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SEPSIS AND DRUGSJHH ICU CME June 2014
Lynn ChooICU Pharmacist
DEFINITIONSThis patient looks “septic”
SIRSInfection
Sepsis
SEPTIC SHOCK
Severe Sepsis
Multi-organ failure
organ dysfunction , tissue hypoperfusion
hypotension despite adequate fluid resuscitation
Temp > 38.3°C or < 36°CHR > 90RR > 20 or PaCO2 < 32
WCC > 12 or < 4
+ other diagnostic criteria
Lactate CRT
Vasopressors +/- Inotropes and more…
Brain confusion, deliriumHeart SBP < 90 (> 40 decrease)Lungs acute lung injuryLiver LFTsGut ileusKidneys stop pee, CrBlood platelets, DIC
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.
COMPLEX INTERACTION
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
intravascular volume + SVR + ( CO) BP + perfusion leaky capillaries vasodilation compensatory
(by HR)
Antibiotics Treat the CAUSE
Vasopressors SVR BP
Oxygenation organ perfusion
Fluid resuscitation intravascular volume BP
Septic shock
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 OsteoMetformin 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 21CXR 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
SURVIVING SEPSIS CAMPAIGNImproving diagnosis, survival and management
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
NEW GUIDELINES 2012
1. Measure serum lactate2. Blood cultures before antibiotics3. Broad spectrum antibiotics4. 30 mL/kg crystalloid for hypotension or lactate ≥ 4 mmol/L
5. Vasopressors (for hypotension despite initial fluid resuscitation) to maintain MAP ≥ 65 mmHg6. 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
SURVIVING SEPSIS CAMPAIGN BUNDLES
To be completed within 6 hours of presentation or diagnosis
To be completed within 3 hours of presentation or diagnosis
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 improvementDiagnosisAntimicrobial therapySource controlInfection prevention
Fluid therapy Inotropic therapyVasopressors Corticosteroids
Blood product administration Renal replacementImmunoglobulins Bicarbonate (do not use..)Selenium DVT prophylaxisMechanical ventilation (ARDS) Stress ulcer prophylaxisSedation, analgesia, and NMB NutritionGlucose control Setting goals of care
Recommendations: Initial Resuscitation and Infection Issues
Recommendations: Haemodynamic Support and Adjunctive Therapy
Recommendations: Other Supportive Therapy of Severe Sepsis
PHARMACOLOGICAL THERAPIESantibiotics . fluids . vasopressors . inotropes . steroids . dvt px . su px
ANTIBIOTICSBut really includes all antimicrobials…
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
Volume of distribution (V): hydrophillic increase in sepsislipophillic 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
Antibiotics
SEPSIS
Increased cardiac output
Leaky capillaries
Multi-organ failure
Increased clearance
Increased volume of
distribution
Decreased clearance
Low plasma concentrations
High plasma concentrations
Adequate initial dosing important Reassess and adjust
Roberts J and Lipman J. Pharmacokinetic issues for antibiotics in thecritically ill patient. Crit Care Med 2009; 37: 840 – 851.
What initial dose would you give?
• Vancomycin
• Gentamicin
• Tazocin
McKenzie. Antibiotic dosing in critical illness. J Antimicrob Chemother 2011; 66 Supp 2: ii25 – ii31
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