Anetseder et al developed a method for detecting persons susceptible to malignant hyperthermia based on production of carbon dioxide after an intramuscular injection of a caffeine solution. This is a minimally invasive procedure that does not necessitate an open muscle biopsy. The authors are from the University of Wurzburg in Germany.


Basis of test: A person susceptible to malignant hyperthermia will respond to caffeine by increasing sarcoplasmic calcium release, which causes contracture of skeletal muscle bundles. This causes an increase in the local partial pressure of carbon dioxide (pCO2). This increase in pCO2 is not seen in non-susceptible persons.



(1) The skin over the selected area of the rectus femoris muscle is cleaned and prepared.

(2) The area is injected with a local anesthetic.

(3) A sterile fiberoptic pCO2 probe (diameter 0.5 mm) with attached microtubing is inserted into the muscle to a depth of 8 cm using an introducer cannula.

(4) A sham test with injection of 500 µL of Ringer's solution through the microtubing is then conducted to demonstrate that the probe is properly functioning.

(5) 500 µL of solution of caffeine 80 mmol/L is then injected through the microtubing.


Measurements of pCO2:

(1) baseline, prior to injections

(2) at 1 minute intervals for an hour after the injection


NOTE: The basal levels of pCO2 is about 42 mm Hg.


Time course of normal or negative patient after injection of saline or caffeine:

(1) pCO2 level drops about 20 mm Hg after injection, with minimum 6-8 minutes after injection

(2) pCO2 gradually increases to baseline at 20 minutes after injection


Time course of positive patient:

(1) pCO2 level drops about 20 mm Hg after caffeine injection, with minimum 6-8 minutes after injection

(2) pCO2 quickly rises to maximum at 15 minutes

(3) pCO2 slowly returns to baseline level at 50-60 minutes after the injection


rate of pCO2 increase in mm Hg per hour =

= ((peak pCO2 level) – (baseline pCO2 level)) / ((minutes to peak pCO2) / 60)




peak pCO2 in mm Hg

61 – 69 mm Hg

<= 47 mm Hg (at or slightly above baseline)

rate of pCO2 increase

50 – 102 mm Hg per hour

<= 5 mm Hg per hour

serum CK 24 hours after the injection

139 – 210 U/L

<= 62 U/L (at or slightly above baseline)


Some possible rules for a positive result:

(1) peak pCO2 is > 10 mm Hg above baseline

(2) rate of pCO2 increase is > 30 mm Hg per hour

(3) serum CK afterwards is > 1.75 times baseline



• The method needs to be validated at other centers.


To read more or access our algorithms and calculators, please log in or register.