An in-vivo metabolic test for detecting malignant hyperthermia susceptibility in humans: a pilot study.
BACKGROUND
In vitro contracture testing to diagnose malignant hyperthermia (MH) susceptibility requires a muscle biopsy, which may be associated with severe side effects for the patient. After investigation of several different protocols, we present a less invasive metabolic test that involves IM injection of caffeine and halothane, and subsequent measurement of interstitial lactate to differentiate between MH susceptible (MHS) and MH non-susceptible (MHN) individuals.


METHODS
Two microdialysis probes with attached microtubing for trigger injection were inserted into the lateral vastus muscle of eight previously diagnosed MHS patients (representing three genetic variants Gly2434Arg, Thr2206Met, and Arg614Cys), seven MHN patients, and seven control individuals. After equilibration and lactate baseline recording, a single bolus of 200 muL caffeine 80 mM and a suspension of 200 muL halothane 4%V/V in soy bean oil (triggers) were injected locally. Lactate was measured spectrophotometrically. Data are presented as medians and interquartile ranges.


RESULTS
Although baseline lactate values were similar in the investigated groups before trigger injection, caffeine increased local lactate in MHS patients significantly more (2.0 [1.8-2.6] mM) than in MHN (0.8 [0.6-1.1] mM) or in control individuals (0.8 [0.6-0.8 mM]). Similarly, halothane lead to a significant lactate increase in MHS compared to MHN and control individuals (8.6 [3.7-8.9] mM vs 0.9 [0.5-1.1] mM and 1.7 [0.9-2.3] mM, respectively). However, a relevant increase of lactate was observed in one MHN and in two control individuals. Systemic hemodynamic and metabolic variables did not differ between the investigated groups.


CONCLUSIONS
Metabolic monitoring of IM lactate after local caffeine and halothane injection may allow less invasive testing to detect MH susceptibility, without systemic side effects.
Schuster
Frank
F
Department of Anesthesiology, University of Würzburg, Würzburg, Germany. Schuster_F@klinik.uni-wuerzburg.de
Metterlein
Thomas
T
Negele
Sabrina
S
Kranke
Peter
P
Muellenbach
Ralf M
RM
Schwemmer
Ulrich
U
Roewer
Norbert
N
Anetseder
Martin
M
D000328:Adult; D001706:Biopsy; D002110:Caffeine / Q000494:pharmacology; D016022:Case-Control Studies; D004198:Disease Susceptibility; D005260:Female; D006221:Halothane / Q000494:pharmacology; D006801:Humans; D007773:Lactates / Q000378:metabolism; D008297:Male; D008305:Malignant Hyperthermia / Q000175:diagnosis* / Q000209:etiology; D008875:Middle Aged; D009132:Muscles / Q000473:pathology; D010865:Pilot Projects; D052097:Quadriceps Muscle / Q000473:pathology
D007773:Lactates; D002110:Caffeine; D006221:Halothane