SEPSIS and DRUGS

1. SEPSIS and DRUGS JHH ICU CME June 2014 Lynn Choo ICU Pharmacist

2. This patient looks “septic” Definitions

3. COMPLEX INTERACTION Temp > 38.3°C or < 36°C HR > 90 RR > 20 or PaCO2< 32 WCC > 12 or < 4 + other diagnostic criteria Brainconfusion, delirium HeartSBP < 90 (> 40 decrease) Lungsacute lung injury Liver  LFTs Gutileus Kidneysstop pee,  Cr Blood platelets, DIC Infection SIRS Lactate  CRT Sepsis organ dysfunction , tissue hypoperfusion Vasopressors +/- Inotropes and more… Severe Sepsis  hypotension despite adequate fluid resuscitation SEPTIC SHOCK Multi-organ failure Levy et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003; 31 (4): 1250 – 56. Bone et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. CHEST 1992;101: 1644 – 55.

4. Bone et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. CHEST 1992;101: 1644 – 55. Pinsky. Septic shock. Medscape Reference: Drugs, Diseases & Procedures updated Oct 25, 2011. Available on www.medscape.com [Accessed 29 March 2012]

5. SEPTIC SHOCK

6. Septic shock  intravascular volume+ SVR+ ( CO)BP +  perfusion leaky capillariesvasodilationcompensatory (by  HR) AntibioticsTreat the CAUSE Fluid resuscitation   intravascular volume   BP Vasopressors SVR  BP Oxygenation   organ perfusion

8. 58 year old female admitted to ICU after 1 day on the ward with respiratory failure requiring intubation. She was agitated and confused prior to intubation. HPC: 3 days of productive cough. SOB. General malaise. PMH: Hypertension, osteoarthritis, T2DM Meds: Ramipril 10 mg d, Atenolol 50 mg d, PanadolOsteo Metformin 1g nocte Prior to intubation:T 35.6°CBP 130/66 HR 98 RR 34 Results:Na 141 K 4 Ur 12.4 Cr 188 WCC 21 CXR left lower lobe consolidation

9. On ICU Day 3, she deteriorateswith increased requirements for ventilatory support and profuse purulent tracheal aspirates. What further information would you require? What is the most likely cause of her deterioration? How will this affect her drug treatments?

10. HNE Resources

11. SEPSIS KILLS PROGRAM

12. http://www.cec.health.nsw.gov.au/programs/sepsis

13. Improving diagnosis, survival and management Surviving sepsis campaign

14. NEW GUIDELINES 2012 www.survivingsepsis.org Dellinger et al. Surviving Sepsis Campaign: international guidelines for the management of severe sepsis and septic shock 2012. CritCare Med 2013; 41: 580 – 637 Further reading: “Surviving sepsis: going beyond the guidelines” Marik P. Annals of Intensive Care 2011; 1: 17. Available online: www.annalsofintensivecare.com/content/1/1/17

15. SURVIVING SEPSIS CAMPAIGN BUNDLES To be completed within 3 hours of presentation or diagnosis • Measure serum lactate • Blood cultures before antibiotics • Broad spectrum antibiotics • 30 mL/kg crystalloid for hypotension or lactate ≥ 4 mmol/L • Vasopressors (for hypotension despite initial fluid resuscitation) to maintain MAP ≥ 65 mmHg • Persistent hypotension despite volume resuscitation (septic shock) or initial lactate ≥ 4 mmol/L • Measure central venous pressure (CVP) *controversial* • Measure central venous oxygen saturation (Scvo2) *controversial* 7. Re-measure lactate if initial lactate was elevated To be completed within 6 hours of presentation or diagnosis Dellinger et al. Surviving Sepsis Campaign: international guidelines for the management of severe sepsis and septic shock 2012. Crit Care Med 2013; 41: 580 – 637

16. Recommendations: Initial Resuscitation and Infection Issues Initial resuscitation (first 6 hours) Goals: CVP 8-12 MAP ≥ 65 UO ≥ 0.5mL/kg/hr ScvO2 ≥ 70% normalise lactate Screening for sepsis and performance improvement Diagnosis Antimicrobial therapy Source control Infection prevention Fluid therapy Inotropic therapy Vasopressors Corticosteroids Blood product administration Renal replacement Immunoglobulins Bicarbonate (do not use..) Selenium DVT prophylaxis Mechanical ventilation (ARDS) Stress ulcer prophylaxis Sedation, analgesia, and NMB Nutrition Glucose controlSetting goals of care Recommendations: Haemodynamic Support and Adjunctive Therapy Recommendations: Other Supportive Therapy of Severe Sepsis

17. antibiotics . fluids . vasopressors . inotropes . steroids . dvtpx . supx Pharmacological therapies

18. But really includes all antimicrobials… ANtibiotics

19. Antibiotics Timingadminister within 1 hour of diagnosis 79.9% survival rate when antibiotics administered within 1 hour. Each hour delay (over first 6 hours) 7.6% decrease in survival. Kumar et al. Critical Care Med 2006; 34 (6): 1589 – 96

20. Antibiotics Loading dosehigh to start with Volume of distribution (V): hydrophillic increase in sepsis lipophillic increase in obese Required plasma concentration (Cp): MICs Renal function plays NO ROLE in calculation of loading dose McKenzie. Antibiotic dosing in critical illness. J AntimicrobChemother 2011; 66 Supp 2: ii25 – ii31 LD = V x Cp

22. Antibiotics Roberts J and Lipman J. Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med 2009; 37: 840 – 851. SEPSIS Increased Leaky Multi-organ cardiac output capillaries failure Increased Increased Decreased volume of clearance clearance distribution Low plasma High plasma concentrations concentrations Adequate initial dosing important Reassess and adjust

23. What initial dose would you give? • Vancomycin • Gentamicin • Tazocin

24. McKenzie. Antibiotic dosing in critical illness. J AntimicrobChemother 2011; 66 Supp 2: ii25 – ii31