Pertinent normal cardiovascular physiology

Abstract

Aggressive fluid resuscitation to achieve a central venous pressure (CVP) greater than 8 mm Hg has been promoted as the standard of care, in the management of patients with severe sepsis and septic shock. However recent clinical trials have demonstrated that this approach does not improve the outcome of patients with severe sepsis and septic shock.

Pathophysiologically, sepsis is characterized by vasoplegia with loss of arterial tone, venodilation with sequestration of blood in the unstressed blood compartment and changes in ventricular function with reduced compliance and reduced preload responsiveness. These data suggest that sepsis is primarily not a volume-depleted state and recent evidence demonstrates that most septic patients are poorly responsive to fluids. Furthermore, almost all of the administered fluid is sequestered in the tissues, resulting in severe oedema in vital organs and, thereby, increasing the risk of organ dysfunction. These data suggest that a physiologic, haemodynamically guided conservative approach to fluid therapy in patients with sepsis would be prudent and would likely reduce the morbidity and improve the outcome of this disease.

Key words: central venous pressure; fluid therapy; pulmonary edema; sepsis; septic shock

In the 19th century, patients with cholera dying from hypovol- aemic shock were treated by venesection or blood-letting.1 2This treatment was considered the standard of care for this dis- order. In the first part of the 21st century patients with septic shock were treated with massive amounts of crystalloids, approaching 17 litres in the first 72 h of hospitalization.3 4 This

approach was considered the standard of care and endorsed by International Guidelines.5–7Clearly, these treatment approaches failed to appreciate the pathophysiological changes of both disor- ders and that the prescribed treatments were harmful. Cholera is a disease associated with profound volume depletion through diarrhoea that requires replacement with i.v. fluids.12Severe sep- sis and septic shock however, are not associated with volume loss. Sepsis is characterized by arterio- and venodilation together with microcirculatory and myocardial dysfunction, with septic

patients being poorly responsive to fluid administration. Never- theless, aggressive fluid resuscitation to achieve a central venous pressure (CVP) greater than 8 mm Hg (‘Early Goal Directed Therapy’ - EGDT), has been considered the standard of care in the management of patients with severe sepsis and septic shock.5–7

However, recent multicentre clinical trials (ProCESS, ARISE and PROMISE) and a meta-analysis of EGDT have demonstrated that this approach does not improve the outcome of patients with se- vere sepsis and septic shock.8–11This article reviews the haemo-

dynamic changes associated with sepsis and provides a rational approach to fluid management in this complex disorder.

© The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Pertinent normal cardiovascular physiology

The amount of blood pumped out of the heart (cardiac output) is equivalent to venous return (volume entering the right atrium).12According to Guyton, venous return is determined by the pres- sure gradient between the peripheral veins and the right atrium (CVP).13The venous system can be divided into two theoretical compartments, the unstressed and stressed volume.14The intra- vascular volume that fills the venous system to the point where intravascular pressure starts to increase is called unstressed vol- ume, whereas the volume that stretches the veins and causes intravascular pressure to increase is called the stressed volume. The mean circulatory filling pressure (MCFP) is conceptualized as the pressure distending the vasculature, when the heart is

stopped (zero flow) and the pressures in all segments of the circu- latory system have equalized.1415The stressed venous system is the major contributor to the MCFP.1415 The MCFP in humans is normally in the range of 8–l0 mm Hg.1415The MCFP is the major determinant of venous return.

The venous system has a large vascular capacitance and a constant compliance in which an increased blood volume is as- sociated with a relatively small change in the MCFP.14However, because of the restraining effects of the pericardium and cardiac cytoskeleton, the diastolic compliance of the normal heart (both

left and right ventricles) reduces as distending volume increases; consequently, with large volume fluid resuscitation, the cardiac filling pressures ( particularly on the right side, i.e. CVP) increase faster than the MCFP, decreasing the gradient for venous re- turn.16–18Organ blood flow is determined by the difference in the pressure between the arterial and venous sides of the circula- tion. The mean arterial pressure (MAP) minus the CVP is there-

fore the overall driving force for organ blood flow. A high CVP therefore decreases the gradient for venous return, while at the same time decreasing organ driving pressure and therefore blood flow. Venous pressure has a much greater effect on micro- circulatory flow than the MAP; provided that the MAP is within an organ’s autoregulatory range, the CVP becomes the major deter-

minant of capillary blood flow.1920

According to the Frank-Starling principle, as left-ventricular (LV) end-diastolic volume (i.e. preload) increases, LV stroke volume (SV) increases until the optimal preload is achieved, at which point the SV remains relatively constant.21This optimal preload is related to the maximal overlap of the actin-

myosin myofibrils. Fluid administration will only increase SV if two conditions are met, namely: i) that the fluid bolus increases the MCFP more than it increases the CVP, thereby increasing the gradient for venous return, and ii) that both ventricles are functioning on the ‘ascending limb’ of the Frank-Starling

curve.2223

The vascular endothelium is coated on the luminal side by a web of membrane-bound glycoproteins and proteoglycans known as the endothelial glycocalyx.24–26 The glycocalyx plays a major role as a vascular barrier, preventing large macromole- cules moving across the endothelium, preventing leucocyte and platelet aggregation and limiting tissue oedema. An intact endo- thelial glycocalyx is a prerequisite of a functioning vascular bar- rier.27Increased cardiac filling pressures after aggressive fluid resuscitation increase the release of natriuretic peptides.2829Natriuretic peptides cleave membrane-bound proteoglycans and glycoproteins (most notably syndecan-1 and hyaluronic acid) off the endothelial glycocalyx.30–32Damage to the glycoca- lyx profoundly increases endothelial permeability. In addition, increased natriuretic peptides inhibit the lymphatic propulsive motor activity reducing lymphatic drainage.33–35

Date: 2016-04-22; view: 605