A 75M presents with several days of cough, fever, and progressive lethargy.
CXR demonstrates RLL pneumonia.
BP 70/50. HR 130. Lactate 5. T38.0
2L bolus NS given.
Antibiotics started.
Bedside sono shows noncollapsing IVC, hyperdynamic LV.
Recheck BP 72/50. Lactate 5.0
DX: Septic shock.
Plan: Central line, start a pressor, then intubate.

Question: What pressor do you want to start with, and why?

We’re going to narrow this down to dopamine versus norepinephrine.

I went into this review expecting an open and shut case for one of these pressors (norepi).

Pathophysiology:
Norepinephrine has alpha 1 and beta adrenergic effects, resulting in vasoconstriction and increased chronotropy and inotropy.

Dopamine, while being the precursor to norepinephrine and epi, has alpha1 and beta adrenergic effects as well.

Of note, dopamine receptors are present in vascular structures, which promote vasodilation when exposed to low levels of dopamine. It has been theorized and shown in models that dopamine via D1 and D2 receptors cause splanchnic and renal vasodilation, so for some time in critical care low dose dopamine was given to critically ill patients with the theoretical hope that it may be protective in improving renal blood flow, diuresis, and decrease the need for dialysis. However this was not borne out in a large multicenter trial and a meta-analysis in 2000 and 2001, and low dose dopamine for renal protection is no longer generally accepted in the critical care literature.

Recent Trials, Reviews, and Recommendations in vasopressor selection:

SOAP II
Comparison of Dopamine and Norepinephrine in the Treatment of Shock
NEJM, 2010

Randomized multicenter trial in Europe. 1679 patients Pts >18 years old who required a vasopressor for treatment of shock were randomized to norepinephrine or dopamine. No significant differences in mortality were found between the two arms. Among subgroups, no mortality difference was noted among those with septic shock, however rate of death in patients with cardiogenic shock was significantly higher in those who received dopamine.

There were more arrhythmic events in patients treated with dopamine than among those treated with norepinephrine (207 events [24.1%] vs. 102 events [12.4%], P<0.001).

 

Efficacy and Safety of Dopamine versus Norepinephrine in the Management of Septic Shock.
Shock, 2010

USA: 252 patients with septic shock were randomized to norepinephrine or dopamine as a first line pressor. There was no significant mortality difference. There were significantly more arrhythmias in the dopamine group, but again, no mortality difference.

There are several meta-analyses published recently, including:

COCHRANE Review: Vasopressors for Hypotensive Shock
2011:

23 randomized controlled trials, 6 vasopressors, 3212 patients, with 1629 mortality outcomes.
Cochrane review concluded that there was no difference in mortality among pressors, and suggested that the choice of vasopressor in shock does not influence the outcome. “There is not sufficient evidence that any one of the investigated vasopressors is clearly superior over others.”

The analysis did not use pre-defined subgroups, meaning they did not comment on pressor choice on particular states of shock (septic, cardiogenic, etc).

 

Meta-analysis using Bayesian network model.
Journal of critical care, 2014

14 studies with 2811 patients.
The review found that norepinephrine reduced mortality compared to Dopamine (OR: 0.80 [95% CI 0.65-0.99]).
The structure of the meta-analysis the authors used is nontraditional and beyond my understanding of study design, but they offer this explanation:
“The approach used in our current study differs from traditional meta-analyses… it is possible to combine the results of direct comparisons to indirect comparisons extrapolated by trials that have treatments in common…”

 

2012 Surviving Sepsis Campaign Guidelines:
Use vasopressors to target a MAP of 65.
Norepinephrine is recommended as first line vasopressor (grade 1B).

 

BACK TO THE CASE:
In examining recent prospective, randomized trials, I was unable to find a mortality benefit for norepinephrine over dopamine in shock, including septic shock. The Cochrane review is also unable to find a mortality difference. A meta-analysis found a mortality difference using advanced statistics, but I need a Newman consult for further clarity on their methods. There is evidence for increased arrhythmias on dopamine, but not in a manner that affected patient mortality.

With that said, the surviving sepsis campaign advocates for norepinephrine as our first line pressor in septic shock, and it is generally accepted in EM practice for now to start norepinephrine as the initial vasopressor in septic shock. So for our gentleman, let’s start norepinephrine.

My take away from this review is that the declaration of “standard care” may rest on RCT results that aren’t as decisive as one expected.

REFERENCES:

Bellomo, R, Chapman, M, Finfer, S, et al Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group.Lancet2000;356,2139-2143

De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, Brasseur A,
Defrance P, Gottignies P, Vincent JL; SOAP II Investigators. Comparison of
dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010 Mar
4;362(9):779-89.Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE,

Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart
K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA,
Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee
including the Pediatric Subgroup. Surviving sepsis campaign: international
guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med.
2013 Feb;41(2):580-637

Havel C, Arrich J, Losert H, Gamper G, Müllner M, Herkner H. Vasopressors for
hypotensive shock. Cochrane Database Syst Rev. 2011 May 11;(5)

Kellum JA, Decker JM. “Use of dopamine in acute renal failure: a meta-analysi” Crit Care Med. 2001 Aug;29(8):1526–31.

Oba Y, Lone NA. Mortality benefit of vasopressor and inotropic agents in
septic shock: A Bayesian network meta-analysis of randomized controlled trials. J
Crit Care. 2014 Oct;29(5):706-10.

Patel GP, Grahe JS, Sperry M, Singla S, Elpern E, Lateef O, Balk RA. Efficacy
and safety of dopamine versus norepinephrine in the management of septic shock.
Shock. 2010 Apr;33(4):375-80.