Central Venous Waveform Analysis and Cardiac Output in a Porcine Model of Endotoxemic Hypotension and Resuscitation

Abstract

BACKGROUND: Cardiac output (CO) is a valuable proxy for perfusion, and governs volume responsiveness during resuscitation from distributive shock. The underappreciated venous system has nuanced physiology that confers valuable hemodynamic information. In this investigation, deconvolution of the central venous waveform by the fast Fourier transformation (FFT) algorithm is performed to assess its ability to constitute a CO surrogate in a porcine model of endotoxemia-induced distributive hypotension and resuscitation. STUDY DESIGN: Ten pigs were anesthetized, catheterized, and intubated. A lipopolysaccharides infusion protocol was used to precipitate low systemic vascular resistance hypotension. Four crystalloid boluses (10 cc/kg) were then given in succession, after which heart rate, mean arterial pressure, thermodilution-derived CO, central venous pressure (CVP), and the central venous waveform were collected, the last undergoing fast Fourier transformation analysis. The amplitude of the fundamental frequency of the central venous waveform’s cardiac wave (f0-CVP) was obtained. Heart rate, mean arterial pressure, CVP, f0-CVP, and CO were plotted over the course of the boluses to determine whether f0-CVP tracked with CO better than the vital signs, or than CVP itself. RESULTS: Distributive hypotension to a 25% mean arterial pressure decrement was achieved, with decreased systemic vascular resistance (mean 918 ± 227 [SD] dyne/s/cm-5 vs 685 ± 180 dyne/s/cm-5; p = 0.038). Full hemodynamic parameters characterizing this model were reported. Slopes of linear regression lines of heart rate, mean arterial pressure, CVP, f0-CVP, and CO were –2.8, 1.7, 1.8, 0.40, and 0.35, respectively, demonstrating that f0-CVP values closely track with CO over the 4-bolus range. CONCLUSIONS: Fast Fourier transformation analysis of the central venous waveform may allow real-time assessment of CO during resuscitation from distributive hypotension, possibly offering a venous-based approach to clinical estimation of volume responsiveness.

The Effect of Fluid Pre-loading on Vital Signs and Hemodynamic Parameters in a Porcine Model of Lipopolysaccharide-Induced Endotoxemia

“…To induce low-SVR hypotension, a previously reported porcine model of intravenous (IV) LPS infusion was used [ 8 ]. In this model, low doses of LPS are known to be associated with an initial increase in pulmonary arterial pressures.…”

“…The protocol of LPS infusion represents a slight adaptation of the method reported by Byrne and colleagues [ 15 ] and has been reported previously [ 8 ]. These experiments were performed under direct veterinary supervision in the designated animal operating room at the University of Minnesota Experimental Surgical Services.…”

“…Maintenance anesthesia was used with 3% isoflurane until the pigs were fully catheterized and then reduced to 2% isoflurane. Ventilatory settings were held at volume control mode with a tidal volume of 10-15 mL/kg, 10-15 breaths/minute, and positive end expiratory pressure at 4 mmHg, on 100% oxygen [ 8 ]. Anesthesia was maintained with 1%-4% inhaled isoflurane.…”

“…While distinct from bacterial sepsis, endotoxemia due to bloodstream seeding with lipopolysaccharides (LPS) similarly produces low-SVR hypotension [ 6 , 7 ]. Models of endotoxemic shock have successfully been used to mimic the hemodynamic perturbations seen in septic shock [ 8 ]. LPS-associated hypotension in pigs is recognized, among other surgical models of sepsis, as a suitable, validated mammalian model of distributive shock with hemodynamic changes sufficiently similar to those seen in human sepsis [ 9 , 10 ].…”

“…Pulmonary arterial pressures, which can become elevated in sepsis or endotoxemia, can also be measured. In this investigation, using a previously validated model of endotoxemic hypotension, a full characterization of hemodynamic parameters is reported [ 8 ]. Uniquely, vital signs, central hemodynamic parameters, and key laboratory measures are compared after controlled resuscitation with NE, both with and without controlled crystalloid pre-resuscitation.…”