Salbutamol Improves Diaphragm Force Generation in Experimental Sepsis

Píriz, Héctor; Nin, Nicolás; Boggia, José; Angulo, Martín; Hurtado, Francisco Javier

doi:10.1016/S1579-2129(08)60027-0

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Objective

In a high percentage of cases, severe sepsis is accompanied by acute respiratory failure, in which weakness of the respiratory muscles plays an important role. Weakened respiratory muscles that are subjected to an increased mechanical load may develop muscle fatigue, with exacerbation of the respiratory failure. Because β2-adrenergic drugs increase muscle contraction force, they may play a role in preventing and managing respiratory failure in septic patients. Our aim was to study the effects of salbutamol on diaphragm function in an animal model of peritoneal sepsis.

Material and Methods

The study included 3 groups of animals: a) a control group (n=7), in which the animals underwent a median laparotomy without visceral manipulation; b) a septic group (n=10), in which peritoneal sepsis was induced by cecal ligation and puncture (CLP); and c) a salbutamol group (n=7), in which peritoneal sepsis (CLP) was treated with salbutamol. Hemodynamic parameters and blood gases were measured in vivo. Diaphragm function was evaluated in vitro.

Results

Salbutamol increased aortic blood flow and heart rate while it reduced mean arterial pressure in the animals with peritoneal sepsis (P<.05). Sepsis produced a significant drop in diaphragmatic force both before and after the application of a muscle-fatigue protocol. Treatment with salbutamol improved muscle contraction force before and after application of the protocol (P<.05).

Conclusions

The use of β2-adrenergic drugs such as salbutamol improves diaphragm function in experimental sepsis. The mechanisms that produce this improvement require further study.

Key words:

Respiratory muscles

Sepsis

Diaphragmatic dysfunction

β2-adrenergic drugs

Objetivo

La sepsis grave se acompaña en un alto porcentaje de casos de insuficiencia respiratoria aguda, donde la debilidad de los músculos respiratorios desempeña un papel importante. Los músculos respiratorios debilitados y sometidos a una carga mecánica aumentada pueden evolucionar a fatiga muscular con agravamiento de la insuficiencia respiratoria. Los fármacos adrenérgicos β2, al mejorar la fuerza de contracción muscular, podrían ser de utilidad en la prevención y el manejo de la insuficiencia respiratoria de pacientes con sepsis. El objetivo de este trabajo ha sido estudiar los efectos del salbutamol en la función diafragmática en un modelo animal de sepsis peritoneal.

Material y Métodos

Se estudiaron 3 grupos de animales: a) grupo control (n = 7), al que se realizó laparotomía mediana sin abordaje visceral;b) grupo sepsis (n = 10), al que se indujo sepsis peritoneal por ligadura y punción cecal (LPC), y c) grupo salbutamol (n = 7), en el que la sepsis peritoneal se trató con salbutamol (LPC + salbutamol). Los parámetros hemodinámicos y los gases sanguíneos se midieron in vivo. La función diafragmática se evaluó in vitro.

Resultados

El salbutamol aumentó el flujo aórtico y la frecuencia cardíaca a la vez que disminuyó la presión arterial media en la sepsis peritoneal (p < 0,05). La sepsis determinó una caída significativa de la fuerza diafragmática tanto antes como después de un protocolo de fatiga muscular. El tratamiento con salbutamol mejoró la fuerza de contracción muscular en ambos casos (p < 0,05).

Conclusiones

El uso de agentes adrenérgicos β2 como el salbutamol mejora la función diafragmática durante la sepsis experimental. Los mecanismos de esta mejoría deben estudiarse en mayor profundidad.

Palabras clave:

Músculos respiratorios

Sepsis

Disfunción diafragmática

Adrenérgicos β2

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