BACKGROUND: In malignant hyperthermia (MH), volatile anesthetics induce hypermetabolism, lactic acidosis and rhabdomyolysis in predisposed patients. The authors hypothesized that intramuscular caffeine and halothane application would increase local lactate concentration in MH susceptible (MHS) individuals more than in non-susceptible (MHN) subjects without initiating the full MH syndrome. METHODS: In 14 MHS, 12 MHN and 7 control individuals, microdialysis probes were placed in the rectus femoris muscle and perfused with Ringer's solution at 1 microl/min. After equilibration, 250 microl caffeine (80 mM) was injected through the first microdialysis probe, halothane 10 vol% dissolved in soybean oil was perfused through a second microdialysis probe and a third probe was used for control measurements. Dialysate samples were analyzed for lactate spectrophotometrically. Systemic hemodynamic and metabolic parameters were measured. Data are presented as median and quartiles. RESULTS: Intramuscular caffeine and halothane significantly increased local peak concentrations of lactate in MHS probands [5.0 mM (3.4-8.1 mM) and 3.7 mM (2.6-5.0 mM), respectively] compared to MHN [1.6 mM (1.3-2.0 mM) and 1.9 mM (1.6-2.0 mM)] or control individuals [2.1 mM (1.9-2.3 mM) and 2.0 mM (1.6-2.1 mM)]. This was accompanied by a higher serum creatine kinase level in the MHS group. Hemodynamic and metabolic parameters were normal in the investigated groups. CONCLUSION: Intramuscular caffeine and halothane application induces a temporary and abnormal increase of local lactate in MHS individuals. No serious systemic side effects occurred. This study presents evidence that metabolic monitoring with local stimulation by caffeine and halothane may allow a minimally invasive diagnosis of MH susceptibility.
BACKGROUND: In malignant hyperthermia (MH), volatile anesthetics induce hypermetabolism, lactic acidosis and rhabdomyolysis in predisposed patients. The authors hypothesized that intramuscular caffeine and halothane application would increase local lactate concentration in MH susceptible (MHS) individuals more than in non-susceptible (MHN) subjects without initiating the full MH syndrome. METHODS: In 14 MHS, 12 MHN and 7 control individuals, microdialysis probes were placed in the rectus femoris muscle and perfused with Ringer's solution at 1 microl/min. After equilibration, 250 microl caffeine (80 mM) was injected through the first microdialysis probe, halothane 10 vol% dissolved in soybean oil was perfused through a second microdialysis probe and a third probe was used for control measurements. Dialysate samples were analyzed for lactate spectrophotometrically. Systemic hemodynamic and metabolic parameters were measured. Data are presented as median and quartiles. RESULTS: Intramuscular caffeine and halothane significantly increased local peak concentrations of lactate in MHS probands [5.0 mM (3.4-8.1 mM) and 3.7 mM (2.6-5.0 mM), respectively] compared to MHN [1.6 mM (1.3-2.0 mM) and 1.9 mM (1.6-2.0 mM)] or control individuals [2.1 mM (1.9-2.3 mM) and 2.0 mM (1.6-2.1 mM)]. This was accompanied by a higher serum creatine kinase level in the MHS group. Hemodynamic and metabolic parameters were normal in the investigated groups. CONCLUSION: Intramuscular caffeine and halothane application induces a temporary and abnormal increase of local lactate in MHS individuals. No serious systemic side effects occurred. This study presents evidence that metabolic monitoring with local stimulation by caffeine and halothane may allow a minimally invasive diagnosis of MH susceptibility.
Authors: Thomas Metterlein; Frank Schuster; Martin Hager; Norbert Roewer; Martin Anetseder Journal: Indian J Pharmacol Date: 2015 Nov-Dec Impact factor: 1.200