SEPSIS AND DRUGS

JHH ICU CME June 2014

Lynn Choo
ICU Pharmacist

This patient looks septic

DEFINITIONS

COMPLEX
INTERACTIO
N

Temp > 38.3C or <

36C

HR
RR

> 90
> 20 or PaCO2

< 32

Infection

WCC > 12 or < 4

+ other diagnostic criteria

SIRS

Sepsis

Brain
Heart

confusion, delirium
SBP < 90 (> 40

decrease)

Lungs
Liver
Gut ileus
Kidneys
Blood

acute lung injury

LFTs
stop pee, Cr
platelets, DIC

Lactate
organ dysfunction , tissue hypoperfusion
CRT

Severe Sepsis

Vasopressors +/Inotropes
and more

hypotension despite adequate fluid resuscit

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.
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

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:
34
Results:
WCC
CXR

T 35.6C

BP 130/66

Na 141
K4
Ur 12.4
21
left lower lobe consolidation

HR 98 RR

Cr 188

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

e 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

e 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

ommendations: Initial Resuscitation and Infection Issues

Initial resuscitation (first 6 hours)
Goals: CVP 8-12
MAP 65
UO 0.5mL/kg/hr
normalise lactate
Screening for sepsis and performance improvement
Diagnosis
Antimicrobial therapy
Source control
Infection prevention

ScvO2 70%

mmendations: Haemodynamic Support and Adjunctive Therapy

Fluid therapy
Vasopressors

Inotropic therapy
Corticosteroids

ommendations: Other Supportive Therapy of Severe Sepsis

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

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):
lipophillic

hydrophillic
increase in sepsis
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

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