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Adjunctive Pharmacotherapy In Sepsis

Adjunctive Pharmacotherapy In Sepsis. นายแพทย์ เฉลิมไทย เอกศิลป์ สถาบันสุขภาพเด็กแห่งชาติมหาราชินี. Insulin Therapy & Glycemic Control. Hyperglycemia is common in critically-ill patients Associated with increased risk of death and substantial morbidity such as

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Adjunctive Pharmacotherapy In Sepsis

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  1. Adjunctive Pharmacotherapy In Sepsis นายแพทย์ เฉลิมไทย เอกศิลป์ สถาบันสุขภาพเด็กแห่งชาติมหาราชินี

  2. Insulin Therapy & Glycemic Control • Hyperglycemia is common in critically-ill patients • Associated with increased risk of death and substantial morbiditysuch as critical-illness polyneuropathy skeletal-muscle wasting and need for prolonged mechanical ventilation increased susceptibility to infections Organs failure

  3. Hyperglycemia in Critically-Ill Patients Van den Berghe G. J Clin Invest 2004; 114 : 1187-1195.

  4. Effects of Hyperglycemia on Critically-Ill Patients

  5. Insulin Therapy In Surgical Patients • RCT : 1,548 Adult receiving MV in surgical-ICU • Intensive therapy (BS 80-110 mg/dl)vs conventional gr (180-200 mg/dl) • Result : decreased mortality and complications • Mortality-Intensive gr vs conventional gr :4.6% vs 8%,P<0.04 • Decreased • mortality 34% • Blooodstream infection 46% • Renal failure 28% • Renal failure requiring dialysis 41% • Critical-illness polyneuropathy 44% • Need for prolong MV 39% GREET VAN DEN BERGHE. N Engl J Med2001;345:1359-67

  6. Intensive Insulin Therapy in The Medical ICU RCT 1,700 Critically-ill patients in Med-ICU Intensive insulin therapy vs conventional gr

  7. Mechanism of Insulin Therapy • Correct hyperglycemia • Decrease cell apoptosis • Anti-inflammatory action • -Suppress production : • inflammatory cytokines, superoxide • -Decrease adhesion molecule soluble : • ICAM-1, E-selectin

  8. Insulin Therapy • Start insulin infusion when BS>110 mg/dl • Strictly control BS: 80-110 mg/dl • Initial dose <0.05 unit/kg/hr-1 unit/kg/hr • Closely monitor BS • After ICU discharge, maintenance of BS<200 mg/dl • Concern about hypoglycemia in pediatric patients • Clinical trial in pediatric patients is on going

  9. Corticosteroid In Sepsis • Anti-inflammatory action of high dose corticosteroidtherapy fails to decrease mortality in sepsis and septic shock. • Adverse drug reactions : superinfection, hyperglycemia, GI bleeding

  10. Adrenal Insufficiency in Critically-Ill Patients • Incidence ranges 0-75% • Adrenal insufficiency is associate with poor outcomes • Mechanism Inflammatory cytokines & mediators suppress the HPA-axis and induces resistance of glucocorticoid receptor

  11. Adrenal Insufficiency in Critically –Ill Patients Felmet K and Caicillo J. .In : Fuhrman BP & Zimmerman J. Pediatric Critical Care.3rd ed. 2006 : 1462-1473.

  12. Diagnosis is so difficult, no consensus • Cortisol level in critically ill patients vary from the healthy normal level to 20 times

  13. Clinical Manifestration of Adrenal Insufficiency Cooper MS and Stewart PM. N Engl J Med 2003; 348: 727-34.

  14. Diagnosis of Adrenal Insufficiency ACTH stimulation < 2 yr : 125 mcg > 2 yr : 250 mcg Pizarro CF. Crit Care Med 2005; 33: 855-859.

  15. Treatment with low dose steroid in patients with septic shock • 300 adults with septic shock • Hydrocortisone(200mg/day)+fludrocortisone (50 mcg/day) vs placebo • ACTH stimulation test to identify cases with adrenal insufficiency • Result : • reduced mortality rate in patients with septic shock and adrenal insufficiency • Adrenal insufficiency -mortality in steroid gr vs placebo :53% vs 63%, p=0.02 Annane D.JAMA 2002;288:862-71.

  16. Systematic review, Meta-analysis 16 RCTs, n=2,063 Result Low dose corticosteroid decreased mortality more rapid for shock reversal no difference of adverse drug events : hyperglycemia,superinfection and GI bleeding High dose corticosteroid did not decreased the mortality Annane D. BMJ2004;329:480-489.

  17. The Effect of Steroids on Survival and Shock during Sepsis Depends on the Dose • Meta-Analysis : 14 RCTs • Results : • Low dose corticosteroid increased survival rate and shock reversal • The treatment effects of steroids on mortality or shock reversal did not statistically significantly differ on the present of adrenal insufficiency or not Minneci PC.Ann Intern Med. 2004;141:47-56.

  18. !! Confusion!!

  19. Mechanism of Low Dose Corticosteroid • Cortisol substitution • Anti-inflammation • Decrease • IL-6,IL-8,soluble E-selectin • neutrophil activation • Increase vascular tone via • inhibit inducible nitric oxide synthase • enhance adrenergic receptor expression • stimulate guanylate cyclase KehD. Am J Respir Crit Care Med 2003 ; 167 : 512 - 520.

  20. Indications for Corticosteroid in Septic Shock • Catecholamine resistance septic shock • withadrenal insufficiency • 2.Catecholamine resistance septic shock • suspected adrenal insufficiency : • purpura fulminans, steroid use, • diseases of hypothalamic-pituitary- adrenal prolonged critically -illness • 3.Catecholamine resistance septic shock ??? Felmet K and Caicillo J.In : Fuhrman BP & Zimmerman J. Pediatric Critical Care.3rd ed.2006 : 1462-1473. Parker MM.Crit Care Med 2004 ; 32 (Suppl.) :S591-S594.

  21. Incidence of Adrenal Insufficiency in Pediatric Patients with Septic Shock • Septic shock 44 % • Catecholamine resistance septic shock 80-100 % Pizarro CF. Crit Care Med 2005; 33: 855-859.

  22. Indications for Corticosteroid in Septic Shock • Catecholamine resistance septic shock • withadrenal insufficiency • 2.Catecholamine resistance septic shock • suspected adrenal insufficiency : • purpura fulminans, steroid use, • diseases of hypothalamic-pituitary- adrenal prolonged critically -illness • 3.Catecholamine resistance septic shock Felmet K and Caicillo J.In : Fuhrman BP & Zimmerman J. Pediatric Critical Care.3rd ed.2006 : 1462-1473. Parker MM.Crit Care Med 2004 ; 32 (Suppl.) :S591-S594.

  23. Which are the appropriate adjunctive pharmacotherapies for this patients ?

  24. Corticosteroid In Septic Shock • Hydrocortisone 1 mg/ kg/ day IV q 8 hr • Fludrocostisone 1 mcg/ kg/ day oral OD • Duration of treatment : 5 -7 days and taper on 4 – 6 subsequent days • Monitor hemodynamic status • Stop vasopressor use Annane D. BMJ2004;329:480-489.

  25. Thank you

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