Department of Intensive Care Medicine UNDERSTANDING CIRCULATORY FAILURE IN SEPSIS

Department of Intensive Care Medicine UNDERSTANDING CIRCULATORY FAILURE IN SEPSIS

UNDERSTANDING CIRCULATORY FAILURE IN SEPSIS a mismatch between tissue perfusion and metabolic demands the heart, the vasculature and alterations in various tissue and cellular functions are involved in the pathophysiology Ö multiorgan dysfunction clinical presentation: Ö highly variable Ö Ö changes over time modified by preceding and concomitant treatment and comorbidities Bloch et al, Intensive Care Med 2016;42:2077 2079

CLINICAL HALLMARKS signs of tissue hypoperfusion hypotension or need for vasopressors to prevent hypotension, despite adequate fluid resuscitation signs of tissue hypoperfusion vary: Ö impaired capillary perfusion Ö Ö Ö oliguria elevated blood lactate altered mentation

SEPTIC SHOCK DEFIES EXPLICIT, OBJECTIVE DEFINITIONS relevant hypotension is patient specific adequate fluid resuscitation is highly subjective

JAMA. 2016;315(8):801-810. doi:10.1001/jama.2016.0287

OPEN QUESTIONS/ MAJOR CONTROVERSIES «need for vasopressors» Ö definition of blood pressure targets «adequate fluid resuscitation»

WHY ARE THESE QUESTIONS IMPORTANT? interventions to achieve the desired blood pressure may influence outcome Ö vasopressor load Ö fluid load fluid resuscitation strategy may influence outcome Ö association of positive fluid balance with increased risk of death «need for vasopressors» and «adequate fluid resuscitation» Ö context and interpretation highly variable effects unknown

NOT RESPONDING, OR NEEDING VASOPRESSORS WHY? hemodynamic pathophysiology in sepsis hypovolemia due to Ö absolute loss of fluid Ö increased permeability favors low cardiac output loss of vascular tone favors high cardiac output Ö low systemic vascular resistance (arterial vasodilatation) Ö reduced resistance to venous return Ö vasodilatation (venous pooling, loss of stressed volume) cardiac dysfunction Ö impaired contractility Ö diastolic dysfunction favors low cardiac output favors low cardiac output

NO CONTROVERSY increasing severity of circulatory failure is associated with increasing mortality delayed treatment Ö increases the severity of circulatory failure in sepsis Ö necessitates more support with fluids and vasoactive drugs Ö increases mortality

BLOOD VOLUME The unstressed volume fills the vasculature before any vessel wall tension develops The stressed volume causes wall tension

BLOOD VOLUME IN SEPSIS stressed volume decreases via two mechanisms Ö shift from stressed to unstressed volume due to vasodilatation Ö loss of total volume due to increased vascular permeability

LOSS OF STRESSED VOLUME IN SEPSIS: shift from stressed to unstressed volume stressed volume unstressed volume vasodilatation

LOSS OF STRESSED VOLUME IN SEPSIS: loss of total volume due to increased vascular permeability 140 hemoconcentration and treatment delay 120 100 hemoglobin (G/L) 80 60 40 20 0 6 hrs 12 hrs 24 hrs baseline start treament Corrêa et al, Crit Care Med 2012; 40:2841 2849

DECREASED STRESSED VOLUME AND VENOUS RETURN blood flow cardiac function curve venous return curve MSFP right atrial pressure decreased venous return, decreased cardiac output adapted from Magder Critical Care 2012, 16:236

LOSS OF STRESSED VOLUME IN SEPSIS: two mechanisms act in combination stressed volume vasodilatation absolute loss of volume vasoconstriction vasoconstriction

VASODILATATION, ABSOLUTE LOSS OF VOLUME, VASOCONSTRICTION blood flow cardiac function curve venous return curve vasodilatation, absolute volume loss, decreased stress volume vasoconstriction, increased stressed volume MSFP right atrial pressure adapted from Magder Critical Care 2012, 16:236

TREATMENT DELAY: increased need of fluids to restore hemodynamics Corrêa et al, Crit Care Med 2012; 40:2841 2849

BLOOD FLOW EVOLUTION DURING UNTREATED SEPSIS Cardiac output (ml/kg/min) 180 160 140 120 100 80 60 40 cardiac output control 6hrs 12hrs 24hrs carotid femoral artery flow flow (mlkg/min) (ml/kg/min 14 8 control 6 control hrs delay 12 6 hrs hrs delay delay 12 24 12 hrs hrs delay delay 24 hrs delay 6 10 8 4 6 4 2 femoral blood flow 20 2 0 baseline sepsis 0 baseline sepsis Corrêa et al, Crit Care Med 2012; 40:2841 2849

BLOOD FLOW EVOLUTION DURING UNTREATED SEPSIS Cardiac output (ml/kg/min) 180 160 140 120 100 80 60 cardiac output control 6hrs 12hrs 24hrs carotid artery flow (ml/kg/min 14 12 10 8 6 4 carotid blood flow control 6 hrs delay 12 hrs delay 24 hrs delay 40 20 2 0 baseline sepsis 0 baseline sepsis Corrêa et al, Crit Care Med 2012; 40:2841 2849)

CEREBRAL BLOOD FLOW IN SEPSIS normotension van den Brule et al, Shock 2017 in press

CEREBRAL BLOOD FLOW IN SEPSIS normotension van den Brule et al, Shock 2017 in press

VASODILATATION, ABSOLUTE VOLUME LOSS: highly variable relative contribution if volume loss due to increased permeability predominates, both unstressed and stressed volume need to be restored if vasodilation is the main mechanism, vasopressors should be combined with judicious use of fluids

VASODILATATION, ABSOLUTE LOSS OF VOLUME, VASOCONSTRICTION and CARDIAC DYSFUNCTION blood flow cardiac function curve venous return curve vasoconstriction, increased stressed volume vasodilatation, absolute volume loss, decreased stress volume cardiac dysfunction MSFP right atrial pressure adapted from Magder Critical Care 2012, 16:236

VASODILATATION, ABSOLUTE VOLUME LOSS: highly variable relative contribution hypotensive patient with cold periphery: Ö more likely to have an absolute volume deficit hypotensive patient with preserved peripheral perfusion: Ö likely to benefit from vasoconstriction CARDIAC DYSFUNCTION? in both scenarios: Ö treatment should normalize venous filling and capillary perfusion Ö rapid increase in venous filling in response to fluids suggests cardiac dysfunction

CARDIAC DYSFUNCTION IN SEPSIS diastolic and systolic function of both ventricles can be affected RV dysfunction is very common but often missed Ö increased pulmonary vascular resistance and increased afterload due to mechanical ventilation all contribute to RV dysfunction and failure Ö volume loading may further worsen RV dysfunction Ö RV dysfunction causes pulse pressure variation

CIRCUIT FACTORS, VENTRICULOARTERIAL COUPLING the elastic properties of the systemic and pulmonary arterial trees (arterial elastance, E a ) influence the ejection of both ventricles (afterload effect) +myocardial dysfunction endsystolic pressure (Pes) E a = Pes/SV endsystolic elastance E es = Pes/(Ves-Vo) indicator of contractility unstressed volume of ventricle SV

CIRCUIT FACTORS, VENTRICULOARTERIAL COUPLING mismatch between ventricular contractility (E es ) and the vascular elastance (E a ) ventriculoarterial decoupling: -E a /E es increases decreased contractility +myocardial dysfunction ventriculoarterial decoupling diastolic dysfunction unstressed volume of ventricle SV

CIRCUIT FACTORS, VENTRICULOARTERIAL COUPLING inefficient use of the mechanical energy provided by the heart both ventricles may become decoupled from their vascular trees in sepsis the clinical relevance of ventriculo-arterial decoupling in circulatory failure in sepsis is poorly understood

CIRCULATORY FAILURE IN SEPSIS - CONCLUSIONS a complex interaction of the circuit and the heart impaired functions of both ventricles loss of stressed volume due to reduced vascular tone and absolute fluid loss limits the venous return venous return is limited further if right atrial pressure increases more than MSFP impaired function of either ventricle may limit attempts to restore the stressed volume avoid unnecessary increases in right atrial pressure vasopressors may impair cardiac function and cause ventriculoarterial decoupling caution!