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SEPSIS AND DRUGS JHH ICU CME June 2014 Lynn Choo ICU Pharmacist This patient looks “septic” DEFINITIONS COMPLEX INTERACTION Temp > 38.3°C or < 36°C HR > 90 RR > 20 or PaCO2 < 32 WCC > 12 or < 4 + other diagnostic criteria Infection SIRS Sepsis Brain Heart Lungs Liver Gut Kidneys Blood confusion, delirium SBP < 90 (> 40 decrease) acute lung injury LFTs ileus stop pee, Cr platelets, DIC organ dysfunction , tissue hypoperfusion Lactate CRT 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. 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] SEPTIC SHOCK Septic shock intravascular volume leaky capillaries + SVR vasodilation + ( CO) BP + perfusion compensatory (by HR) Antibiotics Treat the CAUSE Fluid resuscitation intravascular volume BP Vasopressors SVR BP Oxygenation organ perfusion 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, Panadol Osteo Metformin 1g nocte Prior to intubation: T 35.6°C BP 130/66 HR 98 RR 34 Results: Na 141 K4 Ur 12.4 Cr 188 WCC 21 CXR left lower lobe consolidation On ICU Day 3, she deteriorates with 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? HNE RESOURCES SEPSIS KILLS PROGRAM http://www.cec.health.nsw.gov.au/programs/sepsis Improving diagnosis, survival and management SURVIVING SEPSIS CAMPAIGN NEW GUIDELINES 2012 www.survivingsepsis.org 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 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 SURVIVING SEPSIS CAMPAIGN BUNDLES To be completed within 3 hours of presentation or diagnosis 1. 2. 3. 4. Measure serum lactate Blood cultures before antibiotics Broad spectrum antibiotics 30 mL/kg crystalloid for hypotension or lactate ≥ 4 mmol/L To be completed within 6 hours of presentation or diagnosis 5. Vasopressors (for hypotension despite initial fluid resuscitation) to maintain MAP ≥ 65 mmHg 6. 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 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 Recommendations: Initial Resuscitation and Infection Issues Initial resuscitation (first 6 hours) Goals: CVP 8-12 MAP ≥ 65 UO ≥ 0.5mL/kg/hr Screening for sepsis and performance improvement Diagnosis Antimicrobial therapy Source control Infection prevention ScvO2 ≥ 70% normalise lactate Recommendations: Haemodynamic Support and Adjunctive Therapy Fluid therapy Vasopressors Inotropic therapy Corticosteroids Recommendations: Other Supportive Therapy of Severe Sepsis Blood product administration Immunoglobulins Selenium Mechanical ventilation (ARDS) Sedation, analgesia, and NMB Glucose control Renal replacement Bicarbonate (do not use..) DVT prophylaxis Stress ulcer prophylaxis Nutrition Setting goals of care antibiotics . fluids . vasopressors . inotropes . steroids . dvt px . su px PHARMACOLOGICAL THERAPIES But really includes all antimicrobials… ANTIBIOTICS Antibiotics Timing administer 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 Antibiotics Loading dose high to start with LD = V x Cp Volume of distribution (V): hydrophillic lipophillic Required plasma concentration (Cp): increase in sepsis increase in obese MICs Renal function plays NO ROLE in calculation of loading dose McKenzie. Antibiotic dosing in critical illness. J Antimicrob Chemother 2011; 66 Supp 2: ii25 – ii31 Antibiotics Roberts J and Lipman J. Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med 2009; 37: 840 – 851. SEPSIS Increased cardiac output Leaky capillaries Multi-organ failure Increased clearance Increased volume of distribution Decreased clearance Low plasma High plasma concentrations concentrations Adequate initial dosing important Reassess and adjust What initial dose would you give? • Vancomycin • Gentamicin • Tazocin McKenzie. Antibiotic dosing in critical illness. J Antimicrob Chemother 2011; 66 Supp 2: ii25 – ii31