Impact of analgesics on macro‐ and microcirculatory responses to hemorrhage

Abstract

BACKGROUNDPeripheral vasoconstriction in responseto hemorrhage is critical for blood pressure compensation and vital organperfusion. Opiates and ketamine have been demonstrated to have direct vasoactive effects, but effects on peripheral vasoconstriction response to hemorrhage are unknown for these analgesics. We hypothesize that opioid(fentanyl) impairs blood pressure compensation following hemorrhage due toblunted peripheral vasoconstriction, while ketamine preserves pressure compensation and vasoconstriction.METHODSprague Dawley rats(11–13wk) were randomly assigned to saline (control), fentanyl, or ketamine‐treated groups (n = 9 for each group). Rats were anesthetized within actin and the spinotrapezius muscles were prepared for microcirculatory observation. The arcade arterioles were topically challenged with saline, fentanyl, or ketamine at concentrations relevant to analgesic doses and vascular responses were recorded. After procedurally‐challenged arteriolar diameters returned to baseline, 30% of total blood volumes were removed during a 25 min period. Ten minutes after hemorrhage, rats were treated with a single intravenous(IV) injection of an analgesic dose of fentanyl or ketamine or a comparable volume of saline. Blood pressure, respiratory rate, and arteriolar responses were recorded throughout the experiment.RESULTSBaseline parameters were not different among groups (Table 1). Topical fentanyl induced vasodilation (17 ± 2%, p < 0.01)but ketamine caused vasoconstriction (−15 ± 4%; p < 0.01). IV ketamine and fentanyl failed to affect blood pressure compensation compared with the control group (Figure A). Neither saline nor ketamine altered respiratory rate. However, IV fentanyl induced a prolonged suppression in respiratory rate (>10 minutes, with a peak inhibition at 57 ± 8% of baseline, Figure B). A persistent and similar arteriolar constriction to hemorrhage was observed in the control and ketamine treated groups. However, this compensatory vasoconstriction was absent in the fentanyl‐treated group, which instead exhibited continuous vasodilation (peak change 42 ± 10% of baseline immediately after injection, p <0.01, Figure C). While no mortality occurred with IV saline or ketamine, fentanyl caused an 18% mortality.CONCLUSIONThese results indicate that ketamine preserves, but fentanyl impairs, respiration and peripheral vasoconstrictor response to hemorrhage, although minor effects on initial compensation of systemic hemodynamics appear to be similar. The study suggests that microcirculatory responses may be more sensitive than systemichemo dynamics to predict outcomes during pain management following hemorrhage.Support or Funding InformationThis study was funded by the US Army Medical and Materiel Command, Clinical and Rehabilitative Medicine Research Program.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.