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. 2019 Apr 15;23(1):118.
doi: 10.1186/s13054-019-2414-9.

Cardiovascular determinants of resuscitation from sepsis and septic shock

Fabio Guarracino  1 , Pietro Bertini  1 , Michael R Pinsky  2
Affiliations

Cardiovascular determinants of resuscitation from sepsis and septic shock

Fabio Guarracino et al. Crit Care. .

Abstract

Background: We hypothesized that the cardiovascular responses to Surviving Sepsis Guidelines (SSG)-defined resuscitation are predictable based on the cardiovascular state.

Methods: Fifty-five septic patients treated by SSG were studied before and after volume expansion (VE), and if needed norepinephrine (NE) and dobutamine. We measured mean arterial pressure (MAP), cardiac index (CI), and right atrial pressure (Pra) and calculated pulse pressure and stroke volume variation (PPV and SVV), dynamic arterial elastance (Eadyn), arterial elastance (Ea) and left ventricular (LV) end-systolic elastance (Ees), Ees/Ea (VAC), LV ejection efficiency (LVeff), mean systemic pressure analogue (Pmsa), venous return pressure gradient (Pvr), and cardiac performance (Eh), using standard formulae.

Results: All patients were hypotensive (MAP 56.8 ± 3.1 mmHg) and tachycardic (113.1 ± 7.5 beat min-1), with increased lactate levels (lactate = 5.0 ± 4.2 mmol L-1) with a worsened VAC. CI was variable but > 2 L min-1 M-2 in 74%. Twenty-eight-day mortality was 48% and associated with admission lactate, blood urea nitrogen (BUN), and creatinine levels but not cardiovascular state. In all patients, both MAP and CI improved following VE, as well as cardiac contractility (Ees). Fluid administration improved Pra, Pmsa, and Pvr in all patients, whereas both HR and Ea decreased after VE, thus normalizing VAC. CI increases were proportional to baseline PPV and SVV. CI increases proportionally decreased PPV and SVV. VE increased MAP > 65 mmHg in 35/55 patients. MAP responders had higher PPV, SVV, and Eadyn than non-responders. NE was given to 20/55 patients in septic shock, but increased MAP > 65 mmHg in only 12. NE increased Ea, Eadyn, Pra, Pmsa, and VAC while decreasing HR, PPV, SVV, and LVeff. MAP responders had higher pre-NE Ees and lower VAC. Dobutamine was given to 6/8 patients who remained hypotensive following NE. It increased Ees, MAP, CI, and LVeff, while decreasing HR, Pra, and VAC. At all times and all steps of the protocol, CI changes were proportional to Pvr changes independent of treatment.

Conclusions: The cardiovascular response to SSG-based resuscitation is highly heterogeneous but predictable from pre-treatment measures of cardiovascular state.

Keywords: Blood volume; Clinical trial; Effective circulating blood volume; Heart-lung interactions; Norepinephrine; Ventriculo-arterial coupling.

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Conflict of interest statement

Ethics approval and consent to participate

The study was approved by both institutions’ review boards for human experimentation. All subjects who regained consciousness signed informed consent while those who did not did not sign but by Italian law were permitted to be included in this study.

Consent for publication

The authors agree to waive copyright and allow this manuscript to be published in Critical Care.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Left panel: A stylized representation of the relation between left ventricular (LV) pressure (Plv) or arterial pressure (Pa) and both the LV pressure-volume relations during a cardiac cycle and arterial elastance (Ea) (red line) along with the associated formulae defining end-systolic elastance (Ees) (blue line) and Ea. Stroke work (SW) is the area within the LV pressure-volume loop for one cardiac cycle, while the potential energy (PE) is the area sub served by the Ea and LV end-systolic volume (ESV). LV efficiency (LVef) is the ratio of SW to SW + PE. Right panel: A stylized representation of the relation between steady-state cardiac output (CO) or venous return (VR) and right atrial pressure (Pra) from the perspective of venous return (blue line) and left ventricular output (red line) illustrating global cardiac efficiency (Eh). The zero CO pressure intercept defines mean systemic pressure (Pms). See text for further discussion
Fig. 2
Fig. 2
Impact of resuscitation steps on ventriculo-arterial coupling (above) and venous return to cardiac out (below), using Fig. 1 conventions and abbreviations, and reporting the calculated Ea, Ees, VAC, LVef, and Eh for each step. Asterisk connotes a significant change in the value for the group from the previous condition
Fig. 3
Fig. 3
Relation between resuscitation step-induced changes in cardiac output (ΔCO) and changes in the pressure gradient for venous return (ΔPvr) for all subjects receiving volume expansion (blue), norepinephrine (orange), and dobutamine (red), with their associated linear regression lines
Fig. 4
Fig. 4
Group difference ventriculo-arterial coupling between a mean values for all patients at baseline, and following VE, under NE, if needed, and then, if needed, under dobutamine. b Group differences in relations between those patients who increased their CI > 15% to a VE of 30 mL/kg of crystalloids (responders) from non-responders. c Group differences in relations between those patients who increased their CI > 15% to NE (responders) from non-responders. d Group differences in relations between those patients who increased their CI > 15% to dobutamine (responders) from non-responders. The figure uses the same format, conventions, and abbreviations as Fig. 2 upper panel. LV left ventricle
Fig. 5
Fig. 5
Group differences in venous return to cardiac output relations between a mean values for all patients at baseline, and following VE, under NE, if needed, and then, if needed under dobutamine. b Group differences in relations between those patients who increased their CI > 15% to a VE of 30 mL/kg of crystalloids (responders) from non-responders. c Group differences in relations between those patients who increased their CI > 15% to NE (responders) from non-responders. d Group differences in relations between those patients who increased their CI > 15% to dobutamine (responders) from non-responders. The figure uses the same format, conventions, and abbreviations as Fig. 2 bottom panel
Fig. 6
Fig. 6
Receiver operator characteristic curse for each value for the most informative predictive variable and its threshold value to predict VE-induced changes in cardiac index (ΔCI) (upper panel) and MAP (ΔMAP) relative to baseline PPV and Eadyn (middle panel) for all patients and relation between ΔMAP in response to NE and PPV and Eadyn for all subjects given NE (lower panel)
See this image and copyright information in PMC

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