Isoflurane Inhibits Compensatory Intravascular Volume Expansion After Hemorrhage in Sheep

Abstract

After hemorrhage, blood volume is partially restored by transcapillary refill, a process of spontaneous compensatory intravascular volume expansion that we hypothesized would be inhibited by anesthesia. Six chronically instrumented sheep were subjected to four randomly ordered experiments while conscious or during anesthesia with isoflurane. After plasma volume measurement (indocyanine green), 15% or 45% of the blood volume was withdrawn. To quantify transcapillary refill, mass balance and kinetic calculations utilized repeated measurements of hemoglobin concentration, assuming that transcapillary refill would dilute hemoglobin concentration. After 15% hemorrhage, mean arterial blood pressure remained stable in both conscious and isoflurane-anesthetized sheep (normotensive hemorrhage) but decreased after 45% hemorrhage (hypotensive hemorrhage). After either normotensive or hypotensive hemorrhage, transcapillary refill occurred more rapidly during the first 40 min than during the next 140 min (P < 0.001). In conscious sheep, at 180 min, 57% and 42% of the bled volume had been restored after normotensive and hypotensive hemorrhage, respectively, in contrast to only 13% and 27% (P < 0.001) in isoflurane-anesthetized sheep. A novel kinetic model implicated hemodynamic factors in rapid, early transcapillary refill and decreased plasma oncotic pressure in subsequent slower filling. We conclude that isoflurane inhibits transcapillary refill after both normotensive and hypotensive hemorrhage in sheep.

Effects of anesthesia on fluid volume kinetics after infusion of colloid solution during blood donation

“…Factors contributing to transcapillary refill include a decrease in capillary hydrostatic pressure caused by the constriction of arterioli [18], an increase in total intravascular protein [19], a rise in lymphatic flow [17], and movement of interstitial fluid into the intravascular space caused by the osmotic effect of hyperglycemia [20]. Transcapillary refill varies depending on the volume hemorrhaged, the time since hemorrhage, and the use of anesthetics [6,21]. Isoflurane anesthesia has been reported to inhibit compensatory transcapillary refilling after hemorrhage, resulting in decreased expansion of intravascular volume compared with what is seen in wakeful subjects [6].…”

“…Transcapillary refill varies depending on the volume hemorrhaged, the time since hemorrhage, and the use of anesthetics [6,21]. Isoflurane anesthesia has been reported to inhibit compensatory transcapillary refilling after hemorrhage, resulting in decreased expansion of intravascular volume compared with what is seen in wakeful subjects [6]. Following normotensive (15%) hemorrhage, intravascular volume restoration in anesthetized individuals was only 23% that of wakeful individuals.…”

“…To compensate for lost blood volume after hemorrhage, extravascular fluid is mobilized into the vascular tree by a spontaneous process termed "transcapillary refill", and urinary output is suppressed [5]. Anesthetics per se inhibit transcapillary refill and delay urinary excretion [3,6,7]. Hemorrhage can also lead to intravascular retention of fluids, primarily caused by a reduction in the elimination rate constant [4,8,9].…”

“…Hemorrhage can also lead to intravascular retention of fluids, primarily caused by a reduction in the elimination rate constant [4,8,9]. Because anesthesia impairs transcapillary refill after hemorrhage [6], infusion of crystalloid solution to correct hypovolemia can lead to a higher level of extravascular water retention during anesthesia than is seen in wakeful subjects. Under conditions of combined hemorrhage and anesthesia, however, less tissue edema has been observed following infusion of colloid compared with crystalloid solution [10].…”

The maintenance and monitoring of perioperative blood volume

“…It is compensated for by an initial resetting of the precapillary and postcapillary sphincters leading to the transcapillary refill state that transports fluid and protein from the interstitial space to the intravascular space [31]. Furthermore, cells become resistant to insulin resulting in hyperglycemia [32].…”