2004 Papers - Coviello


Dopamine and Vasopressin Affect Organ Perfusion and Blood Oxygenation Differently in a Piglet Model of Vasodilatory Septic Shock

CPT Lisa C Coviello D.O., Department of Surgery, Tripler Army Medical Center
LTC Chet A Morrison M.D., Department of Surgery, Tripler Army Medical Center
Maren M Chan M.D., Department of Surgery, Tripler Army Medical Center
CPT E M Sawyer M.D., Department of Surgery, Tripler Army Medical Center
MAJ Mathew Chung M.D., FACS Department of Surgery, Tripler Army Medical Center
Catherine FT Uyehara Ph.D., Department of Clinical Investigation, Tripler Army Medical Center

Objective: We have previously shown that vasopressin (VP) may be clinically useful in septic shock as it increases blood pressure and redistributes blood to vital organs. In this study, we compared the effects of dopamine (DA), with VP or no treatment (Control Group=CG) in a piglet model of vasodilatory septic shock. We tested the hypothesis that while DA and VP may both be beneficial in treating septic shock, they affect regional blood flow (RBF) distribution differently.

Study Design: Baseline measurements were taken in pPentobarbital-anesthetized, mechanically ventilated 5-7 day old piglets that were implanted with right atrial, left ventricle, abdominal aorta and vena cava, pulmonary artery, and bladder catheters. Septic shock was induced by intravenous (i.v.) injection of E. coli endotoxin (30µg/kg). After establishment of a sSteady state of vasodilatory shock, defined as a 20% decrease in mean arterial pressure (MAP) from baseline, measurements representing the effect of endotoxin were taken, was established. All piglets were infused with isotonic saline (control group, CG) (0.1 ml/kg/min i.v. control group). A non-treated group received saline alone (NT, n=7). A second group was treated with either DA (50µg/kg/min, n=7) and a third group was treated with VP (100 ng/kg/min, n=8). MAP, mean pulmonary arterial pressure, cardiac output (CO), blood gases, urine output, and RBF (via colored microsphere injection) were measured prior to injection of endotoxinendotoxin-induced (baseline), during steady state vasodilatory shock, and after treatment.

Results: Baseline MAP was 72+3 mm Hg in all groups. The sSystemic hypotension caused by endotoxin observed after endotoxin injection in all groups (MAP = 40 +/- 2 mm Hg) was reversed (82 +/- 3 mmHg, p<0.01) by VP. However, hypotension was refractory to DA (MAP = 43 +/- 4 mm Hg), due to a decrease in CO (p<0.05)(pre-endotoxin 72 +/- 3, CG 40 +/- 2, DA 43+/- 4, VP 82+/- 3mmHg, p<0.01). DA treatment increased sSystemic vascular resistance (SVR) with DA was increased, although not to the level induced by VP (DA from 287 +/- 12 to 343 +/- 48, VP from 311 +/- 31 to 487 +/- 37 dynes•sec/cm5, p<0.01). VP did not increase pulmonary vascular resistance (PVR) to the same degree as it did SVR. Therefore while the PVR/SVR ratio in CG NT (0.56 + 0.06) and DA- treated (0.53 + 0.03) animals were similar, it was reduced in VP-treated animals (0.27 + 0.03, p<0.01). Both There was a significant increase in DA and VP improved arterial blood oxygenation (PaO2) arterial blood oxygenation compared to NT (with DA (84 +/- 1 to 93 +/- 3mmHg, p<0.01). A decrease in O2 consumption was seen with DA (6.3 +/- 0.4 O2/dl, p<0.01) compared to VP (10.3 +/- 1.3 O2/dl) or CGNT (10.4 +/- 1.1 ml O2/dl). DA and VP shunted blood flow away from the skin, muscle, stomach, and large intestine and neither drug altered perfusion of the heart compared to controls. DA increased, whereas VP slightly decreased perfusion of the small intestine (p<0.01). Brain perfusion was unchanged by DA and increased with VP (p<0.02).

Conclusion: DA and VP exert potentially beneficial effects on vital organ perfusion during septic shock although they appear to affect organ perfusion and oxygenation differently. VP appears to improve blood oxygenationPaO2 by its relative sparing of the pulmonary vascular bed of vasoconstriction. In contrast, the mechanism of increased PaO2 by DA is a decrease in O2 extraction which indicates reduced gas exchange at the tissue level. The interesting finding that VP improves brain perfusion may have clinical significance. Improved blood flow to the small intestine by DA may reduce the risk of gut ischemia during shock. Results thus indicate that further study is warranted to determine whether combined therapy with DA and VP may improve outcomes in septic shock better than either drug alone.