Observational Study of Sublingual Microcirculatory Blood Flow Characteristics in Patients Undergoing Transthoracic Esophagectomy

1. Provide the scientific background, rationale and relevance of this project. The microcirculation plays a fundamental role in gas and nutrient exchange; it must constantly adapt by controlling vascular tone and regional blood flow. In disease states, increased permeability may be necessary to produce the inflammatory response. The assessment and quantification of the macrovascular hemodynamics and the assumption that it is reflective of microvascular change is fundamentally flawed. Even when global hemodynamic variables are corrected, many patients with circulatory failure will develop multi organ failure and ultimately die. The recent advent of in vivo microcirculation monitoring has begun to improve our understanding of the relationships between surgery, anesthetic management, and regulation of the microcirculation.

Microcirculatory alteration also occurs in patients undergoing cardiac surgery. Bauer et al first reported that microcirculatory perfusion was transiently altered in humans after cardiopulmonary bypass. Similar findings were reported more recently by other groups. , More importantly, these alterations can also be observed in patients who undergo surgery without cardiopulmonary bypass.3 Furthermore the sublingual microcirculation was still slightly abnormal up to 24 h after surgery in these patients. As in non-cardiac surgery, the severity of perioperative microvascular alterations correlated with peak lactate levels and severity of organ dysfunction after surgery.iii High-risk surgery is a new area in which in vivo microcirculatory alterations have been observed. In patients undergoing high-risk non-cardiac surgery, Jhanji et al observed that the density and proportion of perfused capillaries was lower in the 14 patients who subsequently developed postoperative complications than in the 11 patients with an uneventful postoperative course. Subcutaneous tissue PO2 and laser Doppler cutaneous blood flow did not differ between the groups, further highlighting the lack of sensitivity of these methods to detect heterogeneous perfusion. Interestingly, there was no significant difference in global O2 delivery between the groups.

Non-cardiac thoracic surgeries comprise a subgroup of high risk surgical procedures which have the potential to significantly affect and impair microcirculatory function. A study of patients undergoing esophagectomy demonstrated significant impairment of sublingual microcirculation relative to pancreaticoduodenectomy patients. Esophagectomy surgery produces a profound systemic inflammatory response which correlates to a number of adverse outcomes. Interestingly, the time course of microcirculatory impairment and recovery appears to parallel the SIRS typically seen in surgeries of this type. Transthoracic esophagectomy is typically facilitated by one lung ventilation (OLV) in an effort to optimize surgical exposure to the operative hemithorax. The institution of OLV has the potential to dramatically impair tissue oxygen supply demand relationships via adverse effects on systemic oxygen desaturation, as a result of an increased venous admixture from right to left intrapulmonary shunting, as well as decrements in cardiac output. Cerebral oxygen desaturation accompanying OLV is also well described, though the pathophysiology is not well understood. It is likely, though unproven, that microcirculatory derangements may underly these phenomena. Though the study of microcirculatory dysfunction in thoracic surgery is in its infancy, the body of available evidence at this point supports the following hypotheses; that microcirculatory derangements and dysfunction 1) occur during major surgeries including transthoracic esophagectomy 2) may be related to SIRS, OLV or both, 3) may predict adverse outcomes, and 4) may be amenable to modification via specific therapies.

This is a feasibility study to see if the changes in microcirculatory parameters as observed by the SDF device can accurately diagnose anastomotic and other complications for the purpose of leading to a wider study of microcirculatory derangements as an indicator of risk of surgical complications.

Hypothesis to be Tested:

1. Microcirculatory derangements, as indicated by changes in microcirculation of sublingual tissue, serosa tunica near the surgical division, or the mucosal lining of the stomach near the surgical division, occur during transthoracic esophagectomy and in the perioperative period. ii. Changes in microcirculation predicts post-operative anastomotic complications iii. Changes in microcirculation predicts post-operative complications

Specific Aims

1. Determine whether microcirculatory derangements, as indicated by changes in microcirculation of sublingual tissue, serosa tunica near the surgical division, or the mucosal lining of the stomach near the surgical division, occur during transthoracic esophagectomy involving one lung ventilation (OLV), using a side stream dark field (SDF) imaging system. 1.1. This aim will include measurements of microcirculatory parameters at multiple time points within the perioperative period.
2. Determine the temporal relationship of microcirculatory dysfunction and recovery, if any, at the initiation of OLV, reestablishment of two lung ventilation, and cessation of surgery. 2.1. This aim will include measurements of microcirculatory parameters at multiple time points within the perioperative period.
3. Determine whether observed changes in microcirculation is predictive of postoperative organ dysfunction, and perioperative complications.