What is the next best step (NBS) for a patient in sepsis with hypotension who is unresponsive to all pressors?

From the Guidelines

In a patient with sepsis where all pressors are not working, the next best step would be to consider alternative strategies to support blood pressure and perfusion, as the provided evidence does not directly recommend a specific next step after failure of all pressors. The management of sepsis and septic shock involves a series of interventions aimed at restoring adequate circulation, ensuring sufficient oxygen delivery to tissues, and supporting organ function. According to the Surviving Sepsis Campaign guidelines 1, the initial approach to septic shock includes fluid resuscitation and the use of vasopressors such as norepinephrine, epinephrine, and vasopressin to maintain a mean arterial pressure (MAP) of at least 65 mmHg.

The guidelines suggest a stepwise approach to vasopressor therapy, starting with norepinephrine as the first-choice vasopressor, and considering the addition of other agents like epinephrine or vasopressin based on the patient's response 1. However, in cases where these measures fail to achieve adequate blood pressure, the guidelines do not explicitly outline a next step, emphasizing instead the importance of ongoing reassessment and adjustment of therapy based on the patient's hemodynamic status.

In clinical practice, when conventional vasopressor therapy fails, consideration may be given to other strategies aimed at supporting the patient's cardiovascular system and addressing the underlying pathophysiology of septic shock. This might include the use of inotropes like dobutamine in the presence of myocardial dysfunction, as suggested by the guidelines 1, or the consideration of other interventions such as the use of central alpha-2 agonists, though the latter is not directly addressed in the provided guidelines.

Given the complexity and variability of septic shock, the most critical next step is a thorough reassessment of the patient's condition, including evaluation of fluid status, cardiac function, and the presence of any potential sources of infection that may require source control. This approach is in line with the guidelines' emphasis on frequent reassessment and tailored therapy 1. Ultimately, the management of refractory septic shock requires a multidisciplinary approach, incorporating expertise from critical care, infectious diseases, and other relevant specialties to optimize patient outcomes.

From the FDA Drug Label

DOSAGE & ADMINISTRATION Norepinephrine Bitartrate Injection is a concentrated, potent drug which must be diluted in dextrose containing solutions prior to infusion. An infusion of LEVOPHED should be given into a large vein (see PRECAUTIONS) Restoration of Blood Pressure in Acute Hypotensive States Blood volume depletion should always be corrected as fully as possible before any vasopressor is administered. 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.

The next best step for a patient in sepsis with hypotension who is unresponsive to all pressors is to suspect and correct occult blood volume depletion. The patient should be given fluids to correct blood volume depletion, and the dosage of the pressor agent should be titrated according to the response of the patient. If the patient remains hypotensive, much larger or even enormous daily doses of the pressor agent may be necessary, but this should be done with caution and close monitoring 2.

From the Research

Next Best Step for Sepsis with Hypotension Unresponsive to Pressors

• The patient's condition is critical, and the current treatment with pressors is not effective, as indicated by the lack of response to all pressors 3, 4, 5.
• According to the study by 5, when hypotension is refractory to norepinephrine, it is recommended to add vasopressin, which acts on other vascular receptors than α1-adrenergic receptors.
• Another option could be to consider the use of epinephrine as a second-line vasopressor therapy, as mentioned in 3, although it may be associated with higher rates of metabolic and cardiac adverse effects.
• The study by 6 suggests that the very early administration of vasopressors, preferably during the first hour after diagnosis of septic shock, may have a multimodal action and potential advantages, leading to lower morbidity and mortality in the management of septic patients.
• It is also important to note that the choice of vasopressor should be individualized, and the optimal blood pressure target should be determined based on the patient's specific condition, as suggested by 5.

Considerations for Vasopressor Therapy

• The use of vasopressors should be initiated as soon as possible in patients with septic shock, as recommended by 6.
• The study by 7 found no differences in terms of cardiopulmonary performance, global oxygen transport, and regional hemodynamics when phenylephrine was administered instead of norepinephrine in the initial hemodynamic support of septic shock.
• However, the choice of vasopressor should be based on the patient's specific condition, and the potential benefits and risks of each option should be carefully considered, as mentioned in 3, 4, 5.