Tissue microvascular flow and oxygenation in critically ill patients

Abstract

The use of fluid resuscitation and vasoactive agents to optimise global haemodynamics has been demonstrated to improve outcomes in patients undergoing major surgery and in early sepsis. Whether changes in global haemodynamics result in similar improvements in the microcirculation in critically ill patients remains unclear. The aim of this thesis was to investigate the changes in tissue microvascular flow and oxygenation that occur in patients undergoing major surgery and in those with sepsis, and specifically how haemodynamic therapies may affect these changes. The first part of this thesis investigates the treatment pathway of the high risk surgical patient. Analysis of two large health databases was performed and confirmed the existence of a high risk sub-population within the local surgical population. Only about a third of these high-risk patients were admitted to a critical care unit at any stage during their hospital admission. An observational trial was performed examining the relationship between global oxygen delivery, microvascular flow and tissue oxygenation in 25 surgical patients receiving usual care. Data including global haemodynamics, sublingual and cutaneous microvascular flow, and tissue oxygenation were collected before, and for eight hours after surgery. Abnormalities in sublingual microvascular flow were found to be associated with worse outcomes. 4 A randomised controlled study investigating the effects of two goal directed haemodynamic therapy (GDHT) algorithms on tissue microvascular flow and oxygenation compared to central venous pressure guided fluid therapy in 135 perioperative patients was performed. For eight hours after surgery, intravenous fluid therapy was guided by measurements of central venous pressure (CVP group) or stroke volume (SV group). In a third group stroke volume guided fluid therapy was combined with dopexamine (SV & DPX group). In the SV & DPX group, increased global oxygen delivery was associated with improved sublingual and cutaneous microvascular flow. Microvascular flow remained constant in the SV group but deteriorated in the CVP group. Cutaneous PtO2 improved only in the SV & DPX group. There were no differences in complication rates between groups. The importance of derangements in microvascular flow in patients with established sepsis is well recognized. However, little data is available to describe microvascular changes in early sepsis. Observational data were collected in 16 healthy volunteers and within six hours of presentation in 48 patients with sepsis and severe sepsis. Sublingual microvascular flow was impaired in patients with sepsis and severe sepsis compared to healthy volunteers. Greater alterations in flow were seen with increasing severity of illness. The dose-related effects of vasopressor therapy on microvascular flow and tissue oxygenation in sepsis have not been previously fully investigated. The effects of increasing doses of noradrenaline, targeted to achieve successively greater mean arterial pressures, on microvascular flow and tissue oxygenation in 16 patients with septic shock were investigated. Increasing doses of noradrenaline were associated with improvements in 5 global oxygen delivery, cutaneous PtO2 and cutaneous microvascular red blood cell flux. No changes in sublingual microvascular flow were identified. This thesis confirms the existence of a large sub-population of high risk surgical patients. It demonstrates that abnormal microvascular flow in the perioperative period may be associated with poor outcomes. The use of flow guided fluid therapy alongside low dose dopexamine infusion is shown to improve global haemodynamics, microvascular flow and tissue oxygenation in perioperative patients. Microvascular abnormalities are shown to occur in the earliest stages of sepsis with increasing severity of disease being associated with greater changes. Increasing doses of noradrenaline were found to improve global haemodynamics, cutaneous microvascular flow and cutaneous tissue oxygenation in septic shock. Further work is required to investigate the effects of haemodynamic therapies on microvascular flow and organ dysfunction in critically ill patients and the use of the microcirculation as a resuscitation endpoint.