07 April 2019
Over the last few days I’ve received a number of enquiries regarding the safety of Botox/Botulinum toxin in response to the unfortunate news of a young female patient that passed away in an licensed medical clinic in Singapore, presumably after a Botox injection – Police Probing Case After Woman Dies Following Botox Treatment in Clinic. The actual medical or aesthetic procedure that she underwent and the events that transpired still remain unknown as the details have not been released. However, news outlets in Singapore have run with the news that this young lady underwent Botox injections prior to her death.
I have written this post with the intention of highlighting and sharing some of the pertinent issues and FAQ surrounding the safety of Botox (or botulinum toxin). I feel that it is better to objectively discuss the safety issues and controversies surrounding botulinum toxin rather than to let these assumptions take a life of their own or dismiss a very useful drug (botulinum toxin) that has been used in various medical specialties including neurology and dermatology.
Death due to injection of botulinum toxin from an aesthetic treatment is highly unlikely in my opinion and I will be sharing with you the reasons why I disagree with the premature reports by most media outlets that insinuate that it was Botox that led to her death. Until the post mortem results and investigations are complete, speculations about the cause of death would create unnecessary fear. This incident in Singapore also brings to mind of another widely publicised incident in Hong Kong in November 2018, where another death occured in a plastic surgeon’s clinic after what was reported to be a Botox/botulinum injections that the patient underwent- Hong Kong Plastic Surgeon Arrested for Female Banker’s Suspected Botox Death. The investigations and post mortem reports in Hong Kong did not yield anything conclusive, so it is unclear if Botox injections led to this lady’s death in Hong Kong.
That said, it is understandable that most of you are very worried and concerned about the safety of Botox/ botulinum toxin injections. In my practice in Singapore, Botox/ botulinum toxin is one of the most commonly requested treatments, especially for treatment of wrinkles and jaw slimming/ bruxism.
Although used almost interchangeably in the media, Botox and botulinum toxin are slightly different. Botox is one of the brands of a of neurotoxin called Botulinum toxin A. This neurotoxin is derived from a bacteria called Clostridium Botulinum.
Our nerves send signals to our muscles to cause the muscles to contract i.e. move. These signals occur specifically at nerve endings next to the muscles and these nerve endings are called neuromuscular junctions. Botulinum toxin works by binding to these neuromuscular junctions to interfere with the signal transduction between the nerve endings and the muscles. This prohibits the muscles from contracting or moving and relaxes muscles.
What is botulinum toxin used for? Botulinum toxin is used to treat patients in conditions where the muscles are overactive or hyperactive i.e. the muscles are moving too much or too forcefully. Besides our familiarity with Botulinum toxin in dermatology to treat a variety of conditions such as wrinkles, jaw slimming or bruxism, hyperhidrosis (excessive sweating) and calf slimming; Botox has been used in various medical specialties such as neurology and urology to treat conditions such as migraine, overactive bladder, upper and lower limb spasticity, eye conditions such as strabismus and eyelid spasm (blepharospasm) and cervical dystonia.
When injected into facial muscles like the jaw muscles (masseter muscles), the muscles relax and eventually slim down. This is why botulinum toxin is used to treat bruxism and for jaw slimming to achieve a slimmer, sharper, V shaped face in most Asian countries like Singapore. Likewise, when botulinum toxin is injected in the facial muscles, say the forehead muscles which cause the horizontal creases when we frown; the forehead wrinkles improve.
Clearing the confusion: Botox vs Botulinum toxin
Botox is one of the brands of botulinum toxin that is US FDA approved and approved by Health Science Authority (HSA) in Singapore for use.
At present, there are commercial formulations of botulinum toxin A that are approved by both the US FDA and Singapore’ HSA for treating dermatological conditions: Botox (onabotulinum toxin A), Dysport (abobotulinum toxin A) and Xeomin (incobotulinum toxin A).
Very recently this year, the US FDA has approved another brand of botulinum toxin called Jeuvea for treating facial wrinkles. The manufacturers of Jeuveau claim that with Jeuveau presents a cost effective alternative to Botox and the cost savings can be translated to consumers. However, please note that Jeuveau has not received Singapore’s HSA approval for use in Singapore.
Botox was the first type of botulinum toxin A to receive US FDA approval for treating glabellar wrinkles in 2002, followed by Dysport to receive US FDA approval in 2009 and Xeomin to receive US FDA approval in 2010. Not surprisingly, Botox enjoys the market dominance of brands of botulinum toxin used for aesthetic dermatologic treatments and this is why the brand, Botox is synonymous with botulinum toxin.
Botulinum toxin for commercial use is produced under very strict conditions with multiple steps to ensure the safety of patients and efficacy of treatments. The preparation of Botulinum toxin undergoes multiple steps of extraction and purification before it is eventually crystallised and packaged as the final product that we know it to be- Botox.
Since news of this death supposedly related to Botox went viral in Singapore; a good number of my patients have been very concerned and have asked me whether Botox/ botulinum toxins injections for aesthetic treatments can cause cardiorespiratory failure and death, as suggested by local media outlets. The answer is: Highly unlikely; and let’s look at why so.
As I have explained above, botulinum toxin has to be injected into the muscles to bring about its intended effects of relaxing the muscles. So, assuming that for a patient who underwent botox jaw slimming or anti-wrinkle injections to suffer from cardiorespiratory failure after these injections; two conditions have to be fulfilled:
1. The botulinum toxin injected has travel from the muscles to the heart and lungs and;
2. The dosage of botulinum toxin injected to be lethal enough to cause the heart and lungs to failure.
Let’s examine these two conditions.
1. Diffusion of botulinum toxin reaching the heart and lung muscles from the muscles
So far, data suggests that Botox has a very localised mode of action. This means that when correctly injected into the intended muscle, Botox has a very precise mode of action. In other words, if you were to receive Botox injections to your jaw muscles, your jaw muscles will relax and slim down; but do not expect your forehead or crows feet wrinkles to disappear.
Unintended spread of botulinum toxin into surrounding muscles following injections of Botox is unremarkable when small dosages are used- as is the case with Botox injections to the face for cosmetic purposes1,2. One study showed that the area of diffusion was approximately 2.4-6.0 cm2, 3 (at the concentration closest to that which most doctors in Singapore use for botulinum toxin injections)- this means that the likelihood of Botox spreading to the heart and lung muscles is extremely low.
2. Lethal dose of Botox was injected
What if botulinum toxin diffused from the site of injection and travelled via the bloodstream to the heart and lungs to cause death? So far, the manufacturers of Botox, Allergan have stated that it is not possible to detect Botox in the bloodstream following injection of Botox into muscles at recommended dosages4.
Although unlikely, let us assume, for the sake of the argument, that Botox somehow entered the bloodstream. Logically, for Botox to cause a complication like cardiorespiratory failure and death; a lethal dose must be given. Afterall, it is the dose that makes an elixir a poison.
So far, I was not able to locate any studies or data on the lethal or toxic doses for botox injections related to cosmetic procedures. Whatever information that can be inferred for toxic or lethal doses are extrapolated from animal studies or in human studies unrelated to aesthetic treatments. One study points to a toxic dose of 39U/kg body weight5.
This would mean that for an average Singaporean female who weighs about 50kg, the toxic dose of botox for her would be 50kg x 39U/kg= 1950 units of Botox- a mammoth amount that most doctors would not administer in one setting. One bottle of Botox contains 100 units- so this means that it would require the administration of 20 bottles worth Botox into her! This is unimaginable! In reality, for all the wrinkles of the upper face to be treated (crows feet, glabella and forehead lines)- I almost never exceed 40 units of Botox. Even if masseter muscle botox were also performed at the same setting for jaw slimming- usually less than 30 units of Botox are used per side. The likelihood of a patient exceeding 100 units even with the full works of Botox is almost zero, in my practice. This dose is so hardly close to the lethal dose, so for cardiorespiratory failure to result from aesthetic treatments is very, very unlikely.
As with all drugs, allergy is certainly a possibility. Allergies range from mild reactions like urticaria, (where the skin develops intense itching and wheals) to the other extreme- anaphylaxis. Anaphylaxis is a life threatening condition that causes the airways to narrow (and thereby obstructing breathing) and the blood pressure to plummet.
For an allergic reaction like anaphylaxis to develop, one condition must be met- the patient must have had prior exposure to the trigger- which, in this case, let us presume to be Botox. It has been reported in the news that this lady was known to have had Botox/botulinum toxin injections before- so if she was allergic to botulinum toxin; these allergic reactions would already have been known to her and her doctor. No medical practitioner, who is aware of her allergy would ever administer Botox/botulinum toxin and risk a life threatening reaction.
In the first reported and confirmed case of allergy related to Botox for an aesthetic treatment; the patients was recovered without sequeale6. There is also one reported case of death from Botox due to anaphylaxis- however, this patient was being treated with Botox for neck and back pain and the dose administered was much higher than usually given for approved aesthetic treatments6.
Adverse reactions from Botulinum toxin injections are extremely rare, especially when performed for dermatological or aesthetic treatments by a qualified and experienced doctor.
The uncommon side effects that may occur with Botox injections for the face are:
The US FDA has released a review on the safety and adverse events that occur with Botox injections for aesthetic and medical treatments. *Please note that the dosages of Botox administered for medical treatments like urinary retention are much higher than dosages for aesthetic treatments.* Let’s look at the data.
Over a 13.5 year period from 1989 to 2002; the US FDA received 1437 reports of adverse events related to Botox injections- of which 36 serious events were due to cosmetic treatments8. There were no reports of death from Botox injections related to cosmetic treatments. In these 36 cases of serious events (such as allergic reactions and flu like symptoms) related to cosmetic Botox treatments. For most of these adverse events, there were numerous departures from the recommended Botox dose, dilution, administration, handling, storage and site of injection as advised in the approved labelling8.
Based on current data, I would dare to say that Botox, when properly administered by a qualified doctor who respects handling protocols, is very safe for aesthetic dermatological treatments.
I hope that this post was useful in your understanding of Botox and botulinum toxin. Understandably, there has been a lot of fear mongering about the Botox and the safety of aesthetic treatments in recent weeks but I hope that by objectively discussing and looking at recent data, we can have a clearer understanding of the controversies that surround Botox. Botox, is afterall a very useful drug used by different medical specialties to treat a wide variety of medical conditions like spasticity and urinary incontinence, on top of dermatological treatments.
Bottom line: Botox, like any other medication, should only be administered by a qualified and experienced doctor. In the right hands, it is safe and always make sure that your doctor or clinic is using an approved brand of botulinum toxin. In Singapore, the three most commonly used brands of botulinum toxin are: Botox, Dysport and Xeomin. These brands have also received US FDA approval. In my experience, all three brands have a very good safety profile and patient satisfaction.REFERENCES