What are the guidelines for managing refractory septic shock?

Management of Refractory Septic Shock

For patients with refractory septic shock, a stepwise approach using multiple vasopressors, adjunctive therapies including corticosteroids, and consideration of extracorporeal membrane oxygenation (ECMO) is recommended. 1, 2

Initial Management

• Administer at least 30 mL/kg of IV crystalloid fluid within the first 3 hours of resuscitation, using balanced solutions or normal saline as first-choice fluids 2
• Continue fluid administration using a challenge technique as long as hemodynamic parameters improve, with dynamic measures of fluid responsiveness preferred over static measures 2
• Administer broad-spectrum antimicrobials within the first hour of recognition of septic shock, after obtaining appropriate cultures if this doesn't significantly delay therapy 2
• Identify and implement source control interventions as rapidly as possible, ideally within 12 hours of diagnosis 2

Vasopressor Therapy

• Initiate norepinephrine as the first-choice vasopressor if the patient remains hypotensive despite adequate fluid resuscitation, targeting a mean arterial pressure of 65 mmHg 1, 2
• Add vasopressin (0.01-0.04 units/min) to norepinephrine when an additional agent is needed to maintain adequate blood pressure or to decrease norepinephrine dosage 1
• Consider epinephrine (added to and potentially substituted for norepinephrine) as a third-line agent when additional vasopressor support is needed 1, 3
• For epinephrine administration in septic shock, the suggested dosing infusion rate is 0.05 mcg/kg/min to 2 mcg/kg/min, titrated to achieve desired mean arterial pressure 3
• Avoid dopamine except in highly selected patients with low risk of tachyarrhythmias and absolute or relative bradycardia 1
• Phenylephrine should only be used in specific circumstances: when norepinephrine causes serious arrhythmias, when cardiac output is known to be high with persistently low blood pressure, or as salvage therapy 1

Management of Refractory Shock

• For refractory shock (persistent hypotension despite high-dose vasopressors), consider vasopressin as a first adjunctive option 4, 5
• Administer hydrocortisone 200-300 mg/day for at least 5 days, followed by a tapering dose in patients with refractory shock 1
• Consider angiotensin II as an additional vasopressor option for patients not responding to standard therapy 6, 7
• Evaluate for and reverse pneumothorax, pericardial tamponade, or endocrine emergencies in patients with refractory shock 1
• Consider ECMO for refractory septic shock, particularly in pediatric patients 1

Special Considerations

Pediatric Patients

• Begin peripheral inotropic support until central venous access can be attained in children who are not responsive to fluid resuscitation 1
• For children with low cardiac output and elevated systemic vascular resistance with normal blood pressure, add vasodilator therapies to inotropes 1
• Consider phosphodiesterase III inhibitors in pediatric cases with low cardiac output and normal arterial pressure 1

Hemodynamic Monitoring

• Reassess hemodynamic status frequently through clinical examination and available physiologic variables 2
• Guide resuscitation to normalize lactate levels in patients with elevated lactate as a marker of tissue hypoperfusion 2
• Monitor for signs of fluid overload, including hepatomegaly and rales, especially in pediatric patients 1

Pitfalls and Caveats

• Norepinephrine doses above 1 μg/kg/min are associated with mortality rates exceeding 80%, suggesting the need to implement adjunctive strategies before reaching this dosage 4
• Avoid excessive vasoconstriction when using multiple vasopressors, as this may worsen tissue perfusion 4
• Fluid overresuscitation should be avoided as it can delay organ recovery, prolong ICU stay, and increase mortality 2
• For patients with low ejection fraction, consider smaller fluid boluses with frequent reassessment rather than the standard 30 mL/kg 2
• Recognize that the standard approach may need modification based on individual patient characteristics, particularly cardiac function 2