Lidocaine attenuates sepsis-induced diaphragmatic dysfunction in hamsters.

OBJECTIVE

Sepsis or endotoxemia causes diaphragmatic dysfunction, which may contribute to respiratory distress. Toxic free radicals are partly responsible for the pathogenesis. Lidocaine scavenges the reactive molecules. The purpose of the current study was to examine whether lidocaine prevents the diaphragmatic dysfunction of sepsis.

METHODS

Prospective, randomized animal study.

METHODS

University research laboratory.

METHODS

A total of 40 male Golden-Syrian hamsters.

METHODS

The animals were randomly allocated to one of five groups (n = 8 each): hamsters undergoing sham laparotomy alone and receiving saline infusion (Sham group), those undergoing cecal ligation with puncture (CLP) and receiving an infusion of saline (Sepsis group), those undergoing sham laparotomy and receiving infusion of lidocaine, 2 mg/kg/hr (Sham-LID group), those undergoing CLP and receiving infusion of lidocaine, 1 mg/kg/hr (Sepsis-LID 1 group), and those undergoing CLP and receiving infusion of lidocaine, 2 mg/kg/hr (Sepsis-LID 2 group). Subcutaneous infusion of saline or lidocaine was started 6 hrs before surgery and continued until 24 hrs after the operation when all hamsters were killed.

RESULTS

Diaphragmatic contractility and fatigability were assessed in vitro by using muscle strips excised from the costal diaphragms. Diaphragmatic levels of malondialdehyde (MDA), an index of free radicals-mediated lipid peroxidation, were also measured. Twitch and tetanic tensions in the Sepsis group were reduced compared with the Sham group. Tensions generated during fatigue trials were decreased, and MDA levels were elevated in diaphragms from the Sepsis group. An infusion of 2 mg/kg/hr lidocaine attenuated contractile dysfunction, aggravation of fatigability, and the increase in MDA formation. In contrast, 1 mg/kg/hr lidocaine failed to do so. Electrophysiologic diaphragmatic characteristics in the Sham-LID group were similar to those in the Sham group.

CONCLUSIONS

Pretreatment with 2 mg/kg/hr but not 1 mg/kg/hr lidocaine attenuated sepsis-induced diaphragmatic dysfunction in hamsters assessed by contractile profiles and endurance capacity. This beneficial effect of lidocaine may be attributable, in part, to inhibition of lipid peroxidation in the diaphragm.