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

2. This patient looks “septic”
Definitions

3. 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 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, Available on [Accessed 29 March 2012]

5. Brief reminder of shock.
SEPTIC SHOCK

6.  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

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, 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

9. 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

10. HNE Resources

11. SEPSIS KILLS PROGRAM

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

14. Further reading: “Surviving sepsis: going beyond the guidelines”
NEW GUIDELINES 2012
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:

15. 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 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 control Setting goals of care
Recommendations: Haemodynamic Support and Adjunctive Therapy
Recommendations: Other Supportive Therapy of Severe Sepsis

17. Pharmacological therapies
antibiotics . fluids . vasopressors . inotropes . steroids . dvt px . su px
Pharmacological therapies

18. But really includes all antimicrobials…
ANtibiotics

19. 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

20. 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

22. 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

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

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