Prevention of septic ventilatory depression with naloxone

Little is known of the endorphins' role in sepsis-induced respiratory distress and naloxone's effect as a treatment of it. Thirteen piglets were infused with live Escherichia coli at a rate of 2 to 10 X 10(8) colony-forming units per hour for six hours or until death and were divided into two groups: the septic control group (n = 8), and the naloxone-treated group (n = 5), which received 8 mg/kg/h of naloxone by continuous infusion. Hemodynamic parameters, the intrapulmonary shunt fraction (QS/QT), physiologic dead space (VD/VT), minute ventilation, and blood gas levels were measured. Lung lymph flow was obtained by cannulating the right lymphatic duct. The extravascular lung water weight was also measured. The results showed a significant reduction of QS/QT, VD/VT, and arterial carbon dioxide pressure at one hour and a significant increase of arterial carbon dioxide pressure and minute ventilation at 1, 3, and 4 hours in the naloxone-treated group, compared with the untreated septic group. None of the piglets in the naloxone-treated group developed ventilatory depression, while 75% of those in the untreated septic group did. Among the latter piglets, three died of apnea within one hour. These beneficial effects of naloxone are likely related to its action on the central and peripheral respiratory regulatory mechanisms. A transient protection of the cardiac output and relatively decreased extravascular lung water with naloxone treatment may also, in part, improve the ventilation-perfusion maldistribution and secondarily reduce QS/QT and VD/VT. We conclude that endorphins play a role in septic ventilatory depression and that naloxone is effective in ameliorating it.