From the Guidelines
Refractory distributive shock is treated with a combination of vasopressors, corticosteroids, and adjunctive therapies after ensuring adequate fluid resuscitation, with norepinephrine as the first-line vasopressor therapy. The treatment approach should prioritize maintaining a mean arterial pressure (MAP) of 65 mmHg or higher, and addressing the underlying cause of the shock.
Key Considerations
- First-line vasopressor therapy is norepinephrine starting at 0.01-0.05 mcg/kg/min, titrated to maintain a MAP of 65 mmHg or higher, as recommended by 1 and 2.
- If shock persists despite norepinephrine doses exceeding 0.3 mcg/kg/min, add vasopressin at a fixed dose of 0.03-0.04 units/min, as suggested by 1 and 2.
- For continued hypotension, epinephrine (0.01-0.5 mcg/kg/min) or phenylephrine (0.5-6 mcg/kg/min) can be added, as mentioned in 1.
- Hydrocortisone at 200-300 mg/day in divided doses or as a continuous infusion should be administered for patients requiring high-dose vasopressors, as indicated by 1.
- Consider intravenous vitamin C (1.5 g every 6 hours), thiamine (200 mg every 12 hours), and angiotensin II (starting at 20 ng/kg/min) in severe cases, as suggested by recent clinical practices.
- Methylene blue (1-2 mg/kg over 15-30 minutes) may help in vasoplegic shock by inhibiting nitric oxide synthase, as mentioned in 1.
Pathophysiological Mechanisms
These interventions work by targeting different pathophysiological mechanisms of distributive shock, including:
- Vasodilation
- Capillary leak
- Endothelial dysfunction Continuous hemodynamic monitoring, frequent reassessment, and addressing the underlying cause (such as sepsis, anaphylaxis, or adrenal insufficiency) remain essential components of management, as emphasized by 1 and 2.
From the FDA Drug Label
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. Vasopressin tends to decrease heart rate and cardiac output. The pressor effect is proportional to the infusion rate of exogenous vasopressin. The pressor effect reaches its peak within 15 minutes After stopping the infusion the pressor effect fades within 20 minutes. There is no evidence for tachyphylaxis or tolerance to the pressor effect of vasopressin in patients.
Treatment of Refractory Distributive Shock
- Vasopressin: can be used to increase systemic vascular resistance and mean arterial blood pressure, and reduce the dose requirements for norepinephrine 3.
- Norepinephrine: can be used to restore blood pressure in acute hypotensive states, and its dosage should be titrated according to the response of the patient 4.
- The treatment should be individualized and the dosage of vasopressors should be adjusted based on the patient's response.
- Key considerations: + Correct blood volume depletion before administering vasopressors. + Monitor central venous pressure to detect and treat occult blood volume depletion. + Avoid abrupt withdrawal of vasopressors. + Use the lowest effective dose to maintain adequate blood pressure and tissue perfusion.
From the Research
Treatment of Refractory Distributive Shock
The treatment of refractory distributive shock, particularly in the context of septic shock, involves the use of vasopressors to increase systemic vascular resistance and improve blood pressure. The choice of vasopressor can significantly impact patient outcomes.
- Vasopressor Selection: Studies have compared the efficacy of different vasopressors in treating septic shock. A systematic review and network meta-analysis 5 found that norepinephrine plus dobutamine was associated with the lowest risk of 28-day mortality, followed by epinephrine, vasopressin, and terlipressin.
- Norepinephrine and Vasopressin: A retrospective study 6 compared the use of norepinephrine and vasopressin versus norepinephrine and epinephrine in adults with septic shock. The study found similar shock-free survival durations and mortality rates between the two groups.
- Vasopressin as an Adjuvant Therapy: A review article 7 discussed the use of vasopressin as an adjuvant therapy in patients with refractory septic shock. The article suggested that vasopressin may be a good first option, but evidence remains limited.
- Optimal Blood Pressure Target: A review article 8 discussed the optimal blood pressure target in patients with distributive shock. The article suggested that an initial target mean arterial pressure (MAP) of 65-70 mmHg is probably sufficient in most patients.
- Comparison of Vasopressors: A systematic review and meta-analysis 9 compared the efficacy and safety of different vasopressors in septic shock. The study found that norepinephrine was associated with decreased all-cause mortality and lower risk of major adverse events compared to dopamine.
Key Considerations
When treating refractory distributive shock, it is essential to consider the following:
- Individualized Treatment: Treatment should be individualized based on patient factors, such as age and history of chronic hypertension.
- Monitoring: Close monitoring of hemodynamic variables, blood lactate levels, and venous oxygen saturations is crucial to assess the response to treatment and adequacy of tissue perfusion.
- Adverse Events: The risk of adverse events, such as myocardial infarction, cardiac arrhythmia, and peripheral ischemia, should be carefully considered when selecting a vasopressor.