Presentation

Home , Central venous catheter, SAPS III

ACUTE CIRCULATORY FAILURE Inability for the cells to get enough oxygen in relation to their oxygen needs

OXYGEN AVAILABILITY I am in SHOCK

Arterial hypotension Altered cutaneous perfusion (mottled, clammy skin) I am in Altered mentation (obtundation, disorientation, SHOCK confusion)

Arterial hypotension Altered cutaneous perfusion Decreased (mottled, clammy skin) urine output I am in Altered mentation (obtundation, disorientation, SHOCK confusion)

Arterial hypotension Altered cutaneous perfusion Decreased (mottled, clammy skin) urine output GASTRIC TONOMETRY Influence of monitoring systems on outcome

Gastric intramucosal pH as a therapeutic index of tissue oxygenation in critically ill patients. Gutierrez G et al., Lancet 339:195-9, 1992 EBM ?

260 patients (APACHE II 15-25)

pH > 7.35 pH < 7.35

YES NO YES NO Survival 58 % 42 % 37 % 36 % P < 0.01 P = NS I am in Altered mentation (obtundation, disorientation, SHOCK confusion)

Hyperlactatemia > 2 mEq/L Arterial hypotension Altered cutaneous perfusion Decreased (mottled, clammy skin) urine output SEVERITY CIRCULATORY SHOCK ELEVATED LACTATE

Distributive Hypovolemic Cardiogenic Obstructive

Sepsis Hypovolemia Heart Pulm. failure embolism Infection Pericardial Arrhythmias effusion LACTATE Hospital mortality, % 172,723 blood lactate measurements in 7,155 critically ill patients (4 hospitals) 100 90 80 70 60 Initial 50 lactate 40 levels 30 20 10 0 <1.2 1.2-1.5 1.5-2.0 2.0-4.0 4.0-6.0 >6.0 mEq/L or LACTATE mMol/L 6 Single measurement 5 4 3 2 1 0

TIME SKIN RBC BRAIN GUT MUSCLE

PRODUCTION

0.8 mmol/kg/h lactate (1300 mmol/day for 70 kg)

ELIMINATION

LIVER OTHER TISSUES 2/3 1/3 Blood lactate levels are influenced by

lactate production

more than by

lactate clearance PRODUCTION CLEARANCE

TIME

NATURAL HISTORY OF LACTIC ACIDOSIS AFTER GRAND-MAL SEIZURES Orringer et al, N Engl J Med 297: 796-9, 1977

Lactate levels, mEq/L 14 13 12 11 CLEARANCE 10 9 8 7 6 0 10 20 30 40 50 60 70 Time, min

N = 8 pts (adapted) Serial lactate determinations Vincent et al, Crit Care Med 11: 449-51, 1983 In optimal conditions (good response to fluid administration) Lactate, mEq/L 6

3 2 10 % decrease in 1 hour 1

0 0 1 2 3 4 5 6 7 TIME, hours LACTATE

TIME Conclusions:

Better outcome associated with decreasing blood lactate concentrations - consistent throughout the clinical studies - not limited to septic patients - valid regardless of the initial value - in all groups, changes relatively slow, so that lactate measurements every 1–2 hrs are probably sufficient in most acute conditions. 2019

104 patients

Independent risk factors of 30‐day mortality (multivariable logistic regression)

➢ Δ Lac <2.5%/h, ➢ Baseline lactate >4 mmol/L and ➢ High SAPS III score HEMODYNAMIC STABILIZATION The goals

Adequate MAP without vasopressors The three windows of tissue perfusion Normal skin perfusion Urine output > 0.5 mL/kg/h Preserved mental status Lactate levels normal or decreasing Hypotension Mortality lactate measured late No hypotension lactate measured late

Hypotension lactate measured early

No hypotension lactate measured early Hospital mortality, % 172,723 blood lactate measurements in 7,155 critically ill patients (4 hospitals) 100 90 80 70 60 Initial 50 lactate 40 levels 30 20 10 0 <1.2 1.2-1.5 1.5-2.0 2.0-4.0 4.0-6.0 >6.0 SEVERITY CIRCULATORY SHOCK ELEVATED LACTATE

Distributive Hypovolemic Cardiogenic Obstructive

Sepsis Hypovolemia Heart Pulm. failure embolism Infection Pericardial Arrhythmias effusion The triangle of shock

Arterial hypotension

SHOCK Altered tissue Increeased perfusion blood lactate (oliguria, altered mentation, Microcirculatory abnormalities impaired skin perfusion)

Vincent JL et al, Crit Care 2012 Arterial hypotension

Signs of tissue hypoperfusion ? (oliguria, altered mentation, cutaneous vasoconstriction...)

present absent

blood lactate

> 2 mEq/L < 1.5 mEq/L chronic hypotension ? syncope (if transient) circulatory shock

arterial catheter central venous catheter THE FOUR PATHOPHYSIOLOGIC MECHANISMS I am in SHOCK HYPOVOLEMIC hemorrhage, trauma cholera... CARDIOGENIC myocardial infarction terminal cardiomyopathy valvular disease OBSTRUCTIVE severe arrhythmias pulmonary embolism tamponade tension pneumothorax DISTRIBUTIVE inflammatory response (mediators) Arterial pressure = cardiac output x vascular tone ARTERIAL HYPOTENSION

CARDIAC OUTPUT

HIGH LOW (decreased vascular tone)

Hypovolemic Distributive (trauma, bleeding, diarrhea…) (sepsis, anaphylaxis, pancreatitis…) Cardiogenic (heart failure, valvular disease, major arrhythmia…) Obstructive (tamponade, massive pulm. embolism …) SEPTIC SHOCK

ALTERED O2 EXTRACTION INCREASED O2 DEMAND

IMPAIRED

MYOCARDIAL CONTRACTILITY O2 CONSUMPTION O2

O2 DELIVERY 2019 SOSD Br J Anaesth. 2014 Nov;113(5):740-7

Salvage / Rescue Optimisation Stabilisation De-escalation

Echo/Doppler

CVP Monitoring

ScvO2

Cardiac Output

Signs of fluid responsiveness

Fluid challenge SOSD SOSD JL Vincent & D De Backer

TIME SOSD

Oxygen Central venous catheter Maintenance Tracheal intubation? Fluid challenge (CVP) Diuretics? Fluids Initial fluid loading Arterial catheter Ultrafiltration? Norepinephrine Norepinephrine Taper down for MAP 65-70 mmHg for adequate MAP norepinephrine Cardiac outputCO / SvO2/ ScvO2 Echocardiography Non-invasive ventilatiion

In shock states

High flow oxygen

In shock states 442 patients mechanical ventilation either with FiO2 at 1·0 (hyperoxia)

or FiO2 set to target a SaO2 of 88–95% (normoxia) during the first 24 h …in nature, and by contrast with virtually all other biochemical abnormalities, no animal is ever exposed to hyperoxia. A recommendation to keep SpO2within the low-normal range of 92–96% in all critically ill patients is easily achievable with minimum effort and little cost. The VIP rule (Weil and colleagues)

entilate Oxygen administation V mechanical ventilation ? nfuse IV fluids I Blood transfusions ?

Vasopressor agents ? Pump Dobutamine ? 2018 ‘Fluid overload’

Too much fluid, but where?

The patient has anasarca, but develops septic shock... 2018

The terms hypervolemia and fluid overload are often used interchangeably, yet they do not have the same meaning.

“Fluid overload” may vaguely refer to excess total body water content associated with edema, but it would be better if the term were avoided completely.

The word “hypervolemia” is sufficient to indicate an excess in circulating blood volume and, if present, needs to be properly documented before a strategy of fluid restriction and/or diuretics is applied. AN EDEMATOUS PATIENT

MAY BE HYPOVOLEMIC

Beware of the terms ➢ Hypervolemia ➢ Fluid overload SOSD

Salvage / Rescue Optimisation Stabilisation De-escalation

Echo/Doppler

CVP Monitoring

ScvO2

Cardiac Output

Signs of fluid responsiveness

Fluid challenge MOF

Hypovolemia + vasopressors FLUID ADMINISTRATION

INCREASE IN INCREASE IN CARDIAC FILLING PRESSURES CARDIAC OUTPUT

EDEMA FORMATION INCREASE IN ARTERIAL PRESSURE IMPROVED TISSUE PERFUSION DECREASE IN HEART RATE INCREASED URINE OUTPUT Does this patient need IV fluid ?

Arterial pressure 85/45 mmHg maybe Heart rate 117 / min maybe

Cardiac output 3.9 L/min maybe

Urine output 10 mL/h maybe

ScvO2 60 % maybe Lactate 3.1 mEq/L maybe Central venous pressure 6 mmHg maybe MORE FLUIDS ?

Fully controlled Spontaneous breathing mechanival ventilation (with or without mechanical ventilation) Anesthetized or Deeply sedated/paralyzed

Pulse Pressure Variation (PPV) Stroke Volume Variation (SVV) End-expiratory pause Sigh AIRWAY PRESSURE MECHANICAL cmH2O VENTILATION

0 SPONTANEOUS FLUID RESPONSIVENESSFLUID ARTERIAL PRESSURE AIRWAY PRESSURE Transient decrease in venousreturn Decreased Decreased RV stroke volume Decreased Decreased LV stroke volume (+ (+ reduced RV ejection) Transient increase in Transient decrease (after (after a few beats) intrathoracic pressure in pulse pressure FLUID RESPONSIVENESS

STROKE VOLUME

END-DIASTOLIC VOLUME FLUID RESPONSIVENESS

AP monitoring

Pulse Pressure Variation (PPV)

CO monitoring Stroke Volume Variation (SVV) FLUID RESPONSIVENESS

PPV / SVV

REQUIREMENTS

Mechanical ventilation No spontaneous breathing activity No major arrhythmia Relatively large tidal volume No significant tachypnea No intraabdominal hypertension 2018

Anesth Analg 2019 CI Healthy volunteers (young) 4.0 3.2

10 16 PAOP, mmHg

Respiratory variation in IVC diameter Limited ability to predict fluid responsiveness, particularly in spontaneously ventilating patients. A negative test cannot be used to rule out fluid responsiveness. 2017

Neuromuscular blockade agents were routinely used

N = 319 pts MORE FLUIDS ?

Fully controlled Spontaneous breathing mechanival ventilation (with or without mechanical ventilation) Anesthetized or Deeply sedated/paralyzed

Fluid Pulse Pressure Variation (PPV) challenge Stroke Volume Variation (SVV) End-expiratory pause Sigh FLUID ADMINISTRATION

WILL FLUIDS BE BENEFICIAL ?

Obviously yes Not sure

Fluid loading Fluid challenge The goal of fluid administration

Minimal increase Increase in cardiac filling pressures in cardiac output

No increase Increase in edema in DO2 Improved tissue perfusion FLUID ADMINISTRATION What we desire

The LOWEST hydrostatic pressures associated with hemodynamic stability

Increase in cardiac filling pressures = "The price to pay" MORE IV FLUIDS ?

Minor increase in filling BENEFIT Significant increase in cardiac output CARDIAC OUTPUT

Major increase in filling No significant increase in cardiac output

COST CARDIAC FILLING CENTRAL VENOUS CATHETER

Treatment Monitoring

Easy blood sampling Rapid and safe fluid administration (if no arterial catheter)

Vasopressor agents CVP

ScvO2

A CVP level does not give much information about the response to fluid administration Heenen S, De Backer D, Vincent JL, Crit Care 10(4): R102, 2006

Statistically… a CVP level Static a EDV level cardiac chamber size preferable vs.

PPV / SSV when applicable Dynamic Fluid challenge Passive leg raising measurements The goal of fluid administration

Minimal increase Increase in cardiac filling pressures in cardiac output

No increase Increase in edema in DO2 Improved tissue perfusion Patients who do not respond rapidly to initial fluid boluses or those with insufficient physiologic reserve should be considered for invasive hemodynamic monitoring.

Monitoring filling pressures can be helpful to optimise preload and thus cardiac output.

Observation of little change in the CVP in response to a fluid bolus suggests that the venous capacitance system is not overfilled and that more fluid is indicated. Observation that an increasing CVP is met by reducing MAP-CVP suggests that too much fluid has been given.

FLUID CHALLENGE STROKE VOLUME

CARDIAC OUTPUT PULMONARY Primary EDEMA determinant of oxygen delivery END-DIASTOLIC VOLUME Primary determinant of edema formation CVP / PAOP CARDIAC OUTPUT MONITORING

CARDIAC CARDIAC OUTPUT OUTPUT RESPONDER

CVP / PAOP EDV

CARDIAC CARDIAC OUTPUT OUTPUT NON - RESPONDER

CVP / PAOP EDV The clinical scenario Can this patient benefit from fluids ?

Yes, definitely Maybe e.g. acute bleeding

Fluid challenge Give fluids Positive Negative response response Do not give Fluid loading fluids SURVIVING SEPSIS CAMPAIGN

2016 FLUIDS - AMOUNT

1. We recommend that a fluid challenge technique be applied where fluid administration is continued as long as hemodynamic factors continue to improve.

Best Practice Statement

Crit Care Med 2017 Intensive Care Med 2017 HOW TO ASSESS THE NEED FOR FLUIDS

technique easy/uneasy caveat

Fluid Challenge Easy Often not done properly

PPV, SVV Easy Rarely applicable

Echocardiography Uneasy Not very reliable

Passive leg raising Uneasy Often not done properly

Sometimes difficult to interpret (unless hypovolemia is obvious) The clinical scenario Can this patient benefit from fluids ?

Yes, definitely Maybe e.g. acute bleeding When applicable Signs of fluid responsiveness ?

Yes No ? Fluid challenge Give fluids Positive Negative response response Do not give Fluid loading fluids "fill the tank" INTRAVASCULAR PRESSURE

X'''

X''

X' X

INTRAVASCULAR VOLUME

2017 100 mL HES in 1 min

Anesthesiology, 2011

2017

Biais EFFECTS OF FLUID BOLUSES

Too short time + response CO in any individual

TIME, min

Too long time

Too small effect

Other influences CO on cardiac output

TIME, min What is a fluid challenge?

1 liter in 30 min

200 mL in 5-10 min Repeat? 200 mL in 5-10 min Repeat? 200 mL in 5-10 min WHAT IS A FLUID CHALLENGE?

Give 500 mL is NOT a ‘fluid challenge’

Give 500 mL in 30 min is NOT a ‘fluid challenge’

Give 200 mL in 10 min is NOT a ‘fluid challenge’

Give 200 mL in 10 min and assess the patient’s response

is a ‘fluid challenge’ FLUID CHALLENGE The 4 items to be defined in advance

Example

T ➢The Type of fluids Ringer's lactate R ➢The Rate of infusion 200 mL/10 min O ➢The clinical Objective MAP > 70 mmHg, HR < 115/mi L ➢The safety Limits CVP max 15 mmHg

Vincent JL & Weil MH, Crit Care Med 34: 1333-7, 2006 Fluid challenge

100 – 200 mL 100 – 200 mL 100 – 200 mL assess assess assess assess

TIME Baseline 10 min 20 min 30 min

Do not change anything (vasoactive agents, …) Do not suction the trachea… Do not stimulate the patient… Do not touch the patient ! 100 mL colloids 200 mL crystalloids Vincent JL & Weil MH, Crit Care Med 34: 1333-7, 2006 in 10 min CARDIAC OUTPUT MONITORING

CARDIAC CARDIAC OUTPUT OUTPUT RESPONDER

CVP / PAOP EDV

CARDIAC CARDIAC OUTPUT OUTPUT NON - RESPONDER

CVP / PAOP EDV ECHOCARDIOGRAPHY

2018

speckle-tracking echocardiography (STE) Velocity cm/sec in cm VTI Time sec Velocity time integral 2019

Averaging three measurements within one TTE examination enough for VTI in patients in sinus rhythm (not in atrial fibrillation). Between two TTE examinations performed by the same operator, significant changes in VTI with assessment of the effects of a 500-mL fluid infusion. The effects of fluid loading

Tachycardia Hypotension

Increased Increased CO CO

Slower Higher heart rate arterial pressure HEMODYNAMIC EFFECTS OF FLUID ADMINISTRATION IN FLUID RESPONDERS

Increased vascular tone Low vascular compliance Arterial Pressure

Decreased vascular tone High vascular compliance

Cardiac output

The effects of fluid loading

Tachycardia Hypotension Oliguria

Increased Increased Increased CO CO CO

Slower Higher heart rate arterial pressure Increased urine output PROBLEM = OLIGURIA

Due to hypovolemia?

Fluid challenge 200 mL in 10 min ? too slow Increase in response urine output Effects on global blood flow If increase If no increase Give fluids! Hypovolemia excluded The clinical scenario Can this patient benefit from fluids ?

Yes, definitely Maybe e.g. acute bleeding

Fluid challenge Give fluids Positive Negative response response Do not give Fluid loading fluids FLUID CHALLENGE How many will respond?

Responders Non-responders

50%

25%

75% 2019

143 patients 500 mL crystalloids over 10 min >15% increase in VTI 76 (53%) Fluid responders

37 39 transient persistent

11 French ICUs 2017 Fluid infusion is best initiated with boluses of 20 mL/kg titrated to assuring an adequate blood pressure and clinical monitors of cardiac output including -heart rate -quality of peripheral pulses, capillary refill -level of consciousness and -urine output.

… at least 20 mL/kg of either isotonic crystalloid or 5% albumin (…) within the first hour of presentation. Patients who do not respond rapidly to initial fluid boluses or those with insufficient physiologic reserve should be considered for invasive hemodynamic monitoring.

Monitoring filling pressures can be helpful to optimise preload and thus cardiac output.

Fully controlled Spontaneous breathing mechanical ventilation (with or without mechanical ventilation) Anesthetized or Deeply sedated/paralyzed

Passive Leg Raising (internal fluid challenge) Pulse Pressure Variation (PPV) Fluid Stroke Volume Variation (SVV) Challenge End-expiratory pause (200 mL in 10 min) Large tidal volume Evaluate the clinical response (clinical response / cardiac output change) PASSIVE LEG RAISING

Is there a transient increase in stroke volume?

yes no

FLUID RESPONSIVENESS NO FLUID RESPONSIVENESS PASSIVE LEG RAISING

? ? ? ? ? I just ? ? ? raise the legs… ? What do you mean ? ?

First, PLR should start from the semi-recumbent and not the supine position. Second, the PLR effects must be assessed by a direct measurement of cardiac output and not by the simple measurement of blood pressure. Third, the technique used to measure cardiac output during PLR must be able to detect short-term and transient changes since the PLR effects may vanish after 1 minute. Fourth, cardiac output must be measured not only before and during PLR but also after PLR when the patient has been moved back to the semi-recumbent position, in order to check that it returns to its baseline. Fifth, pain, cough, discomfort, and awakening could provoke adrenergic stimulation, resulting in mistaken interpretation of cardiac output changes. Some simple precautions must be taken to avoid these confounding factors. PLR must be performed by adjusting the bed and not by manually raising the patient’s legs. This patient has a PROBLEM Can this patient benefit from fluids ?

Yes Maybe No e.g. acute bleeding

Signs of fluid responsiveness ?

No Yes Maybe Do not give fluids Give Fluid fluids Fluid loading challenge

Positive Negative response response Do not give fluids Low cardiac filling pressures Arterial hypotension Tachycardia

How to identify Low low the patient cardiac output SvO2 who needs fluids ? Altered skin Altered perfusion microcirculation (OPS, NIRS, …) Small cardiac High PgCO2 Hyperlactatemia chambers The VIP rule (Weil and colleagues)

entilate Oxygen administation V mechanical ventilation ? nfuse IV fluids I Blood transfusions ?

Vasopressor agents ? Pump Dobutamine ? VASOPRESSOR SUPPORT IN SEPTIC SHOCK

" Vasopressor support is added when hypotension persists despite fluid administration." Not ideal

Severe hypotension should always be corrected

2018

Vincent AIC SEPSIS MANAGEMENT

Give noradrenaline as the first line vasopressor How I treat shock

We should always correct severe hypotension How I treat shock

The VIP rule (Weil and colleagues)

entilate Oxygen administation V mechanical ventilation ? nfuse IV fluids I Blood transfusions ?

Vasopressor agents ? Pump Dobutamine ? WHICH BLOOD PRESSURE TARGET? SURVIVING SEPSIS CAMPAIGN

2016 VASOPRESSOR AGENTS We recommend an initial target mean arterial pressure (MAP) of 65 mm Hg in patients with septic shock requiring vasopressors. Grade 1 B Remarks: If initiated, vasopressor dosing should be titrated to an end point reflecting perfusion…

Crit Care Med 2017 Intensive Care Med 2017 MANAGING ARTERIAL HYPOTENSION

Severe hypotension must always be corrected promptly

Blood pressure targets should be individualized THE CHALLENGES

Fluid challenge

Vasopressor challenge

Dobutamine challenge What is the target blood pressure in shock ?

Mean arterial pressure

80 Elderly Atherosclerosis Diuresis ? Chronic hypertension 70 Consciousness ? Skin perfusion ? Young, + 60 No atherosclerosis SvO2, lactate ? No chronic hypertension SEPSIS MANAGEMENT

Always correct severe hypotension VASOPRESSOR AGENTS

DOPAMINE The good The bad

Increased blood flow Increased renal blood flow Risk of arrhythmias Increased splanchnic blood flow Immunosuppression Increased edema clearance (prolactin release) Improved muscle function

NOREPINEPHRINE

Strong vasopressor effect Risk of vasoconstriction

Dopamine vs norepinephrine in shock states De Backer et al, N Engl J Med 362: 779-89, 2010 RISK OF DEATH – NOREPINEPHRINE vs. DOPAMINE

Conclusions: In a large population-based sample of patients with septic shock in the United States, use of dopamine as initial vasopressor was associated with increased mortality among multiple clinical subgroups. ADRENERGIC AGENTS

Isoproterenol Dopexamine b Dobutamine ? Dopamine Epinephrine Norepinephrine Phenylephrine a EPINEPHRINE ? FIGHT OR FLIGHT (preservation of life - muscle activity) WOUNDED ANIMAL

AIMS MEANS

Think INCREASED CEREBRAL BLOOD FLOW

Pump blood INCREASED CORONARY BLOOD FLOW

Maintain blood volume REDUCED SPLANCHNIC BLOOD FLOW

Limit fluid losses REDUCED RENAL BLOOD FLOW Dopamine vs. epinephrine in pediatric septic shock. Ramaswamy KN, Singhi S, Jayashree M, Bansal A, Nallasamy K Pediatr Crit Care Med Sept 2016

Double-blind RCT

epinephrine dopamine N = 29 N = 31

Resolution of shock within first hour N = 12 N = 4

SOFA score on day 3 8 12 Epinephrine vs. norepinephrine in cardiogenic shock Levy et al, Crit Care Med 2011

30 patients (no MI) MAP 65-70 mmHg

Norepi – dobu Epinephrine

Faster heart rate New arrhythmias Increased lactate levels Increased PCO2gap Epinephrine vs. norepinephrine in cardiogenic shock Levy et al, Crit Care Med 2011 EPI

EPI

EPI 2016

Propensity-score matched How I treat septic shock

I AVOID EPINEPHRINE

Tachyarrhythmias Reduced hepato-spanchnic blood flow Increased lactate levels ADRENERGIC AGENTS EFFECTS OF ADRENERGIC AGENTS ON HEPATO-SPLANCHNIC CIRCULATION IN SEPTIC PATIENTS D De Backer, J Creteur, JL Vincent ShO2 Crit Care Med 31: 1659-67, 2003

dopamine low doses epi low doses norepi high doses epi high doses norepi ADRENERGIC AGENTS CARDIAC INDEX L/min.m² 5,5

5 +++ HIGH DOSES 4,5 +++ 4 ***

3,5

3 LOW DOSES 2,5 DOPA NOREPI EPI

Crit Care Med 31: 1659-67, 2003 ADRENERGIC AGENTS FRACTIONAL SPLANCHNIC BLOOD FLOW % 30

25 LOW DOSES

++ 10 HIGH DOSES

5 DOPA NOREPI EPI

Crit Care Med 31: 1659-67, 2003 ADRENERGIC AGENTS

Dopamine is not a first choice Epinephrine is not a first choice SEPSIS MANAGEMENT

ALTERNATIVES TO ADRENERGIC AGENTS? 2018 Vasopressin ? ? ? Relatively late to limit the doses of norepinephrine ? Early ? for endothelial protection (to limit edema formation) ? ? ? ? VASOPRESSIN

POTENTIAL BENEFICIAL EFFECTS Increased vascular tone Increased urine output ? Less edema formation

POTENTIAL SIDE EFFECTS Excessive vasoconstriction / Decreased organ perfusion Hepato-splanchnic ischemia / Altered liver tests Myocardial ischemia / Arrhyhmias Cutaneous lesions Pulmonary hypertension Platelet aggregation Interpretation

Early selepressin administration may protect the microvasculature and limit edema formation 2017 2017

Increased the number of days alive and free of mechanical ventilation

Proportion of DAF ventilation by Day 7 *

Mean, 60% confidence limits *: p=0.01 vs. placebo Selepressin for septic shock Phase II / III Adaptive design Sepsis-ACT

Type of study Placebo-controlled, double-blinded RCT

Population Hemodynamic Patients with septic shock pattern?

Primary end-point 30 day mechanical ventilation & vasopressor free days 2019

N=868 vasopressin

norepinephrine Angiotensin II MANAGEMENT OF HYPOTENSION

Norepinephrine ? ? High cardiac output Vasopressin Vasopressin Good cardiac function High SvO2 Angiotensin II

Evaluate the response

Low cardiac output No vasopressin Myocardial depression No angiotensin II Low SvO2 No phenylephrine

TIME

VASOPLEGIA

Is not just

HYPOTENSION NOS inhibitor 546C88 in patients with septic shock Lopez et al, Crit Care Med 32: 21-30, 2004

70 TREATMENT PLACEBO 59 60 52 49 50 36 40 27 30 15 MORTALITY, % 20

0 Day 3 Day 14 Day 28

N = 797 patients NOS inhibitor 546C88 in patients with septic shock Lopez et al, Crit Care Med 32: 21-30, 2004

PLACEBO

% Survivors% 546C88 MOF

Hypovolemia + Vasopressors THE RISKS OF VASOCONSTRICTION Excessive use of vasopressors

Decreased IncreasedIncreased

Arterial pressure = cardiac output x resistance Treatment of heart failure

Increased Decreased

Arterial pressure = cardiac output x resistance THE DANGERS OF VASOPRESSOR THERAPY

Arterial pressure = cardiac output x resistance

Excessive use of vasopressors CARDIAC OUTPUT

FLUIDS PACEMAKER

PRELOAD HEART RATE

AFTERLOAD CONTRACTILITY DOBUTAMINE VASODILATORS OXYGEN DELIVERY

DO2 = arterial O2 content x cardiac output

Heart rate SaO2 Hemoglobin Preload (PaO2) Contractility Afterload Transfusions Oxygen Fluids PEEP Pacemaker Isoproterenol Dobutamine

Nitrates Therapeutic options SEPSIS THE CHALLENGES

Fluid challenge Vasopressor challenge

Dobutamine challenge

levosimendan placebo Mean SOFA score 6.68 vs. 6.06 Mortality 34.5% vs. 30.9%

• lower likelihood of successful weaning from mechanical ventilation • higher risk of supraventricular tachyarrhythmia MYOCARDIAL DEPRESSION IN SEPTIC SHOCK Poor response to fluid challenge

Increase in No increase cardiac filling pressures in cardiac output

Edema No improvement formation in tissue perfusion

Low SvO2 Poor myocardial function (without anemia) (echocardiography) Do not forget

ScvO2 in complex cases VAPCO2 in complex cases

lactate

VA PCO2 gradients

SvO2 Persisting OK hypoperfusion?

65 %

Reassuring Abnormal (anemia?)

6 mmHg

Delta PCO2 ScvO2 My recommendation

Early goal-directed therapy Late (EGDT) ScvO2 monitoring

Low Normal ScvO2 ScvO2

Elevated VAPCO2

Argument for Argument for More fluids Vasopressor only Transfusion Dobutamine 2018 SvO2

75 % Vasopressors (primarily) 70 %

65 % Fluids 60 % Transfusion 55 % Dobutamine 2018

PaFloV

Arterial Pressure

Blood Flow Blood Volume SOSD