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Apply Vasopressors for Ongoing Hypotension

Apply Vasopressors for Ongoing Hypotension

Corresponding Bundle Item

In the event of hypotension and/or lactate > 4 mmol/L (36 mg/dL), apply vasopressors for hypotension not responding to initial fluid resuscitation to maintain mean arterial pressure (MAP) > 65 mm Hg.

Background

Adequate fluid resuscitation is a prerequisite for the successful and appropriate use of vasopressors in patients with septic shock.  In general, the end points of fluid resuscitation are the same as those for the use of pharmacologic hemodynamic support, i.e. MAP > 65 mm Hg.  Sometimes, fluid resuscitation alone may suffice.

When an appropriate fluid challenge fails to restore an adequate arterial pressure and organ perfusion, therapy with vasopressor agents should be started. Vasopressor therapy may also be required transiently to sustain life and maintain perfusion in the face of life-threatening hypotension, even when hypovolemia has not been resolved or when a fluid challenge is in progress.

Cautions

Although all the vasopressor agents generally result in an increase in blood pressure, concerns remain in clinical practice about their potentially inappropriate or detrimental use:

  • The most obvious of these relates to the inadequately volume-resuscitated patient, in whom vasopressor use may worsen already inadequate organ perfusion. 
  • Even when volume resuscitation has been performed, discussion continues as to whether vasopressor agents may raise blood pressure at the expense of the perfusion of vulnerable organs, most particularly, the kidneys and the gut. 
  • A further concern relates to the possibility that overenthusiastic use, especially if an unnecessarily high blood pressure is targeted, may increase left ventricular work to an unsustainable degree and so worsen cardiac output and end-organ perfusion.  This may be especially harmful in patients with pre-existing heart disease.

Monitoring

Because hypotension is a primary feature of septic shock and improving blood pressure is a therapeutic goal, accurate and continuous measurement of blood pressure is essential. It is therefore customary to use an arterial catheter to enable continuous invasive blood pressure monitoring. The radial artery is the site most frequently chosen, but the femoral artery is also often used. It is important to note that there may be marked differences in the blood pressure recordings at the two sites, especially in patients who are in shock, receiving vasopressors, and still hypovolemic.

Choice of Vasopressors

Either norepinephrine or dopamine (through a central catheter as soon as placement is possible) is the first-choice vasopressor agent to correct hypotension in septic shock. 

Epinephrine or phenylephrine should not be used as first-line vasopressors as part of the treatment of septic shock. Epinephrine decreases splanchnic blood flow, increases gastric mucosal PCO2 production, and decreases pHi, suggesting that the drug alters oxygen supply in the splanchnic circulation. (1-3)  Phenylephrine was reported to reduce splanchnic blood flow and oxygen delivery in septic shock patients. (4)

Vasopressin use may be considered in patients with refractory shock despite adequate fluid resuscitation and high-dose conventional vasopressors.  Pending the outcome of ongoing trials, it is not recommended as a replacement for norepinephrine or dopamine as a first-line agent.

Dopamine

Dopamine increases mean arterial pressure primarily by increasing cardiac index with minimal effects on systemic vascular resistance. The increase in cardiac index is due to an increase in stroke volume and, to a lesser extent, to increased heart rate. (5,6)  

Splanchnic perfusion and the integrity of the gut mucosa may play an important role in the pathogenesis of multiple organ failure. The effect of dopamine on gastric tonometric and splanchnic variables has been evaluated with mixed results.  At low doses, dopamine increases splanchnic oxygen delivery by 65 percent but splanchnic oxygen consumption by only 16 percent. Despite this, dopamine may decrease pHi, perhaps by a direct effect on the gastric mucosal cell. The effects of dopamine on cellular oxygen supply in the gut remain incompletely defined.

Recent studies have shown that dopamine may alter the inflammatory response in septic shock by decreasing the release of a number of hormones, including prolactin. (7)  Other potentially harmful endocrine effects have been demonstrated in trauma patients. (8–11)  In a study of 12 stable mechanically ventilated patients, Dive et al. (12) used intestinal manometry to demonstrate that dopamine resulted in impaired gastroduodenal motility.  Concerns remain that these and other poorly understood biological effects of dopamine might potentially have harmful effects in patients with septic shock.

Norepinephrine

Norepinephrine is a potent a-adrenergic agonist with some b-adrenergic agonist effects.  Norepinephrine therapy usually causes a statistically and clinically significant increase in mean arterial pressure due to the vasoconstrictive effects, with little change in heart rate or cardiac output, leading to increased systemic vascular resistance. (13-15)

In open-label trials, norepinephrine has been shown to increase mean arterial pressure in patients with hypotension resistant to fluid resuscitation and dopamine.  In the past, there was concern that norepinephrine may have negative effects on blood flow in the splanchnic and renal vascular beds, with resultant regional ischemia.  This meant that in the past norepinephrine was commonly reserved for use as a last resort, with predictably poor results.  However, recent experience with the use of norepinephrine in patients with septic shock suggests that it can successfully increase blood pressure without causing the feared deterioration in organ function.  Norepinephrine seems to be more effective than dopamine at reversing hypotension in septic shock patients. (16)

Concern is frequently expressed with regard to the effect of norepinephrine on the kidney. In patients with hypotension and hypovolemia during hemorrhagic shock, for example, norepinephrine and other vasoconstrictor agents may have severe detrimental effects on renal hemodynamics.  Despite the improvement in blood pressure, renal blood flow does not increase, and renal vascular resistance continues to rise. (17)  However, in hyperdynamic septic shock, during which urine flow is believed to decrease mainly because of lowered renal glomerular perfusion pressure, the situation is different. (18)  Norepinephrine markedly improves mean arterial pressure and glomerular filtration.  This is particularly true in the high-output, low-resistance state of many septic shock patients.  After restoration of systemic hemodynamics, urine flow reappears in most patients and renal function improves.  This fact supports the hypothesis that the renal ischemia observed during hyperdynamic septic shock is not worsened by norepinephrine infusion and even suggests that this drug may be effective in improving renal blood flow and renal vascular resistance. (19-22)

Combination Therapies

The effects of dopamine on cellular oxygen supply in the gut remain incompletely defined, and the effects of norepinephrine alone on splanchnic circulation may be difficult to predict. (23-25)  The combination of norepinephrine and dobutamine seems to be more predictable and more appropriate to the goals of septic shock therapy than norepinephrine with dopamine or dopamine alone. (26,27)

References

  1. Levy B, Bollaert FE, Charpentier C, et al. Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock. Intens Care Med. 1997;23:282–287.
  2. Zhou SX, Qiu HB, Huang YZ, et al. Effects of norepinephrine, epinephrine, and norepinephrine-dobutamine on systemic and gastric mucosal oxygenation in septic shock. Acta Pharmacologica Sinica. 2002;23:654–658.
  3. Meier-Hellmann A, Reinhart K, Bredle DL, et al. Epinephrine impairs splanchnic perfusion in septic shock. Crit Care Med. 1997;25:399–404.
  4. Reinelt H, Radermacher P, Kiefer P, et al. Impact of exogenous beta-adrenergic receptor stimulation on hepatosplanchnic oxygen kinetics and metabolic activity in septic shock. Crit Care Med. 1999;27:325–331.
  5. Winslow EJ, Loeb HS, Rahimtoola SH, et al. Hemodynamic studies and results of therapy in 50 patients with bacteremic shock. Am J Med. 1973;54:421–432.
  6. Meier-Hellmann A, Reinhart K, Bredle DL, et al. Epinephrine impairs splanchnic perfusion in septic shock. Crit Care Med. 1997;25:399–404.
  7. Bailey AR, Burchett KR. Effect of low-dose dopamine on serum concentrations of prolactin in critically ill patients. Brit J Anaesth. 1997;78:97–99.
  8. Van den Berghe G, de Zegher F, Lauwers P, et al. Growth hormone secretion in critical illness: Effect of dopamine. J Clin Endo Met. 1994;79:1141–1146.
  9. Van den Berghe G, de Zegher F, Lauwers P, et al. Luteinizing hormone secretion and hypoandrogenaemia in critically ill men: Effect of dopamine. Clin Endo. 1994;41:563–569.
  10. Van den Berghe G, de Zegher F, Lauwers P. Dopamine and the sick euthyroid syndrome in critical illness. Clin Endo. 1994;41:731–737.
  11. Van den Berghe G, de Zegher F, Wouters P, et al. Dehydroepiandrosterone sulphate in critical illness: Effect of dopamine. Clin Endo. 1995;43:457–463.
  12. Dive A, Foret F, Jamart J, et al. Effect of dopamine on gastrointestinal motility during critical illness. Intens Care Med. 2000;26:901–907.
  13. Desjars P, Pinaud M, Potel G, et al. A reappraisal of norepinephrine therapy in human septic shock. Crit Care Med. 1987;15:134–137.
  14. Meadows D, Edwards JD, Wilkins RG, et al. Reversal of intractable septic shock with norepinephrine therapy. Crit Care Med. 1988;16:663–666.
  15. Hesselvik JF, Brodin B. Low-dose norepinephrine in patients with septic shock and oliguria: Effects on afterload, urine flow, and oxygen transport. Crit Care Med. 1989;17:179–180.
  16. Marin C, Papazian L, Perrin G, et al. Norepinephrine or dopamine for the treatment of hyperdynamic septic shock? Chest. 1993;103:1826–1831.
  17. Mills LC, Moyer JH. The effects of various catecholamines on specific vascular hemodynamics in hypotensive and normotensive subjects. Am J Cardiol. 1960;5:652–659.
  18. Bellomo R, Kellum JA, Wisniewski SR, et al. Effects of norepinephrine on the renal vasculature in normal and endotoxemic dogs. AJRCCM. 1999;159:1186–1192.
  19. Redl-Wenzl EM, Armbruster C, Edelmann G, et al. The effects of norepinephrine on hemodynamics and renal function in severe septic shock states. Intens Care Med. 1993;19:151–154.
  20. Fukuoka T, Nishimura M, Imanaka H, et al. Effects of norepinephrine on renal function in septic patients with normal and elevated serum lactate levels. Crit Care Med. 1989;17:1104–1107.
  21. Martin C, Eon B, Saux P, et al. Renal effects of norepinephrine used to treat septic shock patients. Crit Care Med. 1990;18:282–285.
  22. Desjars P, Pinaud M, Bugnon D, et al. Norepinephrine therapy has no deleterious renal effects in human septic shock. Crit Care Med. 1989;17:426–429.
  23. Ruokonen E, Takala J, Kari A, et al. Regional blood flow and oxygen transport in septic shock. Crit Care Med. 1993;21:1296–1303.
  24. Meier-Hellmann A, Reinhart K, Bredle DL, et al. Epinephrine impairs splanchnic perfusion in septic shock. Crit Care Med. 1997;25:399–404.
  25. Neviere R, Mathieu D, Chagnon JL, et al. The contrasting effects of dobutamine and dopamine on gastric mucosal perfusion in septic patients. AJRCCM. 1996;154:1684–1688.
  26. Levy B, Bollaert FE, Charpentier C, et al. Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock. Intens Care Med. 1997;23:282–287.
  27. Zhou SX, Qiu HB, Huang YZ, et al. Effects of norepinephrine, epinephrine, and norepinephrine-dobutamine on systemic and gastric mucosal oxygenation in septic shock. Acta Pharmacologica Sinica. 2002;23:654–658.

Content adapted extensively from

  • Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:858-873.
  • Beale RJ, Hollenberg SM, Vincent JL, et al. Vasopressor and inotropic support in septic shock: An evidence-based review. Crit Care Med. 2004;32(Suppl.):S455–S465

Tips

  1. Include the use of vasopressors on a standardized protocol for the treatment of hypotension not responding to fluid administration.
  2. Be sure that emergency department and intensive care nurses and staff are familiar with the appropriate dosing of dopamine, dobutamine, and norepinephrine.
  3. Do not wait to start vasopressors until a fluid challenge or bolus of intravenous fluid is completed before using vasopressor agents if severe hypotension is present.
  4. If you are unable to wean vasopressors, consider other diagnosis such as depressed cardiac function, adrenal insufficiency, tension pneumothorax or cardiac tamponade, etc.