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Anaesthetics > Inherited diseases relevant to anaesthesia > Flashcards

Inherited diseases relevant to anaesthesia Flashcards

1
Q

What are the 2 key inherited diseases relevant to anaesthesia?

A
  1. Malignant hyperpyrexia (/hyperthermia)
  2. Pseudocholinesterase deficiency
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2
Q

What is malignant hyperpyrexia/ hyperthermia?

A
  • Life-threatening condition resulting from a genetic sensitivity of skeletal muscles to volatile anaesthetics and depolarising neuromuscular blocking drugs
  • Often seen following administration of anaesthetic agents, during or after
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3
Q

What is the physiological/genetic cause of malignant hyperpyrexia?

A
  • Excessive release of Ca2+ from the sarcoplasmic reticulum of skeletal muscle
  • This is associated with defects in a gene on q (long) arm of chromosome 19, encoding the ryanodine receptor, which controls Ca2+ release from the sarcoplasmic reticulum
  • In malignant hyperpyrexia, the ryanodine receptor doesn’t close properly following a stimulus, which leads to excessive calcium release, reabsorbed in the SR in a futile cycle
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4
Q

What type of inheritance pattern does malignant hyperpyrexia follow?

A
  • Autosomal dominant with variable penetrance
  • shows vertical transmission
  • (50% chance child will have it if you have it if you’re heterozygous, 100% if you’re homozygous)
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5
Q

What type of condition may have a similar aetiology/ be related to malignant hyperpyrexia?

A

Neuroleptic malignant syndrome

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6
Q

How common is malignant hyperpyrexia and who is affected?

A
  • Occurs in 1 in 4500 to 1 in 60 000 patients, depending on how close to affected group you are geographically
  • Can affect all races and occurs worldwide
  • Children and younger patients more commonly affected (perhaps because know it exists in affected older adults already?)
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7
Q

Why might it appear that a generation has been skipped rather than the usual vertical transmission for malignant hyperpyrexia?

A

If penetrance is low and parents have only 1 or 2 children, this can happen

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8
Q

What are 6 features of the presentation of malignant hyperpyrexia?

A
  1. Muscular rigidity
  2. Hyperthermia
  3. Rhabdomyolisis
  4. Hypermetabolic state
  5. Increased oxygen consumption
  6. Increased carbon dioxide production
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9
Q

What are the 4 substances produced due to rhabdomyolysis, and which is the most lethal?

A
  1. Myoglobin
  2. Creatine kinase
  3. Creatine phosphate
  4. Potassium - this is the most lethal
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10
Q

What are the 2 key causative agents for malignant hyperpyrexia?

A
  1. Halothane
  2. Suxamethonium
  3. (antipsychotics can also cause ⇒ neuroleptic malignant sydrome)
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11
Q

Does the causative agents of malignant hyperpyrexia lead to a reaction every time?

A

No

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12
Q

Why do hyperpyrexia and muscle damage result from lack of closure of the ryanodine receptor and release of calcium, in malignant hyperpyrexia?

A
  • The process consumes large amounts of ATP and generates excessive heat
  • Muscle cell damaged by depletion of ATP and possibly also the high temperature, and cellular constituents leak into circulation (potassium, creatine, creatine kinase, myoglobin)
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13
Q

What are the first 6 steps to take when someone is suffering from malignant hyperpyrexia?

A
  1. Call for help - too difficult for one person
  2. Stop triggering agents
  3. Hyperventilate with 100% oxygen
  4. Finish or abort procedure
  5. Treat with dantrolene
  6. Cool patient
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14
Q

What is the drug used to treat malignant hyperpyrexia and what is the dose?

A
  • Dantrolene
  • 2mg/kg bolus; may repeat 2mg/kg every 5 minutes, then 1-2mg/kg each hour
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15
Q

How does dantrolene work to treat malignant hyperpyrexia?

A

Prevents Ca2+ release from the sarcoplasmic reticulum

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16
Q
  1. Cold IV normal saline
  2. Cold body cavity lavage
  3. Ice bags to body
  4. Cold nasogastric lavage
  5. Cooling blanket
A

What are 5 ways to cool a patient down who is suffering from malignant hyperpyrexia?

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17
Q

What are 6 further things to treat or monitor when a patient is suffering from malignant hyperpyrexia?

A
  1. Change to clean breathing system not exposed to volatile agents
  2. Monitor and treat acidosis
  3. Promote urine output
  4. Treat hyperkalaemia urgently and effectively
  5. Treat dysrythmias
  6. Monitor creatine kinase, urine myoglobin, and coagulation for 12-24 hours
18
Q

How should acidosis during malignant hyperpyrexia be monitored and managed?

A

Monitor with serial ABGs, give sodium bicarbonate

19
Q

What urine output should be aimed for following malignant hyperpyrexia, and what are 2 drugs that can be given to achieve this?

A
  • maintain >2ml/kg/hour with conscientious fluid management
  • Furosemide and mannitol as appropriate
20
Q

What are 2 drugs that can be used to treat dysrhythmias during malignant hyperpyrexia?

A

Procainamide, calcium chloride

21
Q

What is another drug currently under investigation to treat malignant hyperpyrexia?

A

Azumolene

22
Q

What is the test for malignant hyperpyrexia and what does it involve?

A
  • Caffeine-halothane contracture test (CHCT)
  • Muscle biopsy taken from front of thigh at an approved centre (only a few in UK)
  • fresh biopsy bathed in solution containing caffeine and halothane, observed for contraction
23
Q

What are the sensitivity and specificity of the caffeine-halothane contracture test for malignant hyperpyrexia?

A

97% sensitivity, 78% specificity

24
Q

What are 8 things that should be done for a patient undergoing surgery who is known to be susceptible to malignant hyperpyrexia?

A
  1. Clean machine: remove vaporisers, replace CO2 cannisters, bellows and gas hose
  2. Flush machine for 20 minutes with oxygen, 10L/min
  3. Make sure the MH ‘pack’ is available: drugs and sheet for management, enough in-date dantrolene
  4. Schedule patient as first case of day, arrange ICU/HDU post-op
  5. Consider dantrolene and sedation as pre-medication
  6. Check creatine kinase, FBC, U&E pre-operatively - baseline values to compare
  7. Considered anaesthetic alternatives: monitored anaesthetic care with sedation and local anaesthesia, or GA using non-triggering agents. TIVA can be given
  8. After surgery, check lab values for CK and ABG, monitor patient in an appropriate setting
25
Q

What is pseudocholinesterase deficiency?

A
  • Inherited enzyme abnormality (pseudocholinesterase), in which there is abnormally slow degradation of exogenous choline ester drugs, such as succinylcholine
  • other pathological conditions, physiological alternations, and medications can also lower plasma pseudocholinesterase activity
26
Q

What is the presentations of pseudocholinesterase deficiency and what are 3 examples of drugs that can cause it?

A
  • Prolonged duration of action with:
    • suxamethonium
    • mivacurium
    • ester local anaesthetics: procaine, cocaine
27
Q

What is the normal action of pseudocholinesterase enzyme on suxamethonium?

A
  • hydrolysis and inactivation of approximately 90-95% of an intravenous dose of succinylcholine occurs before it reaches the NMJ.
  • Remaining 5-10% of succinylcholine acts as a receptor agonist at the NMJ
28
Q

How does suxamethonium’s effects on the NMJ usually wear off?

A

By diffusion

29
Q

By how long can the effects of suxamethonium be prolonged in a patient with pseudocholinesterase deficiency?

A

up to 8 hours (vs normal effect of about 2 minutes)

30
Q

In which ethnic groups is inherited suxamethonium deficiency more common?

A

People of European descent (rare in Asians)

31
Q

What genetic mutation can cause pseudocholinesterase deficiency?

A

Gene at E1 locus on the long arm of chromosome 3

32
Q

What proportion of the population is homozygous for the normal pseudocholinesterase genotype, and how is this designated?

A

96%, EuEu

33
Q

What are the 3 types of atypical alleles that 4% of the population carry one or more of?

A
  1. Ea: atypical dibucaine-resistant variant point mutation
  2. Ef: fluoride resistant variant point mutation
  3. Es: silent variant frameshift mutation
34
Q

What will be the phenotype of a single atypical allele involved in pseudocholinesterase deficiency (E1 locus on chromosome 3)?

A

partial deficiency in enzyme activity - slightly prolonged duration of paralysis, longer than 5 minutes but shorter than 1 hour

35
Q

What proportion of the population carry 2 pseudocholinesterase gene allele mutations, and what is the effect of this?

A

Less than 0.1%; will produce clinically significant effects from succinylcholine lasting longer than 1 hour

36
Q

What are 7 causes of apparent pseudocholinesterase deficiency?

A
  1. chronic infections (e.g. tuberculosis)
  2. extensive burn injuries
  3. liver disease
  4. malignancy
  5. severe malnutrition
  6. severe uraemia
  7. some drugs e.g. chlorpromazine, bambuterol, cyclophosphamide, glucocorticoids (high ose)
37
Q

How is pseudocholinesterase deficiency diagnosed?

A
  • Plasma assays of pseudocholinesterase enzyme activity
  • Sample of patient’s plasma incubated with substrate butyrulthiocholine along with indicator chemical 5,5’-dithiobis-(2-nitrobenzoic acid). Assayed using spectrophotometry
38
Q

What are the 3 key aspects of treatment of a patient with pseudocholinesterase deficiency, who has been given suxamethonium?

A
  1. Sedation and ventilation: make sure suxamethonium worn off before giving non-depolarising muscle relaxant. Keep anaesthetised, sedated to point of unconsciousness
  2. FFP
  3. Blood transfusion
39
Q

Should you try to wake up a patient while paralysed who is experiencing prolonged suxamethonium action?

A

no

40
Q

How can you check if a patient with pseudocholinesterase deficiency is still paralused?

A

use nerve stimulator

41
Q

Why are FFP and blood transfusions given in pseudocholinesterase deficiency reactions?

A

FFP contains some pseudocholinesterase, which can help reverse these patients

42
Q

When should FFP be used to treat pseudocholinesterase deficiency?

A

in serious conditions in which there is no pseudocholinesterase at all

Anaesthetics (11 decks)

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