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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:
1. Heart Rate – bradycardia (neurogenic), tachycardia (except those on
B-blockers, or with pacers)
2. BP – widened pulse pressure with distributive shock
3. 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
1. CO = HR x SV; Normal CI = 3.5 – 5.5 L/min/m2
2 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 –and further subdivided into 2 subtypes
-- All but 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++
receptors: receptor bound ---- Gq protein stimulated ---phospholipase C activated ---- DAG and IP3 incr ---- further
protein phosphorylation and alterations in intracellular Ca++
 -- vasoconstrict – present on postsynaptic sympathetic nerves
-- vasodilate and neg chronotropy -- present on presynaptic sympathetic
nerves and acts as feedback inhibition
1 -- incr cardiac fx (inotropy, chronotropy, dromotropy), renin release, etc
-- -- 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  density
-- Transplanted heart and those with chronic CHF – downregulated 
receptor activity
-- Hypoxia – down regulation of receptors in myocardium over time
VasoactiveAdrenergic and Dopaminergic Agents
1 - Epinephrine
-- Potent and  agonism and moderate 2 agonism
-- At lower doses (0.04-0.1 mcg/kg/min),  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 1 agonist and 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 , 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  agonism – incr HR, contractility, SV
with little effect on SVR  increases CO
-- >10 mcg/kg/min leads to predominating 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
-- - selective (mainly 1) but l-isomer has little 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
1
2
1
2
DA
Epi
+++
+++
+++
+++
-
NE
+++
+++
+++
+
-
Dp
- to +++
+
++ to +++
++
+++
Db
- to +
-
+++
+
-
5 - Isoproterenol
-- Pure  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  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,  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