- 1 Epidemiology
- 2 Complications
- 3 Treatment
- 3.1 Antibiotics
- 3.2 Goal-directed resuscitation
- 3.3 Corticosteroids
- 3.4 Activated protein C
- 3.5 Tissue factor pathway inhibitor
- 3.6 Transfusion
- 3.7 Polymyxin B hemoperfusion
- 3.8 Intensive insulin
- 4 Prognosis
- 5 References
In medicine, septic shock is a form of sepsis with "associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status."
Transient myocardial dysfunction may occur in 59% of patients and may resolve within 12 days.
| 291 ED patients
• 34% bacteremia
• 16% mortality
|41% received antibiotics before shock||Time to appropriate antibiotics not associated with mortality|
| Gaieski et al
| 261 ED patients
• 32% bacteremia
• 31% mortality
|<1 hour median delay after hypotension till antibiotics||Time to appropriate antibiotics associated with mortality|
| Kumar et al
| 2154 ICU patients patients
• 34% bacteremia
• 56% mortality
|6 hour median delay after hypotension till antibiotics||Time to appropriate antibiotics associated with survival|
Recommendations for choosing antibiotics are available.
|Trial||Patients||Interventions||Usual care||Outcomes||Results for patients||Comments|
| Early Goal-Directed Therapy Collaborative Group
• Lactate 7.3
• Blood culture positive 35%
• SBP 108 mm Hg
• 90% received antibiotics by 6 hours
|Early Goal-Directed Therapy
Within 72 hrs:
• 100% central lines ScvO2
• 68% transfusion
• 37% vasopressors
• 13606 ml fluid
|Usual care within 72 hrs:
• 100% central lines ScvO2
• 45% transfusion
• 51% vasopressors
• 14101 ml fluid
• Lactate 4.9
• Blood culture positive 30%
• SBP 101 mm Hg
• 97% received antibiotics by 6 hours
| Early Goal-Directed Therapy
Within 72 hrs:
• 93% central lines ScvO2
• 1% transfusion
• 48% vasopressors
• 7253 ml fluid
|Two control groups
In no protocol group within 72 hours:
• 57% central lines
• 2% transfusion
• 43% vasopressors
• 6633 ml fluid
• Lactate 6.7
• Blood culture positive 38%
• SBP 79 mm Hg
• All received antibiotics by 2.8 hours
|Early Goal-Directed Therapy
Within 72 hours:
• 90% central lines ScvO2(6 hrs)
• 14% transfusion (0-6 hrs)
• 67% vasopressors
• 6238 ml fluid
|Usual care within 72 hrs:
• 62% central lines (6 hrs)
• 7% transfusion
• 58% vasopressors
• 6095 ml fluid
The outcomes in the control groups of of more recent trials were much more favorable than in the earlier trials. Reasons may be:
- Less fluid replacement in spite of similar protocols
- Quicker antibiotics
- The use of lower tidal volumes
- Less transfusions of blood.
- Use of blood lactate levels rather than central venous oxygen levels.
- "Isotonic crystalloid was administered in boluses to achieve a central venous pressure of 8 mm Hg or higher"
- "Mean arterial pressure goal of 65 mm Hg or higher, if not achieved with fluid administration, was targeted by initiating and titrating vasopressors (dopamine or norepinephrine)" or goal of 65 mm Hg to 90 mm Hg
- If ScvO2 < 70% or lactate clearance < 10%
Among the choices for vasoconstrictor agents for treating septic shock, a randomized controlled trial concluded that there was no difference between the biogenic amines norepinephrine (plus dobutamine as needed for cardiac output) versus epinephrine. Similarly, another randomized controlled trial found no difference between vasopressin and norepinephrine. Norepinephrine may be better than dopamine according to a meta-analysis.
Clinical practice guidelines by American College of Critical Care Medicine conclude "hydrocortisone should be considered in the management strategy of patients with septic shock, particularly those patients who have responded poorly to fluid resuscitation and vasopressor agents." In a meta-analysis that was included with the guidelines found greater shock reversal (at day 7) with hydrocortisone and a (insignificant) trend towards benefit in mortality".
Regarding whether the use of steroids should be confined to patients with relative adrenal insufficiency, the guidelines state "ACTH stimulation test should not be used to identify those patients with septic shock or ARDS who should receive GC".
Randomized, controlled trials
The most recent meta-analyses of randomized controlled trials conclude benefit. In a meta-analysis that was included with the American College of Critical Care Medicine guidelines found greater shock reversal (at day 7) with hydrocortisone and a (insignificant) trend towards benefit in mortality". Adding fludrocortisone may not help according to a more recent randomized controlled trial.
|Trial||Patients||Interventions||Outcomes||Results for patients with
relative adrenal insufficiency
• Onset of shock ≤ 72 hours
• Adrenal insufficiency: 47%
• SAPS II score: 50
• Intratracheal intubation: 100%
• Arterial lactate: 4.0
|200 mg/day of hydrocortisone for 7 days||28-day mortality||36%||39%||In a post hoc analysis, the sickest patients ("systolic blood pressure persisting at less than 90 mm Hg within 30 hours") had better outcomes when given corticosteroids.|
| French study
• Onset of shock ≤ 3 hours
• Adrenal insufficiency: 76%
• SAPS II score: 59
• Intratracheal intubation: 88%
• Arterial lactate: 4.5
|200 mg/day of hydrocortisone for 7 days
50 microgram/day fludrocortisone
Although the largest and most recent randomized controlled trial (CORTICUS) was negative, its patients were less sick (as evidenced by less stringent inclusion criteria and less mortality in the control group) and mineralcorticoids were not given as a co-treatment as compared to the French trial be Annane. In a post hoc analysis of the CORTICUS study, the sickest patients ("systolic blood pressure persisting at less than 90 mm Hg within 30 hours") had better outcomes when given corticosteroids.
The lack of mineralocorticoid in the new study may not be important. In the new trial, the total hydrocortisone per day in the new trial is 200 mg. This equates to 200/250 or 0.8 mg (800 microgram) fludrocortisone (see relative potency table for corticosteroids). The French study by Annane used 50 microgram daily of fludrocortisone.
Activated protein C
Recombinant human activated protein C, also called drotrecogin alpha, has been shown in a randomized controlled trial to be associated with reduced mortality (number needed to treat (NNT) of 16) in patients with multi-organ failure If this is given, heparin should probably be continued.
Tissue factor pathway inhibitor
Polymyxin B hemoperfusion
Intensive insulin for a target serum glucose of 80 and 110 mg/dL does not help.
The mortality from severe sepsis and septic shock has dropped by almost half since the initial study of goal-directed therapy.
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