Abstract and Introduction
Abstract
Introduction: Disturbances in microcirculatory homeostasis have been hypothesized to play a key role in the pathophysiology of multiple organ dysfunction syndrome and vasopressor-associated ischemic skin lesions. The effects of a supplementary arginine vasopressin (AVP) infusion on microcirculation in vasodilatory shock and postoperative multiple organ dysfunction syndrome are unknown.
Method: Included in the study were 18 patients who had undergone cardiac or major surgery and had a mean arterial blood pressure below 65 mmHg, despite infusion of more than 0.5 µg/kg per min norepinephrine. Patients were randomly assigned to receive a combined infusion of AVP/norepinephrine or norepinephrine alone. Demographic and clinical data were recorded at study entry and after 1 hour. A laser Doppler flowmeter was used to measure the cutaneous microcirculatory response at randomization and after 1 hour. Reactive hyperaemia and oscillatory changes in the Doppler signal were measured during the 3 minutes before and after a 5-minute period of forearm ischaemia.
Results: Patients receiving AVP/norepinephrine had a significantly higher mean arterial pressure (P = 0.047) and higher milrinone requirements (P = 0.025) than did the patients who received norepinephrine only at baseline. Mean arterial blood pressure significantly increased (P < 0.001) and norepinephrine requirements significantly decreased (P < 0.001) in the AVP/norepinephrine group. Patients in the AVP/norepinephrine group exhibited a significantly higher oscillation frequency of the Doppler signal before ischaemia and during reperfusion at randomization. During the study period, there were no differences in either cutaneous reactive hyperaemia or the oscillatory pattern of vascular tone between groups.
Conclusion: Supplementary AVP infusion in patients with advanced vasodilatory shock and severe postoperative multiple organ dysfunction syndrome did not compromise cutaneous reactive hyperaemia and flowmotion when compared with norepinephrine infusion alone.
Introduction
Impaired microcirculatory blood flow has been identified as a key component in the pathophysiology of multiple organ dysfunction syndrome after surgery and in sepsis. The precise mechanisms involved remain unclear but include complex interactions between various factors: increased heterogeneity of capillary blood flow; reduced erythrocyte deformability; endothelial cell dysfunction with increased permeability and apoptosis; altered vasomotor tone; increased numbers of activated neutrophils with more neutrophil-endothelial interactions; and activation of the clotting cascade with formation of microthrombi. De Backer and colleagues identified impaired capillary perfusion, assessed by orthogonal polarization spectrophotometry, as an independent predictor of mortality in severe sepsis. Similarly, Sakr and colleagues observed that patients who died from persistent septic multiple organ dysfunction had markedly impaired microcirculatory perfusion over time compared with surviving patients.
Although macrocirculatory parameters such as mean arterial blood pressure (MAP) and cardiac output are unreliable for predicting microcirculatory homeostasis, there is strong evidence that a certain perfusion pressure — probably a MAP above 65 mmHg if it is combined with adequate cardiac output — is a prerequisite for adequate microcirculatory blood flow. Although vasopressor infusion alone is undoubtedly detrimental to microcirculatory blood flow, it is currently recommended that fluid resuscitation and infusion of inotropic agents to achieve adequate cardiac output be combined with vasopressor therapy in order to realize a reasonable tissue perfusion pressure.
However, in a small group of patients with cardiocirculatory failure, recommended standard therapy alone is not sufficient to attain a MAP necessary to maintain perfusion of an altered microcirculation.
It has been reported that supplementary infusion of arginine vasopressin (AVP) can reliably increase MAP to above 65 mmHg, even in patients with advanced cardiovascular failure who are resistant to standard treatment. However, when AVP was continuously infused in healthy animals it resulted in severe disturbances in capillary blood flow and tissue oxygenation. The effects of a supplementary AVP infusion on microcirculation in humans with severe cardiovascular failure are unknown. Exacerbation of microvascular failure by a therapeutic intervention such as vasopressor therapy would be detrimental to cell oxygenation, organ regeneration and, ultimately, patient survival. Our study group reported a 30.2% incidence of ischaemic skin lesions in patients with advanced vasodilatory shock during supplementary AVP infusion.
This clinical study was conducted to evaluate prospectively the cutaneous microcirculatory response to a combined infusion of AVP and norepinephrine when compared with infusion of norepinephrine alone, using laser Doppler flowmetry in patients with advanced vasodilatory shock and severe postoperative multiple organ dysfunction syndrome ( Table 1 ).