Steroid timing and the implication for the future septic shock trial
wei huang, 1st hospital of Dalian medical university
9 March 2012
Dear editor,
the debates regarding the effects of stress-dose steroid in septic shock patients have long been triggering since the treatment be firstly introduced. So far, we still not very clear whether a key point or points exist for the successful steroid treatment. In our opinion, Dr. Kyeongman Jeon and his colleagues[1] just prove that timing of steroid cast predominant influence on the septic shock patient¿s outcomes .
According to the ¿surviving sepsis campaign¿ guideline[2], stress-dose steroid therapy should be initiated only ¿when hypotension remains poorly responsive to adequate fluid resuscitation and vasopressors¿. However, failure in fluid resuscitation and supporting therapies with vascular active drugs for septic shock patients actually indicate the vulnerable patient¿s hemodynamic situation and global organ perfusion already be very instable and even destroyed, therefore, definitely be link to the a serials of harmful outcomes. With this respect, it is quiet questionable that a ¿delayed¿ steroid therapy, other than a ¿early¿ choice, be recommended in international guideline.
Moreover, There were already many comparisons and interpretations for the different results between Prof. Annane¿s study[3] and CORTICUS trial[4]. We noticed Annane and his cooperators initiated steroid within 3-8 hours of the onset of septic shock symptom and randomization, which very same as Dr. Kyeongman Jeon study(mean 6.5 hours) . By contrast, CORTIUCS investigators started that within 72h, ¿as defined by a systolic blood pressure of less than 90 mm Hg despite adequate fluid replacement or a need for vasopressors for at least 1 hour¿. Theoretically, it is reasonable that exacerbation in hemodynamic parameters last as long as 24-72 hours may easily associated with higher mortality rate in septic shock patients, regardless which drug they prefer after that.
In summary, we believe that Dr. Kyeongman Jeon and previous Prof. Annane¿s studied already highlight tracks we should explore further to rescue our patients. And it is also a very important implication for the future investigations targeting steroid in septic shock, for example, ADRENAL trial(NCT01448109)in Australia and new Zealand. The beneficial effects of aggressive steroid therapy may hide in early treating stage of septic shock.
Reference:
1.Park HY, Suh GY, Song JU, Yoo H, Jo IJ, Shin TG, Lim SY, Woo S, Jeon K: Early initiation of low-dose corticosteroid therapy in the management of septic shock: a retrospective observational study. Crit Care 2012,16:R3.
2.Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008, 36:296-327.
3.Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G,Cohen Y, Azoulay E, Troche G, Chaumet-Riffaud P, Bellissant E: Effect of treatmentwith low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002, 288:862-871.
4.Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J: Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008, 358:111-124.
Critical Care
Steroid timing and the implication for the future septic shock trial
9 March 2012
Dear editor,
the debates regarding the effects of stress-dose steroid in septic shock patients have long been triggering since the treatment be firstly introduced. So far, we still not very clear whether a key point or points exist for the successful steroid treatment. In our opinion, Dr. Kyeongman Jeon and his colleagues[1] just prove that timing of steroid cast predominant influence on the septic shock patient¿s outcomes .
According to the ¿surviving sepsis campaign¿ guideline[2], stress-dose steroid therapy should be initiated only ¿when hypotension remains poorly responsive to adequate fluid resuscitation and vasopressors¿. However, failure in fluid resuscitation and supporting therapies with vascular active drugs for septic shock patients actually indicate the vulnerable patient¿s hemodynamic situation and global organ perfusion already be very instable and even destroyed, therefore, definitely be link to the a serials of harmful outcomes. With this respect, it is quiet questionable that a ¿delayed¿ steroid therapy, other than a ¿early¿ choice, be recommended in international guideline.
Moreover, There were already many comparisons and interpretations for the different results between Prof. Annane¿s study[3] and CORTICUS trial[4]. We noticed Annane and his cooperators initiated steroid within 3-8 hours of the onset of septic shock symptom and randomization, which very same as Dr. Kyeongman Jeon study(mean 6.5 hours) . By contrast, CORTIUCS investigators started that within 72h, ¿as defined by a systolic blood pressure of less than 90 mm Hg despite adequate fluid replacement or a need for vasopressors for at least 1 hour¿. Theoretically, it is reasonable that exacerbation in hemodynamic parameters last as long as 24-72 hours may easily associated with higher mortality rate in septic shock patients, regardless which drug they prefer after that.
In summary, we believe that Dr. Kyeongman Jeon and previous Prof. Annane¿s studied already highlight tracks we should explore further to rescue our patients. And it is also a very important implication for the future investigations targeting steroid in septic shock, for example, ADRENAL trial(NCT01448109)in Australia and new Zealand. The beneficial effects of aggressive steroid therapy may hide in early treating stage of septic shock.
Reference:
1.Park HY, Suh GY, Song JU, Yoo H, Jo IJ, Shin TG, Lim SY, Woo S, Jeon K: Early initiation of low-dose corticosteroid therapy in the management of septic shock: a retrospective observational study. Crit Care 2012,16:R3.
2.Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008, 36:296-327.
3.Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G,Cohen Y, Azoulay E, Troche G, Chaumet-Riffaud P, Bellissant E: Effect of treatmentwith low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002, 288:862-871.
4.Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J: Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008, 358:111-124.
Competing interests
No competing interests.