What is the management of refractory hypotension (low blood pressure) unresponsive to intravenous fluids?

From the Guidelines

For hypotension unresponsive to fluids, initiate vasopressor therapy immediately, with norepinephrine as the first-line agent at 0.01-3 mcg/kg/min titrated to maintain a mean arterial pressure (MAP) of at least 65 mmHg, as recommended by the most recent and highest quality study 1. This approach is based on the latest guidance from the AASLD practice guidance on acute-on-chronic liver failure and the management of critically ill patients with cirrhosis, which emphasizes the importance of early baseline assessment of volume status, perfusion, and cardiovascular function in critically ill patients with cirrhosis. The use of norepinephrine as the first-line agent is supported by its ability to increase blood pressure and improve perfusion, while minimizing the risk of adverse effects. Some key points to consider when using vasopressors include:

• Administering through a central venous catheter when possible, though peripheral administration can be used temporarily while central access is established
• Titration of vasopressors to achieve a target MAP of 65 mmHg, with ongoing assessment of end-organ perfusion
• Consideration of vasopressin as a second-line agent when increasing doses of norepinephrine are required
• Screening for adrenal insufficiency or an empiric trial of hydrocortisone 50 mg i.v. q6h or 200-mg infusion for 7 days or until ICU discharge for treatment of refractory shock requiring high-dose vasopressors in patients with cirrhosis. It is essential to simultaneously identify and treat the underlying cause of shock, which may include sepsis, hemorrhage, cardiac dysfunction, or adrenal insufficiency, and to consider hydrocortisone 200 mg/day in divided doses if adrenal insufficiency is suspected or if there is poor response to vasopressors, as supported by studies such as 1 and 1. Continuous hemodynamic monitoring is crucial, including blood pressure, heart rate, urine output, and mental status, to ensure that the patient is responding to treatment and to minimize the risk of adverse effects. The use of vasopressors, such as norepinephrine, is necessary because persistent hypotension leads to inadequate tissue perfusion, organ dysfunction, and potentially death if not promptly addressed, as highlighted in studies such as 1.

From the FDA Drug Label

Blood volume depletion should always be corrected as fully as possible before any vasopressor is administered. When, as an emergency measure, intraaortic pressures must be maintained to prevent cerebral or coronary artery ischemia, LEVOPHED can be administered before and concurrently with blood volume replacement High Dosage: Great individual variation occurs in the dose required to attain and maintain an adequate blood pressure. In all cases, dosage of LEVOPHED should be titrated according to the response of the patient Occasionally much larger or even enormous daily doses (as high as 68 mg base or 17 vials) may be necessary if the patient remains hypotensive, but occult blood volume depletion should always be suspected and corrected when present.

For hypotension unresponsive to fluids, the use of vasopressors such as norepinephrine or epinephrine may be necessary.

• The initial step is to ensure that blood volume depletion is corrected as fully as possible.
• If the patient remains hypotensive, the dosage of the vasopressor should be titrated according to the patient's response.
• Occult blood volume depletion should always be suspected and corrected when present 2.
• The dosage of epinephrine can be adjusted periodically to achieve the desired mean arterial pressure (MAP), with a suggested dosing infusion rate of 0.05 mcg/kg/min to 2 mcg/kg/min 3.

From the Research

Hypotension Unresponsive to Fluids

• Hypotension that is unresponsive to fluids is a critical condition that requires immediate attention and treatment with vasopressors 4, 5, 6.
• Norepinephrine is the first-line agent recommended for the treatment of hypotension in septic shock, as it helps to correct depressed vascular tone and improve organ perfusion 4, 5, 6.
• The optimal blood pressure target for patients with septic shock is a mean arterial pressure of at least 65 mmHg, although this may need to be individualized based on the patient's condition and medical history 4, 5.

Treatment Options for Refractory Hypotension

• When hypotension is refractory to norepinephrine, adding vasopressin is recommended, as it acts on different vascular receptors and can help to improve blood pressure 4, 5, 6.
• Increasing the dose of norepinephrine further may also be an option, although this should be done with caution and close monitoring of the patient's condition 5, 6.
• Other treatment options for refractory hypotension include the use of epinephrine, angiotensin II, and dopamine, although these should be used with caution and only in specific clinical situations 6, 7.

Clinical Considerations

• The choice of vasopressor and dose should be individualized based on the patient's condition and medical history, as well as the specific clinical situation 5, 6.
• Close monitoring of the patient's blood pressure, organ perfusion, and overall condition is essential when using vasopressors to treat hypotension 4, 5, 6.
• The use of vasopressors should be combined with fluid replacement to prevent and decrease the duration of hypotension in shock with vasodilation 6.