Resuscitation fluids as drugs: targeting the endothelial glycocalyx

Abstract

Fluid resuscitation is an essential intervention in critically ill patients, and its ultimate goal is to restore tissue perfusion. Critical illnesses are often accompanied by glycocalyx degradation caused by inflammatory reactions, hypoperfusion, shock, and so forth, leading to disturbed microcirculatory perfusion and organ dysfunction. Therefore, maintaining or even restoring the glycocalyx integrity may be of high priority in the therapeutic strategy. Like drugs, however, different resuscitation fluids may have beneficial or harmful effects on the integrity of the glycocalyx. The purpose of this article is to review the effects of different resuscitation fluids on the glycocalyx. Many animal studies have shown that normal saline might be associated with glycocalyx degradation, but clinical studies have not confirmed this finding. Hydroxyethyl starch (HES), rather than other synthetic colloids, may restore the glycocalyx. However, the use of HES also leads to serious adverse events such as acute kidney injury and bleeding tendencies. Some studies have suggested that albumin may restore the glycocalyx, whereas others have suggested that balanced crystalloids might aggravate glycocalyx degradation. Notably, most studies did not correct the effects of the infusion rate or fluid volume; therefore, the results of using balanced crystalloids remain unclear. Moreover, mainly animal studies have suggested that plasma may protect and restore glycocalyx integrity, and this still requires confirmation by high-quality clinical studies.

Assessment of Pulmonary Circulation of Critically Ill Patients Based on Critical Care Ultrasound

“…The systemic inflammatory response and excessive release of catecholamines caused by sepsis can lead to excessive degradation of the vascular endothelial glycocalyx, causing damage to vascular endothelial cells [62,63]. Destruction of pulmonary capillary endothelial cells leads to increased pulmonary capillary permeability, which in turn leads to pulmonary interstitial edema and gravity-dependent consolidation [46].…”

Microcirculation and Mitochondria: The Critical Unit

“…Fluid resuscitation is one of the most commonly used interventions in hemodynamic therapy [61]. Based on the understanding of the critical unit, the strategy of fluid resuscitation has gradually moved from targeting macrocirculation to targeting endothelial cells, which is reflected by the increasing attention of clinicians to the effects of different types of resuscitation fluids, which may aggravate or improve glycocalyx shedding, endothelial activation, and coagulation dysfunction [62]. Many experiments have demonstrated that crystalloids and gelatins may cause the degradation and shedding of the EGC; on the contrary, plasma and albumin have protective effects on vascular endothelium and microcirculation [63][64][65].…”

“…The increasing emphasis on microcirculation and the endothelium has greatly impacted the choice of resuscitation fluid in clinical practice. One proposal is to increase the priority of hyperoncotic albumin solutions [62]. Although there have been no high-quality clinical studies to confirm the effects of albumin and plasma on the prognosis of critically ill patients, their potential benefits may inspire new ideas for clinical decision-making.…”

Endothelial Damage and the Microcirculation in Critical Illness

“…Further tests on drugs like Sulodexide, a combination of heparin-sulfate like compound shown to regenerate the glycocalyx in a mouse model of sepsis, that also restores glycocalyx volume in diabetics, should be studied further in critical care [ 169 ]. FFP has shown benefit in animal models as well as models of haemorrhagic shock but there are no high quality studies of its effects restoring the glycocalyx in critical illness [ 170 , 171 ].…”