Should we use steroids in sepsis? J.G. van der Hoeven

Transcription

1 Should we use steroids in sepsis? J.G. van der Hoeven

2 Why I don t like it It is boring.. It usually results in emotional outcries in the audience If any, the effects on outcome are very small You are not going to change your practice anyway

3 Forget the high industrial dose of MP/DXM Annane D. JAMA 2009;301:

4 Recent conclusions In the absence of additional data we suggest that the clinicians use their bedside clinical judgement combined with expert opinion to determine the role of CS treatment in fluid resuscitated patients with VP-dependent septic shock (Patel GP, Balk RA. Am J Respir Crit Care Med 2012) Avoid the use of iv hydrocortisone if adequate fluid resuscitation and vasopressor therapy restore hemodynamic stability (Surviving Sepsis Campaign. Crit Care Med 2013 and Angus DC, vd Poll T. N Engl J Med 2013)

5 CS and 28-D mortality Bollaert PE 1998 Briegel J 1999 Chawla K 1999 Study Annane D 2002 Oppert M 2005 Mussack T 2005 Sprung CL 2008 Arabi YM 2010 TOTAL OR (95% CI) Changsong Wang. Anesth Analg 2014;118:

6 Corticosteroids?

7 CS and (7D) shock reversal Changsong Wang. Anesth Analg 2014;118:

8 Potential adverse events Hyperglycemia Secondary infection from immune suppression Delayed healing Muscle weakness

9 But also.. N = severe sepsis / septic shock BOLD fmri Nguyen DN. Biomed Research International 2014

10 Overall mean cortisol levels over 7 days (μg/dl) Controls P = 0.01 Critically ill Boonen E. N Engl J Med 2013 Cortisol levels are increased in patients with sepsis Sepsis - N = 58 Wen-Hui Tsai. Chinese J Physiol 2014;57:1-7

11 100 P < Overall mean ACTH levels over 7 days (μg/dl) Controls Critically ill Boonen E. N Engl J Med 2013 While ACTH levels are actually low Sepsis - N = 51 Vassiliadi DA. J Clin Endocrinol Metab 2014

12 CriticalIllnessRelatedCorticosteroidInsufficiency - Hypothalamus CRH! AVP - Catecholamines + Angiotensin II Pituitary Serotonin VIP Adrenal ACTH + TNF-α IL-1 IL-6 Increased cortical secretion Reduced cortisol clearance Decreased CBG Increased free cortisol Increased translocation of GC-R into the nucleus Activation or repression of gene transcription Plasma Cell Nucleus

13 CIRCI Inadequate corticosteroid activity for the severity of illness of the patient Stress Total plasma cortisol Free plasma cortisol Interstitial cortisol Activity HSD-1 Expression target genes Activity HSD-2 GC-receptor expression GC-receptor translocation Expression target genes Sick euadrenal state

14 Sepsis and timing of CS Control Steroids 80 Shock Mortality (%) Vasopressor 3.7 ± 4.7 hrs 4.1 ± 3.4 hrs 0 28-D ICU Hospital 1-Year All p-values non-significant Corticosteroids SAPS II 60 ± 19 Annane D. JAMA 2002;288:

15 Sepsis and timing of CS Control Steroids 60 Shock 45? Mortality (%) Vasopressor 79% < 12 hrs 10% hrs 11% > 24 hrs 0 28-D ICU Hospital 1-Year All p-values non-significant Corticosteroids SAPS II 49.5 ± 17.8

16 Sepsis and timing of CS Nonrandomized prospective longitudinal study Adult patients (N = 170) with septic shock treated with NE > 0.5 μg/kg/min and low dose CS Comparison of early (1-9 hrs - first quartile, N = 46) versus late (N = other quartiles) CS administration after start of NE (%) 70 52, ,5 0 Early CS 47,8 P = Total mortality Late CS 69,4 Median time to discontinuation NE 4 D (early) vs 15 D (late) - P < Katsenos CS. Crit Care Med 2014;42:

17 Interaction vasopressin and corticosteroids? VP + CS NE + CS Post hoc analysis VASST trial 60 P = 0.01 N = 589 (296 VP/CS, 293 NE/CS) Primary outcome 28-day Trend to less organ dysfunction in VP/CS group Mortality (%) P = ,9 44,7 45,2 55,5 Corticosteroids increased VP levels D 90 D Russell JA. Crit Care Med 2009;37:

18 RCT Vasopressin ± CS Open label placebo-controlled RCT Septic shock N = 61 VP + CS (31) Vasopressin (max 0.06 U/min) titrated to MAP mmhg Hydrocortison vs placebo with maximum vasopressin infusion Catecholamines if hypotensive VP (8) VP/CS (23) VP + P (30) VP (3) VP/P (27) N=5 Primary outcome: VP levels Gordon AC. Crit Care Med 2014;42:

19 RCT Vasopressin ± CS 3.1 D shorter duration of VP infusion in HC group (P=0.001) 2 D shorter duration of NE infusion in HC group (P=0.015) No difference in mortality, onset of new organ dysfunction and organ failure-free days Plasma vasopressin (pmol/l) Placebo Hydrocortison Time from hydrocortisone/placebo administration (hrs) MCT comparing VP with NE as initial therapy including CS interaction is under way Gordon AC. Crit Care Med 2014;42:

20 My conclusions Low dose prolonged corticosteroid administration reduces 7 D shock reversal but has no effect on mortality Low dose prolonged corticosteroid administration may have relevant side-effects including brain dysfunction CIRCI may be another adaption to critical illness and cannot be diagnosed with routine laboratory tests A beneficial interaction between VP and CS is preliminary

21 and therefore.. Steroids! in! sepsis unless you have a very unstable patient with a rapidly escalating high norepinephrine dose