vasoactive agents in emergency care

8/12/2019 Vasoactive Agents in Emergency Care

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Vasoactive Agents

in Emergency Care

Susan P. Torrey, M.D., FACEP

Baystate Medical Center

Tufts University School of Medicine


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Vasopressors for shock

Cochrane Database of Systematic Reviews

The current available evidence is not

suited to inform clinical practice.

Mullner, et al. 2005


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Adrenergic receptor

physiology

1adrenergic receptors




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Adrenergic receptor

physiology


vasoconstriction of many vascular beds

smooth muscle in arterioles

skin, mucosa, skeletal muscle, kidneys not cerebral and cardiac

positive inotropic response in myocardium

with little effect on heart rate

norepinephrine, epinephrine, +/- dopamine


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Pressure-dependent

vascular beds

Heart and brain (without -receptors)

blood flow as MAP increases

Gut and kidney (with -receptors)

blood flow as MAP to some minimal level then vasoconstriction gut and renal ischemia

Two primary principles of vasopressor use

a minimal MAP is imperative (MAP 65)

excessive vasopressors vital organ

compromise


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Adrenergic receptor

physiology


predominant adrenergic receptor in

myocardium

positive inotropic and chronotropic response

dobutamine, isoproterenol, epinephrine


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Adrenergic receptor

physiology


vasodilation in muscles (bronchial, uterine)

terbutaline (bronchodilator, tocolytic)


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Effects of adrenergic agents

vasopressor 1 2 1 expected effects

Dopamine ++ + ++ CI,MAP,SVR

Dobutamine +++ + + CI, -/ MAP

Isoproterenol +++ +++ 0 HR

Norepinephrine ++ 0 +++ MAP, SVR

Epinephrine +++ ++ +++ CI, MAP

Phenylephrine 0 0 +++ MAP, SVR


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Dopamine

Dose-dependent stimulation Low-dose (< 5 g/kg/min)

dopaminergic receptors

Moderate dose (5-10 g/kg/min)

1stimulationcardiac output

High dose (> 10 g/kg/min)

1stimulationSVR


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Dopamine

Expect MAP of ~ 25%

Adverse effects

tachycardia, tachyarrhythmias

vasoconstriction-induced myocardialischemia

splanchnic perfusion multiple organ

failure


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Dobutamine

Potent nonselctive - and mild -stimulation cardiac contractile force

+/- heart rate

cardiac-filling pressure

Indications decompensated CHF

with norepinephrine if CI 3 L/min/m2

Dosage: 220 g/kg/min


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Epinephrine

Potent - and -agonist vasoconstriction MAP

contractility and heart rate cardiac output

Indicationsfor low cardiac output states

cardiovascular resuscitation

anaphylaxis


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Norepinephrine

Potent 1and 1agonist with little 2activity stimulation vasoconstriction

1effects balanced by reflex activity little

effect on heart rate and cardiac output

Indications

an excellent vasopressor

Dosage: 0.530 g/min


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Phenylephrine

Selectively stimulates 1receptors vasoconstriction SVR

as BP increases, vagal reflexes heart rate

Pure -adrenergic agentno inotropy distributive shock often cardiac depression

restoring MAP without inotropy C.O.


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Phenylephrine

Indications anesthesia-induced hypotension

spinal shock

useful with tachycardia

arrhythmias with other vasopressors


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Isoproterenol

Potent nonselective activity inotropic and chronotropic effects CO

Indications

temporary treatment of bradycardia

overdrive pacing for torsade de pointes


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Vasopressin

Antidiuretic hormone V2receptors on renal tubules water

resorption

An important stress hormone

V1receptors on vessels vasoconstriction

V3receptors in pituitary ACTH production

BP only with relative hypovolemia

SIADH does not cause hypertension


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Vasopressin

Indications catecholamine resistance in sepsis

cardiac arrest unresponsive to epinephrine

may be useful for irreversible shock

Dosage

Shock0.01 to 0.05 U/min by infusion

ACLS40 U as IV bolus


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Push-dose Pressors

Phenylephrine In 3mlsyringe, draw up 1mlfrom vial 10mg/ml

Inject this into 100mlbag normal saline

Thus 100mlphenylephrine of 100g/ml

Draw solution into syringe; each ml = 100g

Dose: 0.52 ml every 2-5 min (50200 g)

Epinephrine

Draw 9mlof NS into 10mlsyringe

Add 1 ml of 1:10,000 epinephrine (100g/ml)

Thus 10 ml of epi at 10 g/ml

Dose: 0.52 ml every 2-5 min (520 g)


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Case #1

50-year-old man with urticaria after bee-sting.

VS: 78/40, 130, 26, 90% O2

Rx: epinephrine 0.3 mg SQ and

diphenhydramine 50 mg IM

continued hypotension with confusion


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Anaphylaxis

Epinephrine 0.30.5 mg (0.30.5 ml of 1:000) SQ absorption slowgive IM

marked vasoconstrictionurticaria

-blocker controversy

epi less effectivegive more

unopposed -effectgive less

U i


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Unresponsive

to IM epinephrine

More epinephrine

Push-dose epinephrine (100gover 5-10 min)

IV infusion0.5 to 1.0 g/min up to 10 g/min

Glucagon

15 mgIV over 5 min

then 515 g/min infusion

Vasopressin ?


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Vasopressin ?

Schummer Anesth Analg2008

Six cases of anesthesia-induced anaphylaxis,

unresponsive to epinephrine and fluids, had

prompt hemodynamic stabilization aftervasopressin (28 U).

Helpful even in patients on -blockers.


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Case #2

70-year-old woman with altered mental status.

PMH: CAD with CHF, HTN, dementia

VS: 80/48, 110, 22, 100.8, 88% O2Labs: WBC, BUN/Cr, CO2, pyuria

remains hypotensive despite 2 liters NS IV


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Current Rx of septic shock

Aggressive fluid resuscitation 4 - 6 liters of crystalloid (or colloid)

Vasopressors to support BP (MAP 65mmHg)

Dopamine or norepinephrine initially

Adjuncts to therapy early antibiotics

Corticosteroid ?

Activated protein C ??

Dellinger Surviving Sepsis Campaign Crit Care Med 2008


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The Evidence

Annane Lancet 2007

prospective, randomized, double-bind study

330 patients with septic shock from France

epinephrineor norepinephrine plus dobutamine titrated to MAP 70mmHg

no difference in 28-day mortality or safety


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The Evidence

Morelli Crit Care 2008

prospective, randomized, controlled study

32 patients with septic shock from Rome

MAP < 65mmHgdespite adequate fluid norepinephrineor phenylephrinefor MAP 65-75

over initial 12 hours, no differences in:

cardiopulmonary performance

global oxygen transport regional hemodynamics


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The Evidence

Myburgh In tens ive Care Med 2008

Prospective, double-blind, randomized

280 patients from Australia

norepinehrineor epinephrinefor MAP 70mmHg no difference to achieve MAP goal or mortality

Epinephrine had significant but transient metabolic

effectswithdrawal of 13% epinephrine group


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The Evidence

DeBacker Lancet 2010

Randomized trial of 1679 patients with shock

either dopamine(to 20g/kg/min) or

norepinephrine (up to 0.19g/kg/min)

no difference in rate of death at 28 days

more arrhythmias in dopamine group (24% vs 12%)


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Initial choice of vasopressor

With cardiac index 3.0 L/min/m2 Norepinephrine is first choice

Phenylephrine, if brief and no cardiac dysfunction

With cardiac index < 3.0 L/min/m2

need more inotropic support

Dopamine

Norepinephrine plus dobutamine

Another possibility

Epinephrinemm

Kellum Curr Opin Crit Care 2002

If high dose vasopressors


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If high-dose vasopressors

arent enough?

Addition of vasopressin may augmentvasopressor treatment in septic shock

Patel Anesth 2002

24 patients with severe septic shock on high-

dose norepinephrine

randomized and blinded to either more norepi or

vasopressin (0.010.08 U/min)

Baseline norepinephrine infusion signficantly

reduced in vasopressin group


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The Evidence

Russell N Engl J Med 2008

Multicenter, randomized, double-blind trial

778 patients with septic shock receiving norepi

received either norepinephrine(5-15g/min) orlow-dose vasopressin(0.01-0.03 U/min)

no significant difference in 28-day mortality or

rates of serious adverse events

In less severe septic shock (norepi < 15 g/min),mortality was lower in vasopressin group (26% vs

36%)


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Case #3

70-year-old man collapses at home

v. fib arrest.After full pre-hospital ACLS

asystole on arrival in ED


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Vasopressin in ACLS

2010 ACLS guidelines pulseless arrest (v. fib, v. tach or asystole) Epinephrine 1 mg IV Q 35 min, or

Vasopressin 40 U as IV bolus x 1

to replace first or second dose epi

European recommendation 1 mg epinephrine alternate 40 U

vasopressin and 1 mg epinephrine Q 3 min

Krismer Crit Care Med 2004 (Wenzel, et al. in Austria)


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The Evidence

Wenzel N Engl J Med 2004

- double-blind, prospective, randomized, controlled

- compared epinephrineand vasopressin

similar for v. fib. and PEAvasopressin better for asystole

- epinephrine more effective after vasopressin ?


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Vasopressin in ACLS

Wenzel N Engl J Med 2004

Vaso Epi

% Survival to Hospital Admit

Ventricular fibrillation 46 43

PEA 33 30

Asystole 29 20

% Survival to Discharge

Asystole 4.7 1.5


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The Evidence

Aung Arch Intern Med 2005

- meta-analysis of 1519 patients with cardiac arrest

from 5 randomized controlled trials

- No clear advantage of vasopressin over epi

- ACLS should not recommend vasopressin in

resusvitation protocols until moredata


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The Evidence

Gueugniaud New Engl J Med 2008

multicenter randomized trial

2894 out-of-hospital cardiac arrest patients

epinephrine/vasopressinvs epinephine combination of drugs was not superior for:

survival to hospital (20.7% vs. 21.3%)

survival to discharge (1.7% vs. 2.3%)


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Case #4

48-year-old man with upper GI bleed.

PMH: cirrhosis

VS: 70/50, 120, 24, 98% O2

Despite aggressive Rx hypotension persists

Intractable hypotension in


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Intractable hypotension in

late-phase hemorrhagic shock

Vasopressin for


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Vasopressin for

irreversible shock

69-year-old man in MVA with extensive injury

- received crystalloid, colloid, hypertonic saline

- hemorrhagic shock2.5 mg epinephrine- asystole arrest40 U vasopressin + CPR

- v. fibrillationdefib with 200 J

- stable BP x 20 minutes (CT and to OR)- retroperitoneal hemorrhage uncontrolled

Haas (Wenzel) J Trauma 2004

Vasopressin for


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Vasopressin for

irreversible shock

Vasopressin for


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Vasopressin for

irreversible shock

Epinephrinedecreased effectiveness hypercapnic acidosis

hypoxia

Vasopressin better than epinephrine better vasopressor during severe acidosis

? inhibition of nitric oxide vasodilation

blood from muscle, and gut heart and brain


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Conclusions

Use norepinephrine, if you need it Add dobutamineif need inotropic help

Dopamine is rarely enough

When all else fails, try epinephrine

Watch vasopressin

vasoactive agents in emergency care

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