The incidence of critical illness in the ED is rising, with greater than 1 million ED patients requiring emergent resuscitation each year. In addition to definitive airway management, hemodynamic support is among the most important life-saving interventions implemented by emergency physicians. When a patient develops persistent hypotension, what is your approach to choosing the right medication for hemodynamic support?
Checklist of questions
Persistent hypotension results in impaired tissue perfusion and is often a late and ominous indication of decompensated shock. Correction of persistent hypotension is imperative, often requiring vasopressors and inotropes. When considering an agent for hemodynamic support, the following checklist can guide your choice 1–4 :
1. Why is the patient hypotensive?
Identifying the cause of the hypotension will allow you to select an agent targeted to the source of the problem. Causes of hypotension include hypovolemia, impaired vascular tone, impaired pump function, or some combination of these problems.
2. Have I optimized volume status and ruled out other diagnoses?
Initial management of the hypotensive patient should target optimizing intravascular volume prior to initiating a vasoactive medication. Vasopressors or inotropes cannot improve malperfusion secondary to isolated hypovolemia (such as hemorrhage, gastrointestinal bleeding or severe dehydration), and use of these agents prior to volume resuscitation can exacerbate existing metabolic derangements. Unrelated conditions that impair preload or cardiac output, including tension pneumothorax and pericardial tamponade, should also be considered prior to initiating vasoactive therapy.
3. How can I pharmacologically redirect blood flow to improve the problem?
Selecting an agent for hemodynamic support is analogous to choosing an antibiotic for infection. You are best guided by matching medication activity to the underlying pathology of the illness.
- Problem with VASCULAR TONE? Phenylephrine is the only agent with exclusive activity at α adrenergic receptors, and vasopressin is the only agent with activity at vasopressin receptors. In this sense, these are pure pressor agents and have no direct impact of pump function. Hypotension from isolated loss of vascular tone is uncommon but can be caused by loss of sympathetic tone from spinal cord injury (“neurogenic shock”).
- Problem with PUMP FUNCTION? Hypotension attributable to isolated acute myocardial compromise can be improved with pharmacologic agents that increase inotropy and contractility. This includes any agent with action at β1 , β2 or dopaminergic receptors. Dobutamine and isoproterenol are the only agents with exclusive activity at β adrenergic receptors. Generally, these are pure intropes and have no vasoconstrictive properties. Hypotension from isolated pump failure can be caused by acute decompensated heart failure or acute coronary syndrome.
- MULTIFACTORIAL problem? Problems that impact both vascular tone and cardiac function require medications that operate at multiple receptors. These include epinephrine, norepinephrine and dopamine. The physiologic impact of dopamine is dose dependent, with preferential increases in pump function at lower doses. Examples of disorders that impact both pump and tone include anaphylaxis (see “Dirty Epi” drip) or septic shock.
4. Will I be limited by side effects of my pressor choice?
Side effects of vasoactive medications are related both to the direct mechanism of action of the agent, as well as the compensatory mechanisms precipitated by them. Concerning side effects of inotropes include dysrhythmias and increased myocardial oxygen demand, whereas vasopressors can cause undesired limitations in blood flow to the gut and kidneys.
|Agent||Primary Receptor||Primary Impact||Potential side effect||Prototypical clinical scenario|
|Phenylephrine||α1||Increased SVR||Reflexive decreased HR||Neurogenic shock|
|Vasopressin||V||Increased SVR||Decreased splanchnic flow||Adjunct for septic shock|
|Dobutamine||β1, β2||Increased inotropy||Transient decreases in SVR (β2 agonsim)||Cardiogenic shock from late-stage heart failure|
|Dopamine (low-dose)||D, β1||Increased inotropy and heart rate||Tachydysrhythmias||Cardiogenic shock, particularly if bradycardic|
|Epinephrine||α1, α2, β1, β2||Increased SVR and inotropy||Tachydysrhythmias and decreased splanchnic flow||Anaphylaxis|
|Norepinephrine||α1, α2, β1>> β2*||Increased SVR and inotropy||Decreased splanchnic and renal flow||Septic shock|
|Dopamine (high-dose)||D, α1, β1>> β2*||Increased SVR and inotropy||Tachydysrhythmias and decreased splanchnic/renal flow||Bradycardic cardiovascular collapse|
|* Controversial whether norepinephrine and high-dose dopamine have any β2 effects. If any, it is likely very low.|
5. When choosing between similar agents, does evidence support use of a specific agent over another?
The majority of evidence comparing pressors head-to-head has been done in patients with septic shock; the largest amount of data has compared high-dose dopamine to norephinephrine. Based on this data, norepinephrine has been associated with lower incidence arrythmias and improved mortality when compared to dopamine.
Epinephrine has been compared with several other regimens both in septic shock and undifferentiated shock. When epinephrine was compared to norepinephrine and dobutamine, all of the agents were equally effective in achieving hemodynamic goals, though epinephrine was associated with increased incidence of tachydysrhythmias and prolonged metabolic derangement when compared to other agents. There was no difference in mortality. Robust data comparing other similar agents in other disease processes are lacking.
Expert Peer Review
Todd gives a great review of vasoactive substance choice. The approach here is really key as there is no “one-size-fits-all” recommendation for vasopressors. In the past, there was little literature to guide our choices when selecting pharmacologic therapy in patients with shock. The majority of the time, the vasoactive substance chosen was done so based on anecdote, personal experience and beliefs (often misbeliefs) about pathophysiology.
In the last 5 years, though, some evidence has emerged to help guide us in our management. One of the really important articles was De Backer et al. in 2010 in NEJM comparing dopamine to norepinephrine in the treatment of undifferentiated shock. This study came form a time when many intensivists could be heard on rounds saying “Levophed, leave-‘em-dead,” and dopamine was still widely used. It was a particularly relevant study to EM because it was undifferentiated shock, which is what we deal with. The study showed no difference in mortality between the two agents but an increased rate of dysrrhythmias in the dopamine group and supported what many ED docs had been saying for years; that norepinephrine was a good drug.
I think few EM docs would argue against epinephrine in anaphylaxis or norepinephrine in septic shock. Cardiogenic shock tends to stir more debate and argument. Ideally, I want an agent that increases cardiac output, decreases afterload and increases coronary filling pressure without increasing myocardial oxygen demand. Although a balloon pump would be ideal, few of us are skilled at this procedure. Interestingly, the De Backer study showed (in a subgroup analysis) that norepinephrine performed better than dopamine in the subset of patients with cardiogenic shock (primary pump failure). The AHA still recommends using different agents based on the patient’s presenting BP (dobutamine if SBP > 90, dopamine if SBP 70-90 and norepinephrine if < 70) based on expert opinion. Dobutamine, however, is a vasodilator and can drop the blood pressure further. Starting these patients with norepinephrine (which will increase myocardial oxygen demand but also increases coronary artery filling), reassessing the LV contractility with bedside ultrasound and adding dobutamine when an adequate MAP is achieved seems like a reasonable approach.
The truth is that we are still learning our way through all of this and no one really knows what’s best but when the hypotensive patient is front of you, we need to be ready to do something and Todd gives us a good way to think about what agent to use.\"
1. De Backer D, Biston P., Devrient J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010; 362:779-789.