Refractory septic shock: A pragmatic approach

The management of refractory septic shock remains extremely challenging. Despite timely intervention, there exists a small subgroup of patients with septic shock who develop progressive multi-organ failure. The authors described a pragmatic, multi-faceted approach published in the journal Critical Care to manage patients with refractory septic shock based on their experience of toxin-mediated sepsis.

Refractory septic shock is variably defined as the presence of hypotension, with end-organ dysfunction, requiring high-dose vasopressor support often greater than 0.5 μg/kg/min norepinephrine or equivalent. Moreover, patients with vasopressor requirements greater than 1 μg/kg/min norepinephrine or equivalent who continue to deteriorate clinically have a reported mortality as high as 80–90 %.

Prashanth Nandhabalan and associates have provided a list of interventions to manage refractory septic shock based on their clinical experience in a specialist referral center described below:

Albumin

• Use balanced crystalloids for initial volume replacement, guided by dynamic cardiac output monitoring and echocardiography, followed by 20% human albumin solution if ongoing fluid resuscitation is required.


• During the early phase of severe shock, target a serum albumin level of > 30 g/l. Albumin maintains plasma oncotic pressure and acts as an antioxidant and as a buffer for acid-base equilibrium.

Hydrocortisone

Administer a hydrocortisone infusion (8 mg/h following a 50-mg bolus) to all patients with refractory septic shock on the basis that these patients are most likely to benefit and there is little evidence of harm.

Femoral arterial access

Use femoral arterial access for invasive blood pressure monitoring. The subsequent increase in measured ‘target means arterial blood pressure (MAP) frequently allows a significant reduction in vasopressor dosing in a considerable proportion of patients.

Lower the MAP target

• Reduce the MAP target in patients with refractory septic shock to 50–55 mmHg. In selected patients without intracranial pathology, this lower MAP target allows a worthwhile reduction in vasopressor requirements leading to improved tissue perfusion and an associated reduction of hyperlactatemia.


• Norepinephrine is commonly used as vasopressor and avoid the use of vasopressin which appears to be associated with an increased risk of peripheral and mesenteric ischemia in patients with refractory septic shock. Early enteral nutrition is also avoided in these patients with refractory septic shock on high-dose vasopressors; we prefer the use of parenteral nutrition until the shock state has resolved.

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Minimise sedation

Minimise sedation in patients with refractory septic shock. Where sedation is required, the first-line strategy is to use a predominantly opiate-based regimen in conjunction with low-dose propofol titrated to a specified target sedation score.

Replacement of thiamine and vitamin C

Give combined vitamin C (4.5 g/day) and thiamine (2.25 g/day) using three pairs of intravenous Pabrinex™ three times per day until shock has resolved.

Adjunctive antimicrobial therapy

In addition to broad-spectrum antibiotics, administer clindamycin to patients with refractory septic shock until initial microbiological analyses have excluded toxin-producing pathogens or until stabilization of organ dysfunction is achieved.

Intravenous immunoglobulin (IVIG)

Early administration of IVIG is likely to offer the optimal prospect of benefit. Initiate treatment with IVIG to progressively deteriorating patients with refractory septic shock secondary to suspected toxin-producing organisms such as group A streptococcus (1 g/kg on day 1, then 0.5 g/kg on days 2 and 3) or Panton-Valentine leukocidin (PVL) Staphylococcus aureus (2 g/kg on day 1, repeated on day 3 if no improvement).

Levosimendan

Administer levosimendan to patients with echocardiographic features of moderate to severely impaired left the ventricular systolic function and impaired end-organ perfusion.

Epoprostenol and heparin

Peripheral ischaemic complications are reduced and hemodynamic compromise is rarely encountered if the prostacyclin infusion is titrated up very slowly. In the setting of disseminated intravascular coagulation and suspicion of end-organ microthrombosis, and in the absence of absolute contra-indications, initiate low-dose intravenous heparin infusion (fixed rate 250–500 IU/h).

Renal replacement therapy

Initiate early haemodiafiltration with doses of 40–60 ml/kg/h. This facilitates rapid temperature control and correction of metabolic acidosis which contributes to a reduction in vasopressor requirements and improved cardiac output.

Extracorporeal support

Finally, in highly selected patients with refractory septic shock (often in the context of severe respiratory failure), extracorporeal technology providing respiratory and/or cardiac support achieves stability and buys time for the therapeutic interventions described above to have an impact. The benefits of extracorporeal support include improved global oxygen delivery, reduced intrathoracic pressures from reduced mechanical ventilatory requirements, improved carbon dioxide clearance and acid-base management, and improved myocardial performance.

“We believe that where established conventional interventions fail to deliver improvements, a different approach using pragmatic strategies is necessary. Many of the interventions described here have proven biological plausibility but lack conclusive evidence. Most of these strategies are relatively inexpensive, widely accessible, and are likely to be available in the majority of institutions”, write the authors.

For reference log on to https://doi.org/10.1186/s13054-018-2144-4