A. Dopamine (Intropin®)

1. Excellent first line agent for nearly any setting of hypotension
2. High doses are as effective as epinephrine in sepsis with less lactic acidosis [1]
3. "Renal" dose initially if tolerated to maintain perfusion to kidneys and mesentery
4. Dosing Schedules
   1. "Renal" doses - may cause selective renal and mesenteric vasodilation (2-4µg/kg/min)
   2. "Cardiac" doses - mainly ß-adrenergic agonist activity (8-12µg/kg/min)
   3. "Pressor" doses - alpha adrenergic agonist activity (>12-15µg/kg/min)
5. This agent is recommended as first line therapy in any patient with hypotension
6. At any dose, a combination of "renal", "cardiac", and "pressor" activities is present
7. Renal range provides no relevant prevention of renal deterioration in ill patients [2,3,11]

B. Norepinephrine (Levofed®)

1. Primarily alpha activity, vasoconstriction with some ß-activity
2. Often preferred second line agent for sepsis and other shock-associated hypotension
3. Provides both peripheral vasoconstriction and good inotropic support
4. Dose of heparin may need to be increased for prophylaxis in patients on vasopressors [4]
5. For septic shock, norepinephrine+dobutamine had similar outcomes (~50% mortality at 90 days) to epinephrine in direct comparison of inotropic support [14]

C. Phenylephrine (Neosynephrine®)

1. Pure alpha adrenergic agonist
2. Used for vasoconstriction, usually as second or third line agent in sepsis

D. Epinephrine (Adrenaline)

1. Alpha and beta agonist activity, used as pressor and inotrope in severe CHF
2. Very strong peripheral vasoconstrictive activity
3. In patients with sepsis or malaria, caused severe lactic acidosis [1]
4. May be used as a single agent in septic shock; similar outcomes as norepinephrine+dobutamine [14]

E. Vasopressin (Pitressin®) and Terlipressin (Glypressin®) [6]

1. Also called antidiuretic hormone (ADH)
2. Endogenous hormone produced in hypothalamus released from posterior pituitary gland
3. Release of ADH with:
   1. Hypotension
   2. Hypovolemia
   3. Increased plasma osmolarity
4. Binds to renal collecting ducts and causes marked water reabsorption
   1. Main action of ADH is to reduce water loss through the kidney
   2. This occurs at serum ADH levels of 1-7pg/mL
   3. Vasopressin V2 receptors primarily involved
5. Vasoconstriction
   1. Activity at much higher levels (10-200pg/mL) binding to V1 receptors
   2. Can cause marked vasoconstriction even in acidosis and presence of nitric oxide (NO)
6. Sepsis [9,10]
   1. Inappropriately low levels found in patients with severe sepsis
   2. Pharmacologic administration of vasopressin in the 150-200pg/mL produces good pressor responses, even in vasoconstrictor resistant states such as sepsis
7. Terlipressin (Glypressin®) [7]
   1. Long acting vasopressin analog with ~5 hour duration of action
   2. Raises blood pressure in norepinephrine resistant shock without rebound hypotension
   3. Terlipressin has been used effectively in hepatorenal syndrome (HRS)
   4. HRS dose is 0.5-2.0 mg over 4-6 hours intravenously
   5. This dose of terlipressin associated with complete renal response in 50-75%
   6. Improvement in renal function usually requires several days
8. Vasopressin in Cardiac Arrest [8]
   1. Vasospressin (Pitressin®) may have some efficacy where epinephrine has failed
   2. Vasopressin 40 Units IV once may be used initially after failed defibrillation
   3. Overall, vasopressin of no benefit over epinephrine for first line arrest treatment
   4. For asystole, vasopressin was superior to epinephrine in all outcomes

F. Dobutamine (Dobutrex®)

1. This is not a vasopressor, but may increase blood pressure by improving cardiac output
2. Primarily a ß1 agonist with some peripheral ß2 activity
3. Increases cardiac output by inotropic and chronotropic acitivity
4. May cause hypotension even in pure cardiac failure due to peripheral vasodilation
5. Rate increasing activity may preclude its use in many patients

G. Levosimendan (LSM; Simdax®) [12,13]

1. Increases calcium sensitivity, vasodilates (opens ATP-sensitive K+ channels)
2. 203 patients with decompensated CHF given dobutamine or LSM
3. LSM superior to dobutamine on hemodynamics and mortality
4. Increased side effects, no benefit on mortality at 6 months versus dobutamine [13]

H. Amrinone and Milrinone

1. Inotropic agents with vasodilatory activity
2. Mild chronotropy
3. Phosphodiesterase inhibitors that block cyclic AMP breakdown
4. Milrinone did not reduce hospitalization and did increase complications in patients with severe exacerbations of CHF [5]
5. Oral milrinone associated with increased risk of death in chronic CHF

References

1. Day NPJ, Phu NH, Bethell DP, et al. 1996. Lancet. 348:219
2. ANZICS Clinical Trials Group. 2000. Lancet. 356(9248):2139
3. Galley HF. 2000. Lancet. 356(9248):2112
4. Dorffler-Melly J, de Jonge E, de Pont AC, et al. 2002. Lancet. 359(9309):849
5. Cuffe MS, Califf RM, Adams KF Jr., et al. 2002. JAMA. 287(12):1541
6. O'Brien A, Clapp L, Singer M. 2002. Lancet. 359(9313):1209
7. Gines P, Guevara M, Arroyo V, Rodes J. 2003. Lancet. 362(9398):1819
8. Wenzel V, Krismer AC, Arntz R, et al. 2004. NEJM. 350(2):105
9. Landry DW and Oliver JA. 2001. NEJM. 345(8):588
10. Schrier RW and Wang W. 2004. NEJM. 351(2):159
11. Friedrich JO, Adhikari N, Herridge MS, Beyene J. 2005. Ann Intern Med. 142(7):510
12. Follath F, Cleland JGF, Just H, et al. 2002. Lancet. 360(9328):196
13. Mebazaa A, Nieminen MS, Packer M, et al. 2007. JAMA. 297(17):1883
14. Annane D, Vignon P, Renault A, et al. 2007. Lancet. 370(9588):676