From the Guidelines
Management of refractory neonatal septic shock requires aggressive intervention with a stepwise approach, prioritizing fluid resuscitation, vasoactive medications, and antimicrobial therapy, with consideration of ECMO for refractory cases, as recommended by the Surviving Sepsis Campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children 1.
Initial Management
Initial management should focus on:
- Fluid resuscitation with crystalloids at 10-20 mL/kg boluses, reassessing after each bolus, with a maximum of 40-60 mL/kg in the first hour
- Ensuring appropriate antimicrobial coverage with ampicillin (50-100 mg/kg/dose) plus gentamicin (4-5 mg/kg/day) or cefotaxime (50 mg/kg/dose), adjusting based on culture results
Vasoactive Medications
If shock persists despite adequate fluid resuscitation, consider:
- Starting dopamine at 5-10 mcg/kg/min, titrating up to 20 mcg/kg/min as needed
- Adding epinephrine at 0.05-0.3 mcg/kg/min or norepinephrine at 0.05-0.5 mcg/kg/min for continued hypotension
Additional Considerations
- Hydrocortisone should be considered at 1-2 mg/kg every 6 hours for catecholamine-resistant shock, particularly with suspected adrenal insufficiency
- Maintain glucose levels between 80-150 mg/dL and correct metabolic acidosis, electrolyte abnormalities, and coagulopathy
- Consider ECMO for refractory cases unresponsive to maximal medical therapy, with a focus on high ECMO flows (> 150 mL/kg/min at 4 h after institution of ECMO) 1
Monitoring
Continuous monitoring of vital signs, urine output (target >1 mL/kg/hr), and perfusion markers is essential to guide therapy and assess response to treatment. This aggressive approach is necessary because neonates have immature cardiovascular systems with limited cardiac contractile reserve and are particularly vulnerable to the inflammatory cascade of septic shock, which can rapidly progress to multi-organ failure if not promptly addressed 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Management of Refractory Neonatal Septic Shock
- The management of refractory neonatal septic shock involves prompt recognition of symptoms and strict adherence to cardiopulmonary resuscitation guidelines 2.
- Fluid administration plays a major role in the initial management of septic shock, and if there is no response to volume filling, inotropes must be infused within one hour of onset (dopamine, dobutamine, adrenaline) 2.
- Life-threatening infections require immediate and aggressive empiric use of antimicrobials, as delays in antibiotic initiation are associated with poor outcome and increased risk of mortality 2, 3.
Initial Resuscitation and Management
- Early and effective fluid resuscitation and vasopressor administration play a crucial role in maintaining tissue perfusion in septic shock patients 4.
- A low diastolic arterial pressure (DAP) correlates with severity of arteriolar vasodilation, compromises left ventricle oxygen supply, and can be used for identifying septic shock patients that would potentially benefit from earlier vasopressor therapy 4.
- Early goal-directed resuscitation that includes aggressive fluid resuscitation of up to 60 mL/kg as boluses of 20 mL/kg by IV push, to achieve desired heart rates and blood pressure, has emerged as mainstay of treatment in the initial stage 5.
Therapeutic Strategies
- Crystalloids are the preferred fluids, while colloids may be used in some situations, and fluid refractory shock warrants use of vasoactive drugs, with dopamine being the first choice 5.
- Norepinephrine is the recommended first-line vasopressor, and if hypotension persists, vasopressin should be considered, followed by epinephrine 3.
- Steroids such as hydrocortisone and fludrocortisone should be considered in those with refractory septic shock 3.
- Targeting clinical therapeutic end-points assists the management, and good supportive care is also essential for improving the outcomes 5.