Capillary Refill Time Response to a Rapid Fluid Challenge in Septic Shock Patients: Pathophysiological Determinants, and Relation to Changes in Systemic, Regional and Microcirculatory Blood Flow

INTRODUCTION Septic shock is associated with a high mortality risk of up to 30-60%. Multiple pathogenic factors can lead to progressive tissue hypoperfusion in the context of severe systemic inflammation. However, despite extensive research on the best monitoring and resuscitation strategy many uncertainties persist. Over-resuscitation, particularly when inducing fluid overload, might contribute to a worse outcome. Fluid overload more likely occurs when fluids are administered to fluid unresponsive patients, but also when inappropriate resuscitation goals are pursued. The systematic use of bedside techniques to determine fluid responsiveness (FR) can help to avoid fluid overload. Moreover, further deleterious fluid administration can be prevented by adding the evaluation of hemodynamic coherence in parallel or sequentially to FR. Further research on this topic is imperative considering not only the extremely high morbidity and mortality of septic shock, but also the increasing economic burden over the health system in both developed and low/medium income countries.

CAPILLARY REFILL TIME (CRT) AS A TARGET FOR FLUID RESUSCITATION IN SEPTIC SHOCK The skin territory lacks auto-regulatory flow control, and therefore, sympathetic activation impairs skin perfusion during circulatory dysfunction, a phenomenon that can be evaluated by peripheral perfusion assessment. Abnormal peripheral perfusion after initial or advanced resuscitation is associated with increased morbidity and mortality. A cold clammy skin, mottling or prolonged CRT have been suggested as triggers for fluid resuscitation in patients with septic shock. Moreover, the excellent prognosis associated with CRT recovery, its rapid-response time to fluid loading, its relative simplicity, its availability in resource-limited settings, and its capacity to change in parallel with perfusion of physiologically relevant territories such as the hepatosplanchnic region, constitute strong reasons to consider CRT as a target for fluid resuscitation in septic shock patients.

THE CONCEPT OF A FLUID CHALLENGE Since absolute or relative hypovolemia is almost universally present in early septic shock, resuscitation starts with fluid loading in pre-ICU settings. Fluid loading is the rapid administration of fluids without necessarily monitoring the response in real-time, when confronting severe life-threatening hypotension and hypoperfusion. In this setting, usually 20-30 ml/kg crystalloids are loaded.

If circulatory dysfunction is not resolved with this initial management, patients are transferred to the ICU, where advanced fluid resuscitation is started with the fundamental objective to increase systemic blood flow. The initial step is assessment of FR. Fluid-responsive patients will increase stroke volume >10 to 15% after receiving a fluid bolus (usually 250 to 500 ml of crystalloids) since they are in the ascending part of the Starling curve. On the contrary, being fluid-unresponsive implies to be in the flat part of the curve where fluids will only lead to congestion without increasing stroke volume.

The standard practice is to perform a fluid challenge in fluid-responsive patient who are still hypoperfused. A fluid challenge consists of a fluid bolus, large and rapid enough, to increase venous return and cardiac output (CO) in fluid responsive patients, and eventually improve tissue perfusion, depending on the status of hemodynamic coherence (see below). Fluid is given as a fluid challenge so that response can be assessed looking at the target, and the need for ongoing fluid therapy ascertained.