Tox - Hyperthermia Flashcards
CVS effects of hyperthermia
Tachycardia, raised cardiac outpuot
Low SVR –> hypotension
Failure to resuscitate –> cold and clammy
Metabolic effects of hyperthermia
Tissue oxygen demand +++
Rise in BMR
Right shift of curve to offset –> increased O2 availability
Immune effects of hyperthermia
Temperature sensitive pathogens are compromised
Leucocyte activity increased –> increased response to infection
How does pyrexial affect critical illness
Usually sepsis.
Temp regulated by hypothalamus
Cytokines from sepsis –> arachidoic acid pathway –> heat produces by PGE2
Managment of pyrexia
1) Minimise heat gain –> environmental factors – bed clothes, heaters, etc,limit shivering –> clonidine/dexmed
2) treat the cause –> drain collections, Abx etc
3) drugs –> paracetamol resets set point –> no mort benefit, Dantrolene when indicated
4) physical methods
Physical methods
Cooling rather than enhancing heat loss
Fan/cool air
Cold packs
Cold blankets
Bladder and abodminal irrigation
Extracorporeal methods
Purpose built methods - artic sun, cool guard
What is the difference between fever, hyperpyrexia and hyperthermia?
- Fever is an upward resetting of the hypothalamus that is brought about by PGE2
in response to infectious or non-infectious causes. It may respond to antipyretic
agents, e.g. paracetamol, NSAIDs. - Hyperpyrexia describes a situation in which body temperature is extremely high
(>41°C), and is associated with severe infections or following head injury.
-Hyperthermia is a core body temperature >37.5°C with a normal hypothalamic
set point, and indicates an imbalance between heat production and loss. There is
no response to antipyretic therapy
What are some of the causes of hyperthermia?
Increased Heat Production
- Drugs (reaction or OD) amphetamine, MDMA, Cocaine, MAOIs, TCAs
- Malignant hyperthermia - Suxamethonium, volatile anaesthetic agents
-Serotonin syndrome
- Neuroleptic malignant syndrome
- Endocrinological disease - Phaemochromocytoma, hyperthyroidism
Reduced Heat Loss
- Increased heat conservation - Neonates, infants
- Non-exertional (environmental) heat stroke
- Exertional heat stroke
- Drugs - Anticholinergic agents
What is malignant hyperthermia?
Malignant hyperthermia (MH) is a rare inherited syndrome with an incidence of 1:10 000 to 1:200 000. It exhibits autosomal dominant inheritance with variable penetrance. The primary defect is in the ryanodine receptor on the sarcoplasmic reticulum, the gene for which is on the long arm of chromosome 19. The RYR1 channel in skeletal muscle allows calcium stored in the sarcoplasm to pass into the cytoplasm.
In MH, an abnormal RYR1 allows excessive calcium release following exposure to trigger agents (halogenated volatile anaesthetics and suxamethonium). This causes sustained skeletal muscle contraction resulting from ATP depletion (ATP is needed for muscle relaxation) leading to muscle rigidity, a combined metabolic and respiratory acidosis and ultimately hyperthermia. There is increased metabolic rate, with increased oxygen consumption, and CO2 and heat production
How is MH managed?
Malignant hyperthermia usually presents soon after induction of anaesthesia. The patient with suspected MH should be managed with an ABCDE approach, and abnormalities treated as they are found. Specific management involves:
1 Stop all potential trigger agents
– Maintain anaesthesia with an intravenous infusion such as propofol
– Maintain oxygenation using a Water’s circuit or bag-valve-mask connected to wall oxygen whilst sourcing a gas-free anaesthetic machine
2 Finish or abandon surgery as soon as possible
3 Start preparing dantrolene immediately (this will usually need at least one extra member of staff as it is laborious and takes time to dissolve)
– Dantrolene uncouples excitation and contraction
– Give dantrolene in boluses of 1 mg/kg, repeated every 10 minutes, to a maximum of 10 mg/kg
4 Hyperventilate with 100% oxygen
5 Instigate cooling
– Cold IV fluids, external and intravascular cooling devices
– Ask the surgeons to pour cool fluid into the abdominal cavity if it is open
– Extracorporeal cooling may be required, e.g. with CVVHF
6 Monitor electrolytes and treat hyperkalaemia aggressively
7 Monitor serum creatine kinase (CK), urine output and myoglobin levels
– Have a low threshold to start high volume fluid therapy for rhabdomyolysis
8 Transfer to ICU and explain events to next of kin
9 Following recovery, refer the patient and their relatives for genetic testing
What is neuroleptic malignant syndrome?
Neuroleptic malignant syndrome (NMS) is a potentially fatal idiosyncratic reaction to antipsychotic agents such as butyrophenones (e.g. haloperidol) and
phenothiazines (e.g. chlorpromazine, prochlorperazine). It results from dopamine antagonism in the striatum and the hypothalamus.
The patient typically presents within the first week of instigation of antipsychotic therapy with altered mental status, features of autonomic disturbance
(including hyperthermia) and extrapyramidal signs (profound bradykinesia
and muscular rigidity, which may be so severe as to cause rhabdomyolysis).
In addition to supportive therapy and cooling, the offending agent should
be withdrawn. Bromocriptine (a dopamine agonist) and dantrolene can be
used as treatment. A period of two weeks should be allowed before restarting any antipsychotic medications. The likelihood of recurrence is approximately 30%.
What is serotonin syndrome?
Serotonin syndrome can result from the interaction of two serotonin-enhancing medications. It may also occur following overdose of a serotonergic drug, or in patients taking MAOIs who eat tyramine-containing foods. Serotonergic drugs fall into five classes:
1 Serotonin precursors, e.g. tryptophan, L-3,4-dihydroxyphenylalanine
(L-DOPA)
2 Serotonin agonists, e.g. LSD, norpethidine (breakdown product of pethidine)
3 Enhance serotonin activity, e.g. MDMA
4 Prevent serotonin reuptake, e.g. SSRIs, tramadol
5 Prevent serotonin breakdown, e.g. MAOIs
The syndrome is classically of rapid onset and presents as a triad of altered mental status, autonomic disturbance (including hyperthermia) and neuromuscular excitability (e.g. tremor, myoclonus, hyperreflexia). Management is both supportive and specific, involving withdrawal of the offending agents, cooling, symptomatic treatment with benzodiazepines and propranolol, and consideration of dantrolene and serotonin antagonists such as cyproheptadine.
