Shock Pharmacologics

Question 1

Fluid Therapies

Answer 1

• Crystalloids are initial fluid choice: 30 mL/kg until stable
• Consider albumin if patients still requiring substantial amounts of crystalloids after initial resuscitation (otherwise, albumin doesn’t provide significant benefit and more costly)
• CVP marker for fluid status (8-12, 12-15 if mechanically ventilated)
• DONT USE HYDROXYETHYL STARCHES

Question 2

Vasopressor Options/First Line

Answer 2

• Goal: MAP >= 65
• Arterial catheter should be placed ASAP
• Norepi: first line - little change to HR/SV, may be more effective at reversing hypotension than dopamine

Question 3

Vasopressor

Answer 3

• Not recommended as single, initial vasopressor
• Used in addition to NE to raise MAP
• Increase BP in vasopressor refractory patients
• Fewer kidney failure patient receive renal replacement compared to NE

Question 4

Epi

Answer 4

• Can be used in addition or as a substitute for NE

- Decreases renal/splanchnic blood flow

Question 5

Phenylephrine

Answer 5

• Not recommended unless NE causes serious arrhythmias
• High CO and persistently low BP, salvage therapy
• Least likely to produce tachycardia (only alpha) but can decrease SV

Question 6

Dopamine

Answer 6

• Alternative to NE when low risk of tachyarrhythmias and absolute/relative bradycardia
• Don’t use low doses for renal perfusion
• May be more arrhythmogenic than NE, but may be useful with compromised systolic fxn

Question 7

Dobutamine

Answer 7

• Inotropic Therapy
• Can be initial or added to vasopressor therapy
• May be useful for myocardial dysfxn (high pressures and low CO) and ongoing signs of hypoperfusion despite having good volume/MAP

Question 8

Antimicrobial Therapy

Answer 8

• Cultures (from two different sites) prior to antibiotic therapy if possible
• IV antimicrobials should be given within the first hour with septic shock/severe sepsis patients (broad spectrum)
• Each hour delayed, decrease in 7.6% survival

Question 9

Corticosteroids

Answer 9

• IV hydrocortisone is reserved for patients with hemodynamic instability despite fluid resuscitation and vasopressor therapy
• Don’t administer in absence of shock
• Taper steroids once vasopressors are no longer required
• Combined with fludrocortisone may have better outcomes

Question 10

Glucose Control

Answer 10

• Initiate insulin when glucose > 180 (target =< 180)

- Blood glucose monitored every 1-2 hours until glucose/insulin infusion are stable, then every 4 hours thereafter

Question 11

DVT Prophylaxis

Answer 11

Daily DVT prophylaxis with LMWH or UFH

• Patients with CI to prophylaxis should receive intermittent compression devices
• Use combination or intermittent pneumatic compression devices and pharm

Question 12

Stress Ulcer Prophylaxis

Answer 12

• H2 blocker or PPI with patients with bleeding risk factors
• Bleeding risk factors: coagulopathy (INR > 1.5 or platelets <50,000), mechanical ventilation for > 48 hours and possibly hypotension
• No risk factors shouldn’t get prophylaxis

Question 13

Cardiac Term Definitions

Answer 13

• Inotropy: altered contractility
• Lusitropy: altered relaxation
• Chronotropy: altered contraction rate (SA node conduction)
• Dromotropy: altered AV node conduction

Question 14

Alpha 1 Agonism

Answer 14

• Agonist for alpha1 receptor GCPR that binds to PLC
• Converts PIP2 to IP3 that opens calcium channel in SR
• Increases calcium release within smooth muscles (contracts and increases BP)

Question 15

Epi Sites/Uses

Answer 15

• All alpha/beta receptors (NOT selective)
• For anaphylactic shock and cardiac arrest/asystole
• Improves breathing and clears airways as well

Question 16

NE Sites/Uses

Answer 16

• Alpha 1/2, Beta 1/3
• Hypotensive shock (vasoconstricts through alpha1)
• Cardiac arrest (increase HR/contractile strength)

Question 17

DA Sites/Uses

Answer 17

• Alpha and beta 1
• [High] bind to B1 - acute decompensated HR
• [VERY high] binds to alpha1 - cardiogenic and septic shock

Question 18

Phenylephrine Sites/Uses

Answer 18

• Alpha1 ONLY (semisynthetic)

- Septic shock, vasoconstriction, nasal decongestant, pupil dilation, hemorrhoids

Question 19

B-adrenergic System MoA

Answer 19

• Agonist binds to B1 receptor GCPR which activated adenyl cyclase
• Converts ATP into cAMP which activates PKA
• Then phosphorylates LTCC and RyR which opens them more (more calcium)
• Also phosphorylates PL which releases from SERCA and causes it to open more to allow more calcium to be available for successive contractions

Question 20

Dobutamine Sites/Uses

Answer 20

• B1 ONLY
• Cardiogenic shock and acute decompensated HF
• Positive inotropy, little effect on chronotropy
• Stereoisomeric specificity cancels out alpha activity

Question 21

Isoproterenol

Answer 21

• Beta 1 and 2
• Treats bradycardia, heart block, and cardiac arrest (positive inotropy and chronotropy)
• Treats asthma (rarely used)

Question 22

Milrinone

Answer 22

• Antagonist of PDE3
• Similar end-result as dobutamine and EPI (positive inotropy)
• Vasodilator effects
• Potentiate the actions of catecholamines

Question 23

Vasopressin Receptors

Answer 23

• V1R located on vascular smooth muscle cells, cardiomyocytes
• Works same mechanism as alpha agonists via PLC
• V2R: located in kidney, works via AC mechanisms and causes antidiuresis (volume retention)
• Decreases in hemorrhagic and septic shock, increased sensitivity

Question 24

NO Vasodilators

Answer 24

• Increases conversion of GTP to cGMP
• Converts myosin and causes relaxation
• Reduces preload and afterload by promoting vascular smooth muscle relaxation
• Leads to decreased workload of the heart and increased CO

Question 25

Nesiritide

Answer 25

• Recombinant BNP
• B-type natriuretic peptides produced by heart due to excessive stretching of cardiomyocytes
• Nesiritide binds to NPRs promotes vasodilation and diuresis by increase cGMP in smooth muscle and negatively regulating RAAS