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

This patient looks “septic” Definitions

SEPTIC SHOCK Multi-organ failure Infection  SIRS Sepsis COMPLEX INTERACTION Temp > 38.3°C or < 36°C HR > 90 RR > 20 or PaCO2 < 32 WCC > 12 or < 4 + other diagnostic criteria Brain confusion, delirium Heart SBP < 90 (> 40 decrease) Lungs acute lung injury Liver  LFTs Gut ileus Kidneys stop pee,  Cr Blood  platelets, DIC Infection  SIRS  Lactate  CRT Sepsis  organ dysfunction , tissue hypoperfusion Severe Sepsis Vasopressors +/- Inotropes and more…  hypotension despite adequate fluid resuscitation Proinflammatory + antiinflammatory mechanisms Complex interaction between infecting pathogen and body’s inflammatory, immune and coagulation responses Systolic BP less than 90mmHg (or fall 60mmHg) Sacrifice of perfusion to minor organs, skin, gut, kidneys Tachycardia to correct systemic under-perfusion Hyperventilation to improve oxygen availability Metabolic acidosis due to lack of oxygen (presence of lactic acid) Mental confusion 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]

Brief reminder of shock. SEPTIC SHOCK

 intravascular volume +  SVR + ( CO)   BP +  perfusion Septic shock  intravascular volume +  SVR + ( CO)   BP +  perfusion leaky capillaries vasodilation 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 K 4 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? 6. CXR changes, ?PCT, renal function 7. VAP 8. Change Abx

HNE Resources

SEPSIS KILLS PROGRAM

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

Surviving sepsis campaign Improving diagnosis, survival and management Surviving sepsis campaign

Further reading: “Surviving sepsis: going beyond the guidelines” 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 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 3 hours of presentation or diagnosis To be completed within 6 hours of presentation or diagnosis Bundles 
A "bundle" is a group of therapies  for a given disease that, when implemented together, may result in better outcomes than if implemented individually. In a bundle, the individual elements included are built around best evidence-based practices.  The science supporting the individual treatment strategies in  a bundle is sufficiently mature such that implementation of the approach should be considered either best practice or a reasonable and generally accepted practice.
 
The purpose of creating a bundle strategy is to clearly articulate a therapeutic framework that will function as a lever for change.  We anticipate that making the Severe Sepsis Bundles standard practice will eliminate the piecemeal or chaotically applied of standards for sepsis care that characterize many clinical environments today.  
 
The Severe Sepsis Bundles have been designed with the hope to allow teams to follow the timing, sequence, and goals in the bundles, to achieve  a 25 percent reduction in mortality due to severe sepsis or septic shock.  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 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 control Setting goals of care Recommendations: Haemodynamic Support and Adjunctive Therapy Recommendations: Other Supportive Therapy of Severe Sepsis

Pharmacological therapies 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  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 Antimicrob Chemother 2011; 66 Supp 2: ii25 – ii31 LD = V x Cp

Adequate initial dosing important 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

What initial dose would you give? Vancomycin Gentamicin Tazocin

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