Overdose: Cocaine
For this episode, we were approached by our friend and colleague George who had a great topic idea. He’d seen a patient suffering from acute cocaine toxicity and felt it would be a good topic to visit and share learning on, as this is something infrequently encountered and discussed in our training.
As the podcasts are an extension of our own CPD, we thought it would be great to work with George on a podcast and share some reflections on a fictitious case, loosely based on our experiences with cocaine toxicity.
What:
Dispatched early in the morning to a 30Y/O Male with reports of shortness of breath and crushing chest pains. Information given by control indicated possibly previous cardiac issues but nothing else.
Crewed with a brand new ECA, briefing on route included cocaine toxicity and how I had never seen it in an ambulance setting and just at festivals. Other possibilities included MI, PE, possibly trauma, chest infection and pericarditis.
In the address, the patient was found lying on the floor. GCS 15. 7/10 crushing chest pain radiating into jaw and left shoulder, short of breath unable to complete full sentences with significant pauses between groups of words.
OBS:
BP: 190/110 mm/Hg
HR: 124 bpm
T: 38.1 C
BGL: 7.2 mmol
RR: 22 /min
GCS: 15/15
12 lead ECG: sinus tachycardia.
It quickly became apparent that there was signs of a 'party' at the address including numerous empty alcohol bottles. Questioning surrounding alcohol intake soon led to drug use where the patient admitted that he had snorted 5-6 lines of cocaine approximately 2 hours prior to the ambulance being called.
The chest pain started 60 minutes following cocaine ingestion and had built to a 7/10 pain score on examination.
During observations, the patient reported an increase of pain to 9/10 and started to become agitated. Patient began to ignore commands and pull at ECG leads and cannula.
Management:
As per JRCALC 10mg of IV diazepam was given slowly over 2 minutes, initially to no response. Shortly following this the patient's GCS reduced and settled at 7. The patinets ABCs were managed appropriately in response to this and the patient was prealerted and blue lighted to the nearest receiving ED.
So What
Cocaine
Cocaine is a compound extracted from the leaves of a South American shrub. Once seen as a “drug of the rich”, it is now a very common recreational drug in the UK. Cocaine is available in different forms and different purities to users, often it is combined with baking soda and ethanol to form “crack” which is smoked. Its important to note that crack cocaine is actually a more “pure” form of the drug, known as a “freebase”. As such users will yield much higher concentrations of the drug into their system when compared to snorting it. This is relevant to consider when discussing overdose.
Its most familiar powder form has a range of purities and strengths also. A gram of less pure powdered cocaine often termed “student coke” or “pub dust” or will typically cost anywhere from £30 -£40, However, as cutting agents like benzocaine become harder to purchase the purity and strength rises. [1] [3]
Understanding the purity of cocaine is difficult for clinicians, as street drugs are so variable in their concentrations, but a gross estimate can be made through price. A user who has paid top dollar for their drugs may have had an especially potent batch. Drug dealers are highly unlikely to offer premium goods for anything less than a premium price. Cheaper drugs are likely to have more additives and potential complications associated with this, discussed below.
Cocaine can be taken in a variety of ways, snorted or smoked is most common (smoked = crack), but it can also be injected. Onset varies with the route as does duration with crack having the shortest duration of around 10 - 20 minutes and IV the longest at around 60 - 90. [5]
“Of note is Cocaines interaction with alcohol. These form a toxic metabolite called cocaethylene, it makes the action of cocaine stronger and last 3 - 5x longer, so toxic effects may be prolonged. Risk of death is increased 20 fold when cocaine and alcohol are mixed”
Pharmacology
Cocaine has a number of properties, firstly it is a local anaesthetic (think of well-known anaesthetics like benzocaine, tetracaine and lidocaine) and was used as such in the early days of medicine. However, due to is other actions and highly addictive properties it is classified as a stimulant narcotic. Its pleasurable qualities, and reasons for its popularity and abuse, come from its action as s a Mono-Amine reuptake inhibitor. This means it binds with reuptake proteins at synaptic junctions and prevents reabsorption of these neurotransmitters. In particular the catecholamines adrenaline, nor-adrenaline, dopamine and the indolamine serotonin. [2,5]
Catecholamines are released during a sympathetic response, whilst this is often talked about in the context of threat and “fight or flight”, it’s important to remember that it is these neurotransmitters that give us feelings of elation and the “adrenaline rush” that comes from doing exciting things. Our brain is hard-wired to reward itself by releasing dopamine, to encourage beneficial behaviour through a process literally named the dopamine reward system. Cocaine in this manner gives you a pat on the head and that hug from your father you’ve strived all your life for…. Dopamine is also involved with thermoregulation and so this is likely contributory to the hyperthermia noted in toxicity. [7]
Adrenaline binds with alpha 1 and beta 1 adrenoreceptors to cause contraction of smooth muscle (vasoconstriction and BP increase) and positive ino- and chronotropic cardiac effects respectively ( increase in contraction force and heart rate) [2]
Seratonin typically referred to as the “feel-good” chemical, has a large part to play in the regulation of body functions, most notably mood. Many of the medications used in depression and mental health problems focus on getting more serotonin into the system.
Understanding this then, we can see why someone might enjoy the “therapeutic” levels of taking cocaine as it gives us an abundance of these chemicals that make us feel great. All the fun of a parachute jump, without being awkwardly strapped to a total stranger.
Assessment:
Cocaine intoxication generates the following signs and symptoms:
Psychological:
Increased energy
Happy mood
Garrulous speech
Physiological:
Tachycardia
Hypertension
Tachypneoa
Fidgeting
Mydrasis
Diaphoresis
Its when patients start to have an overabundance of these neurotransmitters in their system and they begin to have deleterious effects that they encounter problems.
Cocaine Toxicity can cause the following symptoms in patients
Psychological :
Agitation/Combatative
Aggression
Paranoia
Delirium
Physiological:
Significant tachycardia
Palpitations
Chest pain
Myocardial ischemia or infarction (May show as ST elevation on ECG)
Extreme Hypertension
Hyperthermia
Increased tone
Fitting
Stroke
This list is quite a lot to remember and isn’t in itself exhaustive of what can happen. It is far more useful to understand this as a classic Sympathomimetic toxidrome. A collection of symptoms associated with ingestion or overdose of a sympathomimetic medication. The Resus Room podcast did a fantastic summary of Toxidromes that is a must-listen for all prehospital clinicians.
Sympathomimetic Toxidrome: Think MATHS
Mydrasis
Agitation and Arythmia
Tachycardia
Hypertention and Hyperthermia
Seizure and Sweating
The effects of Cocaine toxicity… and the effects of those effects:
Dont forget, that there may be other things at play here. Cocaine overdose can cause, among other things, MI, Aortic Disection, Endocarditis and Stroke. So as always these patients should get a detailed workup where possible and consideration given to these significant sequela.
Management:
Clearly, the management of these patients will be tailored your findings on examination. However, classically these patients will present in a hypertensive crisis, often with chest pain or other signs of ischemic injury due to coronary artery narrowing and spasm. As a result, we are going to discuss the management of the patient above.
Diazepam
Diazepam is a medium-strength, long-acting benzodiazepine, competitively binding GABA receptors in the CNS to reduce CNS excitability, giving it properties as an anticonvulsant, anxiolytic (anxiety-reducing medication) and muscle relaxant. In the context of acute cocaine toxicity, it is helpful in a number of ways.
JRCALC states that paramedics should administer titrated doses of Diazemuls in the context of “severe chest pain” [4]. This helps by relaxing smooth muscle, dropping blood pressure (reduction in preload and afterload), and reducing coronary artery spasm. This improves myocardial oxygen supply whilst also reducing the workload on the heart. Diazepam should be titrated SLOWLY, as when given concomitantly with GTN (discussed below) then there is the risk of dropping blood pressure. Diazepam has a long half-life and so unlike in the context of fitting, where advice is to give 10mg stat to stop the seizure, in this context less is more. Remember you can give more Diazemuls, but you can’t take it back if you’ve given too much.
Consider the patient holistically, a 50 year old with comorbidities who is dehydrated from a long night partying will react very differently to a fit 28 year old who has just had a lot of coke! We should ensure the drugs have enough time to circulate and take effect before taking more. This is discussed further in the podcast and was a key take away point.
Diazepam also assists by acting as a sedative and anxiolytic for these highly adrenalised patients. As in the case above, cocaine will cause agitation and non-compliance with assessment, and whilst this is NOT being given in the same way one might perform proceedural sedation of acute behavioural disturbance, a helpful addition of Diazepams sedative nature, will make the patient more compliant, but crucially more comfortable, as prolonged anxiety is not a nice experience. [6]
This is not an Acute Behavioural Disturbance podcast, nor is it one looking at performing a sedation as the scope of this is too large. It is wise however to take similar precautions that we otherwise would with a proceedural sedation.
It can be helpful to have the patient on High flow o2, to denotrogenate their lungs incase of inadvertant oversedation and respiratory depression
Full monitoring should be applied including nasal end tidal co2 to monitor for respiratory depression and apnoea. If this is absolutely not possible because of agitation and combativness, it should be documented well and applied at the earliest convenience.
Suction, BVM and airway adjuncts should be to hand.
A target should be identified and verbalised to your team. I.e. you are aiming to reduce the Chest pain and agitation but NOT heavily sedate this patinet.
Aspirin:
Asprin is a key factor in an ACS care bundle, and whilst its use is well supported and well evidenced in the literature for ACS, we need to take a considered thought into its use in this case.
JRCALC recommends administering aspirin in cases of chest pain [4], as the vasospasm of cocaine, can potentiate a thromboembolic event. As a result, administering an antiplatelet will be of benefit in preventing this and preventing it from developing further. However, its important to factor in the reason for the patient’s presentation. A thrombus formation will be as a secondary cause to the cocaine toxicity, and administering the aspirin alone will not treat the issue.
We should therefore ensure that preparation of Diazepam and GTN is taking precedence, and the Aspirin is administered at our earliest convenience, perhaps not as our first go-to medication.
GTN:
Glyceral Tri-Nitrate works by undergoing denitrogenation to form nitric oxide (NO) a potent vasodilator. By administering GTN we are combating the vascular constriction caused by the cocaine, improving blood flow and minimising ischemia but also dropping blood pressure. Evidence suggests that it is effective in decreasing BP and in achieving vasodilation, but there were notable cases of a rebound tachycardia that occurs to maintain cardiac output. [6]
We should give GNT cautiously, especially if we are giving it concomitantly with Diazepam as they are both known for dropping blood pressure dramatically. Again, you can always give more, but it’s much harder to take that last dose back if you’ve caused your patient to become syncopal.
Cooling:
Patients experiencing a sympathomimetic toxidrome often become hyperthermic, which can be damaging to our bodies on a cellular level.
Hyperthermia in cocaine toxicity is likely a combination of impaired thermoregulation from dopamine release, excessive muscular activity (given the context in which cocaine is taken or from seizures) and from the increased metabolic activity from catecholamine release. [7]
Its important to begin cooling these patients to avoid cellular injury and minimise the risk of seizures.
Exactly how this is done is likely to be heavily dependant on the situation and the patients’ temperature to determine how aggressively to attempt cooling. Just like with warming people up it’s important to consider all of the ways in which we lose heat, in order to be maximally effective. Think about Conduction, convection, radiation and evaporation when looking at cooling. Take a look at our Hypothermia podcast where we talk about the principles. The Resus room also have an awesome podcast on heat illness. Slightly different mechanism, but the principles of cooling are the same.
PPCI and Thrombolysis:
We felt this was important to touch on. As we have described above, the principle issue causing acute chest pain here is reduced blood supply to the heart (vasoconstriction, reduced cardiac output from tachycardia) and increaed myocardial oxygen demand (tachycardia). This in turn causes ischemia, pain and potentially ECG changes. One could be fooled then for thinking, if we resolve the above, then there is no need for PPCOI, however this is not always the case. Cocaine use is associated with a prothrombotic state, it causes an increase in platelets, increased platelet activation and release of plasminogen activator inhibitor*. Autopsies of cocaine users report increased rates of atherosclerosis and thrombus formation.[8] Therefore we have to consider the high likelyhood that this patient is having a cocaine induced MI and despite treating the effects of cocaine, may still require further treatment.
*plasminogen is key in fibrinolysis, the break down of clots, releasing more of a factor that inhibits its action, therefore increased risk of thrombus formation
In the event anyone is still using Thrombolysis in their service for AMI, then these patients are not a candidate for it as the ST - Elevation MAY not be from a thromboembolic cause. Management is targeted at reducing coronary artery vasoconstriction, clearly, a clot-busting drug will not help with that and will only make the situation worse.
These patients MAY need PPCI, as there is the potential for clot formation as described above. If ST-Elevation remains or troponins show ongoing myocardial injury, then the patient may be a candidate for angiography. If possible and distances allow, conveyance to a hospital with PCI capability is probably preferable.
Other things to consider:
Speedballing: Speedballing is a term given to a combination of both cocaine and heroin, which is normally injected. This is particularly dangerous as one is a stimulant and the other a depressant, and the risk of overdose greater as a result.
Stuffers verses Packers: These are two terms that are often, incorrectly, interchanged. Cocaine STUFFERS refer to occasions where a user, often a dealer, has swallowed or “stuffed” an ammount of cocaine away, to avoid detection by the police. This is a done in a hurried manner, with the drugs in packets not necesarrily desgined to prevent absorbtion. For Cocaine PACKERS thing drugs mules. People who have ingested large ammounts of drugs to be transported a great distance, often across boarders. In either case, if you deal with someone that fits either of these criteria you have to consider the risk of developing toxicity as more and more of the drug gets absorbed. This is also a surgical emergency, so will require transport to a location suitable to deal with this, and requiring an early pre-alert.
Consider activated charcoal: In cases of oral cocaine ingestion, consider the role for activated charcoal. This is best utilised in the early stages of ingestion, ordinarily 1 hour, as usefulness begins to deteriorate the longer it is left [9]. However, there may be some potential benefit, particularly in cases of stuffers / packers where absorbtion may be delayed/prolongued.
Cutting agents: Cocaine can be cut weith a variety of agents including: Benzocaine, phenytoin lidocaine or lignocaine and levamisole.
Levsamisole has been linked with agranulocytosis or neutropenia (loss of white cells) in some users and vasculitis if injected. White cell counts will generally be run in A+E if this is suspected. [9]
Cocaine has been know to be cut previously with phenacetin [10], an early pain killer discontinued in the 80s due to carcinogenic properties, due to its similar appearance to . Whilst likely to be a rare agent, it is still produced and used in certain hair products [11]. Phenacetin and some local anaesthetics( bupivicaine) when cut with cocaine have been known to result in methaemoglobinemia [9], a toxic condition where haem- groups in red blood cells lose their affinity for oxygen, giving people a “silvery blue” skin colour.
Now What:
Take away points: -
Less is more, slow titration of diazepam, can’t take it away
Prepare for inadvertant sedation, ETCO2, oxygen on, obs on, airway kit to hand,
Consideration to the problems that can be caused by toxidrome. ACS, aortic disection, stroke etc
Importance of other ACS drugs aspirin, GTN, morphine if appropriate, but be cautious of effects on blood pressure
Verbalise intentions to team, this is something that others may not be aware of and is definately an uncommon use of diazepam prehospitally.
Remember, clinicians are responsible for their own practice. These podcasts are produced for informative purposes and should not be considered solely sufficient to adjust practice. See "The Legal Bit" for more info.
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1 - https://www.drugwise.org.uk/how-much-do-drugs-cost/
2 - A primer of Drug action Pg 197
3- https://www.drugwise.org.uk/how-pure-are-street-drugs/
4- https://icpgweb.co.uk/#/tab/dash/guideline/G0450
5 - https://canadiem.org/crackcast-e154-cocaine-sympathomimetics/
6- https://www.tandfonline.com/doi/abs/10.3109/15563650.2016.1142090?journalCode=ictx20
8 - https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.107.188950
9- https://www.toxbase.org/poisons-index-a-z/c-products/cocaine/
10- http://news.bbc.co.uk/1/hi/uk/6178026.stm
11- "Health - Product safety - Chemical substances - Phenacetin information sheet". Government of Canada -. Retrieved 29 April 2020.