What is the earliest and most specific sign of malignant hyperthermia?

The Earliest and Most Specific Sign of Malignant Hyperthermia

The earliest and most specific sign of malignant hyperthermia is an increase in end-tidal CO2 (ETCO2) despite attempts to control it by increasing minute ventilation. 1

Pathophysiology and Clinical Manifestations

Malignant hyperthermia (MH) is a potentially fatal hypermetabolic disorder triggered by certain anesthetic agents. The pathophysiological sequence that leads to the clinical manifestations follows a specific pattern:

• Initial clinical features result from homeostatic mechanisms within skeletal muscle cells that compensate for increased cytoplasmic calcium released by triggering drugs 1
• These mechanisms drive increased intermediary metabolism, leading to increased oxygen consumption and carbon dioxide production 1
• The excessive carbon dioxide production manifests as increased ETCO2 in mechanically ventilated patients or increased respiratory rate in spontaneously breathing patients 1
• This increased metabolic activity is resistant to control - it is not possible to easily normalize ETCO2 by increasing minute ventilation during an MH reaction 1

Early Signs in Order of Appearance

1. Increased ETCO2 - The cardinal clinical feature resulting from excessive carbon dioxide production 1

   • This is the earliest and most specific sign that should alert the anesthetist to the possibility of MH 1, 2
   • It appears before temperature elevation in the typical progression of MH 1, 3

2. Tachycardia - Accompanies increased carbon dioxide production due to sympathetic nervous system activation 1

   • The upward trend in heart rate is more useful diagnostically than attainment of a specific value 1
   • May be absent if sympathetic response is obtunded (e.g., by beta-blockers or remifentanil) 1

3. Hyperthermia - Usually starts to increase by the time diagnosis is made 1

   • Often has not reached beyond upper limit of normal by the time treatment is instituted 1
   • Temperature increase that begins before any evidence of increased carbon dioxide production is not caused by MH 1

4. Muscle rigidity - Generalized rigidity during the course of an MH reaction is a worrying development 1

   • May occur even in the presence of non-depolarizing neuromuscular block 1
   • Heralds the stage of an MH reaction that may be irreversible 1

5. Hypotension - Blood pressure response is more variable than other signs 1

   • Balances sympathetic stimulation with peripheral vasodilatory effects of metabolic by-products 1

Diagnostic Approach

The presence of increasing carbon dioxide production and heart rate, with exclusion of alternative causes, should be sufficient to diagnose suspected MH and initiate treatment 1. The timing of MH reactions is highly variable:

• May become apparent within 10 minutes of exposure to triggering agents 1
• Onset may be delayed for several hours, especially with desflurane 1
• More rapid progression tends to occur when both suxamethonium and a potent inhalational anesthetic have been administered 1

Clinical Importance

Early recognition and intervention are critical for patient survival 4. Delay in commencing treatment is associated with increased mortality and complications 1:

• Mortality from MH has decreased from 80% thirty years ago to <5% with prompt recognition and treatment 5
• An unexplained, unexpected progressive increase in carbon dioxide production should lead to a high index of suspicion 1
• End-tidal CO2 monitoring has proven efficacy in early detection of MH in at-risk patients 2

Management Priorities

When MH is suspected based on rising ETCO2, immediate actions should include:

• Eliminate the triggering agent (turn off and remove vaporizer, give 100% oxygen) 1
• Administer dantrolene sodium as a specific antidote 1
• Commence active body cooling 1
• Increase minute ventilation 2-3 times normal 1
• Insert activated charcoal filters on inspiratory and expiratory limbs of circuit if available 1