Original ArticleAssessment of endothelial glycocalyx disruption in term parturients receiving a fluid bolus before spinal anesthesia: a prospective observational study
Introduction
A common consequence of spinal anesthesia in healthy parturients undergoing cesarean delivery (CD) is hypotension with the overall incidence ranging from 53% to 71%.1, 2 Post-spinal hypotension results from multiple physiologic alterations in the cardiovascular system secondary to a local anesthetic-mediated sympathectomy. This causes both an increase in venous capacitance, with a resultant decrease in venous return, and a decrease in arterial resistance. As a result, there is a reduction in blood pressure. Despite the risk of hypotension, spinal anesthesia is the preferred anesthetic for parturients undergoing CD. One common practice, endorsed by the American Society of Anesthesiologists Task Force on Obstetric Anesthesia, is volume loading before placement of a spinal block.3 However, several reports indicate that prophylactic crystalloid fluid loading is ineffective in eliminating spinal-induced hypotension.4, 5 Co-administration of a phenylephrine infusion is an effective method to prevent post-spinal hypotension.6 Despite this recent advance, a mechanism explaining the lack of response to volume loading in parturients undergoing spinal anesthesia for CD remains unclear.
In recent years, the classic Starling principle of pressure and oncotic gradients driving fluid balance has been called into question, adding the importance of endothelial glycocalyx (EG) to the equation.7, 8, 9 The EG is an intricate meshwork of membrane-bound molecules and side chains composed of different proteoglycans and glycoproteins that line the vascular endothelium. These molecules include selectins, integrins, tissue factor, absorbed plasma proteins, and glycosaminoglycans (GAG), that when intact, play many important physiological roles including regulation of blood flow, coagulation, and inflammation.10, 11, 12 Another vital function of the EG is to prevent the extravasation of intravascular fluid into the interstitial space via maintenance of an oncotic gradient.13, 14 Studies have shown that the EG is vulnerable to destruction. Several pathological processes responsible for the disruption of the EG include ischemia-reperfusion injury, endotoxins, hyperglycemia, and atrial natriuretic peptide (ANP).15, 16, 17, 18 Two macromolecules present in the EG have been studied, and increased levels in the blood are noted to correlate with shedding of the EG. These are heparan sulfate (HS), the most common GAG on the EG, and syndecan-1 (Sy-1), a membrane-bound proteoglycan.15, 19
Despite data supporting multiple mechanisms for EG destruction, no studies have addressed if prophylactic volume loading causes disruption of the EG. Rehm et al. showed that volume loading normovolemic patients leads to less retention of the infused fluid.20 Although the EG was not examined in the study, it could be questioned whether hypervolemia-induced destruction of the EG resulted in the loss of the infused fluid. Disruption of the EG and loss of intravascular fluid is a potential explanation for the overall ineffectiveness of a fluid bolus in preventing spinal-induced hypotension in healthy parturients undergoing CD. We hypothesized that a rapid fluid bolus in normovolemic parturients receiving spinal anesthesia for CD as a means of preventing hypotension disrupts the EG by either mechanical stress or atrial stretch causing release of ANP.
Section snippets
Methods
This study was approved by the University of Alabama at Birmingham Institutional Review Board, and all patients gave written informed consent. Eligible participants for this study were term parturients without maternal or fetal complications or preexisting disease and a body mass index <40 kg/m2 presenting for elective CD under spinal anesthesia.
The primary outcome of this study was to determine if the EG is disrupted in healthy parturients given a prophylactic crystalloid bolus before spinal
Results
A total of 30 patients were enrolled from August 2012 to February 2013. One participant was excluded from analysis due to a blood storage error.
For HS, we observed a baseline median value of 12.58 ng/mL [interquartile range (IQR) 9.17, 22.02] and a post-bolus value of 12.83 ng/mL [IQR 9.72, 22.03]. The baseline median value for Sy-1 was 289.5 ng/mL [IQR 245.7, 306.8] with a post-bolus value of 278.7 ng/mL [IQR 215.9, 311.9]. When our glycocalyx markers were adjusted by dividing raw values by the
Discussion
An important scientific advancement has been the implication of the EG in modulating transvascular fluid exchange. Although studied in other clinical settings, examination of the EG during pregnancy is a new area of investigation. Recently, the EG biomarkers HS and Sy-1 were compared in healthy women followed throughout pregnancy and healthy non-pregnant controls. Sy-1 was found to be significantly increased, likely secondary to release from syncytiotrophoblast cells; whereas, HS levels
Disclosure
Sole funding for this project was provided through departmental funds and had no involvement in the study design, data collection, and analysis. The authors report no conflicts of interest.
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