JC: Illicit Drug Induced Hyperthermia: A Time-Critical Toxicological Emergency

Drug induced hyperthermia is something we touched on in the early days of St Emlyn’s following some gtruly tragic cases comring through Virchester. Sadly it’s not confined to us here and Emergency departments (EDs) across the UK and beyond are becoming increasingly familiar with this condition often associated with mass gatherings and music festivals. While much attention has been paid to harm reduction strategies, clinical management remains complex and high-risk—particularly when hyperthermia is involved. This week we have a great paper by Nic Ionmhain, McArdle and Berling, published in Emergency Medicine Australasia , which offers an important and timely update on the recognition and management of Illicit Drug Induced Hyperthermia (IDIH). I’ve dealt with several of these, and I’ve also been involved in the investigation of deaths and I think there is room for improvement. I’ve certainly changed my management over the years and I’d encourage you to do the same. It’s a remarkable presentation where fast action may well save a life. The abstract is below, but as always please do read the paper yourself.

IDIH is a specific and serious clinical entity that differs significantly from more commonly recognised causes of elevated body temperature. It is associated with a range of illicit substances—most commonly MDMA (ecstasy), methamphetamine, cocaine and related stimulants—and frequently presents in young, otherwise healthy individuals. As the authors note, it is best conceptualised as a “High Acuity, Low Occurrence” (HALO) event: rare, but associated with high morbidity and mortality, particularly if not promptly recognised and managed.

Abstract

Illicit drug induced hyperthermia (IDIH) is a life-­ threatening emergency requiring timely recognition and management. The pathophysiology of hyperthermia secondary to illicit drug toxicity can be associated with and complicated by additional precipitants such as exertion and high ambient temperature (> 31°C). We present cases highlighting the clinical features, morbidity and mortality associated with IDIH. The priorities of management include interventions to decrease ongoing heat production, active cooling and targeted supportive care. Temperature control should ideally be achieved within 15 min to prevent irreversible organ injury. IDIH presentations may be viewed as a high acuity low occurrence (HALO) event. As such, we recommend the use of a specific IDIH protocol and early consultation with clinical toxicology specialists for hyperthermia presentations with suspected illicit drug use.

The Case for Urgency

Unlike fever, which represents a regulated increase in the body’s set point temperature as part of an immune response, hyperthermia is unregulated and pathological. In the context of IDIH, the mechanisms responsible are multiple, complex, and synergistic. There is an uncontrolled increase in heat production, impaired heat dissipation, and failure of central thermoregulation—all driven by the pharmacological effects of stimulant drugs, compounded by environmental and behavioural factors such as dancing, dehydration and high ambient temperatures. This situation can be sharply exacerbated by restraint from policing or healthcare professionals

Also remember that some drugs such as fentanyl and tramadol can also cause hyperthermia (and they are not stimulants).

Hyperthermia above 40°C is directly cytotoxic. Animal models suggest that irreversible cellular injury begins within 15 minutes of reaching this threshold. Every minute of delay increases the risk of multi-organ failure and death. In the context of the ED, where triage, assessment, and treatment often unfold over longer time frames, this represents a true emergency within an emergency.

Clinical Categorisation and Risk Stratification

The authors propose a pragmatic stratification system to assist with early clinical decision-making. IDIH can be categorised based on core temperature and associated clinical features:

• Mild: Core temperature 37.5–38°C without additional high-risk features.
• Moderate: Core temperature 38.1–38.9°C or associated signs of sympathetic overdrive such as tachycardia or hypertension.
• Severe: Core temperature >39°C or any signs of altered mental status, agitation, confusion, or overt organ dysfunction.

This framework is particularly helpful in the ED environment, providing a trigger for escalation. Severe IDIH requires immediate and aggressive intervention and you should be involving experienced resuscitation doctors in emergency and critical care.

Two Cases, Two Trajectories

The paper presents two illustrative case studies, each demonstrating the potential trajectory of IDIH and the importance of  early, aggressive treatment.

In the first case, a 36-year-old man with a history of methamphetamine use was found unresponsive in 30°C ambient heat, with a GCS of 3 and a temperature of 43.2°C. Rapid cooling was initiated with ice packs, cold IV fluids, a cooling blanket, and paralysis. He was intubated early, treated with benzodiazepines and vasopressors, and admitted to intensive care. Normothermia was achieved within three hours, and he was discharged without sequelae after eight days.

The second case tells a far more tragic story. A 25-year-old woman presented following MDMA ingestion at a summer music festival. Her temperature was 42°C, she was agitated and hypotensive, and initial investigations revealed severe metabolic acidosis and hyperkalaemia. Despite aggressive management including sedation, paralysis, CRRT and supportive ICU care, she developed multi-organ failure and died on Day 15 of admission.

The contrasting outcomes underscore the importance of early recognition, rapid sedation, and fast, aggressive cooling. In many ways, IDIH is a condition in which the window for salvage is both narrow and closing rapidly from the moment of presentation.

I have seen both of these scenarios play out in Virchester. I’d also point out an interesting, perhaps even disappointing outcome of the cases I have seen. In cases like the first one I’ve sometimes been left with the impression that I/we ‘overreacted’ as the patient ended up doing fine and they were just a bit hot. In the second case when things go wrong the accusations are that I/we failed. It’s an odd one really and perhaps reflects some of the complacency and perhaps victim blaming that can be associated with victims of poisoning. Please make sure that you and your teams don’t fall into these cognitive traps. An averted crisis is indistinguishable from an “overreaction.”

Mechanisms of Injury

The authors provide a comprehensive summary of the physiological and pathophysiological mechanisms involved in IDIH. These can be broadly grouped into three domains:

1. Increased Heat Production: Sympathomimetic drugs increase motor activity, leading to increased muscular thermogenesis. Additionally, beta-3 adrenergic stimulation induces non-shivering thermogenesis via mitochondrial uncoupling.
2. Decreased Heat Dissipation: Peripheral vasoconstriction can reduce heat transfer to the skin (probably a noradrenaline effect)
3. Dysregulation of Thermoregulation: Serotonin affects hypothalamic control of body temperature.

In practice, these mechanisms often overlap and amplify one another. A typical presentation occurs at music festivals, where a young person ingests a stimulant, dances for several hours in high temperatures, becomes dehydrated, and ultimately collapses. By the time they reach medical care, their physiology is spiralling into chaos. Anecdotally I’ve seen more of this in muscular young men who are perhaps able to generate. ahigher degree of muscular heat and therefore are perhaps more at risk (I have seen in small females too, so this is not a rule).

Clinical Management: Priorities and Pitfalls

The management of IDIH must be decisive, systematic, and prioritised around two core goals: cessation of heat generation and acceleration of heat loss. The authors provide a practical protocol that EDs could adapt locally. Central to this is the early use of sedation.

Sedation and Motor Control

Sedation is not simply for agitation control—it is a life-saving intervention in IDIH. Agitated patients generate excessive heat through muscle activity and are unable to co-operate with cooling measures. Physical restraint risks worsening catecholamine surges and provoking cardiac arrest. Benzodiazepines are the first-line agent, often in high doses. Where patients are severely agitated or obtunded, early intubation and paralysis should be strongly considered. I would avoid suxamethonium for obvious reaons.

Additional agents such as ketamine or droperidol may be useful adjuncts for managing pre-intubation agitation, but should not delay definitive control of the airway and muscle activity.

Cooling Methods: Internal and External

A wide array of cooling strategies are available, each with advantages and limitations. The key point is that no single method is sufficient—multiple methods should be used simultaneously, and initiated as early as possible.

Passive Cooling measures (removal of clothing, fans, exposure to cool air) are easy to implement but of limited efficacy in isolation.

Active External Cooling includes:

• Ice packs to the axillae, groin and neck
• Misting combined with fans
• Cooling blankets (e.g. Altrix or Arctic Sun). I like the artic sun for this if available. Largely because folks in Virchester are familiar with it and it’s potentially portable. Patients will probably bneed to be intubated to tolerate this.
• Ice water immersion, which is highly effective but logistically complex

Active Internal Cooling strategies include:

• Administration of cold IV fluids (4°C), which can achieve a 1–2°C reduction
• CRRT without a blood warmer, useful when managing concurrent acidosis or hyperkalaemia
• Cooling catheter systems (e.g. Zoll Cool Line), where available
• ECMO, which provides both cooling and organ support in select ICU patients

Ice water immersion is widely regarded as the gold standard, capable of reducing core temperature by 8–10°C per hour. However, it requires appropriate infrastructure, staff training, and careful monitoring. The authors recommend local EDs consider simulating and rehearsing its use, particularly in centres receiving high volumes of toxicological cases or festival-related presentations. I have done this by placing a patient on a vacuum mattress and moulding it into what effectively becomes a shallow paddling pool sort of configuration. This can then be used with iced water to cool patients. You probably have a vacuum mattress in your ED, so why not try this out? It’s not so great if you have a large/tall patient, but see if you can make it work.

Temperature should be monitored continuously, preferably via a core probe, with a target of <38°C within 15 minutes of ED arrival. This may sound ambitious, but the available evidence supports the notion that rapid defervescence is the single most important predictor of survival. I can’t support this comment enough!

Interestingly there is no mention of drug therapy in this paper. In the UK a number of antidotes have been suggested including cyproheptadine and chlorpromazine for serotonin syndromes, and these are listed in the BNF. In the past it was also recommended to give Dantrolene. I’ve always been worried about a focus on drugs rather than cooling and so I’m happy to see them de-emphasised in this paper. I am aware of occasions where clinicians have focused on preparing dantrolene (which is a pain to make up)( whilst failing to actually cool the patient. Priorities, priorities, priorities are cool, coool, cooooooollll.

Practically though….

There is a broader systems issue underpinning this discussion. IDIH is rare in most settings and does not lend itself to clinical experience built over repeated exposures. As a result, clinicians often lack the familiarity or cognitive scripts to recognise and manage it effectively. The authors argue that local IDIH protocols and training—including simulation-based exercises—can bridge this gap. As someone who works in prehospital settings then the challenges are even greater as there may well be less opportunity for specific therapies/actions.

In addition, they advocate for early consultation with clinical toxicologists or Poisons Information Centres, who can support with case-specific guidance. As emergency physicians, we are often called upon to manage rare but critical presentations. Having clear pathways and access to expert advice can make the difference between a good and a tragic outcome.

Reflections and Implications

The publication of this paper is timely. Recreational drug use, warmer climates, and the popularity of outdoor music events mean that presentations of IDIH may be something we all see from time to time. Beyond the ED, this paper has implications for public health and harm reduction. Education around the risks of hyperthermia, particularly in festival environments, is essential. So too is training for prehospital and event medicine providers, who are often the first to assess and manage these patients. The emphasis must be on early sedation, cooling, and transport to definitive care.

The authors have done a great job summarising the evidence and providing practical solutions. I would recommend downloading the paper and looking at their flow diagrams which are great aide-memoires too.

Conclusion

Illicit Drug Induced Hyperthermia is a rare but deadly syndrome. It predominantly affects young, otherwise healthy individuals, and its outcome hinges on early intervention. The two pillars of management—cessation of heat generation via sedation and rapid cooling via multiple modalities—must be initiated early and aggressively. Emergency departments should be prepared for these cases, both in terms of equipment and cognitive readiness.

References and further reading:

1. Nic Ionmhain Ú, McArdle K, Berling I. Illicit Drug Induced Hyperthermia (IDIH). Emergency Medicine Australasia. 2025;37:e70065. doi:10.1111/1742-6723.70065
2. Simon Carley, “JC: Recreational drug induced hyperthermia. St.Emlyn’s,” in St.Emlyn’s, October 20, 2013, https://www.stemlynsblog.org/drug-induced-hyperthermia-st-emlyns/.
3. Gregory Yates, “When things get exciting: Thoughts on the recent EMCRIT episode on serotonin syndromes.,” in St.Emlyn’s, June 10, 2025, https://www.stemlynsblog.org/when-things-get-exciting-thoughts-on-the-recent-emcrit-episode-on-serotonin-syndromes/.
4. Overview of serotonin syndrome. Iqbal MM, Basil MJ, Kaplan J, Iqbal MT. Ann Clin Psychiatry. 2012 Nov;24(4):310-8.
5. UK TOXBASE http://www.npis.org/toxbase.html
6. Prevention, recognition, and management of serotonin syndrome. Ables AZ, Nagubilli R. Am Fam Physician. 2010 May 1;81(9):1139-42.
7. Diagnosis and treatment of drug-induced hyperthermia. Musselman ME, Saely S.Am J Health Syst Pharm. 2013 Jan 1;70(1):34-42. doi: 10.2146/ajhp110543.
8. Treatment of four psychiatric emergencies in the intensive care unit. Bienvenu OJ, Neufeld KJ, Needham DM. Crit Care Med. 2012 Sep;40(9):2662-70. doi: 10.1097/CCM.0b013e31825ae0f8.
9. Serotonin syndrome vs neuroleptic malignant syndrome: a contrast of causes, diagnoses, and management.
10. Perry PJ, Wilborn CA. Ann Clin Psychiatry. 2012 May;24(2):155-62.Good case on GasClass here