Effects of dexmedetomidine on dynamic preload indices, and on global and regional perfusion indices in dogs undergoing acute hipovolemia followed by volume replacement

Abstract

Increases in dynamic preload indices (pulse pressure variation: delta PP, negative variation of systolic pressure: delta down) identify individuals that are in the ascending portion of the Frank-Starling curve, where systolic function (stroke volume) may be improved via increases in preload achieved by volume expansion. The central hypothesis of the present study is that dexmedetomidine, because of its vasoconstrictive action leading to centralization of the circulating volume, inhibits or reduces the expected increase in preload indices (Delta PP, Delta down) induced by hypovolemic states in isoflurane anesthetized dogs. The second hypothesis is that dexmedetomidine induced vasoconstritction would aggravate the peripheral and splancnic hypoperfusion (evaluated by orthogonal polarization imaging and gastric tonometry, respectively) induced by acute hypovolemia. In the scenario of vasoconstriction/high systemic vascular resistance attributed to dexmedetomidine, it was also hypothesized that some global perfusion indices (PvO2/SvO2) would show low sensitivity for detecting progressive hypovolemic states. A total of 6 male and female adult dogs weighing between 20 and 30 kg will be used. During the Phase 1 of the study, the effects of 2 mcg/kg/hour of dexmedetomidine on the isoflurane minimum alveolar concentration (MAC) will be determined during a 4 hour constant rate infusion. One-week after concluding Phase 1, the same animals will be anesthetized in two different occasions. During one anesthetic episode, animals will be anesthetized with a placebo infusion (0.9% NaCl) and 1.3 MAC of isoflurane alone whereas during another episode, a dexmedetomidine infusion (2 mcg/kg/hour) will be combined with 1.3 MAC of isoflurane (ISO/DEX treatment) in a randomized crossover design, allowing 2 week intervals between anesthetic procedures. The end-tidal isoflurane in the ISO/DEX treatment will be reduced based on the MAC study carried out during phase 1 in order to result in equipotent (1.3 MAC) concentrations of isoflurane in both treatments. Neuromuscular blocking will be achieved by means of atracurium (0.2 mg/kg bolus, followed by 0.1 mg/kg/hour). The dynamic (delta PP and delta down) and static (stroke volume, central venous pressure, pulmonary artery occlusion pressure) preload indices, and the global (cardiac output, mixed venous O2 saturation, lactate) and regional (gastric tonometry, orthogonal polarization imaging) perfusion indices will be recorded during volume controlled ventilation (expired tidal volume: 15 ml/kg, inspiration-to-expiration ratio: 1/2, inspired O2 fraction of 0.6 and respiratory rate adjusted to maintain eucapnia). Two hours after starting placebo or dexmedetomidine infusions, baseline data will be collected and the exsanguination will be started with the removal of 32 mL/kg of blood (40% of circulating volume) divided into 4 cumulative stages (8, 16, 24, and 32 mL/kg of blood). Variables will be collected at the end of each cumulative stage and during volume replacement with shed blood. (AU)