Venous Return and Effective Circulatory Michael R. Pinsky, MD, Dr hc Department of Critical Care Medicine University of Pittsburgh Bedside Cardiovascular Physiology

• Exploring the Determinants of – Mean systemic pressure – Cardiac performance – Blood flow distribution • Deconstructing Systemic – Arterial critical closing pressure – Arterial and venous resistance The

Cardiac Output

Q (l/min)

0 10 Pra (mm Hg) Defining the Determinants of Venous Return Using a Right Bypass Preparation

Guyton et al. Am J Physiol 189:609-15, 1957 The Venous ReturnCurve

Venous Return 0 P ra VR = CO = (P = = COVR Guyton et al. Am J Slope = 1 /RVR =1 Slope ms P - P ms ra Physiol ) /RVR P ra 189:609 = P = ms - 15, 1957 Matching of the Venous Return Curve with the Cardiac Function Curve

Cardiac Output Equilibrium Point Q (l/min) Venous Return

0 Pra (mm Hg) 10 Guyton et al. Am J Physiol 189:609-15, 1957 Venous Return and LV Output

DPVR= Pms - Pra CO

Eh = [Pms-Pra]/Pms

RVR = [Pms - Pra]/CO Pms

0 0 Pra Matching of the Venous Return Curve with the Cardiac Function Curve

A. Normal

A B. Reduced Cardiac Q C Performance B (l/min) C. Volume Infusion

0 10 Pra (mm Hg) Mean Systemic Pressure

• Static determinants: – Blood volume – Vasomotor tone • Dynamic determinants: –Blood flow distribution –Venous conductance (1/resistance) The Venous Return Curve Static Determinants

Hypervolemia

Normal Blood Volume Q (l/min) Hypovolemia

0 10 Pra (mm Hg) The Venous Return Curve Static Determinants

Increased Vasomotor Tone

Normal Vasomotor Tone Q (l/min) Decreased Vasomotor Tone

0 10 Pra (mm Hg) How to Measure Pms • Total circulatory arrest equilibrium pressure – Guyton et al. Am J Physiol 189:609-15, 1957 • Dynamic swings in the SVrv/Pra relation – Pinsky. J Appl Physiol 56:1237-45, 1984 • End-inspiratory hold (CPAP) – Versprille & Jansen. Pfliigers Arch 405:226-33, 1985 – Maas et al. Crit Care Med 37: 912-8, 2009 • Modeling flow capacitance and resistance – Parkin. Crit Care Resusc 1: 311-21, 1999 • Peripheral vascular stop flow equilibrium – Maas et al. Crit Care 12: S37, 2008 Spontaneous Ventilation Positive-Pressure Ventilation SVrv (ml/kg) Time (sec)

Pratm (mm Hg)

Ppl (mm Hg)

CVP (mm Hg)

Pinsky. J Appl Physiol 56:1237-45, 1984 Instantaneous Venous Return Curve

SVRV (ml)

0 10 Pra (mm Hg)

Pinsky. J Appl Physiol 56:1237-45, 1984 Instantaneous Venous Return Curve

n=26 r = 0.9014 p < 0.001

Pinsky. J Appl Physiol 56:1237-45, 1984 Inspiratory Pause Method of Calculating Pmcf

Vesprille & Jansen. Pfliigers Arch 405:226-33, 1985 Measuring Mean Systemic Filling Pressure at the Bedside Using Inspiratory Holds

Maas et al. Crit Care Med 37: 912-8, 2009 Measuring Pms at the Bedside using Inspiratory Holds

CPAP 5, 7.5, 10 and 12.5 6  Supine Head up position  Supine + volume

4

Volume loading Post-op (L/min) (L/min) Cardiac Surgery Patient

2

COmf COmf a b c Head-up tilt b a c

0 0 5 10 15 20 25 30 35 Pcv (mmHg)

Maas et al. Crit Care Med 37:912-8, 2009 Measuring Pms at the Bedside Calculating Vascular Compliance

35

30

25

20

15

Pmsf (mmHg) 10

5 b a c

0 -300 -200 -100 0 100 200 300 400 500 600 change in blood volume (mL)

Maas et al. Crit Care Med 37:912-8, 2009 Measuring Pms at the Bedside using peripheral pressure stop-flow technique

Radial arterial pressure

Vascular Occlusion

Stop-flow Equilibrium pressure Venous pressure

Maas et al. Intensive Care Med 38:1452-60, 2012 Measuring Pms at the Bedside using Peripheral Arterial Pressure Stop- Flow Technique

Maas et al. Intensive Care Med 38:1452-60, 2012 Measuring Pms at the Bedside using peripheral pressure stop-flow technique

20

15

10

5

0

-5 change Parm [mmHg] Parm change

-10

-15

-20 -20 -10 0 10 20 change Pmsf [mmHg]

Maas et al. Intensive Care Med 38:1452-60, 2012 Alternative to Measuring Pms Navigator Applied Physiology

Pms = (Vs + Vus)/(Cvs + Cas)

Vs = (Rvs x CO + Pra) Cv

assuming Cas/Cvs = 1/24 and Ras/Rvs = 25/1

Pms = 0.96Pra + 0.04Pa + 0.96 x c x CO

Where c = 0.96 x 1/26 x resting SVR (mm Hg/L/min) SVR dependent on anthropomorphic data Parkin. Crit Care Resusc 1: 311-21, 1999 (age, weight, length). Calculated Pms (Pmsa) tracks measured Pmsf with definable bias

Mass et al. Intensive Crit Care 38:1452-60, 2012 Changes is calculated Pms tract measured Pmcf in humans

20

y = 0,5262x R2 = 0,7606 15

10

5 dPmsa (mmHg) dPmsa 0 -10 -5 0 5 10 15 20

-5

-10 dPmsf (mmHg)

Mass et al. Intensive Crit Care 38:1452-60, 2012 If you know Pms you know the Effective Circulating Blood Volume

• Pms is a function of stressed and unstressed volume • Changes in Pms are a function of changes in blood flow distribution and vascular compliance • DPms/Dvolume = Functional Compliance Changes in Pmsa during Fluid challenge in Post-surgical ICU patients dVR = Pmsa - Pra

Pmsa increased with infusion dVR increased in responders

Cecconi et al. Intensive Care Med 39:1299-1305, 2013 Relation Between Blood Volume Vessel and Mean Systemic Pressure cross-sectional

area Volume Stressed Compliance = DV/DP Blood Volume Capacitance = Total Volume

Vascular Pressure Unstressed Volume Unstressed

Mean Systemic Pressure Effect of Changes in Total Blood Volume and Unstressed Volume on Mean Systemic Pressure

Volume Expansion

Vasoconstriction

Volume Stressed Blood Volume

Dilation Volume Constriction Unstressed Volume Unstressed

Mean Systemic Pressure Primary Mechanism for Increasing Venous Return

Decrease Unstressed Volume 1500 simultaneous measurements of Blood Volume and CVP in a heterogeneous cohort of 188 ICU patients

CVP r=0.27 (mmHg)

Deficit or Excess Blood Volume (ml/M2) Shippy et al. Crit Care Med 12:107-12, 1984 Instantaneous Venous Return and Endotoxic Shock

+400

+300

+200 +100 Baseline

Endotoxemia

+400 +300 +200 +100

Endotoxemia increases Rrv and Unstressed Volume

Pinsky & Matuschak J Crit Care 1:16-36, 1986 Pmsa accurately follows Pmsi in dogs during normal and endotoxic volume changing conditions 30,00

20,00 Pms (mmHg)

10,00 Endotoxin-Pmsi

Endotosin-Pmsa

Control-Pmsi

Control-Pmsa Pooled standard error

0,00 0 +100 +200 +300 +400 -300 -200 -100 0 Volume Challenge (mL) Lee et al. J Crit Care 28:880, 2013 Measuring Stressed Volume (Vs) in a Humans Using the Stop-Flow Parm Technique Systemic VascularSystemic Compliance Vascular Compliance Curves curve of for Responders volume responders 500

400

Stressed300 volume was estimated to be ~20 ml/kg

200

100

0 0 5 10 15

Systemic Vascular ComplianceCompliance curve nonresponders Curves of Non-Responders

500

400

300

Stressed200 volume was estimated to be ~30 ml/kg Volume change (mL) 100

0 0 5 10 15 20 25 30 35 40 45 50 Pmsf (mmHg) Geerts et al. J Clin Monit Comp 24:377-84, 2010 The Venous Return Curve Dynamic Determinants: Changes in Resistance to Venous Return

Increased Vasomotor Tone

Q (l/min) Decreased Vasomotor Tone

0 10 Pra (mm Hg) Decreasing Norepinephrine Decreases Cardiac Output in Septic Patients

Stable on norepinephrine

Following a decrease in norepinephrine

Persichini et al. Crit Care Med 40:3146-53, 2012 Effect of Dobutamine on Mean Systemic Pressure

100 Right atrium Aorta 90 Pao dobutamine Pao baseline Pao 80

70

60

50

40

baseline dobutamine

30 dobutamine

Rv

Rv

Pao, Pcv and Psf [mmHg] Psf and Pcv Pao,

20

baseline dobutamine Psf dobutamine

10

Rsys Rsys Pcv Rsys 0 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5

Rv and Rsys [mmHg.s.ml-1)

Geerts et al. J Clin Monit Comp 24:377-84, 2010 Effect of Dobutamine on Mean Systemic Pressure

Geerts et al. J Clin Monit Comp 24:377-84, 2010 Cardiac Output

Venous Return Cardiac Output and Venous Return Together Maximize Blood Flow 0 Dobutamine Rest Cardiac Output 20 VenousReturn Hemodynamic Effect of Propofol

de Wit et al. BJA 116:784-9, 2016 Hemodynamic Effect of Propofol

de Wit et al. BJA 116:784-9, 2016 Hemodynamic Effect of Propofol

de Wit et al. BJA 116:784-9, 2016 Systemic Venous Return Conclusions

Venous return is the primary determinant of cardiac output Cardiac output can only increase if DVR increases, RVR decreases or both But DVR and RVR are defined by arterial blood flow distribution to the tissues Which itself is defined by tissue oxygen demands Ventricular pump function defines the mean circulating blood volume necessary to maintain this steady state by setting right atrial pressure Thank You