Dellinger, R Phillip MD, FCCM; Rhodes, Andrews MD; Vincent, Jean-Louis MD, PhD Author Information
Introduction: Hypercapnia may cause hemodynamic improvement in septic shock due to neuroadrenal stimulation. The aim of this study was to investigate whether hypercapnia has similar effects to dobutamine in a clinically relevant model of septic shock. Methods: Twenty-one anesthetized, mechanically ventilated, invasively monitored female sheep (BW: 27.5  2.5 Kg) received 1.5 g/kg body weight feces intraperitoneally to induce septic shock. Ringer's lactate and 6% hydroxyethyl starch solutions were infused throughout the experiment to sustain normovolemia. No antibiotics or vasoactive agents were used. Two hours after injection of feces, animals were randomized to one of three groups: Hypercapnia: carbon dioxide was given at FiCO2 of 4.1% throughout the experiment to maintain PaCO2 between 55 and 65 mmHg; dobutamine: dobutamine was infused intravenously at a dose of 7 g/kg/min throughout the experiment; control: no treatment. In the dobutamine and control groups, PaCO2 was maintained between 35 and 45 mmHg. All animals were monitored until spontaneous death. Result: All animals developed a hyperdynamic phase associated with an increase in pulmonary vascular resistance, and lactic acidosis. PaCO2 was significantly higher in the hypercapnia group than in the other two groups (P < 0.05). Animals in the hypercapnia and dobutamine groups maintained higher mean arterial pressure, higher stroke volume, higher heart rate and higher oxygen delivery than the control animals; they also had lower lactate concentrations (P < 0.05). There were no differences in these parameters between the hypercapnia and dobutamine groups. Animals treated with hypercapnia had a higher PaO2/FiO2 and lower wet/dry ratio than the other two groups. There were no differences in survival times in the three groups (P = 0.65). Conclusion: Hypercapnia improved gas exchange, decreased pulmonary edema formation and induced similar hemodynamic effects to dobutamine infusion in this clinically relevant model of septic shock in sheep.
Despite the low selenium content in the body (20-40 mg), selenoenzymes play an important role in antioxidant defense in humans. Selenium administration may be associated with improved outcomes, but further studies are needed to determine the precise mechanism of action. Studies are also needed to determine optimal dosing regimens, and to identify those patients in whom this approach is likely to be most effective. Currently, doses below the tolerable upper intake level (400 microg) may be used in supplementation. Higher doses (up to the level of no adverse effect, 800 microg) may be of interest and need to be studied further. The pro-oxidant effects of selenocompounds, especially sodium selenite, which vary depending on the compound, dose, and concentration, also need to be assessed further for their toxicity and potential therapeutic use in patients with septic shock.
SCOPUS: le.j