This chapter addresses Section L2(i) from the 2017 CICM Primary Syllabus, which expects the exam candidates to have an "understanding of the pharmacology of neuromuscular blocking drugs". And if a whole chapter feels like an inordinate amount of attention to lavish upon a drug that twenty years ago was already being described as obsolete, the reader is reminded that it was the subject of five out of twelve past CICM First Part Exam SAQs on NMJ blockers:
It seems this drug has a warm comfortable seat reserved at the table of the examiners, and appears in ICU and anaesthesia basic sciences curricula so often that one could list "exam stress" as one of its adverse effects. To become familiar with it would therefore be to the overall advantage of all critical care exam candidates, even those who never intend to use it in their clinical practice. And we can only hope that this latter group will slowly become dominant in critical care exam committees, displacing the sux-users out of their emeritus chairs and into respected obscurity, so perhaps in another twenty years exam candidates will no longer have to deal with this terrible drug, the strongest property of which is undoubtedly its resistance to the strongest evidence of its own harm.
Name Suxamethonium Class Depolarising NMJ blocker Chemistry Bis-choline esther Routes of administration IV or IM only Absorption Poor absorption; minimal oral bioavailability Solubility pKa=at least 13.0; good water solubility; basically insoluble in lipid Distribution VOD=0.14L/kg, 20% protein-bound Target receptor Nicotinic acetylcholine receptors at the neuromuscular junction Metabolism Metabolised by butyrylcholinesterase.
Butylcholinesterase deficiency is a genetic condition which results in delayed clearance of suxamethnium.
Butylcholinesterase activity may also be deficient in liver disease, renal failure, malignancy, pregnancy, in malnutrition, following cardiopulmonary bypass, or due to the effect of drugs (eg. organophosphates, neostigmine, metaclopramide, cocaaine, MAOIs, or the oral contraceptive pill).
Elimination Minimal renal or hepattic clearance Time course of action Half-life 1-2 minutes (duration of action 5-6 minutes) Mechanism of action By binding to and activating the nicotinic acetylcholine receptor, suxamethonium depolarises the motor endplate of the neuromuscular junction, resulting in an action potential. After the membrane is depolarised, suxamethonium maintains it in a partially depolarised state, preventing the perijunctional voltage-gated sodium channels from returning to the active state. This prevents the generation of any further action potentials, blocking the junction. Clinical effects Depolarising neuromuscular junction blockade; also a series of adverse effects:
- Masseter spasm
- Bradycardia (direct muscarinic effects) ,
or tachycardia (ganglionic sympathomimentic effect)
- Increased intraocular pressure
- Increased intracranial pressure
- Hyperkalemia, which may become lifethreatening in stroke, spinal injury, burns, chronic immobility, or critical illness
- Increased intragastric pressure, transiently
Single best reference for further information Lee (2009)
There are excellent articles for the frugal reader here, and they fall into an interesting pattern. It appears that there is a trend for eminent sole authors to write about this drug, likely drawing on extensive personal experience with its use. For example, in 1972, David Gibb from St Vincent's Hospital in Sydney wrote a series of excellent papers on suxamethonium which remain awesome (in spite of their age) and free (because of it). There are Parts I, II and III, because everything he had to say would not have been possible to confine into a single issue of Anaesthesia and Intensive Care. Similarly, Chingmuh Lee wrote some amazing words about this substance in 1994, for Baillière's Clinical Anaesthesiology, and then again in 2009.
The name "suxamethonium" has a lot more "x" in it than one normally expects from medical nomenclature, making it sound somewhat made-up, but it is apparently viewed as equally valid to the name "succinylcholine", mainly because there are multiple different accurate ways to chemically classify this drug. For example, according to Gibb (1972),
"Suxamethonim may be regarded as a condensation of two molecules of acetylcholine, a dicholine ester of succinic acid, a methodnium compound, or a substitution product of the hydrocarbon decane".
The original term to describe this molecule was actually "succinyl-cholin", first hyphenated by Hunt and Taveaux in 1906, when they were reporting on the chemical properties of numerous choline derivatives they created (among which were the old familiar acetylcholine, butyrylcholine which can also act as a neurotransmitter, benzoylcholine which is also a bit of an NMJ blocker, and many others). Apparently they had no idea it was a muscle relaxant because their test animals were paralysed with curare, and all they would have seen would have been the "marked slowing of the heart", one of the autonomic adverse effects of this drug.
The succynyl and the choline make sense (succinic acid joins the cholines in the middle), and many authors prefer this version. The other name, however, is no less widespread. The "methonium" comes from the methyl groups surround the quaternary ammonium atoms in suxamethonium, and the prefix"suxa", which also means "sweet" in High Elvish, is - as far as anyone able to tell - simply a phonological representation of how one pronounces the succ in succinic, rather than any sort of formal chemical term in its own right. Suxamethonium is therefore the cruder, less refined name for this drug, made to be abbreviated into "sux" and barked across noisy operating rooms or emergency resus bays. It will therefore be the default term for the rest of this chapter, breaking with the tradition of Deranged Physiology, which typically uses the most pompously difficult wording for everything.
Following from the more professional statements among the above, the most appropriate chemical family to adopt suxamethonium would be the methonium family, i.e. substances which have one or more ammonium atoms with three methyl groups. These relatives would include:
The interrelatedness of these is made more obvious from seeing their molecular structures:
Anyway. For the purposes of the CICM exams, it would be unwise to classify suxamethonium as "condensation of two molecules of acetylcholine". The class of drug is "depolarising neuromuscular blocker", as a functional classification is preferred for these agents (for one, it tells you what they do, and it also happens to vaguely correspond to chemical structure). As such, suxamethonium has several functional classmates:
These last three would surely be unrecognisable to modern readers. They are a long-lost ancient tribe of choline esters, briefly mentioned by Bowman (1962) when they were already becoming obsolete. Of these, the reader need not know very much. Suxethonium is distinguished by being even shorter-acting than suxamethonium, and by presenting as a lyophilized powder for reconstitution, making it ideal for a storage in a seldom-used resuscitation trolley which you never intend to check. In contrast, carbolonium is distinguishable by its long duration of action, which may be undesirable; and dioxinium is interesting mainly because it appears only have ever been used in Russia.
It is extremely difficult to find a straight answer for what the pKa of suxamethonium is, perhaps because it is a drug so loyal to being ionised that only the most nightmarishly alkaline environment would force 50% of it out of aqueous solution. Payne (1958) mentions that the pKa of suxamethonium, decamethonium and gallamine is over 13, but does not give a precise pKa value, implying that nobody has made an alkali strong enough to find the pKa for them, giving up at a pH of 13. This tracks with Roy & Varin (2004), according to whom suxamethonium has the lowest lipid solubility of any NMJ blocker. This has implications for its behaviour as a drug.
Suxamethonium is, as far as anyone can tell, poorly absorbed from the GI tract, mainly for reasons of its extremely poor lipid solubility, which makes it very reluctant to cross the various membranes barriers it would face down there. We have it on empirical data that it does get absorbed just a little, because a 22-year-old psychiatric patient intentionally swallowed 500mg of it in the procedure room of their electroconvulsive therapy appointment, and developed some trivial lower limb fasciculations (though no other features of NMJ blockade). Jain et al (2022), who reported this case, noted that no respiratory parameters were affected, and the patient had a completely normal ABG during the subsequent hours of observation. There being no other data about the oral bioavailability of suxamethonium, this case report is the only information we have to support the assertion that suxamethonium does not get enough oral absorption to be clinically or toxicological relevant.
If indigenous cultures can use intramuscular dart-borne NMJ blockers to paralyse small animals, then surely we can apply the same technique to our elective patients? So was the reasoning of McDonald & Bryce-Smith (1955), who phrased their rationale much more poetically:
"...The South American Indican hunting his prey and unable to administer an intravenous dose of his lethal "Wourali", was satisfied if his quarry suffered a more lingering fate from a poison dart quivering in its muscles. By the same token, an anaeshetist, unless he has the sleight of hand which comes to few, will find difficulty in canalising the veins of a small wriggling infant with whom he is occasionally presented. "
The article is otherwise excellent and readers willing to suspend their exam preparation are strongly encouraged to pour a drink and read it, as it includes some properly unhinged material. For example, authors treat the reader to a personal communication from Goetz (1955), whose team, while trying to capture live giraffes for haemodynamic experiments, "reverted to poison arrows fired by members of the University of Capetown Archery Club to assist in their capture".
In short, for those scenarios where intravenous access is challenging, the subject uncooperative, and paralysis must be induced emergently, suxamethonium can be administered as an intramuscular injection. It is in fact among the very few NMJ blockers that can be safely and reliably administered in this way. All the other neuromuscular junction blockers can also be administered IM but the rate of their onset is so slow that Shaw et al (2015) could not recommend for them to be used in this way. Only suxamethonium gave reliable intubation conditions when given IM, and the dose was 4mg/kg (as opposed to the IV dose of 1mg/kg). The timing of onset is imperfect (1-2 minutes is probably the fastest one should expect), but with a little denitrogenation of the FRC, the patient should still be well oxygenated though apnoeic at the end, permitting tubes, gas, calm, and hopefully IV access.
From the complete lack of lipid solubility, the reader may be able to guess that suxamethonium is mainly confined to the body water. Indeed, the volume of distribution is said to be 0.14 L/kg, according to a common PI document; but this may well be an educated guess, as this drug is notoriously difficult to assay. For one, it tends to rapidly degrade in even chilled blood samples, which means reliable measurements of concentration (on which VOD calculations depend) are basically impossible. Many textbooks simply leave that column blank. The CICM trainee looking for a number to rote-memorise could do worse than 0.14L/kg, but from the perspective of learning a concept, it would probably just be better to remember that , in terms of clinical usefulness, the volume of distribution is a variable mainly relevant to drugs which we intend to give as loading doses, or drugs which we intend to dialyse.
Protein binding of suxamethonium is similar difficult to study, because to chill or freeze the sample would alter the binding kinetics, and all the sux from the fresh sample would have been long-degraded by the time it gets to the lab. Roy & Varin (2004) managed to get around this with an in vitro assay in which the plasma pseudocholinesterase was inhibited by echothiophate, allowing plenty of time for the free fraction to be extracted by ultrafiltration. They estimated a protein binding fraction of about 20%, which means about 80% of plasma suxamethonium is free to wreak havoc among your receptors.
From Torda et al (1997), it appears the plasma half-life of suxamethonium is 47 seconds. This weirdly specific value is repeated in a lot of textbooks and is therefore somehow more believable than a more generalisable range (1-2 minutes) which would better represent the population. The main metabolic pathway for suxamethonium is to be degraded rapidly and completely by plasma cholinesterase, sometimes referred to as "pseudocholinesterase" because it is an impostor that resembles "true" synaptic acetylcholinesterase, with different substrate preferences (it prefers to hydrolyse butyrylcholine much more than acetylcholine, in contrast to the latter, and the preferred nomenclature for this enzyme these days is "butyrylcholinesterase").
Remarkably, nobody is really clear on what its biological role is supposed to be. For example, there's no butyrylcholine around for it to metabolise in the human blood or tissues. It may have none, or nothing in the evolutionarily modern human. In their chapter for Comprehensive Toxicology, Lockeridge et al (2018), start by blankly stating that "Butyrylcholinesterase has no unique physiological function that cannot be compensated by other enzymes". Remove this gene from a mouse, and the mouse enjoys a nice long normal life. Remove this gene from a human, and they are similarly unperturbed, until one day they encounter an anaesthetist, and discover that this enzyme is missing in the course of having a prolonged suxamethonium experience. In the event that one is indeed congentially deficient in pseudocholinesterase, suxamethonium does eventually end up being eliminated, albeit slowly and awkwardly, by a combination of renal clearance and (probably) some sort of non-specific esterase hydrolysis. The breakdown products are succinylmonocholine and then succinic acid and choline.
Say one is deficient in pseudocholinesterase. What might have taken it away? The college answer to Question 10 from the second paper of 2020 suggests the examiners wanted the candidates to think "beyond genetic deficiency". This is pretty reasonable, as true genetic pseudocholinesterase deficiency is rare, whereas the rest of these are fairly common. Soliday et al (2010) is an excellent free resource for this subject, and the final few pages of their paper are dedicated to acquired causes of reduced pseudocholinesterase activity, which can be summarised as follows:
In the event one finds themselves deficient in pseudocholinesterase, and under the effects of suxamethonium for an unexpectedly long period of time, one has two main options:
Given that this drug has survived in the formularies for so many decades, the mechanisms of its action are well-acknowledged legend, and nobody seems to feel the need to write anything about its functions in the modern era. Gibb (1974) is probably the most comprehensive summary, but to get explanations for all the strange terminology around this topic (eg. "accommodation", the phases of block, etc) one needs to range far and wide. The following series of summaries and pictograms is an ambitious attempt to centrifuge all this material down to some kind of concentrated sediment, hopefully helping the exam candidate who is not satisfied with merely memorising the words.
The resting membrane potential of the motor endplate is at around -90 mV. It for some reason felt necessary to establish these baseline conditions before continuing, at risk of alienating readers for whom this information is already completely familiar.
Suxamethonium binds to the nicotinic receptors. Specifically, if you wanted to sound clever at the vivas, you'd be able to say that it is an orthosteric agonist of the nicotinic receptor, i.e. it binds to the receptor in the same place where the endogenous ligand would bind. This is of course perfectly logical as a structurally suxamethonium is just two acetylcholine molecule pharmacophores joined by some random organic acid. It is therefore able to bind the exact same sites at the two α-subunits of a nicotinic receptor.
Suxamethonium activates the nicotinic receptor. The normal effect of opening this receptor is to allow cation traffic: an inward current of sodium, as well as an outward current of potassium, which lead to the depolarisation of the endplate membrane. This is exactly the same thing that happens with the binding of acetylcholine. The membrane potential overshoots zero to approach the Nernst potential for the membrane, and then busy little chloride and potassium channels start trying to repolarise it again, aiming to return to the resting potential of around -90 mV.
The depolarised membrane produces a transient action potential. When the endplate potential reaches the threshold of around -70 mV, voltage-gated sodium channels open, and a wave of depolarisation spreads from the motor endplate, creating the fasciculations we see, or so it is thought. There's actually several theories as to why the fasciculations occur, and this is only one of them.
The suxamethonium continues to have an abnormally long effect on the receptor. The normal lifespan of acetylcholine in the synapse is less than a millisecond, owing to the enthusiastic activity of high-affinity acetylcholinesterase. Not so for suxamethonium, which is resistant to degradation, and which remains in position to stabilise the channel in an open but desensitised state (Goswami et al, 2023). Cation traffic therefore continues, and the membrane remains depolarized. Gissen & Nastuk (1970) tortured some frog muscle with different concentrations of sux and found that this depolarised value seems to be somewhere around -30 to -60 mV.
The partially depolarised junction achieves an inexcitable state. The term sometimes used to describe this state is "accommodation", which is an archaic term established by some of the first investigators of the neuromuscular junction, such as Hill et al (1936). They determined that, if the membrane of an excitable cell was very gradually depolarised, and then maintained in the partially depolarised state, the threshold for "proper" full depolarisation would also change, making depolarisation impossible. The cells that had "accommodated" in this way were therefore insensitive to further depolarising stimuli. The modern explanation of the mechanism behind this holds that this insensitivity is due to the inactivation of perijunctional sodium channels which close, but never enter a "ready" active state, because the membrane around them is not back to its resting potential.
Phase I block or "accommodation block" is the term given to this state. It does not last very long, at least for suxamethonium. During this period, anything that increases the amount of acetylcholine at the junction (eg. acetylcholinesterase inhibitors) tends to deepen the block and increase its duration, as all the extra acetylcholine merely depolarises more receptors and makes the membrane even less likely to return to restig potential. The surrounding voltage-gated sodium channels therefore remain inactive. Because of this, pot-tetanic potentiation does not work - the release of extra acetylcholine does nothing to reverse the paralysis. During this time, it is still possible to stimulate the muscle directly using electrical current, and the twitches will all be of the same amplitude.
The membrane gradually returns to resting membrane potential, but remains blocked, in a state which is sometimes referred to as "Phase II block". This can happen following a single large dose of suxamethonium, or with multiple doses. The mechanisms underlying this remain obscure. Often, an article may offer explanations without any references to point the reader to experimental evidence, suggesting that al we have is speculation. For example, Appiah-Ankam & Hunter (2004) attribute the block to presynaptic inhibition of acetylcholine mobilisation, and suggest that the repolarisation happens naturally because of the activity of Na+/K+ ATPase. Phase II block is characterised by the fade observed during train-of-four testing, and by the reversibility of the block with extra acetylcholine (eg. using neostigmine), or by using suxamethonium itself, as it develops paradoxical self-antagonism.
Desensitisation of the nicotinic receptors can occur, which is distinct from Phase 2 block, and which is characterised by nicotinic receptor becoming fixed and unresponsive in the inactive state. It is thought that receptors are constantly transitioning to and from this state under physiologically normal conditions, and that the main reason for this is the need to prevent "overexcitation" of the neuromuscular junction, whatever that is. During a period of desensitization, the junction becomes more susceptible to the effects of nodepolarising agents (which also disable the receptors, but by a different mechanism); but the block is not reversible with acetylcholinesterase inhibitors, because the insensitive receptors couldn't care less about your acetylcholine. The situation is complicated by the fact that some authors had historically referred to Phase II block as "desensitization block", leading to nomenclature rage. The modern trainee is fortunate, because with the diminishing use of suxamethonium in ICU and operating theatres the number of examiners who are sufficiently familiar with this drug is diminishing, which reduces the likelihood of questions about it appearing in the exams. The last time ANZCA did this to their trainees appears to have been 2007.
There are plenty of them, and yet they somehow have failed to deter even the anaesthetists, a notoriously risk-averse species, in spite of abundant evidence to suggest that it is dangerous. To borrow words from Lee, "no drug in anaesthesia is more problematic than suxamethonium and yet no drug has survived crisis after crisis as suxamethonium has". It is safe to say that suxamethonium probably wouldn't have made it through the usual regulatory hurdles of modern drug approval processes, and it remains on the formularies only because generations of anaesthetists are drilled in the careful art of using it safely. Even if one is so turned off that they vow to never use it themselves, a list of these complications is worth remembering, in case one ever ends up inheriting a victim from one of their sux-using colleagues.
What follows is an attempt to force this list of complications into some sort of A-B-C-D-E structure, as this is how the author usually tries to organise his notoriously disorganised brain.
Masseter spasm: Yes, this drug, intended to make intubation easier by relaxing muscles, can occasionally make it impossible to open the patient's mouth, leading to an awkward scuffle at the airway. The mechanism for this seems to be some kind of localised subclinical variety of malignant hyperthermia; ketaminenightmares.com uses an excellent turn of phrase ("forme fruste", literally "crude" or "unfinished") to describe this incomplete or limited manifestation of something that is supposed to be a huge scary systemic phenomenon. Leary & Ellis (1990) mention that about 50% of the patients who surprise their anesthetist with masseter spasm also go on to demonstrate features of "proper" malignant hyperthermia in future testing. Interestingly, from their experiment it appears that most normal people also develop an increase in masseter tone, usually immediately following the period of fasciculations, and lasting only a few seconds:
So, if your intubation attempt is frustrated by masseter spasm, worry not; and reach not for the dantrolene. The frustration will be shortlived. It typically wears off within 60-90 seconds, and one merely needs to watch the sats with nerves of steel, counting the seconds as you dream of better intubating conditions.
Bradycardia, or at least a noticeable reduction in heart rate, is a phenomenon occasionally seen with normal doses of suxamethonium. Being simply two acetylcholine molecules suxed together, one might expect that non-nicotinic acetylcholine receptors will also show at least some passing interest in this drug. This direct muscarinic agonist effect is often seen in children, or with subsequent doses of suxamethonium (if for whatever reason you are possessed to give it more than once). The effect is not trivial: Lupprian et al (1960) remarked that "of the seven instances of ventricular standstill produced in this series, six occurred after a repeat dose of 50 mg. or more of suxamethonium had been given, and lasted from three to five and a half seconds".
Tachycardia, stupidly, is also listed as one of the possible adverse effects. "However, more often than not, suxamethonium (especially in a large dose) causes tachycardia and hypertension, which may follow an initial bradycardia", states Lee (2009) immediately after discussing the vagal agonist effects, and again without explanation. Where does this come from, and is it real? Enough articles mention tachycardia in response to suxamethonium (at least as many as mention bradycardia), and in the vast majority of these the human or animal subjects were thankfully anaesthetised, which calls into question the purity of the data - i.e., was it the sux or was it the thiopentone you gave that caused the haemodynamic effects? Brave heroes who administered suxamethonium to adult human patients suffering from various forms of coma (i.e unconscious but not anaesthetised) do report a transient 27% increase in heart rate and a minor (5%) increase in blood pressure, which the authors attributed to the heartward redistribution of venous volume during the period of fasciculations. There does not appear to be an explanation for this effect in the literature, and most authors seem to flail vaguely to dismissing it as some kind of nonspecific or indirect sympathetic mechanism.
Increased intraocular pressure is listed as a consequence of suxamethonium use, and appears to be a serious thing, with about 10-20mmHg increase in intraocular pressure reported by experiments such as Cook (1981). The pressure increase is fortunately short-lasting, and disappears over about 5-10 minutes, but one might feel some tingle of concern about it, particularly when anaesthetising somebody with an injury to the globe of the eye (for example). "But why", one might ask? Where one reads about this, one often finds a seemingly preposterous explanation, that the pressure increases as the result of extraocular muscle contraction, apparently squeezing the eyeball from all sides. If the resource has the decency to quote a reference for this, that reference is usually a paper by Linkoff et al (1955), but this is far from a definitive explanation. Linkoff and colleagues measured the intraocular pressure of anaesthetised cats, and did nothing to record extraocular muscle tension directly, merely remarking that "a response of the extraocular muscles to the drug seemed a likely solution". In their defense, they did sequentially cut the extraocular muscles, and this did result in a progressive decrease in the rise of intraocular pressure with each severed muscle, suggesting that there may be something to this hypothesis. The extraocular muscles are indeed histochemical and physiologically unique, in the sense that they are affected very differently by drugs and disease (as compared to the other skeletal muscle) but the question or whether or not they squish the globe remains unsettled, as other authors have found that sux increases intraocular pressure in the human eye with the extraocular muscles detached. In short, the exam candidate should be prepared to talk about the causes of this phenomenon with complete confidence, because just about anything they say is as likely to be accurate as any other thing.
Increased intracranial pressure would probably be somewhat more concerning, considering the comparative organism-level importance of the brain. Most primary exam level resources tend to report this adverse effect as gospel. To be sure, cats with raised ICP (27 mmHg) almost doubled it (47 mmHg) following a bolus of sux. However, small studies in brain-injured humans (Kovarik et al, 1994, as well as everything quoted by Clancy et al, 2001) did not find any such effect. Human evidence in support of this effect is basically limited to Marsh et al (1980), who intubated eight humans for elective brain tumour surgery using suxamethonium, and who reported a small but statistically significant increase in ICP. That study is weirdly popular (cited 54 times!) but apparently not popular enough to exist even as an online abstract. In short, CICM trainees should be instructed to repeat this in their exams, and to immediately return to disbelieving it when they pass.
Myalgia and fasciculations are a major problem for the casual user of suxamethonium, because their elective patients will twitch hideously, terrify the medical students in the operating theatre, and then wake up sore, complaining about their anaesthetic. "The large number of proposed remedies means that none works well", quips Lee (2009), after mentioning that the fasciculations "may look cruel to observers" and quoting his younger self as a reference. To say that the myalgia is a consequence of the fasciculations seems logical, but is in fact not supported by any evidence whatsoever, and the CICM exam candidate is warned against linking the two in their written answers. Certainly various methods of defasciculating patients prior to an induction dose of sux have not yielded any appreciable improvement in subsequent myalgia.
Hyperkalemia is a complication of the use of suxamethonium in multiple or large doses. Hovgaard et al (2021) explain this phenomenon very well. To summarise their main points:
There are many scenarios where these channels can be abnormal or abnormally numerous: burns, trauma, immobilisation, prolonged nondepolarising blockade, stroke, spinal injury, neurological diseases such as Guillain-Barre syndrome, and weird tumours like rhabdomyosarcoma that uncontrollably express muscle surface proteins (including nicotinic receptors). Immature receptors, such as those that sprout everywhere following denervation or immobilisation, tend to be open for longer, and they appear in ridiculous numbers at the neuromuscular junction and along the myocyte membrane. Martyn et al (2005) report that the increase in receptor density can be seen even within 6-12 hours, and can cause dangerous hyperkalemia by 48-72 hours. By that stage, their number can increase by a factor of 100, and the resulting rise in potassium is often large enough to produce cardiac arrest. Before the connection between sux and hyperkalemia was made, it was possible to enrol critical ill patients into studies where suxamethonium was administered to observe serum electrolytes, and some (eg. Birch et al, 1969) reported increases of up to 4.0 mmol/L over three minutes. If you manage to survive, the hyperkalemia is fortunately short-lived, as the Na+/K+ ATPase sucks it back inside the cells over the subsequent 10-15 minutes.
Increased intragastric pressure also seems to be an adverse effect first reported in the 1960s and 1970s, which has subsequently attained the status of Undeniable Anaesthetic Truth, and has propagated through generations of trainees who learn it, age, grow grey, and teach it to others. One of the most recent and most quoted of the old studies seems to be a piece by Smith et al (1978). The investigators helpfully summarised and referenced the findings by the older authors in a table (below), as well as measuring their own data to arrive at a conclusion.
That conclusion was, that the transient effect of abdominal wall fasciculations has the effect of increasing intragastric pressure for a short peak, which had ended up over 32 mmHg for some of the patients. The clinically relevant upshot of this is that the raised pressure might expel some of the contents of the stomach into the airway, and produce aspiration. Whether this happens in reality is still questionable. As Smith et al themselves remark, "the use of distended balloons for recording pressure inside the
stomach is open to error as contraction of the stomach has the effect of squeezing a balloon and inducing a much greater pressure than exists in the open-ended organ through which waves of peristalsis pass". The administration of suxamethonium does not result in immediate defaecation, one might point out, which means those sphincters are probably going to do their job, even in the face of a little fasciculatory stress.
Interactions with itself are an adverse drug effect. Specifically, we are talking about repeated doses, or sustained infusion. The effect of these is Phase II block, and a gradual decrease in the effect of suxamethonium, of which increasing doses are required. An excellent paper by Payne (1959) demonstrates this beautifully via this TOF recording from a finger flexion twitch, observed in a patient receving regular doses of suxamethonium:
This patient was getting doses of suxamethonium every 30 seconds, in case the reader is wondering. The duration of effect is also prolonged by this. Ultimately, Phase II block develops, which is resistant to acetylcholinesterase, and which takes some minutes to wear off. "Attempts at reversal of the block often result in just enough muscle power to make lung ventilation difficult but not enough to sustain a patent airway and adequate spontaneous breathing", Lee complains, perhaps drawing on personal experience. Apparently, the dose safety threshold to avoid this sort of thing is about 2-4mg/kg over 30-40 minutes.
In Question 10 from the first paper of 2018, examiners asked for "advantages (15% of marks) and disadvantages (85% of marks) of the clinical use of suxamethonium." The relative weight of these marks is very expressive. Reaching for something positive to say, the examiners even listed "pre-mixed" as one of the advantages, as if reconstituting a vecuronium ampoule is somehow a massive barrier to its routine use. But this raises the question: what, in the modern era, are the advantages of suxamethonium?