In patients with cardiogenic shock, should we prefer dopamine or norepinephrine?
In 2010, an article published on NEJM seemed to give an answer for reference, and the guide was rewritten accordingly. In the latest guidance in the emergency field, “2015 FICS Adult Cardiogenic Shock Management Recommendations,” the use of norepinephrine is clearly and strongly recommended instead of dopamine as the preferred measure to maintain perfusion pressure. This subverts the clinical practice of medication for many years.
Under the guidance of the guidelines, norepinephrine has been used as the preferred medication for cardiogenic shock rescue in some major hospitals.
This article published on NEJM rewritten guidelines
The trial included 1,679 shock patients randomized to dopamine (858) and norepinephrine (821) using dopamine 20 μg/(kg·min) or norepinephrine 0.19 μg/(kg·min), when the use of these drugs can not maintain the patient’s blood pressure, you can increase the open-label norepinephrine, epinephrine or vasopressin.
The primary endpoint of the study was 28-day mortality, and secondary endpoints included days without organ support and incidence of adverse events.
The results showed no significant difference in 28-day mortality between the two groups (52.5% vs. 48.5% for dopamine vs. norepinephrine, OR 1.17, 95% CI 0.97 to 1.42, p=0.10). However, the arrhythmia events in the dopamine group were higher than those in the norepinephrine group (dopamine vs. norepinephrine 24.1 % vs 12.4%, p<0.001).
Subgroup analysis showed that dopamine was associated with increased 28-day mortality in 280 patients with cardiogenic shock compared with norepinephrine.
The study concluded that shock patients use dopamine as a first-line booster drug. Compared with norepinephrine, although there was no significant difference in overall mortality between the two groups, the dopamine group had higher levels in the cardiogenic shock subgroup analysis. Mortality and more incidence of arrhythmia. This correlation was not found in patients with septic shock or hypovolemic shock.
Judging from the conclusions of the study, it seems that the superiority and inferiority are already clear. However, can the conclusion of this study be directly applied to the clinic? Professor He Ben questioned this.
He believes that the reliability of the results is still questionable.
1. The dopamine dose has exceeded the cardiac dose range
Since the target blood pressure after administration was not determined, it was decided by the tube bed doctor. In this study, the maximum dose allowed for the dopamine group was as high as 20 ug/(kg·min).
According to the study protocol, doctors were allowed to add norepinephrine or other vasopressors only when the dose of dopamine was as high as 20 ug/(kg·min) and blood pressure did not reach the desired target value. In this way, the majority of patients assigned to the dopamine group had received doses of drugs far beyond the cardiac dose range. This high concentration of dopamine has a severe vasoconstrictor effect.
Assuming that the maximum dose allowed for dopamine in this study is 10 μg/(kg·min), will the results be the same?
2. The conclusion of the study cannot be simply applied to clinical practice
Among the subjects studied, there were 135 cases and 145 cases of cardiogenic shock subgroups in the two groups, accounting for less than 17%. Some of these patients have pericardial tamponade, pulmonary embolism, valvular disease, dilated cardiomyopathy, and other cardiopulmonary bypass diseases. Cardiogenic shock caused by myocardial infarction accounts for only about 50% of these patients.
Professor He Ben believes that hemodynamic changes in patients with these different mechanisms. It is expected to maintain blood pressure from a high-dose titration of a vasoactive drug and receive randomization of two different mechanisms of vasoactive drugs in an extreme medical state. This is in itself inhuman and even ethical. Through these confounding factors, many patients with different hemodynamic changes, but all of whom are known as “cardiogenic shock,” have come up with the so-called “good and bad” of vasoactive drugs with two different mechanisms of action. I am afraid it is difficult to fit a person with true cardiogenic shock.
In the critical state of cardiogenic shock, should it be treated according to pathophysiological changes, or should it be treated according to “evidence-based medicine”?
In all cases of left valvular heart disease (mitral valve, aortic valve regurgitation, and even ventricular septal rupture), noradrenaline, which preferentially increases peripheral vascular resistance, leads to further deterioration of hemodynamics and is clinically contraindicated.
Left heart obstructive diseases, such as mitral stenosis, aortic stenosis or hypertrophic obstructive cardiomyopathy, rely mainly on the release of mechanical stenosis for the correction of hypotension. At this time, the role of vasoactive drugs is very limited.
The key to hypotension caused by pericardial tamponade and pulmonary insufficiency is the release of mechanical causes.
Myocardial infarction caused by myocardial infarction in large areas of cardiogenic shock, the peripheral vascular resistance has often been compensatory increase, and then the use of vasoconstrictor drugs to increase peripheral vascular resistance to maintain blood pressure, will make the left ventricular afterload significantly increased.
For a long time, the rescue drugs of shock, especially cardiogenic shock, need to be combined carefully according to the clinical state and according to the different hemodynamic mechanism by the bedside. It is not scientific to solve the problem through the simple use of a kind of drug.
3. Dopamine and arrhythmia
Atrial arrhythmias are expected
From the study results, it can be seen that the incidence of arrhythmia is higher in the dopamine group, and most of them are atrial fibrillation. Atrial arrhythmias, especially atrial fibrillation, are expected to occur during dose-escalation as an agonist of β-adrenergic-based drugs. However, the article did not mention whether these patients had atrial fibrillation prior to enrollment in the group. The proportion of arrhythmias in the subgroup and the proportion of withdrawals due to them were not mentioned.
4. Norepinephrine and myocardial infarction
The side effects of the drug are alarming
In contrast, the proportion of drugs that cause myocardial infarction was 19 in the dopamine group (2.2%) and 25 in the norepinephrine group (3.0%). Although there was no statistical significance, the effect of norepinephrine on the coronary arteries, The cause of coronary artery contraction and spasm is clear. There are also many reports suggesting that the use of high-dose vasoconstrictor drugs (such as norepinephrine) can increase the mortality of patients with cardiogenic shock.
5. Other drug side effects
From another point of view, the dose of dopamine is too large
The proportion of skin ischaemia in the two groups was 5.6% in the dopamine group and 4.1% in the norepinephrine group. Although this did not reach statistical significance, it also indicates from another point of view that the dose of dopamine in the study was large enough to be considered as The use of vasoconstrictors has eliminated the “strength” of the heart.
Dopamine and norepinephrine choose one? The two drugs are not rivals but partners
In the rescue of cardiogenic shock, it should be preferred dopamine or norepinephrine? Prof. He Ben believes that these two drugs are not related to one another.
In cardiogenic shock, pump failure leads to a reduction in cardiac output and leads to peripheral hypoperfusion. At this time, boosting is more important than vasoconstriction. In fact, to solve the root cause of cardiogenic shock – pump failure can solve the fundamental problem, at this time consider the use of positive inotropic drugs to correct pump failure. If norepinephrine is applied, the peripheral resistance will be too high due to excessive and powerful vasoconstrictive effects, which will increase the cardiac afterload and secondly, the renal perfusion deficit, resulting in prerenal AKI (acute kidney injury), which in turn leads to indirect Cardiogenic shock worsens.
In another perspective, the application of dopamine or norepinephrine in patients with cardiogenic shock depends on the balance between CO (cardiac output) and TPR (peripheral vascular resistance) of the patient. Is peripheral vascular resistance too low or cardiac output? Each patient may have different stages and different changes. It requires doctors to carefully screen and adjust them according to actual conditions.
One of the targets for dopamine and norepinephrine is CO and one is TPR. The two are not rivals and are partners. They must attempt to make optimal choices in the two unequal advantages, and it is not appropriate to use a single drug. Based on this clinical trial, it is also not suitable for clinical practice, and the results cannot be simply applied to the clinic but should be treated according to actual conditions.