Current Management of Gram-Negative Septic Shock

Jean-Louis Vincent; Wasineenart Mongkolpun


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

In This Article

Hemodynamic Support

Resuscitation for patients with septic shock requires both fluid and vasopressor agents. The overall resuscitation period will follow four phases that can be summarized by the letters SOSD:[15]

  1. Salvage – this is a short phase during which fluids and vasopressor agents are administered with little monitoring, the aim being to keep the patient alive and minimize deterioration in organ function. It is difficult to give fluids by formula, because individual requirements vary substantially from one patient to the other. Therefore, monitoring equipment should be placed as soon as possible.

  2. Optimization – during this phase, fluid administration rates are adjusted according to the results obtained from various monitoring techniques and clinical evaluation.

  3. Stabilization – fluid administration rates are maintained to insure patient stability, but fluid boluses are no longer necessary and doses of vasoactive agents kept constant.

  4. De-escalation – fluid administration is limited to allow for elimination of edema fluid and vasopressor agents are decreased.

The duration of each of the four phases can vary substantially from one case to another, but recognizing these phases can help to identify the priorities in patient management.


Fluids are always required, not only to correct true hypovolemia because of poor intake and increased internal (edema) and external losses, but also to compensate for the vasodilation associated with the sepsis process and help to achieve the hyperkinetic (high cardiac output) state required in sepsis. Hence, the fundamental reason for fluid administration is to improve tissue perfusion by increasing cardiac output, and the risk is that excess fluids will increase cardiac filling pressures, with increased edema formation.

Physicians must consider these two aspects when prescribing fluids and arrange for the two components, that is, cardiac output or an index of tissue perfusion and a cardiac filling pressure, usually the central venous pressure, to be monitored. When the benefit/risk ratio becomes too low, that is, when cardiac output increases proportionately less than filling pressures, fluid administration should be stopped. The fluid challenge technique should include only small amounts of fluids given over a 10-min period, to avoid the risks of fluid overload.[16] Similarly, fluid administration should be stopped when the immediate risk of poor tissue perfusion seems to be substantially attenuated. This strategy is also applied in children and neonates.[17] One should avoid giving large amounts of fluids over a relatively long period of time because if the patient does not respond, too much fluid will have been given with the associated risks of fluid overload and no benefit.

During the optimization phase, attempts to assess likely fluid responsiveness can be tried before any fluid administration is given. One option is the assessment of pulse pressure variation or stroke volume variation in patients who do not stimulate the respirator, but this is a relatively rare condition, limiting the usefulness of this approach. A passive leg raising maneuver can also be considered, but this technique is more complex than it appears, as it requires careful and continuous assessment of stroke volume during the test. Hence, the fluid challenge is still the preferred method to assess ongoing fluid needs and enable the benefits of fluid infusion to be maximized (increase cardiac output) while minimizing the risks (edema formation). Unfortunately, just assessing the degree of edema does not help evaluate fluid requirements and the term 'fluid overload' can be misleading.[18]

Crystalloids are considered as the initial fluid of choice, although albumin can have a place early in patients who are already edematous in a context of hypoalbuminemia (patients with decompensated cirrhosis represent a typical example), and later if the patient has already received large amounts of crystalloids. Saline solution can be selected initially in the absence of severe acidosis, but chloride levels must be monitored[19] because hyperchloremia can have deleterious effects, most notably on the kidneys. Otherwise, balanced solutions (Ringer's lactate or Plasmalyte R) represent the best option.

Vasoactive Agents

Norepinephrine is the vasopressor of choice; dopamine should no longer be used in this setting.[20] Epinephrine is also best avoided because it is more likely to induce arrhythmias, can reduce splanchnic blood flow, and may increase blood lactate levels as a result of increased cellular metabolism. The place of angiotensin II is not yet well defined, but it may be of value in patients with renal failure[21] or in acute respiratory distress syndrome (in which angiotensin II levels may decrease and become inadequate).[22]

In patients who poorly tolerate fluids, administration of dobutamine may be considered to increase cardiac output; small doses are usually sufficient. A low central venous oxygen saturation value can be a useful trigger for administration of dobutamine or for a blood transfusion if the hemoglobin concentration is decreased.