St.Emlyn’s exists in the city of Virchester and is known for its lively night life. This is great for the emergency department as it attracts a steady supply of junior docs and nurses who want to live and work in a vibrant and incredibly diverse population, the flip side of this is that we sometimes have to deal with the consequences of a 24 hour lifestyle.
We have previously raised concerns about the use of PMA in the UK with a number of deaths reported in the press suggesting links to this drug. Now St.Emlyn’s is a realistic place. We’re not into telling people what to do (just try and be safe folks) rather our realism is about the clinical approach to the management of our patients who may come to harm through the use of drugs and alcohol.
Over the years we have been faced with several extremely unwell patients who present from nightclubs/saunas/bars with hyperthermia which is suspected to be drug-induced. These cases are rare, but can be extremely challenging to the resuscitationist.
The UK press have recently suggested that a number of deaths may be linked to the use of MDMA and PMA like drugs with cases cropping up across the country (such as PMA). All emergency physicians in the UK may see patients in the resus room with the complications of drug induced hyperthermia so perhaps now is the right time to stop and think about what we are going to do about it. This is not a systematic review, there are plenty papers out there to guide your base knowledge, rather we want to focus on the practicalities around probablistic decision making and treatment for the some of the most complex patients we see. I’m also really interested to hear others experiences.
This blog builds on some excellent #FOAMed resources that are already out there (check the links and references), but as it’s a current problem in the UK and the literature is patchy I think it’s worth a re-iteration. If I’ve got anything wrong then drop in a comment so we can incorporate it into the blog.
[DDET What do we mean by drug induced hyperthermia?]
That much is obvious, but what is not so obvious is how it differs from fever. In brief fever is a centrally mediated effect. The brain sets a new temperature for the body to achieve and it activiates mechanisms to achieve this (for example shivering). Hyperthermia is different, the rise in temperature is not centrally regulated, rather it is a result of an increase in the metabolic state of the patient as a whole. Simply put we can think of fever is centrally driven, whereas hyperthermia is peripherally driven (though combinations of the two may occur).
I have an entirely non-evidence based notion that this seems to be more of a problem in muscular males as presumably an increased muscle mass allows a more rapid and more sustained rise in metabolic activity and thus temperature rise. That’s my experience anyway and it seems to make patho-physiological sense. [/DDET]
[DDET What drugs are we talking about?]
There are a number of drugs that can induce a rise in body temperature. A recent publication in Am J. Syst Pharm highlights 5 groups of drug induced hyperthermia syndromes. It’s a great article and I would recommend a read of the full paper.
The 5 groups are described as….. (with thanks to LITFL)
- Neuroleptic malignant syndrome. Typically caused by antipsychotic drugs.
- Serotonin syndromes. Caused by quite a broad range of drugs that increase serotonin but includes amphetamines, PMA and MDMA (ecstacy)
- Anticholinergic syndromes. Caused by a broad range of drugs with anticholinergic properties. Tricyclic drugs for example.
- Sympathomimetic syndromes. Commonly cocaine, MDMA, cocaine, amphetamines.
- Malignant Hyperpyrexia (MH). An autosomal dominant disorder of skeletal muscle precipitated by inhalational anaesthetics and neuro-muscular blocking agentes.
So, five main groups of drugs that we may encounter, some more common than others. The paper is good and well worth a read, having said that the data on which it is based is pretty patchy comprising mostly case reports and consensus approaches to management. [/DDET]
[DDET Disclaimer and how to find someone brighter than me…..]
If you choose to read on then this blog represents an interpretation of the easily accessible data and is a summary of how I am organising my thoughts for the next time I meet this rather terrifying scenario, I would not use this as a guide though.
If I face this problem tonight I will be better prepared, but I will without doubt contact our poisons unit for the latest and best advice available. I would strongly recommend you do the same, I am aware that they are collating information about these rare events at the moment and so you would not only be helping your own patient but also contributing to the expertise for future patients (basically it’s the right thing to do).[/DDET]
[DDET But we’re focusing on ED patients brought in from nightclubs right?]
In this blog yes, and there is a reason for that. The really challenging group for us are patients where the cause is not obvious or revealed. Sudden onset of hyperthermia following induction of anaesthesia indicates MH, and there are guidelines for that. Similarly patients with known drug use or overdose (if we know they are on antipsychotics for example) lend themselves to a diagnosis and a treatment regimen.
That’s not the experience of the emergency physician in the resus room. We often know little or nothing beyond the age of the patient and where they came from.[/DDET]
[DDET Are all patients critically ill?]
Not at all. It’s not unusual to find patients with an elevated core temperature following a drug assisted night out in Virchester. This may be as a result of the drug ingestion, but a bit of vigorous dancing (which is allegedly quite common in nightclubs) puts the core temperature up, and these are often hot places to exercise. So it can be difficult to ascertain how much of a rise in the core temperature is due to environment, drug use or a combination of the two. We see lots of people with small rises in core temperature (up to 38-39C) who appear to have self limiting clinical courses and a rapid resolution.
However, a small subset of patients can present in extremis with high core temperatures, muscle rigidity, cardiovascular instability and coma. These patients are critically unwell and require urgent management.
These are typically young, previously fit and well people who did not embark on their evening with the intention of ending up in the resus room. They deserve our absolute best as emergency and critical care physicians. [/DDET]
[DDET So, what’s the cause?]
If a clear history of what has been taken, by whom and when is absent (and it’s usually missing) then we must take a probalistic approach to management. So, a young patient, brought from a party/late night event with altered conscious level or agitation and hyperthermia then it is likely to be a result of street drug use and therefore the likely culprits will one of, or a combination of….
- MDMA (ecstacy)
- Mephedrone (and derivatives)
You’re probably not going to know for sure but that’s OK. You are resuscitationists and that means that the clinical history of some of our sickest patients is at best limited and often absent. The treatment will have to progress along fairly generic principles if we are to do our best for the patient.
These drugs are most likely to result in a clinical toxidrome most like a serotonin syndrome or sympathomimetic type syndrome. That’s probably as much as we will know but it does give us a starting point for therapy. Muscle rigidity is a feature of the most unwell patients in our experience and that lends itself to a treatment regime based on a provisional diagnosis of severe serotonin syndrome. [/DDET]
[DDET So what can we do about it?]
- Remove the cause if you can.
It’s good to separate the drug from the patient. That’s easy to say but in our experience drugs have been ingested some time earlier. How much, when and in what combination will be unknown and there is probably little that you can do about this. However, you would avoid any drugs that can cause serotonin syndromes during your resuscitation.
- Cool the patient
Cooling the patient is a good thing. The rise in core temperature is itself damaging to the patient and is a cause of death. I like to think about this in two ways. Firstly we need to allow heat to dissipate from the body, so we can use ice, cool fluids, tepid sponging, arctic sun etc. This should not present too many problems in a well stocked ED as you should have the equipment to cool post cardiac arrest already – so use that. Patients with a temperature over 39C should be actively cooled.
- Consider how the temperature has risen
It’s likely that that main driver for an increase in core temperature in the patients we see is muscular activity. Muscles are great ways to increase body temperature (think of shivering) and a reduction in muscular activity can help reduce any further rise. UK Poisons centres & others recommend a few things to help reduce the engine that is producing the heat.
- Benzodiazepines or haloperoidol can be used to sedate the patient. OK, that’s fine in patients who are not too sick, but for critically ill patients it’s worth considering this step carefully. It may reduce muscle activity through sedation but it may also adversely affect the conscious level. Sedation as a half way house in patients who are critically ill always makes me nervous pre-RSI. Post intubation then sure, benzodiazepines are fine and may well be a good choice.
- Dantrolene is mentioned in many guidelines as a drug that acts directly on muscle cells to cause relaxation and a reduction in activity. It is a mainstay of treatment in malignant hyperthermia and neuroleptic malignant syndrome where it works. It is recommended in several papers and toxicology guidelines and I’ve personally seen it given in critically unwell patients, but it is debatable whether it has a specific mechanism in non MH/NMS patients. Some authors suggest that there is little data to support it’s use and that it should be avoided. However, I have seen it used in extremely unwell patients where we are attempting to do everything possible to save a life, and whilst it remains on the UK toxbase recommendations then I suspect it will continue to be given here.
- Cyproheptadine & Chlorpromazine may be a specific antidote in serotonin syndrome though interestingly this is not mentioned in some UK guidance for PMA (but is in the serotonin syndrome sections). I have little experience with this drug and there is little in the literature, and I’d love to hear from others who may have experience in its use.
- Do you need to intubate, paralyse and ventilate?
Consider intubation, paralysis and ventilation for the critically ill. In fact actively consider this in patients who present with temperatures above 40C and keep this decision under regular review if simple measures are failing. However, consider the potential risks involved and adjust your strategy accordingly.
This is a difficult situation and you must think hard about the risks and benefits of proceeding with an anaesthetic. These may be some of the hardest patients to manage in the resus room. Serotonin syndromes have a number of complications that will make the induction of anaesthesia extremely hazardous.
- Alterered conscious level
It is entirely possible that your patient may have altered consciousness, hyperkalaemia, muscular rigidity, hyperthermia and cardiovascular instability as they arrive in the resus room. Achieving a safe induction of anaesthesia is going to be complex and requires expert help. We can assume some principles here though.
- Get a point of care blood gas (that also gives you a K+, Ca++, Lactate, Glucose) and manage any major abnormality.
- Avoid depolarising neuro-muscular blocking agents (Suxamethonium increases muscular activity and raises K+)
- Good vascular access and IV fluids.
- Optimise first pass success.
- Plan for post intubation care – including the possibility of post intubation cardiac arrest (which is why that blood gas is so important to look for treatable causes in advance).
My thoughts on early and repeated consideration of the need for intubation and paralysis is based on the possibility of ending up in the situation described above. It’s a real marker of a resuscitationist to be able to decide when the right time to proceed with intubation and paralysis has arrived. Too early and you expose your patient to risk, too late and you risk disaster.
decreased GCS is associated with increased aspiration risk
- GCS<12 is a somewhat arbitrary threshold; GCS 8 has not been validated in toxicological settings
- prolonged or recurrent seizures
Intubation, ventilation and paralysis may be indicated for severe serotonin syndrome independent of the need for airway protection:
- truncal rigidity impeding ventilation
- hyperthermia (T39.5C+)
- rising PaCO2
- rising CK
I think this is a sensible set or criteria that I could use in resus to guide me in making the right decision at the right time.
- Look for other complications
If they are not already present on arrival then you should actively seek complications such as hypertension, hypoglycaemia, convulsions, cardiovascular instability, acidaemia and hyperkalaemia are all early and late hazards and you should be vigilant to their presence and to their onset. Once found they can be managed along conventional lines. Rhabdomyolysis is common in patients with significant rigidity and should be sought for and managed along conventional management guidelines.
[DDET Summary: Looking to help the next patient]
Clearly there are many potential pitfalls in the management of patients with drug induced hyperthermia secondary to recreational drug use. Our patients are usually young, active and healthy patients who for some reason have a night that goes badly wrong for them. They present to us in clinical states that are some of the most challenging that we may face as resuscitationists. It’s high stakes medicine for both the patient and the clinical team as the critical care management may in itself precipitate a sudden deterioration.
Hopefully this blog and a bit of intra-cranial simulation will prepare you for if (and probably when) you face a case of recreational drug induced hyperthermia. [/DDET]
UK TOXBASE http://www.npis.org/toxbase.html