Shock Syndromes I

viii.

Balanced crystalloid solutions may lead to hyponatremia (with lactated Ringer’s solution) or

cardiotoxicity (with acetate-containing solutions) when administered in large volumes. Caution

should be used with these solutions in patients with brain injury because of the risk of cerebral

edema and in those with hyperkalemia because they contain potassium (lactated Ringer

solution contains 4 mmol/L of potassium, Plasma-Lyte A contains 5 mmol/L of potassium).

A study of 7000 critically ill patients requiring fluid resuscitation compared a low-molecular-

weight, low-molar-substitution (130/0.4) hydroxyethyl starch solution with 0.9% sodium

chloride. Ninety-day mortality between the hydroxyethyl starch and 0.9% sodium chloride

groups did not differ (18.0% vs. 17.0%, p=0.26), but patients allocated to hydroxyethyl starch

had a greater need for renal replacement therapy (7.0% vs. 5.8%, p=0.04) and a higher incidence

of adverse events (5.3% vs. 2.8%, p<0.001).

ii.

A systematic review and meta-analysis that analyzed only unbiased trials found an association

between hydroxyethyl starch use and increased patient mortality (RR 1.09; 95% CI, 1.02–1.17;

p=0.02) and need for renal replacement therapy (RR 1.32; 95% CI, 1.15–1.50; p<0.001).

Vasopressors and inotropes in shock

A multicenter randomized trial, the SOAP II trial, included patients requiring vasopressors for shock

of any type and excluded those requiring vasopressors for more than 4 hours before enrollment.

Enrolled patients were allocated to either blinded norepinephrine or dopamine. Twenty-eight–day

mortality between patients receiving dopamine and those receiving norepinephrine did not differ

(52.5% vs. 48.5%, p=0.10), but patients receiving dopamine more often developed an arrhythmia

(24.1% vs. 12.4%, p<0.001), required open-label norepinephrine (26% vs. 20%, p<0.001), and had

fewer open-label vasopressor-free days (12.6 days vs. 14.2 days, p=0.007).

A predefined subgroup analysis evaluated the influence of shock type on the outcome. Patients

with cardiogenic shock allocated to dopamine had a higher mortality rate than those allocated

to norepinephrine (log-rank p=0.03). However, the overall effect of treatment did not differ

among the shock subgroups (interaction p=0.87), suggesting that the reported differences in

mortality according to subgroup are spurious.

ii.

These data suggest that although norepinephrine does not improve mortality compared with

dopamine, it is safer and more effective at increasing a patient’s blood pressure. Given these

data, a case could be made for norepinephrine as the first-line vasoactive medication of choice

in all shock types.

A multicenter randomized trial comparing norepinephrine with epinephrine for patients with

undifferentiated shock found no difference between agents in the time to achieving a goal MAP

(median 40 hours vs. 35.1 hours, p=0.26) or median number of vasopressor-free days at day 28

(25.4 days vs. 26.0 days, p=0.31). However, patients allocated to epinephrine had higher heart rates

and lactic acid concentrations on the first study day (but not on subsequent days) and were more

often withdrawn from the study by the treating clinician (12.9% vs. 2.8%, p=0.002). These data

suggest that epinephrine has no efficacy benefits over norepinephrine and is associated with an

increased incidence of adverse effects.

In a systematic review and meta-analysis of vasopressors for patients with circulatory shock of

all types, all-cause mortality did not differ in any comparison of different vasopressor agents or

combinations.

Single vasopressors evaluated included norepinephrine (reference group), dopamine,

epinephrine, terlipressin, vasopressin, and phenylephrine. Vasopressor combinations included

norepinephrine plus dobutamine and norepinephrine plus dopexamine (which were compared

with epinephrine).