Environmental Emergencies
Question 104 of 180
You are presenting a teaching session on drug-related hyperthermia to your junior colleagues. You have a quiz round where you ask: 'Which of the following clinical features would make a diagnosis of serotonin syndrome more likely compared to neuroleptic malignant syndrome?'
Answer:
Neuroleptic malignant syndrome vs serotonin syndrome identical features:- Hypertension
- Tachycardia
- Tachypnoea
- Hyperthermia (> 40°C)
- Hypersalivation
- Diaphoresis
- Altered mental state
- Hyporeflexia vs hyperreflexia
- 'Lead-pipe-' rigidity vs rigidity with clonus
- Normal pupils vs dilated pupils
- Reduced sluggish bowel sounds vs hyperactive bowel sounds
Drug-Related Hyperthermia
Environmental Emergencies / Pharmacology & Poisoning
Last Updated: 21st April 2023
Malignant hyperthermia
- Malignant hyperthermia (MH) is a life-threatening disorder of skeletal muscle homeostasis. Its inheritance is autosomal dominant with an incidence of around 1 in 30,000.
- The most common triggers are suxamethonium and volatile anaesthetics (e.g. halothane, isoflurane, desflurane, and sevoflurane).
- Diagnosis can be difficult and it may present insidiously over hours, or as an acute life-threatening event at induction.
Recognition:
Hyperthermia itself may be a late feature, as are the effects of rhabdomyolysis. Signs can be considered in two groups: direct muscle effects and the effects of increased metabolism.
- Direct muscle effects
- Masseter muscle spasm (MMS):
- May indicate MH but is not pathognomonic since it also occurs in a few normal patients, especially children, after suxamethonium administration
- After injection of suxamethonium, MMS will cause trismus at a time when relaxation would normally have been expected, but it does not usually persist long enough to hinder attempts at intubation
- Treat prolonged MMS as a potential case of MH
- Masseter muscle spasm (MMS):
- Effects of increased metabolism:
- Unexplained increase in ETCO2
- Unexplained tachycardia
- Unexplained tachypnoea
- Unexplained increase in oxygen requirement
- Temperature changes (late sign)
Management:
- Immediate management
- Stop all trigger agents
- Call for help and allocate specific tasks
- Install clean breathing system and hyperventilate with 100% O2 high flow
- Maintain anaesthesia with intravenous agent
- Abandon/finish surgery as soon as possible
- Muscle relaxation with non-depolarising neuromuscular blocking drug
- Monitoring and treatment
- Give dantrolene sodium as soon as the diagnosis is considered:
- 2.5mg/kg immediate iv bolus
- Repeat 1mg/kg boluses as required to max 10mg/kg
- Initiate active cooling avoiding vasoconstriction
- Check plasma creatine kinase (CK) as soon as possible
- Further treatment:
- Hyperkalaemia: calcium chloride, glucose/insulin, sodium bicarbonate
- Arrhythmias: magnesium/amiodarone/metoprolol (avoid calcium channel blockers)
- Metabolic acidosis: hyperventilate, sodium bicarbonate
- Myoglobinaemia: forced alkaline diuresis (mannitol/furosemide/sodium bicarbonate), renal replacement therapy
- Disseminated intravascular coagulation (DIC): FFP, cryoprecipitate, platelets
- Continuous monitoring:
- Core and peripheral temperature
- ETCO2
- SpO2
- ECG
- Invasive blood pressure
- CVP
- Repeated bloods:
- ABG
- U&Es (potassium)
- FBC (haematocrit/platelets)
- Coagulation
- Give dantrolene sodium as soon as the diagnosis is considered:
- Follow-up
- Continue monitoring in ICU, repeat dantrolene as necessary
- Monitor for acute kidney injury and compartment syndrome
- Repeat CK
- Consider alternative diagnoses (e.g. sepsis, pheochromocytoma, thyroid storm, myopathy)
- Counsel patient and family members
- Refer to MH unit
Neuroleptic malignant syndrome (NMS)
- A potentially life-threatening complication of treatment with antipsychotic drugs, or abrupt withdrawal of dopamine agonists.
- Characterised by a tetrad of altered mental status, muscle rigidity, autonomic instability, and hyperthermia.
- A diagnosis of exclusion. A careful assessment, including physical examination and comprehensive tests, is required to exclude other potential causes.
- NMS is a medical emergency. Treatment consists of immediate cessation of the offending medication and provision of supportive measures (hydration and cooling). Additional treatment may be considered if supportive interventions fail, such as benzodiazepines, dantrolene and dopaminergic agents such as bromocriptine and amantadine.
- A delay of at least 2 weeks in restarting antipsychotic treatment is advised following full resolution of an NMS episode.
Serotonin syndrome (SS)
- Clinical manifestation of excess serotonin in the central nervous system, resulting from the therapeutic use or overdose of serotonergic drugs.
- Characterised by a triad of clinical features: neuromuscular excitation, autonomic effects, and altered mental status.
- Diagnosis is clinical and should be based on the Hunter Serotonin Toxicity Criteria (HSTC), of which clonus is a key diagnostic feature. Severe serotonin toxicity is a medical emergency that often requires emergency treatment.
- Treatment is guided by the severity of toxicity and involves cessation of the drug(s), supportive care, and the use of specific anti-serotonergic drugs in select patients (e.g. chlorpromazine).
Neuroleptic malignant syndrome vs serotonin syndrome
| Neuroleptic Malignant Syndrome | Serotonin Syndrome | |
|---|---|---|
| Causative agents | Dopamine antagonists | Serotonergic agents |
| Onset | Gradual (days) | Rapid (hours) |
| Similar features |
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| Distinct features |
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| Lab findings |
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| Management |
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
