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Department of Anesthesiology and Intensive Care, University of Muenster, Muenster, Germany
Address correspondence and reprint requests to Martin Westphal, MD, Klinik und Poliklinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Münster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany. Address e-mail to Martin. Westphal{at}gmx.net
Since arginine vasopressin (AVP) may reduce cardiac output and, in proportion, oxygen delivery, we studied the efficacy of dopexamine (DPX) as an adjunct to AVP infusion. After 1 h of continuous AVP infusion (0.04 U/min) in healthy sheep (n = 7), DPX was additionally administered in incremental doses (1, 5, and 10 µg · kg–1 · min–1; each dose for 30 min). After a 24-h period of recovery, endotoxin was continuously infused in the same sheep to induce and maintain a hypotensive/hyperdynamic circulation. After 16 h of endotoxemia, AVP and DPX were given as described previously. AVP infusion increased systemic vascular resistance index and decreased cardiac index in both healthy and endotoxemic conditions (P < 0.001 each). This was accompanied by an augmented pulmonary vascular resistance index in endotoxemia (159 ± 13 dynes · cm–5 · m–2 versus 202 ± 16 dynes · cm–5 · m–2) and a decrease in oxygen delivery index (health: 842 ± 66 mL · min–2 · m–2 versus 475 ± 38 mL · min–2 · m–2; endotoxemia: 1073 ± 49 mL · min–2 · m–2 versus 613 ± 44 mL · min–2 · m–2) and mixed venous oxygen content (health: 63% ± 2% versus 47% ± 2%; endotoxemia: 68% ± 2% versus 51% ± 3%; P < 0.001 each). Small doses of DPX (1 and 5 µg · kg–1 · min–1) improved not only the AVP-associated depressions in cardiac index, oxygen delivery index, and mixed venous oxygen content, but also the pulmonary vasopressive effect in both groups. While large-dose DPX (10 µg · kg–1 · min–1) also reduced mean pulmonary arterial pressure in endotoxemia (27 ± 1 mm Hg versus 23 ± 1 mm Hg; P < 0.05 versus baseline), mean arterial blood pressure decreased (105 ± 4 mm Hg versus 80 ± 3 mm Hg) and heart rate increased (84 ± 4 bpm versus 136 ± 9 bpm; P < 0.001 versus AVP alone), thereby limiting its therapeutic use.
IMPLICATIONS: Because vasopressin decreases cardiac output and oxygen delivery, we investigated the use of dopexamine as an adjunct to vasopressin infusion. During experimental endotoxemia, small doses of dopexamine reversed the arginine vasopressin-linked depression in cardiac index, thereby improving oxygen supply. Although large-dose dopexamine (10 µg · kg–1 · min–1) improved the pulmonary circulation, systemic hypotension and tachycardia occurred.
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