Septic shock: Difference between revisions
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====Randomized, controlled trials==== | ====Randomized, controlled trials==== | ||
The most recent [[meta-analysis|meta-analyses]] of [[randomized controlled trial]]s conclude benefit.<ref name="pmid19509383">{{cite journal |author=Annane D, Bellissant E, Bollaert PE, ''et al.'' |title=Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review |journal=JAMA |volume=301 |issue=22 |pages=2362–75 |year=2009 |month=June |pmid=19509383 |doi=10.1001/jama.2009.815 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=19509383 |issn=}}</ref><ref name="pmid18496365"/> <!--[[Meta-analysis|Meta-analyses]] of the French trial and prior trials have concluded that steroids are beneficial but these analyses did not include the CORTICUS trial published in 2008.<ref name="pmid15238370">{{cite journal |author=Minneci PC, Deans KJ, Banks SM, Eichacker PQ, Natanson C |title=Meta-analysis: the effect of steroids on survival and shock during sepsis depends on the dose |journal=Ann. Intern. Med. |volume=141 |issue=1 |pages=47–56 |year=2004 |month=July |pmid=15238370 |doi= |url= |issn=}}</ref><ref name="pmid15289273">{{cite journal |author=Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, Kupfer Y |title=Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis |journal=BMJ |volume=329 |issue=7464 |pages=480 |year=2004 |month=August |pmid=15289273 |pmc=515196 |doi=10.1136/bmj.38181.482222.55 |url=http://bmj.com/cgi/pmidlookup?view=long&pmid=15289273 |issn=}}</ref>--> 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 (insignficant) trend towards benefit in mortality".<ref name="pmid18496365">{{cite journal |author=Marik PE, Pastores SM, Annane D, ''et al'' |title=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 |journal=Crit. Care Med. |volume=36 |issue=6 |pages=1937–49 |year=2008 |month=June |pmid=18496365 |doi=10.1097/CCM.0b013e31817603ba |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?doi=10.1097/CCM.0b013e31817603ba |issn=}}</ref> | |||
{| class="wikitable" | {| class="wikitable" | ||
|+ Major trials of low dose corticosteroids for septic shock among patients with relative adrenal insufficiency.<ref name="pmid18184957">{{cite journal |author=Sprung CL, Annane D, Keh D, ''et al'' |title=Hydrocortisone therapy for patients with septic shock |journal=N. Engl. J. Med. |volume=358 |issue=2 |pages=111–24 |year=2008 |pmid=18184957 |doi=10.1056/NEJMoa071366 |issn=|url=http://content.nejm.org/cgi/content/full/358/2/111}}</ref><ref name="pmid12186604">{{cite journal |author=Annane D, Sébille V, Charpentier C, ''et al'' |title=Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock |journal=JAMA |volume=288 |issue=7 |pages=862–71 |year=2002 |month=August |pmid=12186604 |doi= |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=12186604 |issn=}}</ref> | |+ Major trials of low dose corticosteroids for septic shock among patients with relative adrenal insufficiency.<ref name="pmid18184957">{{cite journal |author=Sprung CL, Annane D, Keh D, ''et al'' |title=Hydrocortisone therapy for patients with septic shock |journal=N. Engl. J. Med. |volume=358 |issue=2 |pages=111–24 |year=2008 |pmid=18184957 |doi=10.1056/NEJMoa071366 |issn=|url=http://content.nejm.org/cgi/content/full/358/2/111}}</ref><ref name="pmid12186604">{{cite journal |author=Annane D, Sébille V, Charpentier C, ''et al'' |title=Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock |journal=JAMA |volume=288 |issue=7 |pages=862–71 |year=2002 |month=August |pmid=12186604 |doi= |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=12186604 |issn=}}</ref> | ||
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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 [[corticosteroid]]s). The French study by Annane used 50 microgram daily of fludrocortisone.<ref name="pmid12186604"/> | 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 [[corticosteroid]]s). The French study by Annane used 50 microgram daily of fludrocortisone.<ref name="pmid12186604"/> | ||
===Activated protein C=== | ===Activated protein C=== | ||
Revision as of 10:20, 6 July 2009
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."[1]
Complications
Myocardial dysfunction
Transient myocardial dysfunction may occur in 59% of patients and may resolve within 12 days.[2]
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.[3] Similarly, another randomized controlled trial found no difference between vasopressin and norepinephrine.[4]
Corticosteroids
Practice guidelines
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."[5] 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".[5]
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".[5]
Randomized, controlled trials
The most recent meta-analyses of randomized controlled trials conclude benefit.[6][5] 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 (insignficant) trend towards benefit in mortality".[5]
| Trial | Patients | Interventions | Outcomes | Results for patients with relative adrenal insufficiency |
Comments | |
|---|---|---|---|---|---|---|
| Control | Intervention | |||||
| CORTICUS[7] 2008 |
499 patients • 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.[7] |
| French study[8] 2002 |
300 patients • 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 |
28-day mortality | 63% | 53% | |
Although the largest and most recent randomized controlled trial (CORTICUS[7]) 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[8]. 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.[7]
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.[8]
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]
Polymyxin B hemoperfusion
Polymyxin B hemoperfusion may be beneficial according to a systematic review of randomized controlled trials.[12]
References
- ↑ Anonymous (2024), Septic shock (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Post F, Weilemann LS, Messow CM, Sinning C, Münzel T (November 2008). "B-type natriuretic peptide as a marker for sepsis-induced myocardial depression in intensive care patients". Crit. Care Med. 36 (11): 3030–7. DOI:10.1097/CCM.0b013e31818b9153. PMID 18824903. Research Blogging.
- ↑ 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.
- ↑ 5.0 5.1 5.2 5.3 5.4 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.
- ↑ Annane D, Bellissant E, Bollaert PE, et al. (June 2009). "Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review". JAMA 301 (22): 2362–75. DOI:10.1001/jama.2009.815. PMID 19509383. Research Blogging.
- ↑ 7.0 7.1 7.2 7.3 7.4 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 - ↑ 8.0 8.1 8.2 8.3 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]
- ↑ 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.
- ↑ Cruz DN, Perazella MA, Bellomo R, et al. (2007). "Effectiveness of polymyxin B-immobilized fiber column in sepsis: a systematic review". Crit Care 11 (2): R47. DOI:10.1186/cc5780. PMID 17448226. PMC 2206475. Research Blogging.