Is dobutamine (dobutamine) + norepinephrine (norepinephrine) more effective than adrenaline (epinephrine) alone in critically ill patients requiring vasopressor and inotropic support?

From the Guidelines

The combination of dobutamine and norepinephrine is generally considered more effective than epinephrine alone in critically ill patients requiring both vasopressor and inotropic support. This combination allows for more targeted and titrated therapy, with norepinephrine primarily providing vasoconstriction to maintain blood pressure while dobutamine enhances cardiac contractility and cardiac output. According to the most recent guidelines, such as the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1, norepinephrine is recommended as the first-choice vasopressor, and dobutamine is suggested for use in patients who show evidence of persistent hypoperfusion despite adequate fluid loading and the use of vasopressor agents.

The dosing of these medications can be tailored to the individual patient's needs, with norepinephrine starting at 0.01-0.1 mcg/kg/min and titrated to maintain mean arterial pressure ≥65 mmHg, while dobutamine is initiated at 2.5-5 mcg/kg/min and titrated up to 20 mcg/kg/min based on cardiac output response. Epinephrine, when used alone, provides both inotropic and vasopressor effects but in a less controllable manner, potentially causing excessive tachycardia, arrhythmias, and increased myocardial oxygen consumption, as noted in a global perspective on vasoactive agents in shock 1.

Key points to consider when choosing between dobutamine + norepinephrine and epinephrine alone include:

• The ability to independently adjust each medication to achieve the desired hemodynamic goals while minimizing adverse effects
• The potential for epinephrine to cause lactic acidosis and impair splanchnic circulation, which may worsen outcomes in critically ill patients
• The importance of individualizing therapy based on the specific clinical scenario, underlying pathophysiology, and patient response to therapy, as emphasized in the surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016 1.

Overall, the combination of dobutamine and norepinephrine offers a more nuanced and controllable approach to managing critically ill patients requiring both vasopressor and inotropic support, and is generally preferred over epinephrine alone.

From the Research

Comparison of Dobutamine + Norepinephrine and Adrenaline Alone

• The effectiveness of dobutamine + norepinephrine versus adrenaline alone in critically ill patients requiring vasopressor and inotropic support is a topic of interest in intensive care medicine 2.
• Studies suggest that norepinephrine is an appropriate first-line vasopressor for patients with shock, including cardiogenic or septic shock, due to its lower risk of adverse events compared to other catecholamine vasopressors 2.
• If tissue and organ perfusion remain inadequate, an inotrope such as dobutamine may be added to increase cardiac output 2.
• Research comparing the combination of dobutamine and norepinephrine to adrenaline alone is limited, but one study found that adrenaline tended to induce greater values for cardiac index and oxygen transport compared to the combination of dobutamine and norepinephrine 3.
• However, the same study found that adrenaline also induced significantly greater values of gastric mucosal blood flow compared to the combination of dobutamine and norepinephrine 3.

Hemodynamic Effects

• Dobutamine has been shown to increase cardiac index, oxygen delivery, and oxygen consumption, while decreasing mean arterial pressure, pulmonary artery and wedge pressures, and systemic and pulmonary vascular resistances 4.
• The combination of dobutamine and vasopressin therapy has been studied in a porcine model of severe endotoxic shock, and found to be ineffective in increasing cardiac output or improving mesenteric blood flow 5.
• Vasopressin was found to shunt microcirculatory flow from the skin and GI tract to vital organs such as the brain, liver, and kidneys, which was not altered with the addition of dobutamine 5.

Clinical Implications

• The choice of vasopressor and inotrope therapy should be individualized based on the patient's specific pathophysiology and hemodynamic goals 2.
• Further research is needed to determine the optimal combination and dosing of vasopressors and inotropes in critically ill patients 6.
• The use of dobutamine and norepinephrine in combination may be beneficial in certain patients, but the evidence is limited and more studies are needed to fully understand its effects 3, 5.