Why start vasopressin in septic shock without maximizing the dose of norepinephrine (noradrenaline) first?

From the Guidelines

Starting vasopressin before maximizing norepinephrine doses in septic shock can be beneficial in certain clinical scenarios, as it allows for catecholamine-sparing effects and provides complementary vasopressor support. The most recent and highest quality study, 1, suggests that norepinephrine is recommended as the first-line vasopressor agent to maintain adequate organ perfusion pressure in patients with septic shock. However, the study also mentions that vasopressin deficiency has been documented in cirrhosis as well as in many shock states. Key points to consider when deciding to start vasopressin include:

• The patient's norepinephrine requirements, typically when they reach 0.25-0.5 mcg/kg/minute
• The potential benefits of catecholamine-sparing effects, reducing the risk of adverse effects such as tachyarrhythmias, myocardial ischemia, and digital ischemia
• The complementary vasopressor support provided by vasopressin, which works through a different mechanism (V1 receptors) than norepinephrine (alpha-adrenergic receptors)
• The effectiveness of vasopressin in acidotic environments, where catecholamines may have reduced efficacy
• The potential to preserve renal perfusion better than escalating norepinephrine alone According to the Surviving Sepsis Campaign Guidelines, 1, vasopressin can be added to norepinephrine with the intent of either raising mean arterial pressure or decreasing norepinephrine dosage. The guidelines suggest starting vasopressors peripherally to restore mean arterial pressure rather than delaying until central venous access is secured, and recommend invasive arterial monitoring as soon as practical, 1. Overall, the decision to start vasopressin before maximizing norepinephrine doses should be based on individual patient needs and clinical scenarios, with the goal of achieving better hemodynamic stability and minimizing side effects.

From the FDA Drug Label

The recommended starting dose is: Septic Shock: 0.01 units/minute Titrate up by 0.005 units/minute at 10-to 15-minute intervals until the target blood pressure is reached. In patients with vasodilatory shock vasopressin in therapeutic doses increases systemic vascular resistance and mean arterial blood pressure and reduces the dose requirements for norepinephrine.

The FDA drug label does not provide a direct answer to why vasopressin should be started without maximizing the dose of norepinephrine first. However, it can be inferred that vasopressin may be started at a low dose and titrated up to reduce the dose requirements for norepinephrine, as it increases systemic vascular resistance and mean arterial blood pressure in patients with vasodilatory shock 2, 2.

• Key points:
  • Vasopressin can be started at a low dose of 0.01 units/minute in septic shock.
  • The dose can be titrated up by 0.005 units/minute at 10-to 15-minute intervals until the target blood pressure is reached.
  • Vasopressin may reduce the dose requirements for norepinephrine in patients with vasodilatory shock.

From the Research

Rationale for Starting Vasopressin in Septic Shock

• The decision to start vasopressin in septic shock without maximizing the dose of norepinephrine first is based on several factors, including the patient's response to initial treatment and the presence of refractory hypotension 3.
• Vasopressin is recommended as an add-on therapy to norepinephrine in cases of septic shock that are refractory to norepinephrine alone, as it acts on different vascular receptors and can help to improve blood pressure and organ perfusion 3, 4.
• Some studies suggest that vasopressin may be considered as a first-line vasopressor in septic shock patients with certain risk factors, such as those at high risk of renal failure requiring renal replacement therapy 5, 6.

Comparison of Vasopressin and Norepinephrine

• Several studies have compared the use of vasopressin and norepinephrine in septic shock, with some finding similar outcomes in terms of mortality and duration of hospitalization 5, 4.
• However, one study found that patients treated with vasopressin had a lower requirement for renal replacement therapy compared to those treated with norepinephrine 5.
• Another study found that vasopressin exhibited faster time to shock reversal in the unadjusted analysis, but this difference was not maintained in the multivariable analysis 6.

Clinical Considerations

• The choice of vasopressor and the timing of its initiation should be individualized based on the patient's clinical condition and response to treatment 3, 7.
• Early and effective fluid resuscitation and vasopressor administration are crucial in maintaining tissue perfusion in septic shock patients 7.
• The balance between fluids and vasopressors to maintain target mean arterial pressure is a topic of ongoing controversy, and further research is needed to determine the optimal approach 7.