use of vasopressors in sepsis resuscitation.pdf

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Use of Vasopressors in Sepsis Resuscitation

:Guideline Update 2012

นพ.ธรรมศักด ิทวิชศรี

หน่วยเวชบาํบดัวิกฤต

ฝ่ายวิสัญญีวิทยา

โรงพยาบาลจุฬาลงกรณ์

The Sepsis Continuum

A clinical response arising from a nonspecific insult, with 2 of the following: T >38oC or <36oC HR >90 beats/min RR >20/minWBC >12,000/mm3

or <4,000/mm3 or >10% bands

SIRS = systemic inflammatory response syndrome

SIRS with apresumedor confirmed infectiousprocess

Chest 1992;101:1644.

SepsisSIRSSevere Sepsis

SepticShock

Sepsis with organ failure

Refractoryhypotension

Severe sepsis definition = sepsis-induced tissue hypoperfusion or organ dysfunction

Crit Care Med 2013; 41:580–637

Septic shock ; a complex interaction-pathologic vasodilation-relative and absolute hypovolemia-myocardial dysfunction-altered blood flow distribution

Sepsis initiates coagulation by activating endothelium to expression of TF coagulation cascademicrovascular thrombi & obstruction distal

ischemia & tissue hypoxia-clinical consequences of the changes in coagulation caused by sepsis are

levels of markers of DIC & widespread organ dysfunction

Systemic vasodilationmay be primarily counteracted by early initiation of vasopressor support

Rational to treat absolute hypovolemiaresulting from plasma extravasation with aggressive fluid challenge

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Crit Care Med 2007; 35:1599–1608

Sepsis-induced cardiac dysfunction

Echocardiographic studies suggest that 40% to 50% of patients with prolonged septic shock develop myocardial depression

Early aggressive, goal-directed therapy improves the outcome of patients who have severe sepsis & present to ER

N Engl J Med 2001;345:1368-77

Early identification of patients at high risk for cardiovascular collapse & Early therapeutic intervention to restore a balance between oxygen

delivery & demand

N Engl J Med 2001;345:1368-77

N Engl J Med 2001;345:1368-77

N Engl J Med 2001;345:1368-77

Surviving Sepsis Campaign (SSC) and the Institute for Healthcare

Improvement recommend implementation of

6-hr resuscitation bundle

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SURVIVING SEPSIS CAMPAIGN BUNDLES

Crit Care Med 2013; 41:580–637

Fluid Therapy

Fluid Therapy of Severe Sepsis

Crit Care Med 2013; 41:580–637

PROCON

MAY BE

SHOULD BE

Fluid challenge technique

Large amounts of fluids Limited period of time

Close monitoring

Patient’s responseAvoid pulmonary edema

Will cardiac output increase with fluid loading?

- blood pressure- SvO2- heart rate- blood lactate

Current Opinion in Critical Care 2005, 11:264—270

2mmHg

The change in CO. should be in the range of 300 ml/min

2mmHg

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The changes in aortic blood flow induced by PLR are highly predictive of preload responsiveness in ventilated patients, even in the presence of spontaneous respiratory efforts or arrhythmias

Crit Care Med 2006; 34:1402–1407

Vasopressors

Vasopressor therapy initially to target a mean arterial pressure (MAP) of 65 mm Hg (grade 1C)

Norepinephrine as the first choice vasopressor (grade 1B)

Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2012

Crit Care Med 2013; 41:580–637

Objective: To examine the effect of titrating NE to different levels of MAP on systemic and regional indices of perfusion

Effects of perfusion pressure on tissue perfusion in septic shock

Crit Care Med 2000;28:2729–2732

Patients: 10 pts. with the diagnosis of septic shock who required pressor agents to maintain a MAP ≥ 60 mm Hg after fluid resuscitation to a PAOP ≥ 12 mm Hg

Interventions: NE was titrated to MAP of 65, 75,and 85 mm Hg in 10 patients with septic shock

Conclusions: Increasing the MAP from 65 mm Hg to 85 mm Hg with NE does not significantly affect

Crit Care Med 2000;28:2729–2732

- systemic oxygen metabolism- skin microcirculatory blood flow - urine output- splanchnic perfusion

The aim of vasopressor therapy is to improve tissue perfusion pressure while avoiding excessive vasoconstriction

Adequate fluid resuscitation is a fundamental aspect of the hemodynamic managementof patients with septic shock

but using vasopressors early as an emergency measure in patientswith severe shock is frequently necessary

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Brain: Reversal of consciousness Heart: Improvement of BP, PR

no signs of myocardial ischemia

Kidney: Urine output > 0.5ml/kg/hrSkin : warm, good skin perfusion

Adequate driving pressure & flow>> sustain organ homeostasis

Reversal of lactic acidosis

Does my patient need an increase in CO. ??

Norepinephrine Compared With Dopamine in Severe Sepsis Summary of Evidence

Crit Care Med 2013; 41:580–637

•Norepinephrine may be more effective at reversing hypotension

•Dopamine may be particularly useful in patients with compromised systolic function

Crit Care Med 2012; 40:725–730

In the two trials that reported arrhythmias, these were more frequent with dopamine than with norepinephrine(RR, 2.34; CI, 1.46 –3.77; p = .001)

Dopamine was associated with an increased risk of death (RR, 1.12; CI,1.01–1.20; p =.035)

Safety about the administration of low-dose dopamine ?

:Transient decrease in T-cell function

:Decreases growth-hormone secretion negative nitrogen balance in critical illness

:proarrhythmic effect

Crit Care Med 2006; 34:589–597 Crit Care Med 2006; 34:589–597

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But no clinical study has definitely indicated that one catecholamine is superior to another, so that at present no agent should be preferredover the other

Epinephrine (added to and potentially substituted for norepinephrine) when an additional agent is needed to maintain adequate blood pressure (grade 2B)


Crit Care Med 2013; 41:580–637

Lancet 2007; 370: 676–84

to compare the efficacy and safety of norepinephrine plus dobutamine (whenever needed) with those of epinephrine alone in septic shock

prospective, multicentre, randomised, double-blind study was done in 330 pts with septic shock admitted to one of 19 participating ICU in France

Lancet 2007; 370: 676–84

Lancet 2007; 370: 676–84

There is no evidence for a difference in efficacy and safety

between epinephrine alone & norepinephrine plus dobutamine

for the management of septic shock

Lancet 2007; 370: 676–84

Should be the first alternative to norepinephrine!

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Prospective, double-blind, randomisedcontrolled trialSetting: 4 Australian university-affiliated multidisciplinary ICUs280 patients were randomised to receive either epinephrine or norepinephrine.

Intensive Care Med (2008) 34:2226–2234 Intensive Care Med (2008) 34:2226–2234

Kaplan-Meier estimates for probability of achievement of MAP goal between epinephrine and norepinephrine

Epinephrine was associated with the development of significant but transient metabolic effects that prompted the withdrawal of 18/139 (12.9%) patients from the study byattending clinicians

Vasopressin 0.03 units/minute can be added to norepinephrine (NE) with intent of either raising MAP or decreasing NE dosage (UG)


Crit Care Med 2013; 41:580–637

Low dose vasopressin is not recommended as the single initial vasopressor for treatment of sepsis-induced hypotension and vasopressin doses higher than 0.03-0.04 units/minute should be reserved for salvage therapy (failure to achieve adequate MAP with other vasopressor agents) (UG)

Vasopressin is a direct vasoconstrictor without inotropic or chronotropic effects

may result in CO andhepatosplanchnic flow

most published reports excludepatients from treatment with vasopressinif the CI is < 2 or 2.5 L/min/m2, and itshould be used with caution in patientswith cardiac dysfunction

Crit Care Clin 22 (2006) 187– 197

infusion of low-dose vasopressin(0.01– 0.04 units/min yielding plasma levels of 20–100 pg/mL)

restores plasma levels to values found during comparable degrees of hypotension from other origins (20–30 pg/mL)

Crit Care Med 2007 Vol. 35, No. 9 (Suppl.)

“relative vasopressin deficiency in septic shock”

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N Engl J Med 2008;358:877-87

RCT trial patients (who had septic shock and were receiving a minimum of 5 μg of NE/min) were assigned to receive either low-dose vasopressin (0.01- 0.03 U/min) or NE (5-15 μg/min) in addition to open-label vasopressors

The primary end point was the mortality rate 28 days after the start of infusions

Low-dose vasopressin did not reduce mortality rates as compared with NEamong patients with septic shock who were treated with catecholamine vasopressors

N Engl J Med 2008;358:877-87

N Engl J Med 2008;358:877-87

< 15 μg/min NE

The effects of low-dose vasopressin as a “catecholamine-sparing drug,” not the effects in catecholamine-unresponsive refractory shock

45 septic shock patients with MAP < 65 mmHg were randomized to receive continuous infusions of either terlipressin (1.3 μg/kg/h), vasopressin (0.03 U/min) or norepinephrine (15 μg/min; n = 15 per group)

Critical Care 2009, 13:R130

In all groups, open-label norepinephrine was added to achieve a mean arterial pressure between 65 and 75 mmHg, if necessary

Continuous infusion of a relatively low dose of TP (1.3 μg/kg/h) was effective in reversing sepsis-induced hypotension and in reducing NE requirements

Critical Care 2009, 13:R130

Higher doses of vasopressin have been associated with cardiac, digital, and splanchnic ischemia and should be reserved for situations where alternative vasopressors have failed

Crit Care Med 2003; 31:1394–1398

Dopamine as an alternative vasopressor agent to norepinephrine only in highly selected patients (eg, patients with low risk oftachyarrhythmias and absolute or relative bradycardia) (grade 2C)


Crit Care Med 2013; 41:580–637

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Phenylephrine is not recommended in the treatment of septic shock except in circumstances where

(a) Norepinephrine is associated with serious arrhythmias

(b) Cardiac output is known to be high and blood pressure persistently low

(c) As salvage therapy when combined inotrope/vasopressor drugs and low dose vasopressin have failed to achieve MAP target (grade 1C)


Crit Care Med 2013; 41:580–637

Low-dose dopaminenot be used for renal protection(1A)

All patients requiring vasopressorshave an arterial catheter placed as soon as practical if resources are available(UG)


Crit Care Med 2013; 41:580–637

Arterial catheter provides a more accurate and reproducible measurement of arterial pressure (also allows beat-to-beat analysis)

Anesthesiology 2005; 103:419–28

Inotropic Therapy

Dobutamine infusionadministered in the presence

of myocardial dysfunction assuggested by elevated cardiacfilling pressures and low C.O.


Crit Care Med 2013; 41:580–637

Dobutamine is the first-choiceinotrope for patients with measured or suspected low CO in the presence of adequate left ventricular filling

pressure & adequate MAP

If used in the presence of low BP, it should be combined

with vasopressor therapy

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Against the use of a strategy to increase Cardiac Index to

predetermined supranormal levels


Crit Care Med 2013; 41:580–637

P values are for the comparison of mortality rates among the three groups

N Engl J Med 1995;333:1025-32

There are recognized limitations to ventricular filling pressure estimates as surrogates for fluid resuscitation

However, measurement of CVP is currently the most readily obtainable

target for fluid resuscitation

There may be advantages to targetingfluid resuscitation to flow and perhaps to

volumetric indices (and even to microcirculation changes)

arterial pulse contour analysis allow stroke volumevariation (SVV) to be tracked continuously

volunteer sepsis

MICROCIRCULATION

TAKE HOME

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•Vasopressors are indicated to maintain MAP >65 mm Hg, both during and following adequate fluid resuscitation•Norepinephrine are the vasopressorsof choice in the treatment of septic shock •Norepinephrine may be combined with dobutamine when cardiac output is being measured

RECOMMENDATIONS FOR HEMODYNAMIC SUPPORT OF SEPTIC PATIENTS •Epinephrine, phenylephrine, &

vasopressin are not recommended as first-line agents •Vasopressin may be considered forsalvage therapy•Low-dose dopamine is not recommended for the purpose of renal protection•Dobutamine is recommended as theagent of choice to increase cardiac output

• Resuscitation“more earlymore effective”

• Monitor in ICU & arterial cannulation

• Clinical end points MAP,HR, urine output, skin

perfusion, mental status, & indexes of tissue perfusion

( blood lactate conc. & SvO2)

use of vasopressors in sepsis resuscitation.pdf

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