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