Septic shock: Difference between revisions
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===Activated protein C=== | ===Activated protein C=== | ||
[[Recombinant protein|Recombinant]] human activated [[protein C]], also called [[drotrecogin alpha]], has been shown in a [[randomized | [[Recombinant protein|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<ref>Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr; Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001 Mar 8;344(10):699-709. PMID 11236773</ref> If this is given, [[heparin]] should probably be continued.<ref name="pmid17556722">{{cite journal |author=Levi M, Levy M, Williams MD, ''et al'' |title=Prophylactic heparin in patients with severe sepsis treated with drotrecogin alfa (activated) |journal=Am. J. Respir. Crit. Care Med. |volume=176 |issue=5 |pages=483–90 |year=2007 |pmid=17556722 |doi=10.1164/rccm.200612-1803OC}}</ref> | ||
===Tissue factor pathway inhibitor === | ===Tissue factor pathway inhibitor === | ||
Revision as of 09:30, 12 November 2008
Septic shock is a condition in medicine in which sepsis is "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."[1]
Treatment
Vasopressors
Among the choices for pressors, a randomized controlled trial concluded that there was no difference between the biogenic amines norepinephrine (plus dobutamine as needed for cardiac output) versus epinephrine.[2] Similarly, another randomized controlled trial found no difference between vasopressin and norepinephrine.[3]
Corticosteroids
| CORTICUS, 2008[4] | French study, 2002[5] | |
|---|---|---|
| Patients: | ||
| Prevalence of adrenal insufficiency | 47% | 76% |
| onset of shock | within the previous 72 hours | within the previous 3 hours |
| SAPS II score (higher is sicker) |
50 | 59 |
| Intervention | 200 mg/day of hydrocortisone | 200 mg/day of hydrocortisone 50 microgram/day fludrocortisone |
| Results: | ||
| 28-day survival in control group | 69% | 27% |
| Mortality at 28 days | no reduction in mortality regardless of adrenal insufficiency |
reduced mortality for patients with adrenal insufficiency |
- Practice guidelines and 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."[6]
In a meta-analysis that was included with the guidelines found greater shock reversal (at day 7) with hydrocortisone and a (insignficant) trend towards benefit in mortality".[6]
Prior meta-analyses have concluded that steroids are beneficial but these analyses did not include the CORICUS trial published in 2008.[7][8]
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".[6] The recommendation is based on the similar impact of steroids on shock reversal at seven days regardless of adrenal status. However, mortality data in the French study by Annane only found benefit in the patients with relative adrenal insufficiency. Although the CORTICUS study by Sprung found no mortality benefit, these patients were not as ill. 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.[4] Thus, confining steroids to the sickest patients who also have relative adrenal insufficiency is supported by mortality data.
- Details of individual trials
Corticosteroids, perhaps if combined with a mineralocorticoid, may reduce mortality among selected patients who have relative adrenal insufficiency[5] It is unclear whether the corticosteroids should be combined with mineralocorticoids and whether the medications should be reserved for the sickest patients (those with persistent hypotension).
Although the largest and most recent randomized controlled trial 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.[4] 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.[4]
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.[5]
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[9] If this is given, heparin should probably be continued.[10]
Tissue factor pathway inhibitor
Recombinant human tissue factor (thromboplastin) pathway inhibitor, also called tifacogin, was found not to be effective in a randomized controlled trial.[11]
References
- ↑ Anonymous (2024), Septic shock (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Annane D, Vignon P, Renault A, et al (2007). "Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial". Lancet 370 (9588): 676-84. DOI:10.1016/S0140-6736(07)61344-0. PMID 17720019. Research Blogging.
- ↑ Russell, J. A., Walley, K. R., Singer, J., Gordon, A. C., Hebert, P. C., Cooper, D. J., et al. (2008). Vasopressin versus norepinephrine infusion in patients with septic shock, N Engl J Med, 358(9), 877-887. DOI:10.1056/NEJMoa067373.
- ↑ 4.0 4.1 4.2 4.3 Sprung CL, Annane D, Keh D, et al (2008). "Hydrocortisone therapy for patients with septic shock". N. Engl. J. Med. 358 (2): 111–24. DOI:10.1056/NEJMoa071366. PMID 18184957. Research Blogging.
Cite error: Invalid
<ref>tag; name "pmid18184957" defined multiple times with different content - ↑ 5.0 5.1 5.2 Annane D, Sébille V, Charpentier C, et al (August 2002). "Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock". JAMA 288 (7): 862–71. PMID 12186604. [e]
- ↑ 6.0 6.1 6.2 Marik PE, Pastores SM, Annane D, et al (June 2008). "Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine". Crit. Care Med. 36 (6): 1937–49. DOI:10.1097/CCM.0b013e31817603ba. PMID 18496365. Research Blogging.
- ↑ Minneci PC, Deans KJ, Banks SM, Eichacker PQ, Natanson C (July 2004). "Meta-analysis: the effect of steroids on survival and shock during sepsis depends on the dose". Ann. Intern. Med. 141 (1): 47–56. PMID 15238370. [e]
- ↑ Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, Kupfer Y (August 2004). "Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis". BMJ 329 (7464): 480. DOI:10.1136/bmj.38181.482222.55. PMID 15289273. PMC 515196. Research Blogging.
- ↑ Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr; Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001 Mar 8;344(10):699-709. PMID 11236773
- ↑ Levi M, Levy M, Williams MD, et al (2007). "Prophylactic heparin in patients with severe sepsis treated with drotrecogin alfa (activated)". Am. J. Respir. Crit. Care Med. 176 (5): 483–90. DOI:10.1164/rccm.200612-1803OC. PMID 17556722. Research Blogging.
- ↑ Abraham E, Reinhart K, Opal S, et al (July 2003). "Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial". JAMA 290 (2): 238–47. DOI:10.1001/jama.290.2.238. PMID 12851279. Research Blogging.