Current Management of Gram-Negative Septic Shock

Jean-Louis Vincent; Wasineenart Mongkolpun


Curr Opin Infect Dis. 2018;31(6):600-605. 

In This Article

Modulation of the Host Response

As experimental studies first began to elucidate the mechanisms underlying the inflammatory response to infection, multiple molecules involved in initiating or propagating the response have become potential targets for therapeutic intervention. Yet, although many agents have reached clinical trials, none has so far been persistently shown to have beneficial effects on patient outcomes.


Recent results have shed new light on the ongoing debate regarding corticosteroid use in sepsis. In the presence of severe septic shock, administration of moderate doses of hydrocortisone (200 mg/day) should be considered[23] until shock is resolved, because relative adrenal insufficiency may develop.


Vasopressin should not be considered as just another vasopressor agent, but as a form of hormonal support, because vasopressin stores may be decreased in septic shock. However, the exact place for vasopressin administration in patients with sepsis is hard to define. Vasopressin derivatives may perhaps decrease edema formation[24] but carry the risk of inducing severe vasoconstriction and decreasing blood flow to the cutaneous, splanchnic, and coronary regions. If vasopressin is used, it should be administered in small doses of about 0.03 U/min without titration, and only in hyperkinetic states demonstrated by the presence of high cardiac output.

Gamma Globulins

Although there is no place for routine administration of gamma globulins in patients with sepsis, a recent clinical trial suggested a benefit of an IgM-enriched mixture in patients with severe community-acquired pneumonia who had low IgM levels and significant inflammatory response.[25]

Extracorporeal Removal of Toxins

One cannot discard the role of endotoxin in the pathophysiology of Gram-negative sepsis, but antiendotoxin strategies have not been particularly effective. Moreover, endotoxin is not released only in Gram-negative infections; indeed, measuring endotoxin levels is not very helpful to distinguish Gram-negative from Gram-positive infections.[26] Nevertheless, given the role of endotoxin and other mediators in sepsis pathophysiology, there is a sound rationale behind a potential beneficial effect of extracorporeal techniques to remove these compounds, including hemofiltration, hemoadsorption, and coupled plasma filtration adsorption. However, although appealing, the effectiveness of this approach is difficult to demonstrate. Many studies have reported some hemodynamic improvement, but questions remain regarding the optimal device, timing, duration, and frequency of treatment,[27] as well as how to insure that only excess harmful compounds are removed. The use of polymyxin-based hemoperfusion to remove endotoxin has not been shown to be successful and is not currently recommended.[28]


Although attempts to modulate the immune response in sepsis have largely focused on immunosuppressive therapies, more recently the potential importance of immunostimulatory approaches has been increasingly raised, with the recognition that patients with sepsis also develop immunosuppression. Importantly, the immune status of patients with sepsis varies among patients and in the same patient during the course of their disease. Some promising immunostimulatory strategies include interferon-gamma, granulocyte–macrophage colony stimulating factor, interleukin-7, and anti-programmed cell death protein 1 antibodies.[29]


The use of pharmaconutrition – the supplementation of feeds with various macronutrients (e.g., glutamine, arginine, and fish oil) and micronutrients (e.g., selenium, vitamin C, vitamin E) – to improve outcomes has generated considerable interest in patients with sepsis. However, clinical trials have failed to consistently demonstrate any positive effects of the different supplements on outcomes and there is no evidence to support the routine use of macronutrient supplements in patients with sepsis.[30,31] Supplementation with vitamins or selenium should not be provided except in certain cases of malnutrition resulting in deficient levels. In patients with septic shock, nutrition can be withheld completely.[32]