This document discusses types of shock, goals of therapy for different shock states, and vasopressor pharmacology. It defines hypovolemic, cardiogenic, septic, neurogenic, and combined shocks. The goals for hypovolemic shock are to increase preload with fluids, while cardiogenic shock aims to increase cardiac output with drugs like dopamine or dobutamine. Septic and neurogenic shock goals are to first increase preload then increase afterload with vasopressors like norepinephrine, phenylephrine, and vasopressin. Norepinephrine is usually the initial vasopressor, while other drugs like dopamine, epinephrine, vasopressin may be used as adjunct
4. Objectives
Define shock.
Define and interpret various hemodynamic
parameters [mean arterial pressure (MAP),
preload, afterload, Cardiac output (CO)].
List types, causes, and symptoms of shock.
Describe the pharmacology, doses and use of
vasopressors.
Explain practical issues with using
vasopressors.
Apply knowledge to a patient with a shock
syndrome
5. Shock
A state of cellular and tissue hypoxia due to
reduced oxygen delivery and/or increased
oxygen consumption or inadequate oxygen
utilization.
SBP < 90 mmHg or reduction of > 40 mmHg
with perfusion abnormalities* despite
adequate fluid resuscitation.
* End organ hypoperfusion (lactic acidosis, oliguria,
mental status deterioration).
6. Preload (PCWP)
Represents the amount
of blood available to the
left ventricle for pumping
and is influenced by
venous return to the left
atrium.
Normal = 12 - 18 mmHg
Dry < 12 mmHg
Wet > 18 mmHg
7. Afterload (SVR)
Represents the ventricular wall
tension required for expulsion
of ventricular blood volume
into the aorta during
contraction.
Normal = 1000 - 1600 dynes-sec/m2
Arterial dilation < 800 dynes-sec/m2
Arterial constriction > 1800 dynes-sec/m2
8. Definitions
MAP = 1/3 SBP + 2/3 DBP
MAP = CO X SVR
CO = HR X SV
The stroke volume is
determined by:
Preload
Afterload
Myocardial contractility
SVR is
determined by:
Vessel length
Blood viscosity
Vessel tone
13. Hypovolemic Shock
Goal is to increase preload (PCWP) by
replacing fluid loss with blood, crystalloid,
or colloid.
14. Cardiogenic Shock
Goal is to increase cardiac output
(CO) with inotropic pharmacotherapy
(dobutamine) and reduce afterload
(SVR) with vasodilators.
15. Septic Shock
Goal is to increase preload (PCWP) with
fluid replacement (crystalloid, then
colloid), then increase afterload (SVR)
with vasopressor (e.g. dopamine,
norepinephrine, phenylephrine,
vasopressin).
16. Neurogenic Shock
Goal is to increase afterload (SVR)
with vasopressor (e.g. phenylephrine,
norepinephrine).
17. Combined Shock
Patients with pancreatitis or sepsis have
distributive shock but may have hypovolemic
and cardiogenic component.
Patients with cardiomyopathy may present
with cardiogenic shock and hypovolemic
shock.
Patients with severe traumatic injury may
have hemorrhagic and distributive shock
Patients with spinal cord injury can have
distributive and cardiogenic shock.
18. Vasopressors Goals of Therapy
PCWP = 8 to 12 mm Hg ( up to 15 mm Hg in
specific patients).
MAP ≥ 65 mm Hg.
Mixed venous Oxygen saturation (SvO2) ≥ 65%.
Central venous Oxygen saturation (ScvO2) ≥
70%.
Lactate Clearance ≥ 20%.
20. Dopamine (Dop)
• Receptors: D1, D2, β1, α1
*
• Use:
• At (3 to 10 mcg / Kg/ min), increases CO in
cardiogenic shock.
• At (10 to 20 mcg / Kg/ min), increases
afterload (SVR) and urine output in septic
shock.
• Dose: 1 to 20 mcg / kg/ min.
• Monitoring: Blood pressure (BP); Heart
rate (HR); urine output, renal function, serum
glucose, CO, PCWP, and SVR.
21. Dobutamine (Dob)
• Receptors: β1, β2, α1
• Use: Increase CO and decrease
afterload in cardiogenic shock.
• Dose: 1 to 20 mcg / kg/ min.
• Monitoring: BP, ECG, renal function,
urine output, CO, PCWP, and SVR.
22. Norepinephrine (Nepi)
• Receptors: α1, β1, β2
• Use: Increase afterload (SVR) in septic
and neurogenic shock.
• Dose: 8 to 20 mcg / min.
• Monitoring: BP, HR, CO, urine output,
infusion site for extravasation or
necrosis.
23. Epinephrine (Epi)
• Receptors: α1, β1, β2
• Use: Increase afterload (SVR) in
neurogenic shock or as an add on in
septic shock.
• Dose: 1 to 10 mcg / min.
• Monitoring: BP, HR, continuous cardiac
monitoring, serum lactate, site of
infusion for blanching/extravasation.
24. Phenylephrine (Phen)
• Receptors: α1
• Use: Increase afterload (SVR) in
neurogenic shock, or as salvage - add on
- to other vasopressors.
• Dose: 100 to 180 mcg / min.
• Monitoring: BP, HR, CO, local skin
blanching, extravasation.
25. Vasopressin (Vas)
• Depleted in septic shock
• Receptors:
1. Vascular V1 receptors: Cause
vasoconstriction.
2. Renal V1 and V2 receptors: Increases GFR
and net increase urine output.
3. Pituitary gland V3: Increase serum cortisol.
• Dose: 0.02 to 0.04 units / min.
• Monitoring: Fluid input, urine output, HR,
BP, skin blanching.
26. Vasopressors Pharmacology
Dop Dob Nepi Epi Phen Vas
α1
✚ ✚✚ ✚✚✚ ✚✚✚ ✚✚✚ 0
β1
✚ ✚✚✚ ✚✚ ✚✚ 0 0
β2
0 ✚✚✚ ✚⁄✚✚ ✚✚ 0 0
D1,D2
✚✚ 0 0 0 0 0
V1, V2
0 0 0 0 0 ✚
Dose
1 to 20
mcg/kg/min
1 to 20
mcg/kg/min
8 to 20
mcg/mi
n
1 to 10
mcg/min
100 to 180
mcg/min
0.02 to 0.04
units/min
27. Vasopressor IV Infusion Chart
Medication Indication Bolus
Initial IV infusion
Titration
Usual
dose
Maximum
dose /
duration
Diluent /
Line
Dobutamine
Decreased cardiac
output
No Bolus
0.5 to 1
mcg / Kg / min By 2.5
mcg / kg /min
According to
response ~
every 5 min
2 to 20
mcg /
kg /min
҂ Up to 40
mcg / Kg /
min
NS / D5W /
LR
Do Not add
Sod
Bicarbonate
Peripheral
Dobutamine
Post cardiac
Arrest
ACLS
5 to 10
mcg /Kg / min
0.5 to 1
mcg / Kg / min
2 to 20
mcg /
kg /min
Dopamine
Cardiogenic/septic
Shock, CHF/ renal
failure
No Bolus 2 to 5 mcg/kg/min
5 to 10
mcg/kg/min
increments
¥ Up to 20 -
50
mcg / kg
/min
NS / D5W
Do Not add
Sod
Bicarbonate
Central
Line
Epinephrine3
Hypotension /
Septic Shock or as
an add on to other
vasopressors
No Bolus
₠ 0.1 to 0.5
mcg / Kg /min
0.05 to 0.2
mcg/kg/minute
every 10- 15
min to target
MAP
1 to 10
mcg /
min
€ Up to 10
mcg / min
NS / D5W
Central
Line
Epinephrine
Asystole/
pulseless arrest
ACLS
1 mg IV or I.O. Give 1 mg every 3 to 5 min until return of
spontaneous circulation.
Up to 0.2
mg / Kg
(total dose)
In BB and
CCB
overdose
NS / D5W/
LR
Central
Line*2.5 mg endotracheal Dilute in 5 to 10 ml NS or sterile water
Epinephrine Anaphylaxis
o mg IV
over 5 min
5 to 15 mcg / min
Norepinephrine4
Levophed®
Hypotension /
Shock
No Bolus 8 to 12 mcg /min
Titrate to
desired
response by
2 mcg / min
1 to
4
mcg
/min
Up to 20
mcg / min
NS / D5W
Central
Line
28. Summary
Types of Shocks: hypovolemic, Cardiogenic, Septic,
neurogenic.
Hypovolemic Shock: goal is to increase preload with
fluids1st.
Cardiogenic Shock: goal is to increase cardiac output
(CI) with dopamine (1-10μg /Kg/min), or dobutamine.
Septic Shock: goal is to increase preload with fluids1st ,
then increase afterload with, dopamine, norepinephrine,
phenylephrine, or vasopressin.
Neurogenic Shock: goal is to increase afterload with
norepinephrine, phenylephrine.
29. Summary
Nepi is the initial vasopressor, 8 to 20 μg / min.
Dop alternative to Nepi in patients with low CO or HR. Dop
receptor effect is dose dependent, 1 to 20 μg / kg / min.
Dob used in patients with cardiogenic shock 1 to 20 μg / kg /
min.
Epi used as an add on to increase MAP, 1 to 10 μg / min.
Vasopressin used as an add on to Nepi to increase MAP,
0.03 Unit / min.
Phen used in neurogenic shock or as an add on to increase
MAP, 100-180 μg / min.
Notas do Editor
Shock can be caused by any condition that reduces blood flow, including:
Heart problems (such as heart attack or heart failure)
Low blood volume (as with heavy bleeding or dehydration)
Changes in blood vessels (as with infection or severe allergic reactions)
Certain medications that significantly reduce heart function or blood pressure
Shock is often associated with heavy external or internal bleeding from a serious injury. Spinal injuries can also cause shock.
Toxic shock syndrome is an example of a type of shock from an infection.
The general goal of therapy during resuscitation is to achieve and maintain MAP above 65 mmHg while ensuring adequate perfusion to the critical organs.
Measure preload (PCWP, LVEDP) when mitral valve open.
Definition of afterload: the pressure against which the left ventricle must pump.
Influenced by aortic impedance (aortic wall compliance, arterial resistance, blood viscosity), preload, and ventricular wall thickness.
The major physiologic determinants of tissue perfusion (and systemic blood pressure [BP]) are cardiac output (CO) and systemic vascular resistance (SVR):
Shock can be classified into 4 main types:
Distributive shock is characterized by severe peripheral vasodilatation
Cardiogenic shock is due to intracardiac causes of cardiac pump failure that result in reduced cardiac output (CO).
Hypovolemic shock is due to reduced intravascular volume (ie, reduced preload), which, in turn, reduces CO
Obstructive — Obstructive shock is due to extracardiac causes of cardiac pump failure and often associated with poor right ventricle output.
The causes of obstructive shock can be divided into the following two categories, listed in the sections below (pulmonary vascular and mechanical)
Pulmonary vascular — Most cases of obstructive shock are due to right ventricular failure from hemodynamically significant pulmonary embolism (PE) or severe pulmonary hypertension (PH).
Mechanical — Patients in this category present clinically as hypovolemic shock because their primary physiologic disturbance is decreased preload, rather than pump failure (eg, reduced venous return to the right atrium or inadequate right ventricle filling). Mechanical causes of obstructive shock include the following:Cardiac tamponade – Cardiac tamponade, which may be acute or subacute, is characterized by the accumulation of pericardial fluid under pressure. Variants include low pressure (occult) and regional cardiac tamponade.
Constrictive pericarditis – Constrictive pericarditis is the result of scarring and consequent loss of elasticity of the pericardial sac. Pericardial constriction is typically chronic, but variants include subacute, transient, and occult constriction.
Effusive-constrictive pericarditis – Effusive-constrictive pericarditis is characterized by underlying constrictive physiology with a coexisting pericardial effusion, usually with cardiac tamponade. Such patients may be mistakenly thought to have only cardiac tamponade; however, elevation of the right atrial and pulmonary wedge pressures after drainage of the pericardial fluid points to the underlying constrictive process.
Septic shock: Due to systemic inflammatory response syndrome (SIRS) and arterial dilation associated with infection.
Neurogenic shock: Due to loss of alpha1 regulation with spinal cord injury. – traumatic brain injury, spinal cord injury, mitochondrial dysfunction cause distributive shock due to autonomic dysfunction.
Anaphylactic shock – bee stings, food and drug allergies
SIRS: (systemic inflammatory response syndrome) – burns, trauma, pancreatitis, postmyocardial infarction, post coronary bypass, post cardiac arrest, viscus perforation, amniotic fluid embolism, air embolism, fat embolism, idiopathic systemic capillary leak syndrome.
Drugs and toxins – vasodilatory agents (eg, overdose narcotics), insect bites, transfusion reactions, heavy metal poisoning, toxic shock syndrome, carbon monoxide and cyanide poisoning.
Drugs and toxins –Endocrine shock – adrenal crisis, myxedema coma
Cardiogenic shock: Due to cardiac dysfunction secondary to MI, dysrhythmia, heart failure, etc.
Tension pneumothorax: Air in the pleural space.
Cardiac tamponade, which may be acute or subacute, is characterized by the accumulation of pericardial fluid under pressure. Variants include low pressure (occult) and regional cardiac tamponade.
Constrictive pericarditis – Constrictive pericarditis is the result of scarring and consequent loss of elasticity of the pericardial sac. Pericardial constriction is typically chronic, but variants include subacute, transient, and occult constriction.
Effusive-constrictive pericarditis – Effusive-constrictive pericarditis is characterized by underlying constrictive physiology with a coexisting pericardial effusion, usually with cardiac tamponade. Such patients may be mistakenly thought to have only cardiac tamponade; however, elevation of the right atrial and pulmonary wedge pressures after drainage of the pericardial fluid points to the underlying constrictive process.
vasodilators such as (phosphodiesterase inhibitor, nitrates, nitroprusside, ACE inhibitor) and diuretics (furosemide).
Patients often present with combined forms of shock. Examples include:
Patients with shock from sepsis or pancreatitis primarily have distributive shock (due to the effects of inflammatory and anti-inflammatory cascades on vascular permeability and peripheral vasodilation); however, they also often have a hypovolemic component (due to decreased oral intake, insensible losses, vomiting, diarrhea) and a cardiogenic component (due to inflammation-related myocardial depression).
Patients with underlying cardiomyopathy may present with hypovolemic shock (from over-diuresis) and cardiogenic shock (from inadequate compensatory tachycardia and/or stroke volume).
Patients with severe traumatic injury may have hemorrhagic shock from blood loss as well as distributive shock from SIRS or, less commonly, fat embolism.
Patients with trauma to the spinal cord can have distributive shock from injury-related autonomic dysfunction and cardiogenic shock from myocardial depression.
Patients with a ruptured left ventricular free wall aneurysm can have cardiogenic shock from primary pump failure, obstructive shock from cardiac tamponade when blood loss is contained by the pericardial sac, and hemorrhagic shock when blood loss is not contained by the pericardial sac.
The general understanding is that Goals of therapy with vasopressors should be predetermined and should optmize global and regional parameters ( e.g., cardiac, renal mesentric, and periphery) to normalize cellular metabolism.
PCWP of 15 in mechanically ventillated patients, pre-existing LVD, or pts with abdominal distention)
Stimulation of α 1 cause peripheral vascular constriction and increase SVR. Effect on the heart is increase contractility in a slowed heart. No effect on HR.
Stimulation of β 1β 2 increase heart contractility and renal output.
Stimulation of β 2 cause vasodilatation and decrease SVR
Stimulation of D1 receptors cause produce renal, coronary, and mesentric vasodilatation.
V1 stimulation causes vasodilatation in the cerebral , pulmonary , coronary, and selected renal vascular bed by enhancing endothelial
NO release. It has minimal inotropic or chronotropic effect.
V2 increase fluid retention in the renal collecting tubule . With net effect between vascular V1 effect and renal V2 to increase urine output. Stimulation of V1 receptors cause vasoconstriction in skin, skeletal muscle, fat tissue, pancreas, and thyroid gland.
Vasopressin also increase the activity of adrenergic receptors. V3 increase serum cortisol conc by stimulating ACTH from pituitary gland.
No longer considered 1st line agent due to potential tachyarrhythmia secondary to stimulation of endogenous NE secretion. Also, may worsen hypoxemia and depress ventilation.
Should be used as an alternative to NE in highly selected patients with low CO and / or low HR and at very low risk of arrhythmias.
MOA: * Stimulates both adrenergic and dopaminergic receptors, lower doses are mainly dopaminergic stimulating and produce renal and mesenteric vasodilation, higher doses also are both dopaminergic and beta1-adrenergic stimulating and produce cardiac stimulation and renal vasodilation; large doses stimulate alpha-adrenergic receptors
Onset 5 min; duration 5 min.
Nonlinear kinetics
ADR: angina , A.fib, HTN, hypotension, tach, or bradycardia, vasoconstriction --gangerene (at higher doses).
N & V.; Increase IOP; Azotemia
Used alone or added to vasopressor therapy in the presence of (a) Myocardial dysfunction as suggested by elevated filling pressure, and low CO, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate MAP.
MOA: Stimulates beta1-adrenergic receptors, causing increased contractility and heart rate, with little effect on beta2- or alpha-receptors. Lowers central venous pressure and wedge pressure, but has little effect on pulmonary vascular resistance
ADR: Ventricular premature contraction; angina pectoris; chest pain; hypotension; HTN; phlebitis; hypokalemia
Onset 1 to 10 minHalf life 2 min
NEPI has combined strong α1 agonist activity with less potent β1 agonist effect and weak β2 stimulation.
NE is the initial vasopressor of choice, produce either no change or some increase in CO
Start at 8 to 12 mcg / min and titrate to desired MAP by 2 mcg every minute till max 20 mcg / min
Two randomised studies comparing NEPI with dopamine showed similar 28 days mortality with less tachyarrhythmia's with NEPI. HR doesn’t increase significantly due to minimal stimulation of cardiac β1 receptors in septic shock and reflex bradycardia from increased SVR.
Limitation: not available in premixed ready to use form.
ADR: Arrhythmia, bradycardia, digital ischemia, headache, anxiety; dyspnea
Mechanism of action: Stimulates alpha-, beta1-, and beta2-adrenergic receptors resulting in relaxation of smooth muscle of the bronchial tree, cardiac stimulation (increasing myocardial oxygen consumption), and dilation of skeletal muscle vasculature; small doses can cause vasodilation via beta2-vascular receptors; large doses may produce constriction of skeletal and vascular smooth muscle.
At the high Epi infusion rate , predominantly α effects are observed, and SVR, MAP are increased.. While Epi is usually reserved as the vasopressor of last resort due to peripheral vasoconstriction, particularly splanchnic and renal beds. { 2nd line agent according to current guidelines}
(Added or substituted) should be used when an additional agent is needed to maintain adequate blood pressure.
Two RCT compared Epi with NEPI in septic shock- time to recovery and 28 mortality was similar but one study was stopped early due to the tachyarrhythmia's. Epi was associated with lower lactate clearance and lower arterial PH , increassed gylcolysis.
Onset of action: Bronchodilation: SubQ: ~5 to 10 minutes; Inhalation: ~1 minute
Half-life elimination: IV: <5 minutes
MOA: Potent, direct-acting alpha-adrenergic agonist with virtually no beta-adrenergic activity; produces systemic arterial vasoconstriction. Such increases in systemic vascular resistance result in dose dependent increases in systolic and diastolic blood pressure and slight reductions in heart rate and cardiac output especially in patients with heart failure.
It is also, an option in patients with hypotension and tachyarrhythmia.
It is particularly usefu alternative in pts who cannot tolerate tachycardia or tachyarrhythmia associated with other agents ( dopamine, dobutamine and epi).
0.03 Unit/ min may be added to NE with the intent of raising MAP, or decreasing NE dose.
MOA:
Vascular V1 receptors enhance calcium release from sarcoplasmic reticulum resulting in vasoconstriction
Renal V2 receptors enhance fluid retention in collecting tubules but V1 cause vasoconstriction of efferent and relative vasodilatation of afferent increases GFR: net effect is increase urine output.
Vasopressin at dosage exceeding 0.04 Unit /m is associated with ischemia of mesentric mucosa, myocardium and skin.
At present it is not considered as an alternative to NE but can be used as an adjunctive in pts refractory to catecholamine despite fluid resuscitation.
Dose titration and monitoring of vasopressors should be guided by the “ best clinical response” while minimizing Myocardial ischemia ( tachydysrhythmias, trops, ECG change) , renal ( GFR and / or urine output), splanchnic/ gastric ( low mucosal PH, bowel ischemia), or peripheral ( cold extremities) hypo perfusion, and worsening of partial pressure of arterial oxygen, (PaO2), pulmonary artery occlusive pressure ( PAOP), and other hemodynamic variables.
Discontinuation of vasopressors should be weaned down slowly.
