxygen (repeatable) or 250 mcg IV (additional low doses also acceptable)
Paediatric (< two years): 0.15 mg/kg with a minimum dose of 2.5 mg nebulised aerosol with 6 to 8 LPM of oxygen (repeatable)(additional low doses also acceptable)
Hyperkalaemia: Continuous nebulised solution of 10 to 20 mg
Preterm Labour: 10 mcg/min IV titrated to effect to max dose of 45 mcg/min
MDI: 2 to 4 puffs as needed every 1-4 hours
We’d love to hear your comments, questions, criticisms, commendations, and corrections!
In the 1970's and 80's I grew up in Toronto the younger of two boys. Like most boys, my brother and I fought a lot. Despite this, it seemed excessive one night when he unexpectedly swung down from his upper bunk onto my chest and started pummelling me with his fists before passing out unconscious on the floor.
I remember yelling "MOM! Bernie's dead" and then a flurry of activity occurred … which I don't remember … which resulted in my brother being taken away by ambulance officers in the middle in the night.
His asthma had overcome him, and with his last breath fading his only thought was to wake me up as definitively as possible so that I could potentially get help before he died.
Many decades later I remember sitting with my youngest daughter Evelyn in a desert in the Middle East, about as far from Toronto as you could get - temporally, culturally and geographically - listening through my stethoscope as her lungs progressively shut down in deadly, asthmatic bronchospasm.
I don't know the names of the ambulance officers who whisked my brother away that night, men who almost certainly inspired me to take up the profession I love, nor do I know the names of the nurses and doctors who cared for him in the hospital that night. But I do know the name of the man who saved his life. And, surprisingly, he was the same man who saved the life of my daughter decades later, on the other side of the planet.
His name was David Jack, and he was born on February 22, 1924 in the Scottish town of Fife, as the youngest of six children to a coal miner. Sir David Jack, was the man who invented Salbutamol.
Hello and welcome to the Paramedicine.com podcast – I’m here to take you on a Paramedic TRIP - Translating Research Into Practice. My name is Marc Colbeck and I’m at the ACU recording studio in Brisbane, Australia.
This is the All About Pharmacology podcast, and in this second podcast of the series we’ll be learning All About Salbutamol. In this podcast, I’m going to be giving an overview of the drug. I’m going to be talking about the history of salbutamol and then I’m going to go through the mechanism of action of salbutamol, which means I’ll be describing what it does in the body down to the receptor level so that you can really understand what salbutamol is all about. I’ll also be reviewing how to administer salbutamol and some of the indications and precautions you need to be aware of. At the end of this podcast we’ll have covered all you need to know to be able to use salbutamol safely and effectively as a paramedic. Welcome to the podcast.
History of Asthma
Salbutamol is primarily, although not exclusively, a drug that is used to treat asthma.
Asthma as a disease has been known to humanity for well over 10,000 years, and during most of that time our ancestors thought it was due to an imbalance of humours in the body.  In particular, they believed there was too much phlegm in the body, either descending down from the brain or up from the womb, as the case may be.
In about 800 BC Homer was the first to use the word asthma in writing that still exists. In his epic poem, The Illiad he describes Zeus waking up as the Greeks are trying to push a line of Trojans back and finding Hector, the leader of the Trojans, breathing painfully and vomiting blood. The word Homer uses to describe Hector’s laboured breathing is “asthmati”. Apparently, the word was used at the time to describe noisy, laboured breathing in general. 
The earliest treatments for asthma focused on living a balanced life in terms of diet, rest and social activities, and of course praying to the God’s for mercy.
When that didn’t work, more bizarre treatments were attempted, such as eating the lungs of foxes, bloodletting, avoiding any source of heat, or as Aetius horribly recommended in about 500 AD, multiple, cauterizing burns to the chest to remove the causative humours. 
The ancient Egyptians described their treatment of asthma by inhaling the fumes of dried and crushed herbs, such as tobacco, datura stramonium, black henbane, and belladonna. 
Astute botanists who are listening to this podcast, and I’m sure there are many, will probably have picked up that tobacco, datura stramonium, henbane, and belladonna all belong to a family of plants known as the Solanaceae (so-la-nay-see), which are sometimes also called the ‘deadly nightshades’. These plants produce alkaloids which block the effects of the parasympathetic nervous system. Since the parasympathetic system has a role in asthma, it was not surprising that these plants gave some relief to asthma sufferers.
In 1923 the drug ephedrine was introduced into Western medicine as a treatment from asthma. Ephedrine also has herbal roots, as it was derived from another alkaloid plant, Ephedra sineca, which had been in use for thousands of years in China as a treatment for asthma. Ephedrine chemical structure is similar to adrenaline and, like adrenaline, it is non-selective, acting as both an alpha and beta receptor agonist. .
Today we use more powerful synthetic drugs which block the parasympathetic system to help asthma sufferers and those with a slow heart rate too, but we’ll discuss those in a later podcast.
Interestingly, up until the 1950’s - which was about the time we realized that smoking causes cancer - specially formulated ‘asthma cigarettes’ were the mainstay of treatment. For example, an 1890’s advertisement glowed that asthma cigarettes were: ‘agreeable to use, certain in their effects, harmless in their action [and] safely smoked by ladies and children’. This was despite the fact that it wasn’t uncommon for such cigarettes to include cannabis, potash, and even arsenic. Despite much better remedies becoming available, asthma cigarettes persisted in some circles until well into the 1980’s! 
As we noted in the previous podcast “All About Adrenaline”, adrenaline was discovered in 1901 by Jokichi Takamine  and shortly after, Solomon Solis-Cohen was the first to administer it therapeutically to asthmatics, with great success . From that point on, adrenaline became a life-saving drug for asthmatic sufferers. However, adrenaline is a very powerful drug that also has potent and undesirable effects on the heart and blood vessels. It certainly helped asthma sufferers, but it wasn’t a pleasant experience, and it could potentially be disastrous for those with pre-existing high blood pressure or weak hearts.
Adrenaline to Isoprenaline 
In the late 1920s and early 1930s the synthetic sympathomimetics synephrine and phenylephrine were developed by the pharmaceutical firm C.H Boehringer Sohn in Ingelheim (Germany) in partnership with the Department of Pharmacology at the nearby Vienna University. The drugs were found to have very powerful cardiovascular effects. Realizing that you could tailor artificial drugs to emphasize or deemphasize certain characteristics of adrenaline made pharmaceutical chemists hopeful that they could alter the structure of adrenaline to create different drugs that would de-emphasize the cardiovascular effects of adrenaline and instead isolate its bronchodilator effects.
The Viennese scientists invented a novel device cobbled together from flasks, pumps and pistons which created a breath-to-breath graph of how much gas was going into the lungs of a test subject. They published their method and it became a popular tool for measuring bronchial reactions to different drugs.
Dogs were attached to the machine and they were administered an already familiar drug called pilocarpine, which was known to cause bronchoconstriction. The researchers watched the bronchoconstriction occur on their graph, and then they began administering the various molecular reconfigurations of adrenaline they had made to the dogs to see if those reconfigurations had any bronchodilatory effects.
In one reconfiguration of adrenaline which they created they had replaced a section of its atoms with a similar, but not identical, configuration of other atoms called an isopropyl group, and this version of adrenaline, with the isopropyl group in it, was called ‘isoprenaline’.
On November 18, 1938 the German chemists at the University of Vienna began experiments with nebulized isoprenaline and found it had the same bronchodilatory effects as adrenaline only at 1/10th of the dose, which was great because it meant the cardiovascular effects of the drug wouldn’t be as strong.
To ensure that their canine results were transferable to humans they enlisted the help of a colleague of theirs, a human this time, who had asthma.
In our modern era of meticulously careful drug testing and byzantine layers of ethics approval this is hard to imagine, but they basically just grabbed a bunch of the new drug off the bench, gave it to their colleague and said: “let us know if it works”. The mind boggles. But it worked! Further tests in an asthma ward of a local hospital showed great results and isoprenaline was introduced in 1940, at the beginning of the Second World War, as a new drug for asthma in humans.
The drug didn’t spread to the UK or America until after the war, but when it did the World Health Organisation endorsed the generic name isoprenaline for worldwide use. Americans of course called it something else. In America, the drug is known as isoproterenol.
Nebulized isoprenaline became the drug of choice for treating bronchospasm and for decades was found in every ER around the world. It was the one drug that doctors reached for when they were faced with a critical asthmatic patient. In all likelihood, your parents or grandparents, or perhaps their friends, were treated with it.
The Pressurized Metered Dose Inhaler (pMDI)
However, one of the problems with isoprenaline was that it was very short acting . So, asthmatics often needed repeated treatments, and it was difficult, for example, for them to get through the night without having to wake for repeated dosings.
Another problem with isoprenaline was with its administration. Getting it aerosolized so that patients could inhale it was difficult to do with the technology of the day, but it was critically important if the drug was to be effective. If isoprenaline was injected intramuscularly or intravenously it still had a very strong positive chronotropic effect, which meant it caused significant tachycardia.
After isopreanline’s introduction in the mid 1940’s, the only way to administer it was through a cumbersome, and fragile glass, squeeze-bulb nebulizer, similar in design to the old-fashioned perfume spray bottles that your grandmother uses. It wasn’t optimal, but it was still an improvement on adrenaline.
In the 1950’s, the squeeze-bulb administration of isoproterenol was widespread, but still frustrating. By chance, one-day, a 13-year-old American asthma sufferer asked her dad “why can’t they just put my asthma medicine into a spray can”?
Serendipitously, her father just happened to be George Maison, the president of Riker laboratories, which just happened to have a pharmaceutical development laboratory. George, the father, instructed his staff to see if putting isoprenaline in a spray-can was a feasible idea.
Of course, one of the problems they had to address was that when you press down on a spray can, it just keeps spraying. Recognizing that this would cause an epidemic of isoprenaline overdoses they focused on a ‘spray can’ that would deliver only one metered dose at a time.
Remarkably, they developed a metered dose inhaler and delivered it to the market within two years, from start to finish - again, something that would be unimaginable today - and thus the pressurized metered dose inhaler, or the MDI (which most patients simply call a ‘puffer’) was introduced to the world, and the first drug it puffed out to grateful asthmatics everywhere was isoprenaline .
In time, as better bronchodilators were discovered - a story we’ll get to in just a minute - isoprenaline fell out of favour as a bronchodilator, but we still use it intravenously today for the tachycardic side effect that the doctors of parents and grandparents, and their friends, found so frustrating. We now use it, among other indications, as a last-ditch drug for patients who are profoundly bradycardic and not responding to transcutaneous pacing.
It’s rare now for any medics except interfacility critical care paramedics to use the drug, but it still exists. I only used it once or twice as a Critical Care Paramedic when I was working in Toronto and in Queensland where I live now, for example, only the highest level of flight paramedics are allowed to use isoprenaline, but only if it has already been started by the sending institution and only after consultation with their medical control . I’d say that’s a fairly common scenario for when and how paramedics run isoprenaline today. So I’m not going to discuss it in detail in this podcast.
Despite the great success that isoprenaline initially had over adrenaline, there were still concerns about it. As it became a more widespread therapy in the 1960’s, subsequent to the introduction of the metered dose inhaler to deliver it, it was linked with a large spike in deaths in at least six different countries. However, other countries that were also using isoprenaline did not experience this dramatic rise in deaths, and there is a continuing, heated debate in epidemiological circles about what came to be called the ‘inhaled beta agonist hypothesis’. Was isoprenaline killing patients? We worried it might be. It’s a deeper hole than I want to go down in this podcast, but look in the show notes on paramedicine.com for the 1998 Pearce and Hensley article if you want to know more , . Suffice it to say, that isoprenaline had its critics and the medical community continued to search for a better treatment.
Adrenaline to Salbutamol
Adrenaline was discovered in 1901 but it took until 1948 for scientists to realise that adrenaline acted on at least two distinct receptors. It was in that year that Raymond Ahlquist  published his historical article in the American Journal of Physiology outlining this discovery and introducing the terms alpha and beta receptors for the first time.
Almost 20 years after that, in 1967, Lands et al. published in Nature magazine their discovery that there were actually two different beta receptors, and that only one of those beta receptors - the beta 2 receptor - was the one responsible for bronchodilation. 
Now the chase was on, because this lead researchers to hope that they could find agonists that were selective to beta two receptors, which would hopefully allow them to develop a powerful bronchodilator with none of the beta 1, inotropic and chronotropic effects that plagued adrenaline and, to a lesser extent, isoprenaline.
This is about the time that Sir David Jack began working in pharmacology for the Glaxo company. Glaxo had begun as a rather unglamorous producer of powdered infant formula. “Glaxo builds bonnie babies” as the ads used to say, but they became a tentative entrant into the pharmaceutical development industry as they began to produce generic copies of drugs that had already been discovered by others.
Sir Jack had been hired as the head of research for Glaxo in 1961. His ambitious goal was to create treatments for the most common ailments plaguing society, and he turned his team to the concern of asthma . Affecting approximately 1 in 20 people, and with no cure, asthma was (and still is) a debilitating disease that literally took one’s breath away. Operating from a small laboratory in the small town of Ware, Sir Jack created and led what is arguably one of the most medically influential and financially successful groups of pharmacological research scientists in history.
His team went back to adrenaline and, like the Viennese chemists in the 1930’s, started taking it apart and rebuilding it, with slight variations, over and over again, testing each time to see if they could build a better bronchodilator.
Imagine, if you will, taking apart the same small group of about 7 Lego blocks and rebuilding them with slightly different blocks each time; taking one block out and trying dozens of different ones, and then taking another out and replacing it with dozens of different ones again, and all the time testing to see if what you built had the effects that you wanted. Now imagine that it takes about week every time you make a single change, and that you do it over 100 times, over about two years. That’s what the Glaxo team under Sir Jack’s leadership did until they finally came up with a variation on adrenaline that was over 500 times more potent at the beta 2 receptors in the lungs than the beta one receptors in the heart.  Jackpot.
The drug was named salbutamol generically, but in 1969 when they invented it Glaxo called it Ventolin, and it was absolutely revolutionary. It was one of the first superstar drugs and today the product, and its various successors still earns GlaxoSmithKline, as the company is now called, over $1 billion dollars a year. And yes, that’s billion … with a B.
They didn’t stop with salbutamol however. Salbutamol is a short acting beta agonist - it only lasts about 4 hours – which, like isoprenaline, isn’t long enough to make it through the night. So, once they discovered salbutamol they continued to deconstruct and reconstruct the salbutamol molecule, the way they originally had with adrenaline. By fiddling with the nitrogen substituent of the molecule they eventually discovered a form of salbutamol that lasted up to 12 hours. The generic name for that drug is salmeterol, and Glaxo marketed it as Serevent. Serevent is still in widespread use today, and you’ll see that many of your patients are taking it regularly.
As paramedics however, we use the shorter acting salbutamol as a bronchodilator, among other drugs, to treat our asthmatic patients.
Sir Jack went on to develop other important drugs as well. In 1972 his team introduced beclomethasone dipropionate, an anti-inflammatory steroid inhalant launched as Becotide, as well as fluticasone propionate, a synthetic corticosteroid which is inhaled for asthma, but also can be used as a cream for eczema and psoriasis. These drugs are called asthma preventers because, if they are used regularly, they prevent asthma attaches from happening in the first place.
The combination of salmeterol and fluticasone propionate into one inhaler, called Advair or Seretide, that patients can take twice daily has finally brought a disease that has plagued humanity since the beginning of our recorded history under reasonable control for millions of sufferers around the world.
So much for history.
Let’s turn now and take a closer look at the drug salbutamol in detail. As paramedics, how do we use this drug?
By now you should be well acquainted with salbutamol’s mechanism of action. It’s a highly selective, short acting, beta 2 receptor agonist that causes bronchodilation for up to 4 hours.
You might wonder how stimulating beta 2 receptors alleviates bronchospasm in our lungs. The physiology of this is actually quite interesting. If you’re aware of how muscles in our body contract you know that calcium is an important agent in facilitating muscle contraction. Muscles have two proteins called actin and myosin. These two proteins slide over each other during contraction, that how muscles shorten. Most of the time however, one of those proteins – myosin – is covered by another protein called tropomyosin. When myosin is covered by tropomyosin, muscles can’t contract. This is where calcium comes into play. Calcium causes the tropomyosin to be retracted from the myosin, allowing it to interact with troponin, which thus allows the muscle to be able to contract. Activation of beta 2 receptors causes a chemical cascade of events to happen inside muscles cells which results in calcium that is in the smooth muscle cell either being ejected from the cell or bound up. Beta 2 activation therefore results in lower levels of free calcium in the cell. Low levels of calcium in the cell means that calcium is relatively unavailable to remove the tropomyosin from the myosin. That makes it more difficult for the bronchial smooth muscles to contract, which results in bronchodilation.
Delivery of salbutamol is inhalational, either by metered dose inhaler (MDI) or by nebulised mask. MDI’s are generally the preferred delivery method because the particles they produce, which are inhaled by the patient, are much smaller than the particles produced by nebulizers. The smaller particles from the MDI’s penetrate further into the lungs than the larger particles from nebulizers, and therefore less drug is required to produce the same effect . Therefore, we generally avoid using nebulizers unless the patient is unable to coordinate the use of an MDI.
One instance in which we sometimes will make an exception to this rule is when we arrive at an asthmatic patient in extremis who was been repeatedly taking salbutamol by MDI. At that point, they will be quite explicit that they don’t want more salbutamol from YOUR MDI – they want what they will describe as ‘the real stuff’, which means a nebulizer. There’s a strongly reassuring placebo effect for many patients to getting salbutamol by nebulizer, so as long as it’s not contraindicated, then I generally go ahead and give it. It’s easier than arguing.
MDI’s typically deliver 100 micrograms per actuation (which means per puff), and the typical adult dose is 4-8 puffs every 20 minutes for up to 4 hours, then every 1 to 4 hours as needed.
In children less than twelve years old we use less of the drug. A normal dose for a pediatric MDIs is 90 micrograms per actuation instead a hundred, but we still give 4-8 puffs every 20 minutes or so for an hour (as opposed to up to 4 hours in adults) and then again, every 1 to 4 hours as needed.
It’s best to use a spacer for the delivery of salbutamol, in both kids and adults, otherwise the spray can land and bind to the oropharynx which decreases the amount of drug actually delivered to the lungs. Spacers keep the nebulized particles floating until they are properly inhaled. We never re-use spacers in different patients because of the risk of contamination, so when you leave the patient in the hospital, just leave the spacer you used with them.
Up to 90% of people with asthma inhalers do not use them correctly, which increases their risk of hospitalization by up to 50%. Surprisingly, this is also true in asthmatic patients who have been using their inhalers for years, most of whom are absolutely confident they are using theirs correctly. In fact, 6 out of 7 patients who were absolutely confident that they knew how to take their asthma medication were discovered to be doing it incorrectly when supervised.
Further compounding the problem is the depressing finding that somewhere between 15-69% of healthcare professionals, regardless of their actual profession, are able to demonstrate correct inhaler use .
So as paramedics we have two responsibilities. The first is to make sure that WE are using inhalers correctly, and the second is to use the opportunity our presence affords to explain to our patients how to use the MDI properly so that they end up using them properly too, which will hopefully help with their asthma, and can decrease the amount they have to call us by up to 50%.
The first point to be aware of is that you have to shake the salbutamol MDI well before you use it to distribute the medication properly, and you should prime the MDI by releasing several puffs before you begin to administer it to the patient .
It’s also often necessary to prime the spacer. Standard plastic spacers will carry an electrostatic charge. Some spacers are specifically designed to be antistatic and they don’t develop a charge, and any disposable cardboard spacers won’t carry a charge either, but spacers that DO carry an electrostatic charge will require some preparation before you use them. If you’re not sure if the chamber is antistatic or not, just assume that it is and prepare them properly.
Before I describe how to prepare the chambers let me tell you why we do it at all, so that you’re convinced it’s important.
When small salbutamol particles are aerosolized into an aero chamber any electrostatic charge in that chamber will cause the salbutamol particles to adhere to the chamber walls, thus making the drug particles unavailable to the patient. In order to overcome this, it’s necessary to prime the chamber by releasing a whole bunch of salbutamol into it to overcome the static charge. How much salbutamol should you spray into the chamber to overcome the charge? We’re not exactly sure, but the manufacturers recommend that you spray 10 puffs from the chamber just to be sure. So, if you spray 10 puffs from the MDI into the chamber before you begin to administer it to the patient then you’ll have more than adequately primed the MDI and also properly primed the aerochamber.
The chambers should be washed every week in warm soapy water, and then left to air dry, and drying them with a towel will create more electrostatic charge. They should be replaced about every year, so if the patient is presenting with their own chamber it would be good to ask them how old it is. If it’s over a year, tell them to throw it out and get a new one.
Usually I leave the puffer with the patient along with the spacer, but if your service doesn’t allow that then you should wash the MDI in warm, soapy water before you use it again on another patient.
Inhaling slowly with a single breath after each single puff of the MDI and asking the patient to hold their breath for about 5 seconds at the end of their inhalation is the best way to deliver the drug. If you spray several puffs into the aerochamber before the patient inhales, which is something I’ve seen people do in a mistaken attempt to make sure that there is a lot of drug in the chamber when they inhale, the particles of drug can agglomerate together and then drop out of their onto the chamber, making them unavailable for inhalation.
So, to summarise all of that, here’s how you deliver salbutamol using a metered dose inhaler. First, shake the MDI several times, then connect it to a chamber and spray 10 sprays into the chamber. Then, have the patient take the chamber connector into their mouth, or firmly hold the mask over their face – depending on how the chamber is built – and spray only one puff of the MDI into the chamber. Have the patient take a deep breath and hold it for at least 5 seconds and then have them exhale. Once they’ve exhaled administer another puff into the chamber and repeat the process until you’ve delivered as much drug as required. Explain to the patient what you are doing, and why, so that you can help ensure that they are using their equipment properly, which will help them to avoid needing to call us again. When done you should ideally be leaving the MDI and chamber with the patient.
There are lots of good videos on the internet showing how to do this properly. The website national asthma dot org dot au has some good ones. Look for the ‘how to’ videos under the ‘Living with asthma’ tab.
Now let’s talk about administering salbutamol via a gas driven nebulizer mask. The dose of salbutamol in nebulisers is usually 2.5 to 5 mg every 20 minutes.
Because salbutamol usually comes as 2.5 mg of drug in 2.5 millilitres of fluid that means we either put one nebule of drug into the mask and add 2.5 millilitres of saline, or we put in 2 nebules, for a total of 5 mg of drug and we nebulise that.
In kids less than 12 years old the recommended dose is 0.15 mg/kg with a minimum starting dose of 2.5 mg (or one nebule), then 0.15-0.3 mg/kg (to a maximum of 10 mg) every 1 to 4 hours as needed.
’ll be honest though, even though no manufacturer recommends this, every paediatric hospital I’ve ever been in just runs continuous salbutamol on really sick kids. I think their reasoning is that kids have strong hearts and they can handle the alpha and beta 1 side effects. I’m not telling you that YOU should do that, I’m just telling you what I’ve seen, and you can draw your own conclusions. As always, you should follow the CPGs of the service you work for.
Be careful though, about using nebulisers, if you think your patient has an infection or disease that can be transmitted by respiratory droplets such as the cold or flu, mumps, whooping cough, rubella or tuberculosis. Generally, if your asthmatic patient is sick and having an acute-on-chronic attack because of the underlying cold or flu, then I’d start with the MDI. If you have to switch to the nebuliser, then you (and your partner) should be putting on a properly fitted N95 mask to protect yourself.
When you’re done the call make sure you wash your pen, your stethoscope, your glasses, your holster and anything else the nebulized droplets might have settled on that you could later touch, including the stretcher and other surfaces in the back of the ambulance. Otherwise they might act as what we call ‘fomites’. Fomites are objects that carry germs or viruses. Diseases that spread by droplet transmission, fecal–oral transmission, or contact transmission often do so via fomites. This is the reason why you need to wash the puffer in warm soapy water if you keep it and intend to use it on another patient. You don’t want it to become a fomite.
Fomite transmission is one of the reasons why we tend to prefer using an MDI instead of using a nebuliser. In fact, I remember during the SARS crisis in the early 2000’s in Toronto we had the nebulisers taken off the ambulances because we were doing everything we could to cut the vectors of transmission. The bottom line, and the one you should keep in mind, is that nebulisers are dirty and increase the chances of disease transmission.
Interestingly, there is another indication for salbutamol, another instance where we use it, that has nothing to do with bronchospasm or shortness of breath at all. Do you know what it is?
It’s hyperkalemia.  If we have reason to suspect that our patient has high levels of potassium in their blood, we can use salbutamol to temporarily fix that, regardless of whether they are short of breath of not.
High levels of potassium can occur if patients are in kidney failure, or have hypoaldosteronism, or rhabdomyolysis or trauma. Hyperkalemia can be fatal, in fact, potassium is the lethal drug they inject into prisoners to stop their heart in places that still have the death penalty, so hyperkalemia is something that needs to be addressed urgently. We usually can tell if a patient is hyperkalemic by looking for characteristic changes on their 12 lead ECG.
Salbutamol stimulates the sodium-potassium pump in our cells and, as a result, ends up driving more potassium into the cells and out of our blood stream. This lowers the serum levels of potassium and keeps potassium away from our heart, where it is most dangerous.
On a related note, if you have reason to believe that your patient might have very, very low potassium then obviously using an agent that can lower their serum potassium levels even more is something we should avoid. There is a hereditary condition called hypokalemic periodic paralysis which, as the name implies, has low levels of serum potassium as a part of its profile. If you do come across one of these rare cases, be cautious about administering salbutamol, because it can lower their serum potassium dangerously.
Salbutamol can also increase blood sugar levels although this usually doesn’t present much a problem for most patients. In the rare setting of the dangerously hyperglycemic asthmatic you should monitor their blood sugar levels, especially with prolonged administration of salbutamol, but generally this isn’t a very big issue for us as paramedics.
Salbutamol actually is generally quite a safe drug and, like adrenaline, in the setting of deadly bronchospasm there are no contraindications to its use. Maintaining your patient’s airway is your priority.
However, it’s good to keep in mind that salbutamol still does have some alpha one and beta one activity, so you should watch your patient’s blood pressure, heart rate, ECG, levels of agitation, and watch for tremors. The shaky, anxious, tachycardic, hypertensive patient who is throwing off frequent multiform PVCs might be that way because of too much salbutamol. I’ve seen patient’s like this who have been on their salbutamol nebuliser continuously for hours before they call us. Be cautious about administering even more salbutamol to these patients, especially if they have a weak heart.
The agitation that salbutamol can cause comes about because beta agonists can cause increased CNS firing. For that reason, we’re often cautious about giving the drug to patients who have seizure disorders, although again, in the setting of deadly bronchospasm the airway comes first.
For the same reason, we’re cautious about giving salbutamol to patients who have taken psychostimulants such as cocaine, amphetamine, ephedrine, MDMA (or ecstasy) or even (rarely) excessive amounts of common agents such as tobacco or coffee. Alcohol withdrawal can have similar psychostimulant effects and salbutamol should also be used with caution in this setting. If you’re forced to use it, make sure you are monitoring your patient closely and discontinue the drug if their vitals or their behaviour become dangerous.
Another particularly ominous side effect of salbutamol is that in about 10% of patients it can have the paradoxical effect of increasing bronchospasm and exacerbating your patient’s dyspnea. Sometimes, if your patient is getting worse, it’s hard to determine if it’s because of their underlying disease, or because of a paradoxical effect to the salbutamol. Certainly, if your patient suddenly gets much, much worse as soon as you start administering the salbutamol, you should keep this rare complication in mind as one possible cause of their rapid deterioration.
Also worrisome is the fact that some patients can have immediate hypersensitivity reactions, characterized by urticaria, angioedema, rash, and possibly even full-blown anaphylaxis. If this occurs - no matter what the drug - you obviously discontinue the causative agent and treat the patient symptomatically.
You should also be aware that salbutamol can act as what we call a tocolytic. A tocolytic is an agent that shuts down labour contractions. Salbutamol acts as a tocolytic, but it’s not at all a good one, so we don’t use salbutamol in order to intentionally slow or stop labour in pregnant patients. There are other, better drugs for that. And if you have a patient who is in active, healthy labour then we avoid giving salbutamol because it can interfere with or even interrupt that process. However, once again, if mom is in severe, life-threatening bronchospastic asthma then salbutamol is the drug of choice, and so we give it.
Salbutamol has some important drug interactions, many of which are similar to adrenaline, as they are drugs which are quite similar to each other.
Since salbutamol is a beta agonist, beta blockers that the patient is taking can possibly interfere with its ability to broncohodilate their lungs. So, don’t be surprised if the asthmatic patient your treating, who is on beta blockers, seems to be resistant to the effects of the drug. Especially if it’s a non-selective beta blocker.
Monoamine oxidase inhibitors, which can decrease your body’s ability to break down salbutamol, can enhance its adverse or toxic effects because the drug ends up staying in your body, and exerting its effects, for longer.
Drugs that prolong the cardiac QT interval can have an increased effect if combined with salbutamol. The list of drugs that can do this is long and includes antibiotics, antifungals, antivirals, antiarrhythmics, antidepressants, antipsychotics and antihistamines. Several paramedic drugs can do this as well, such as amiodarone, haloperidol, droperidol, and ondansetron, so be careful about administering these in combination with salbutamol – especially if the patient already has a long QT interval.
If the QT interval is increased too much your patient might begin to show runs of V tach, and these can progress to full Torsades de Pointe. In this case cardioversion, or an infusion of IV magnesium sulphate is the treatment of choice. If these don’t work, we might fall back on an old friend to increase the heart rate, which decreases the QT interval, and can hopefully terminate the Torsades. That old friend? Isoprenaline. How’s that for coming full circle?
So, with that, we’ll end our look at salbutamol. This is going to be a drug that you use a lot, and it’s a life saver.
Let me tell you one last story, because I know I’m going to hear about it if I only mention one of my two daughters in this episode.
When my oldest daughter Denise was born I had almost a year off of work for parental leave, and I loved every minute of it. When I returned to work I was doing a special shift on standby, all night, outside of an emergency department that had just closed permanently. Interestingly, it was at the same hospital that my brother and I had been born in all those years ago. The worry was that people might show up to the closed doors, panic, and not know what to do. So, they parked an ambulance outside all night with one paramedic in it. That was me.
On my very first shift back after the year off I was sitting in the front seat, reading over my clinical practice guidelines for the first time in a very, very long time and realising I probably should have done that before I went back to work, when a car came careening into the drop off zone behind me, ending up with its wheels half on the curb. I saw a panicked mother open the back door and lift out an apparently lifeless 10-year-old. She saw the closed doors of the ER just as I yelled ‘over here’ and she came running over. I set up the child in the back of the ambulance as the mom told me about his history of asthma. I set up a nebulizer of salbutamol and called for a transport unit to come lights and sirens for a pre-arrest child. They arrived about 8 minutes later to see a happy, wide awake child breathing easily through a mask of nebulized salbutamol.
Thank you, Sir David Jack. You saved another one.
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And that is, All About Salbutamol. I hope this podcast has helped you to understand not only the fascinating history of salbutamol but also how it works at a cellular level, and how we use it as paramedics to help save lives and reduce suffering every day in the field.
Thanks for listening, I’m Marc Colbeck and you can reach me via firstname.lastname@example.org. That’s m-a-r-c at paramedicine.com. Or you can visit the paramedicine.com website and join us there. There is a full transcript of this podcast, with references, that you can download to help you study. I’d love to hear your comments, questions, criticisms, commendations, and corrections!
Until next time, keep on studying, keep on caring, and keep safe out there.
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