Peripheral vascular decoupling in porcine endotoxic shock 1 2

40 Cardiac output measurement from arterial pressure waveforms presumes a defined relationship 41 between the arterial pulse pressure (PP), vascular compliance (C) and resistance (R). Cardiac 42 output estimates degrade if these assumptions are incorrect. We hypothesized that sepsis would 43 differentially alter central and peripheral vasomotor tone decoupling the usual pressure wave 44 propagation from central to peripheral sites. We assessed arterial input impedance (Z), C and R 45 from central and peripheral arterial pressures and aortic blood flow in an anesthetized porcine 46 model (n=19) of fluid resuscitated endotoxic shock induced by endotoxin infusion (7 μg/kg/h 47 increased to 14 and 20 μg/kg/h every 10 minutes and stopped when mean arterial pressure 48 <40mmHg or SvO2 <45%). Aortic, femoral and radial artery pressures and aortic and radial 49 artery flows were measured. Z was calculated by FFT of flow and pressure data. R and C were 50 derived using a two-element Windkessel model. Arterial PP increased from aortic to femoral and 51 radial sites. During stable endotoxemia with fluid resuscitation aortic and radial blood flows 52 returned to or exceed baseline while mean arterial pressure remain similarly decreased at all 53 three sites. However, aortic PP exceeded both femoral and radial arterial PP. Although Z, R and 54 C derived from aortic and radial pressure and aortic flow were similar during baseline, Z 55 increases and C decreases when derived from aortic pressure whereas Z decreases and C 56 increases when derived from radial pressure, while R decreased similarly with both pressure 57 signals. This central-to-peripheral vascular tone decoupling, as quantified by the difference in 58 calculated Z and C from aortic and radial artery pressure may explain the decreasing precision of 59 peripheral arterial pressure profile algorithms in assessing cardiac output in septic shock patients 60 and suggests that different algorithms taking this vascular decoupling into account may be 61 necessary to improve their precision in this patient population. 62 by 10.0. 33.6 on S etem er 2, 2017 http://jaysiology.org/ D ow nladed fom Introduction 63 Beat-to-beat estimates of left ventricular (LV) stroke volume and cardiac output from the arterial 64 pressure waveform have been studied since the original work of Hamilton and Remington over 65 60 years ago (12). Such measurements of cardiac output from the arterial pressure waveform 66 presume a defined relationship between the arterial pulse pressure (PP) profile, vascular 67 compliance (C) and resistance (R) or that if they change, they do so in a uniform fashion. Such 68 cardiac output estimates degrade if these assumptions are incorrect. Recently, commercial 69 devices have evolved to report LV stroke volume and cardiac output from the direct measure of 70 peripheral arterial pressure via an indwelling arterial catheter (3, 5). These devices are presently 71 being used to aid in clinical decision making. However, concern exists as to the accuracy of 72 these devices under conditions wherein peripheral vasomotor tone changes. The arterial pulse is 73 created by LV stroke volume into the central arterial compartment as quantified by a transfer 74 function (12). If arterial elastance and compliance remain constant, then central arterial PP will 75 vary directly with LV stroke volume. Unfortunately, most indwelling arterial catheters sample a 76 more peripheral arterial pressure signal, whose waveform may be altered in unexpected ways as 77 arterial tone, pulse wave velocity and LV contractility vary. For this reason, it has been 78 concluded that after a 1-hr calibration free period recalibration of these devices may be needed 79 (13). Such repetitive recalibration may not be feasible in the clinical setting. 80