Shock, Pressors, and Inotropes - Stony Brook Medicine



SHOCK, PRESSORS, AND INOTROPES

Shock

- Definition: Syndrome initiated by acute systemic hypoperfusion, leading to tissue hypoxia and vital organ dysfunction, or perfusion inadequate to meet metabolic demands of the tissue.

- Types:

1. Hypovolemic – hemorrhagic vs nonhemorrhagic

2. Obstructive – mechanical obstruction to cardiac ouput; examples include cardiac tamponade, pulmonary emboli, tension pneumothorax

3. Cardiogenic – primary pump failure; can be secondary to reduced contractility (cardiomyopathy), ventricular outflow tract obstr. (pulmonary emboli, AS), ventricular filling defects (MS), valvular failure, dysrhythmias, etc.

4. Distributive – maldistribution of blood flow; best example is sepsis but can be seen with liver dysfx, hyperthyroidism, etc.

a. Neurogenic – autonomic dysfunction secondary to CNS injury above the upper thoracic level; sec to autonomic dysfunction and is characterized by hypotension, bradycardia, and warm skin.

5. Spinal – sec to decreased sympathetic outflow from higher centers

Monitoring and Diagnosis of Shock

- Vital Signs:

Heart Rate – bradycardia (neurogenic), tachycardia (except those on B-blockers, or with pacers)

BP – widened pulse pressure with distributive shock

Urine output – one of the earliest signs of inadequate perfusion at the tissue level

4. Other – mental status, skin turgor, etc

- Laboratory Evaluation

1. Base Deficit – Normal = -3 ( +3

2. Lactate levels – secondary to increased anaerobic metabolism or decreased excretion through kidney

3. Intramucosal pH monitoring

- Invasive hemodynamic monitoring; venous SaO2

MANAGEMENT OF SHOCK; PRESSORS AND INOTROPES

Physiology of Shock: Oxygen Transport

-- Delivery of O2 (DO2) = Cardiac Index (CI) x O2 Content (CaO2)

Normal values = 620 +/- 50 ml/min/m2

-- CaO2 = (1.34 x Hgb x SaO2) + (0.0031 x PaO2)

-- Cardiac Output

CO = HR x SV; Normal CI = 3.5 – 5.5 L/min/m2

Stroke volume is determined by preload, afterload, and contractility

Initial Management

-- Restoration of intravascular volume; crystalloid vs colloid

-- Improve O2- carrying capacity

-- Improvement of perfusion, i.e. inotropes

Receptor physiology

1- Adrenergic receptors

-- Cell membrane glycoproteins;

-- 2 types – α and β further subdivided into 2 subtypes

-- All but α1 involve cAMP as the second messenger: receptor bound ---- G-protein stimulated ---- GDP released, GTP binds to G-protein ---- adenylyl cyclase stimulated or inhibited (depending on the receptor and G protein) -- ATP conversion to cAMP stimulated or inhibited which affects other protein kinases ---- phosphorylation of other proteins that alter intracellular Ca++

−− α 1 receptors: receptor bound ---- Gq protein stimulated ---- phospholipase C activated ---- DAG and IP3 incr ---- further protein phosphorylation and alterations in intracellular Ca++

− α 1 -- vasoconstrict – present on postsynaptic sympathetic nerves

− α 2 -- vasodilate and neg chronotropy -- present on presynaptic sympathetic nerves and acts as feedback inhibition

− β1 -- incr cardiac fx (inotropy, chronotropy, dromotropy), renin release, etc -- β2 -- affects vascular and bronchiolar tone by relaxing smooth muscle

2- Dopaminergic receptors

-- Also glycoproteins with 2 subtypes

-- Also act on adenylate cyclase and affect cAMP levels

-- DA1 – postsynaptic receptors located in renal, splanchnic, coronary and cerebral vascular beds, etc; stimulation results in smooth muscle relaxation

-- DA2 – presynaptic receptors located in carotid body; decrease afferent neural input to CNS and decrease hypoxic ventilatory drive (which has implications in pts with decreased CO2 responsiveness)

3 - Regulation of receptors

-- Desensitization occurs from prolonged exposure, which leads to decreased numbers of receptors, uncoupling of receptors from adenylate cyclase, and changes in second messenger concentrations.

-- Peripheral vascular responses to adrenergic agonists develop at different rates and ages so there will be variability in responses

-- Corticosteroids and thyroid hormone --- increase β density

-- Transplanted heart and those with chronic CHF – downregulated β receptor activity

-- Hypoxia – down regulation of β receptors in myocardium over time

Vasoactive Adrenergic and Dopaminergic Agents

1 - Epinephrine

-- Potent α and β1 agonism and moderate β2 agonism

-- At lower doses (0.04-0.1 mcg/kg/min), β effects predominate (incr CO, HR, decr SVR, etc)

-- At higher doses, vasoconstriction and venoconstriction

-- Potent renal/splanchnic vasoconstrictor even at low doses (countered by incr CO)

-- Also increases glucose and renin activity

-- Indication: useful in providing inotropic support in pts with severe CV collapse particularly in those unresponsive to Dp

-- T½ = 3 minutes; dose = 0.1-1.0 mcg/kg/min

2 - Norepinephrine

-- Potent β1 agonist and α agonism – (+) inotropy and vasoconstrictor

-- Increases BP – systolic > diastolic, CO unchanged or decreased

-- Decreases renal and mesenteric perfusion and increases afterload

-- Major indications: hyperdynamic shock that does not respond to volume or Dp

-- T½ = 2 minutes; dose = 0.05-0.1 mcg/kg/min

-- Adverse rxns: local infiltrate, which can cause necrosis – tx’d with phentolamine

3 - Dopamine

-- Naturally occurring precursor of NE; also induces its release

-- Has a dose dependent effect on α, β, and DA receptors:

-- < 2-5 mcg/kg/min stimulate DA1 receptors to incr renal, mesenteric, cerebral, and coronary perfusion

-- 5-10 mcg/kg/min lead to β agonism – incr HR, contractility, SV with little effect on SVR ( increases CO

-- >10 mcg/kg/min leads to predominating α effects with vaso- and venoconstriction; also decr mesenteric and renal perfusion, incr coronary resistance and myocardial work

-- Also can increase pulm art pressures and resistance in those with pulm HTN; can exacerbate hypoxic pulm vasoconstriction

-- Indication: used for decreased CO, BP, or for augmentation of RBF

-- T½ = 2 minutes; dose =1-20 mcg/kg/min

4 - Dobutamine

-- synthetic catecholamine

-- β- selective (mainly β1) but l-isomer has little α effects

-- Increases contractility and HR with some decr in SVR

-- Indications: used in pts with low CO states

-- T½ = 2 min; dose =1-20 mcg/kg/min

| |α1 |α2 |β1 |β2 |DA |

|Epi |+++ |+++ |+++ |+++ |- |

|NE |+++ |+++ |+++ |+ |- |

|Dp |- to +++ |+ |++ to +++ |++ |+++ |

|Db |- to + |- |+++ |+ |- |

5 - Isoproterenol

-- Pure β agonism – increased inotropy/chronotropy and vasodilates (increased pulse pressure because of a rise in SBP and a decr in DBP)

-- Also acts as a pulmonary vasodilator

-- Indications – may be used in low cardiac output states but tachycardia and decr preload may compromise CO; can be used for bradycardia

-- T½ =1.5 min; dose = 0.05-0.1 mcg/kg/min

6 - Phenylephrine

-- Synthetic α1 agonist

-- Indications – useful in spinal shock, hyperdynamic shock, TET spells

-- Dose = 0.1-0.5 mcg/kg/min

Other Vasoactive Agents

1 - Amrinone

-- Bypyridine derivative with marked vasodilator effects and slight (+)inotropy

-- Phosphodiesterase inhibitor that increases cAMP and intracellular Ca+

-- Side effects: LFT abnormalities and decreases platelets

-- Dose= 3-10 mcg/kg/min

2 - Milrinone

-- 15x more inotropy than Amrinone with similar vasodilation

-- Increases coronary perfusion, CO, skeletal muscle perfusion and splanchnic perfusion

-- Indications: useful in pts with CHF, cardiogenic shock, hypodynamic septic shock, β receptor down regulation

-- Dose= 0.25-0.75 mcg/kg/min

3 - Nitroprusside

-- Mechanism not completely understood but appears to be similar to NO, which increases cGMP by activation of cGMP kinase that subsequently decreases intracellular Ca++

-- Dilates arteries and veins – has variable effects on CO

-- Indication: hypertensive emergencies, severe cardiogenic shock

-- Disadvantages: nonselective vasodilator so theoretically should not be used with increased ICP, also lose hypoxic pulmonary vasoconstriction

Metabolized into CN and metHgb (methylene blue contraindicated)

-- Dose= 0.25-8 mcg/kg/min; duration=1-5 minutes

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