Hemodynamic Stabilisation in Septic shock

Dr. T.R.Chandrashekar

Intensivist K.R. Hospital

Bangalore

• Shock is defined as a life-threatening, generalized maldistribution of blood flow resulting in failure to deliver and/or utilize adequate amounts of oxygen, leading to tissue dysoxia.

• Hypotension [SBP < 90 mmHg, SBP decrease of 40 mmHg from baseline, or mean arterial pressure (MAP) < 65 mmHg], while commonly present, should not be required to define shock.

• Shock requires evidence of inadequate tissue perfusion on physical examination.

Shock

Septic shock

• The definition underscore a few points

• 1) Blood flow at a adequate pressure (MAP)> 65mmHg

• Shock can still occur with a normal perfusion.

• Delivery and utilisation of O2 at cellular level-abnormalities are the hall mark of septic shock.

Septic shock

MacrocirculationPerfusion with adequate oxygen

Microcirculation Improper delivery and utilisation

Mitochondrial dysfuction

Microcirculatory and Mitochondrial Distress syndrome

(MMDS)MMDS = sepsis +genes+ therapy + time

Hostgenetic background

co-morbidity

HIT infectiontraumaburnsetc.

timetherapy

MMDS

Figure 2

Adequate perfusion pressure

MAP>=65mmHg

Adequate oxygen delivery

CO x Hb x SPO2 x 1.34 + .003 x PaO2

Optimisation of Macrocirculation • Assessment • Clinical Hypotension Tachycardia Altered mental status Delayed capillary refill Decreased urine output Cool skin Cold extremities

• Hemodynamic parameters

• Organ perfusion

• Goals • HEMODYNAMCS

• CVP = 8–12 mm Hg

• MAP > = 65 mm Hg

• CI >=2.5- 3 L/min/m2

• O2 DELIVERY• Arterial Hgb SpO2 > 93%

• ScVO2 > =70 mm Hg

• Blood Lactate Conc < 2 mM/L

• Hematocrit >=30%

• ORGAN PERFUSION• CNS - improved sensorium• Skin - warm, well perfused• Renal - Urine output >=0.5ml/kg/hr

Hemodynamic Truths

• Tachycardia is never a good thing

• Hypotension is always pathological

• There is no normal cardiac output

• CVP is only elevated in disease

• Peripheral edema is of cosmetic concern

Volume Vesseltone

Heart function

If shock is prolonged, mechanisms of shock are combined

Physiologic Classification of Physiologic Classification of Acute Circulatory InsufficiencyAcute Circulatory Insufficiency

Fluids / blood Vasopressors Inotropes

The questionThe question “Will my patient respond “Will my patient respond to fluids?”to fluids?” cannot be accurately cannot be accurately

answered by any ‘preload’ parameteranswered by any ‘preload’ parameterPrinciples of Volume challenge

To test Starling’s law the fluid needs to be given quickly – the faster it is given the less that is needed

It makes no sense to test “preload” responses over long periods of time (eg Kumar et al 2004)

The type of fluid is not critical if given quickly enough

There needs to be a change in CVP to know that Starling’s Law has been tested

PRELOAD assessment-Volume • To look at CVP/ PAOP• Always CVP is in relation to CO

Volume responsive

Volume unresponsive

Add dopamine or dobutamine

Volume

SV

Decreased contractility

Right atrial volume

–The actual value of the CVP is determined by the interaction of Cardiac function and return function

return function

cardiac function

PRELOAD assessment

• Attempts to assess EDV through surrogate measures– CVP, Ppao, LV end-diastolic area, RV EDV,

intrathoracic blood volume

5. A fluid challenge and flow response remain the gold standard for assessing fluid responsiveness

6. The functional range of CVP/Pra is small so that technical factors are important

Importance of leveling Transmural pressure Position on waveform

CO

Preload

Fluid Responsiveness is a dynamic parameter Fluid Responsiveness is a dynamic parameter that reflects the degree by which the CO that reflects the degree by which the CO

responds to changes in preloadresponds to changes in preload

““Will my patient respond to fluids?”Will my patient respond to fluids?”

Dynamic (functional) parameters

SPV / dDown, PPV, SVV, RSVT, SPV / dDown, PPV, SVV, RSVT, OthersOthers

• ‘‘RULE OF THUMB’RULE OF THUMB’

• (in the absence of any confounding factors(in the absence of any confounding factors))

• If If SPV > 10 mmHg (or 10%), SVV>10%, PPV>13% --- SPV > 10 mmHg (or 10%), SVV>10%, PPV>13% --- probable significant volume responsiveness (may indeed probable significant volume responsiveness (may indeed signify hypovolemia!)signify hypovolemia!)

• Spontaneously breathing patientsSpontaneously breathing patients • Passive leg raising testPassive leg raising test

MV PATIENTS

• Fluid resuscitation may consist of natural or artificial colloids or crystalloids• No evidenced-based support for one type of

fluid over another• Crystalloids have a much larger volume of

distribution compared to colloids• Crystalloid resuscitation requires more fluid to

achieve the same endpoints as colloid• Crystalloids result in more edema

Fluid Therapy: Choice of Fluid

Grade C

Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

• Fluid challenge in patients with suspected hypovolemia may be given• 500 - 1000 mL of crystalloids over 30 mins• 300 - 500 mL of colloids over 30 mins• Repeat based on response and tolerance• Input is typically greater than output due to

venodilation and capillary leak• Most patients require continuing aggressive fluid

resuscitation during the first 24 hours of management

Fluid Therapy: Fluid Challenge

Grade E

Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

SHOCK

MAP < 65mmHgOliguria (<0.5ml/Kg/hour)

Clinical signs of tissue hypoperfusion

1) Clinical approach

-HR/BP-Peripheral perfusion-Impact of volume loading-Urine output

2) CVP/SvcO2

3) Echocardiographyshould preceed any CO monitoring

Predominant RVF or global F

PAC catheter

Predominant LVFany CO monitoring

First step

Second step

Third step

Fourth step

Mixed/central venous O2 saturationMixed/central venous O2 saturation

o marker of global supply/demand balanceo falls in low output states e.g. heart failureo prognosticator of outcome, failure to wean…o elevated in resuscitated sepsis

o microvascular shunting??o decreased cellular utilisation??

o mixed venous vs central venous differenceso one landmark ScvO2-targetted study

(Rivers)

75%

Factors that influence mixed and central venous Factors that influence mixed and central venous SOSO22

VO2 DO2 DO2 VO2 Stress

Pain

Hyperthermia

Shivering

PaO2

Hb

Cardiac output

PaO2

Hb

Cardiac output

Hypothermia

Anesthesia

_ +

Mixed/central SvO2Mixed/central SvO2

o PA catheter use decline .. ∆ reliance on ScvO2

o Useful in global low output stateso Limited in established sepsis (other than identification of low values)

SvO2 closely correlates with ScvO2SvO2 closely correlates with ScvO2

The major problems with the interpretation of ScvO2

• Like the CO, a low SvO2 tells you that something is wrong, but not what is wrong and what should be done about it (fluids? inotropes?).

• When the SvO2 is normal or high -one cannot assume that all is well (e.g., CO normal) since in septic patients the ScvO2 may be elevated due to an abnormally low O2 extraction.

InsertCVP/SvcO2

SvO2 >70% SvO2 <70%

Sepsis?

Repeat Fluid challenge250ml/ 5mins

Haemodynamic improvement ?

Consider global/right ventricular failure

Echocardiography that preceeds cardiac output monitoring

Yes

Continue until normal values

obtained

No

Vasopressors

Hypovolaemic/Haemorrhagic/

cause?

No response

Continue until normal values obtained

Haemodynamicimprovement

Repeat fluid challenge(250ml/5mins)or transfusion if necessary.

Echocardiography that preceeds CO monitoring

CVP N or lowCVP high CVP low

How to differentiate between Contractility vs Vasomotor tone

• Echocardiography • Cardiac output monitoring

INTERPRETATION OF CARDIAC OUTPUT

Do we have a problem ?

Arterial hypotension Tachycardia Oliguria

Increase incardiac output

FLUIDS ?

Do we need to measurecardiac output ?

DOBUTAMINE ?

Why/when would I want to measure CO or SV in shock?

• Failure hemodynamic management based on clinical signs and CVP-ScvO2; this should always direct to echocardiography

• Echocardiography should, ideally, always preceed CO monitoring

• CO monitoring shoud be a PAC catheter in case of RV dysfunction while any CO monitoring, less invasive than PAC, should be favored for LV dysfunction

http://gateway.ut.ovid.com/gw1/ovidweb.cgi?View+Image=00003246-200505000-00033%7CFF1&S=IDNJHKOAFFJEHM00D&WebLinkReturn=Full+Text%3DL%7CS.sh.15.16%7C0%7C00003246-200505000-00033

The way I do

• After adequate fluid resusciation

• Start with nor adrenaline then add dobutamine- looking at contractility and SVR

• If MAP <65 mmHg

• Add adrenaline or contemplate

• Vasopressin or phenylephrine

• Initiate vasopressor therapy if appropriate fluid challenge fails to restore adequate blood pressure and organ perfusion

• Vasopressor therapy should also be used transiently in the face of life-threatening hypotension, even when fluid challenge is in progress

• Either norepinephrine or dopamine are first line agents to correct hypotension in septic shock

• Norepinephrine is more potent than dopamine and may be more effective at reversing hypotension in septic shock patients

• Dopamine may be particularly useful in patients with compromised systolic function but causes more tachycardia and may be more arrhythmogenic

Vasopressors Grade E

Grade D

• Low dose dopamine should not be used for renal protection in severe sepsis

• An arterial catheter -Vasopressors Arterial catheters provide more accurate and

reproducible measurement of arterial pressure Vasopressin may be considered in refractory shock

patients that are refractory to fluid resuscitation and high dose vasopressors

• Infusion rate of 0.01-0.04 units/min in adults• May decrease stroke volume

Vasopressors (cont)Grade B

Grade E

Grade E

• In patients with low cardiac output despite adequate fluid resuscitation, dobutamine may be used to increase cardiac output • Should be combined with vasopressor therapy in the

presence of hypotension

• It is not recommended to increase cardiac index to target an arbitrarily predefined elevated level • Patients with severe sepsis failed to benefit from

increasing oxygen delivery to supranormal levels by use of dobutamine

Inotropic TherapyGrade E

Grade A

Hemodynamic Patterns with Prognostic Value

• A lower heart rate at the onset of disease is predictive of survival.

• Normalization within 24 hours of either tachycardia or elevated cardiac index is associated with survival. Persistence of hyperdynamic state increases likelihood of death.

• A low ejection fraction and ventricular dilatation are also associated with survival. This perhaps reflects Frank-Starling compensation of sepsis induced myocardial depression.

•Even with the ‘best’ parameters it is not always easy to make the right decision.………

“…Our understanding of hemodynamic mechanisms (in distributive shock) depends not so much on the total volume of blood that flows past the aortic valve or the cardiac output as on the amount of blood delivered to the exchange sites. Even though cardiac output may be substantial, if that blood flow does not arrive at the exchange sites, the ultimate metabolic detriment is no different from low cardiac output without shunt flow.”

Weil MH, Shubin H (1971) Adv Exp Med Biol 23:13-23.

Why the microcirculation is important in shock.

1. It is where oxygen exchange takes place.

2. It plays a central role in the immune system.

3. During sepsis and shock it the first to go and last to recover.

4. Rescue of the microcirculation = resuscitation end-point.

Shunting model of sepsisShunting model of sepsis

O2

lactateCO2

vvaa

Implication : that active recruitment of the microcirculationis an important component of resuscitation.

Ince C & Sinaasappel M (1999) Crit Care Med 27:1369-1377

Spronk P, Zandstra D, Ince C (2004) Critical Care 8:462-468

Sepsis is a disease of the microcirculation

Mitochondrial Dysfunction in Cell Injury

Increased cytosolic Ca2+, oxidative stress, lipid peroxidation

Mitochondrial PermeabilityTransition

Cytochrome c and other pro-apoptotic proteins

ApoptosisRobbins & Cotran Robbins & Cotran Pathologic Basis of Disease: 2005Pathologic Basis of Disease: 2005

Functional and Morphologic Consequences of Decreased ATP During Cell Injury

Ischemia

Oxidative PhosphorylationATP

Na pump

Influx of Ca2+

H20, and Na+

Efflux of K+

ER swellingCell swellingBlebs

Clumpingchromatin

Anaerobic glycolysis

GlycogenpH

Lipid deposition

Detachment of ribosomes

Protein synthesis

Energy failure

BE - Lactate

Pump failure or

mitochondrial dysfunction

Hemodynamic failure

Pump failure

Volume test

VO2 Lactate

Mitochondrial dysfunction

VO2 Lactate

Dobutamine test

VO2 Lactate

VO2 Lactate

Hemodynamic and mitochondrial failure

Microcirculation assessment

• Tissue perfusion• Gastric tonometry

Orthogonal polarizationspectral (OPS) imaging

Capillary flow in sepsis

Microcirculation Recruitment Manoeuvres Ince C (2005) Critical Care 9:S13-S19

Correct pathological flow heterogeneity, microcirculatory shunting and restore autoregulatory dysfunction by control of inflammation, vascular function and coagulation.

Avontuur (1997) Cardiovas Res 35:368-376.

Siegmund M (2005) Inten Care Med 31:985-992.

Open the microcirculation and keep it open by support of the pump, fluids, vasodilators and restricted use of vasopressor agents. :

Boerma (2005) Acta Anaesthesiol Scand. 49(9):1387-90. Spronk (2001) The Lancet 360:1395-1396

Siegemund (2006) Intensive Care Med

Sublingual OPS imaging in a patient with septic shock after pressure guided volume resuscitation.

the same patient after subsequent nitroglycerin 0.5 mg ivbolus

Nitroglycerin promotes microvascular Nitroglycerin promotes microvascular recruitment in septic and cardiogenic recruitment in septic and cardiogenic

shock patientsshock patients

Spronk, Ince, Gardien, Mathura, Oudemans-van Straaten, Zandstra DF. (2002) The Lancet 360:1395-1396.

Conclusions

1) Distributive shock has a bad prognosis with difficult to define hemodynamics end-points.

2) It causes a distributive defect at the apillary level of the microcirculation causing functional shunting of weak microcirculatory units.

3) It is the reason why distributive shock cannot be adeqautely monitored by systemic hemodynamic parameters.

4) OPS/SDF en tissue capnography provide an integrative evaluation of the functional state of the microcirculation.

5) Microcirculatory Recruitment Maneuvres are affective in correcting distributive shock

Take home thoughts

• Time is important-EGDT Energy failure may be due to primitive

hemodynamic inadequacy and/or mitochondrial dysfunction

• Prolonged energy failure leads to irreversible mitochondrial dysfunction (necrosis - apoptosis

• Once MMDS starts shock becomes irreversible• First optimise macrocirculation

Some “Pretty Good” Cardiovascular Management Goals

• Fluid resuscitation to keep a CI > 2.5 l/min/m2 with a Ppao < 20 mm Hg

• Add inotropic support if unable to sustain CI within this Ppao limit

• Vasopressors to maintain a mean arterial pressure > 65 mm Hg

• If measures of organ perfusion available (urine output, PCO2, tissue blood flow, Serum lactate, base deficit ) use them to guide response to therapy.

• Trends may be more important than absolute values