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Norad vs Dopamine

Norad vs Dopamine. Five randomized trials ( n = 1993 patients with septic shock) comparing norepinephrine to dopamine

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Norad vs Dopamine

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  1. Noradvs Dopamine • Five randomized trials (n = 1993 patients with septic shock) comparing norepinephrineto dopamine • Does not support the routine use of dopamine in the management of septic shock. The relative risk of short-term mortality was 0.91 (95% CI, 0.84−1.00;fixed effect; I2 = 0%) in favor of norepinephrine. • Patel GP, Grahe JS, Sperry M, et al: Efficacy and safety of dopamine versus norepinephrine in the management of septic shock. Shock 2010; 33:375–380 • De Backer D, Biston P, Devriendt J, et al; SOAP II Investigators:Comparisonof dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010; 362:779–789 • De Backer D, Aldecoa C, Njimi H, et al: Dopamine versus norepinephrine in the treatment of septic shock: A meta-analysis*. Crit Care Med 2012; 40:725–730

  2. Dopamine • A recent metaanalysis showed dopamine was associated with an increased risk (RR, 1.10 [1.01−1.20]; p = 0.035); in the two trials that reported arrhythmias, these were more frequent with dopamine than with norepinephrine (RR, 2.34 [1.46−3.77]; p = 0.001) (153). • De Backer D, Aldecoa C, Njimi H, et al: Dopamine versus norepinephrine in the treatment of septic shock: A meta-analysis*. Crit Care Med 2012; 40:725–730

  3. Adrenaline • Although some human and animal studies suggest epinephrine has deleterious effects on splanchniccirculation and produces hyperlactatemia, no clinical evidence shows that epinephrine results in worse outcomes, and it should be the first alternative to norepinephrine. • 4 randomized trials (n = 540) comparing norepinephrineto epinephrine found no evidence for differences in the risk of dying (RR, 0.96; CI, 0.77−1.21; fixed effect; I2 = 0%). • Epinephrine may increase aerobic lactate production via stimulation of skeletal muscles’ β2-adrenergic receptors and thus may prevent the use of lactate clearance to guide resuscitation. • Annane D, Vignon P, Renault A, et al; CATS Study Group: Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: A randomised trial. Lancet 2007; 370:676–684 • Myburgh JA, Higgins A, Jovanovska A, et al; CAT Study investigators: A comparison of epinephrine and norepinephrine in critically ill patients. Intensive Care Med 2008; 34:2226–2234

  4. Phenylephrine • With its almost pure α-adrenergic effects, phenylephrineis the adrenergic agent least likely to produce tachycardia, but it may decrease stroke volume and is therefore not recommended for use in the treatment of septic shock except in circumstances where norepinephrine is: • a) associated with serious arrhythmias, • b) cardiac output is known to be high, • c) as salvage therapy when other vasopressor agents have failed to achieve target MAP. • Morelli A, Ertmer C, Rehberg S, et al: Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: A randomized, controlled trial. Crit Care 2008; 12:R143

  5. Vasopressin • Studies show that vasopressin concentrations are elevated in early septic shock, but decrease to normal range in the majority of patients between 24 and 48 hrs as shock continues. This has been called relative vasopressin deficiency because in the presence of hypotension, vasopressin would be expected to be elevated. The significance of this finding is unknown. • Vasopressin levels in septic shock have been reported to be lower than anticipated for a shock state. • Low doses of vasopressin may be effective in raising blood pressure in patients, refractory to other vasopressors and may have other potential physiologic benefits. • Lauzier F, Lévy B, Lamarre P, et al: Vasopressin or norepinephrinein early hyperdynamic septic shock: A randomized clinical trial. Intensive Care Med 2006; 32:1782–1789

  6. The VASST trial, an RCT comparing norepinephrinealone to norepinephrine plus vasopressin at 0.03 U/min, showed no difference in outcome in the intent-to treat population. • An a priori defined subgroup analysis demonstrated that survival among patients receiving < 15 μg/min norepinephrine at the time of randomization was better with the addition of vasopressin; however, the pretrialrationale for this stratification was based on exploring potential benefit in the population requiring ≥ 15 μg/min norepinephrine. • Higher doses of vasopressin have been associated with cardiac, digital, and splanchnic ischemia and should be reserved for situations where alternative vasopressors have failed. • Seven trials (n = 963 patients with septic shock) comparing norepinephrinewith vasopressin (or terlipressin) does not support the routine use of vasopressin or its analogterlipressin The relative risk of dying was 1.12 (95% CI, 0.96−1.30; fixed effects; I2 = 0%). The risk of supraventricular arrhythmias was increased with norepinephrine (RR, 7.25; 95% CI, 2.30−22.90; fixed effect;I2 = 0%) • Russell JA, Walley KR, Singer J, et al; VASST Investigators: Vasopressin versus norepinephrine infusion in patients with septic shock.NEngl J Med 2008; 358:877–887

  7. Cardiac output measurement targeting maintenance of a normal or elevated flow is desirable when these pure vasopressorsare instituted.

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