Post on 26-May-2020
Sepsis
Sept 2013
A/Prof John Ferguson
jferguson@hnehealth.nsw.gov.au
www.hicsiganz.org (nepal)
• 1. Which of the following best describes
the meaning of the term "severe sepsis"
– a. An infection which leads to death
– b. An infection with a SIRS response
– c. Sepsis in an immunosompromised host
– d. Sepsis leading to acute organ dysfunction
– e. An infection plus at least 3 SIRS criteria
Overview
• Definitions & Pathogenesis
• Burden and causes of sepsis
• Identifying septic patients: patient
assessment
• Approach to septic patient
• CEC Sepsis Kills Project
Strong Genetic Component
• Sorensen (1988)
– Large cohort of adult adoptees (960 families) in Denmark
– Examined risk of premature death (before age 50) in biological parents vs adopted children
– If one biological parent had premature death, risk in child
• All cause: 1.71
• Cancers 1.19
• Infections 4.52
Overview
• Definitions & Pathogenesis
• Burden and causes of sepsis
• Identifying septic patients: patient
assessment
• Approach to septic patient
• CEC Sepsis Kills Project
Burden of disease: developing
countries
• higher overall burden and higher mortality than
USA
• advanced HIV infection a strong risk factor for
bacteraemia, sepsis and mortality
• Other prevalent risk factors for sepsis- e.g.
– Unsafe water or food
– malnutrition
– tuberculosis
– other chronic diseases such as diabetes
– severe malaria
Sources of sepsis
Community-acquired infections
• Primary sepsis- no apparent focus
• Skin/soft tissue
• GIT - enteritis
• Urinary tract infection
• Biliary tract/abdomen
• Pneumonia
• Meningitis
Healthcare-associated (nosocomial)
• Intravenous lines
• Urine (catheter associated)
• Wounds (post op or post trauma)
• Pneumonia (Ventilator, post-operative)
• Neonates
Why is sepsis important?
• Leading cause of death in intensive care
• Estimated 18 million cases/year worldwide1
• 215,000 deaths per year in USA 2
• Estimated 13,000 ICU admissions and 4,875 deaths from severe sepsis in ANZ each year 3
1 Slade (2003) Crit Care; 7:1-2
2 Angus (2001) Crit Care Med; 29:1303
3 Finfer (2004) Int Care Med; 30:589
Why is sepsis important?
• 28-day mortality in Australia/USA – Sepsis 10-30% – Severe sepsis 25-40% – Septic shock 30-60%
• Long-term outcomes are even worse • These high mortality rates continue despite
– Advanced supportive care – Aggressive antibiotic and surgical
management of infection
Isolate pattern Hunter New England Health ,
Newcastle, Australia 2010
• An important study – highly relevant to Nepal
Lancet 2011
Nosocomial
BSI incidence
x 40 higher
than
community
patient
incidence
Causes of nosocomial BSI
(children and adults)
• IV line-associated sepsis
– Peripheral cannulae
– Central lines
– ICU and non-ICU
• Catheter associated urinary infection
• Surgical wound (post-operative) infections
• Decubitus ulcers
• Pneumonia
MRSA only in one case
Gives a useful survey of the presentations and mortality risk factors
Febrile outpatient children only – relatively high pathogen isolation
rates
• BHI broth, small 5mL sample for adults, subculture BA and Maconkey agar incubated
aerobically
• Nosocomial isolates not distinguished
• Oxacillin used for detection of MRSA – none detected (cefoxitin should have been used)
• No mention of contamination rates
Overview
• Definitions & Pathogenesis
• Burden and causes of sepsis
• Identifying septic patients: patient
assessment
• Approach to septic patient
A cautionary tale- 56 yr male
oesophagectomy, Dec 09
• Chemotherapy (from Sept), ceased smoking in September
• Community MRSA colonised detected upon admission to ICU after the operation (no treatment required)
• In ward, uncomplicated progress to day 5 post op, devices still in place- right internal jugular line, peripherally inserted central line, jejunostomy and NG tube, bilateral chest drains
Progress – day 5 post-op
• 7pm- nurse entry-temp – 38º C, hr 96, bp, resps. saturation normal
– no clinical review requested
• later that night RMO entry (UNTIMED ENTRY, probably midnight) – ‘feeling well’, no chills or rigors
– temp 39º, BP 137/67, HR not quoted – was 121/m, rr 20.
– chest ‘clear’, abdomen ‘soft’ DIAGNOSIS- ‘no obvious site of infection’
– NO MENTION OF STATUS OF INDWELLING DEVICES
– RMO’s Plan:
• MSU, blood culture- forms filled out for blood collector
• Day surgical team review requested but NO DIRECT HANDOVER GIVEN TO THE TEAM
Progress day 6-7 post-op
• Morning team (day 6)- UNTIMED entry – ‘afebrile’,
– Plan: • chest physio,
• pain team review requested
• Evening RMO (UNTIMED entry) – dyspnoea
– saturations 86% on 2 litres, resp rate elevated, HR 120/m
– bronchial breathing right base
– CXR, ICU referral
– Antibiotics commenced
• Day 7 post op – blood culture positive for ‘Staph.’ IV Vancomycin added.
– Died soon after in ICU with fulminant sepsis/ acidosis
– Staph. identified as MRSA
Day 6 white cell count 45 (requested by night
RMO)
(team did not review result until later)
day 6 CXR evening after ICU admission
• Cause of
death-
nosocomial
MRSA
pneumonia
Initiative of the Clinical Excellence
Commission, NSW Australia
Overview
• Definitions & Pathogenesis
• Burden and causes of sepsis
• Identifying septic patients: patient
assessment
• Approach to septic patient
• CEC Sepsis Kills Project
Approach to septic patient 1. Clinical assessment- origin of patient, HIV, past
medical history including diabetes?, immunosuppressive medication
2. Laboratory diagnostic testing
3. Antibiotics after cultures- as early as possible
4. Administer oxygen
5. Resuscitation – ‘EARLY GOAL-DIRECTED THERAPY
6. Source: identification and control
7. Adequate glycaemic control (keep blood glucose near normal )
8. Consider corticosteroids – patients unresponsive to fluid challenge/ vasopressors
Approach to septic patient 1. Clinical assessment- origin of patient, HIV, past
medical history including diabetes?, immunosuppressive medication
2. Laboratory diagnostic testing
3. Antibiotics after cultures- as early as possible
4. Administer oxygen
5. Resuscitation – ‘EARLY GOAL-DIRECTED THERAPY
6. Source: identification and control
7. Adequate glycaemic control (keep blood glucose near normal )
8. Consider corticosteroids – patients unresponsive to fluid challenge/ vasopressors
Lab. diagnostic testing
• Urinalysis/microscopy
• Cultures BEFORE treatment (blood, urine, wound swab other)
• Full blood count (bands (precursor forms of neutrophils), neutrophils, platelets, haematocrit- all relevant)
• Electrolytes, creatinine
• Blood coagulation
• Lactate (blood gas machine)
Questions: blood cultures
1. Is patient identified correctly and sample/request form completed ?
2. What antiseptic is used for skin preparation?
3. What volume of blood is sampled?
4. Is more than one set collected each time?
5. Are the culture bottles inoculated BEFORE the full blood count or electrolyte tubes?
6. Are contamination rates too high? (3% or less target )
7. Should a commercial system be put in place?
Volume of sampling
• Adults – yield of pathogens increases in direct proportion to volume 2 to 30mLs
• Additional yield with higher volumes
• Collection of two sets is best practice
– Increases volume of sample
– Allows to distinguish between contamination and significant isolates for organisms such as coagulase negative staph
Blood culture contamination
• 2012 – 13068 blood cultures collected JHH/RNC 3.9% contamination rate
• Best collection practice can achieve rates of < 3%
• Contamination costs! – Unnecessary treatment
– Unreliable detection of infections due to potential contaminant organisms such as coagulase negative staph
Approach to septic patient 1. Clinical assessment- HIV, TB, malnutrition,
past medical history, immunity
2. Laboratory diagnostic testing
3. Antibiotics – within 1 hour
4. Administer oxygen
5. Resuscitation – ‘EARLY GOAL-DIRECTED THERAPY
6. Source: identification and control
7. Adequate glycaemic control (keep blood glucose near normal )
8. Consider corticosteroids – patients unresponsive to fluid challenge/ vasopressors
Kumar: Crit Care Med 2006; 34:1589–1596)
Mortality
increases
by 7.6%
per hour of
delay
Kumar: Crit Care Med 2006; 34:1589–1596)
3. Antibiotics for sepsis
• Choice of antibiotic(s) depend on:
– Locally demonstrated resistance patterns- essential regular microbiological surveillance required!
– Community versus nosocomial onset
– Presumed site/origin of infection
If the infecting organism is not covered by the initial antibiotic(s), then higher mortality occurs.
On smart
phone app
“Sepsis Kills
Sepsis
Guide”
Cumulative antibiograms
needed! • Distinguish community from nosocomial isolates
• Document likely source of sepsis
• Identify the best empirical regimen to use
• Incorporate this in to the local guideline
Aminoglycosides- effective/safe
usage • Aminoglycosides are the most rapidly Gram
negative bactericidal agent; must be given at high initial dose (concentration dependent killing)
• Toxicity relates to prolonged usage – avoid > 3 days; switch to alterative if possible
• Dependent on local susceptibility pattern, gentamicin may represent a good initial drug of choice
Antibiotic Guidelines
2010
Short term empirical therapy with gentamicin
• Initial dose: based on age
• Number of empiric doses: based on renal function
• NO monitoring is required for patients receiving short course treatment
• Few indications for > 3 days treatment
Approach to septic patient 1. Clinical assessment- HIV, TB, malnutrition,
past medical history, immunity
2. Laboratory diagnostic testing
3. Antibiotics – within 1 hr
4. Administer oxygen
5. Resuscitation – ‘EARLY GOAL-DIRECTED THERAPY
6. Source: identification and control
7. Adequate glycaemic control (keep blood glucose near normal )
8. Consider corticosteroids – patients unresponsive to fluid challenge/ vasopressors
Fluids
• SAFE
– 6997 critically ill
– 0.9% Saline vs 4% Albumin
– No difference in mortality
– Trend to benefit of albumin in sepsis
subgroup
• OR for mortality 0.87 [0.74-1.02]
• aOR for mortality 0.71 [0.52-0.97]
1. SAFE investigators NEJM; 350:2247
Fluids in severe sepsis
• Most physicians under-fill
• Fluid overload/pulmonary oedema is easier to
treat than established septic shock
– (If there is access to modern ICUs)
• Eg. The Rivers EGDT trial, a mean of 5 litres of
IV fluid was needed in the first 6 hours
• In adults with septic shock, fluid boluses of
500ml should be given every 15 minutes until
goals are met or 3 litres have been given
Vasopressors
• NAd better than Dopamine
– 1,679 patients with shock1
– 28-Day mortality 48.5% NAd, 52.5% DA (p=0.07)
– Arrhythmias 12.4% NAd, 24.1% DA (p<0.001)
• Vasopressin plus Nad no better than NAd
– 778 patients septic shock on NAd 5 mcg/minute
– 28-Day mortality Nad 39.3%, VP 35.4%, p=0.11
1. De Backer (2010), NEJM: 362: 779 2. Russell (2008).
NEJM; 358: 877
5. Resuscitation – ‘EARLY GOAL-
DIRECTED THERAPY
Evidence base: late correction of hypotension coupled with positive fluid balance is associated with excess mortality in patients with sepsis
• Start IV fluids early even if not hypotensive,
• Correct hypotension/shock with aggressive IV fluid boluses:
– Adults: crystalloid 20 mls/kg + repeat x 1-2;
– Infants < 12m: 80ml/kg over 5hr
– Children < 5yrs: give over 2.5 hrs
• Reassess every 1-2hrs and adjust as necessary
• If no response to fluid loading then vasopressors need to be considered
Lactate predicts outcome and helps
gauge response to treatment
NB. Normal lactate does not exclude sepsis
From Howell et al.
Approach to septic patient 1. Clinical assessment- HIV, TB, malnutrition,
past medical history, immunity
2. Laboratory diagnostic testing
3. Antibiotics – within 1 hr
4. Administer oxygen
5. Resuscitation – ‘EARLY GOAL-DIRECTED THERAPY
6. Source: identification and control
7. Adequate glycaemic control (keep blood glucose near normal)
8. Consider corticosteroids – patients unresponsive to fluid challenge/ vasopressors
6. Source identification and
control
• Clinical evaluation
• Imaging to find the abscess/ infection
• Surgery often required to drain the
infection
• Removal of infected devices or drips
Clinical microbiologist may be able to suggest
the likely source of sepsis based on the
organism isolated.
Staph. aureus BSI: source control
issues very important
from local protocol in Newcastle, Australia
Staph. aureus BSI
from local protocol in Newcastle, Australia
7. Glycaemic control: intensive
insulin therapy
• Tight blood sugar control increases mortality
• Earlier studies suggested benefit1
• NICE-SUGAR2
– 6,104 medical and surgical ICU patients
– BSL targets 4.5-6 (81 to 108 mg per deciliter) versus
<10 (< 180mg/dL)
– Mortality 27.5% vs 24.9% (p<0.05)
– Severe hypoglycaemia 6.8% vs 0.5%
1. van den Berghe (2001); 345: 1359
2. NICE-SUGAR investigators (2009), NEJM; 360: 1283
8. Steroids for all? – still
controversial • Annane study
– 300 refractory septic shock within 8 hours of onset
– Hydrocortisone 50mg q6h + fludrocortisone
– 28-Day mortality decreased 55% vs 61%
– Inadequate adrenal reserve group 53% vs 63%
• CORTICUS – 499 septic shock within 72h (not refractory)
– Hydrocortisone 50mg q6h
– 28-Day mortality no change 35% vs 32%
– Faster reversal of shock 3.3 vs 5.8 days
– No difference according to “adrenal reserve”
Corticus study
N Engl J Med. 2008 Jan 10;358(2):111-24.
Hydrocortisone therapy for patients with septic
shock.
“Hydrocortisone did not improve survival or reversal of
shock in patients with septic shock, either overall or in
patients who did not have a response to corticotropin,
although hydrocortisone hastened reversal of shock in
patients in whom shock was reversed.”
However, patient in refractory shock or who is
already has adrenal suppression must receive
replacement therapy
Male 75 yrs, Haemodialysis initiated 24/12/12 Cubital fossa cannula – ED inserted; remained for 3 days
Painful swollen knee 27/12; PDx Gout, given steroids