Sepsis - WordPress.com · Sepsis Sept 2013 A/Prof John Ferguson [email protected] (nepal) ... • Pneumonia • Meningitis Healthcare-associated (nosocomial) • Intravenous

Sepsis

Sept 2013

A/Prof John Ferguson

[email protected]

www.hicsiganz.org (nepal)

mailto:[email protected]

http://www.hicsiganz.org/

• 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




assessment



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




assessment


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




assessment



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


3. Antibiotics after cultures- as early as possible






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


3. Antibiotics – within 1 hour






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




3. Antibiotics – within 1 hr






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.




3. Antibiotics – within 1 hr




7. Adequate glycaemic control (keep blood glucose near normal)


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

http://www.cec.health.nsw.gov.au/programs/sepsis

http://www.cec.health.nsw.gov.au/programs/sepsis

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Sepsis - WordPress.com · Sepsis Sept 2013 A/Prof John Ferguson [email protected] (nepal) ... • Pneumonia • Meningitis Healthcare-associated (nosocomial) • Intravenous