Sepsis

Dr. Peter Jones Emergency Medicine Specialist

Department of Emergency Medicine Auckland City Hospital

Objectives
Understand the current nomenclature Know the local organisms Understand the spectrum of presenting illness Get a handle on the basic treatment Introduce novel treatments

Department of Emergency Medicine Auckland City Hospital

Definitions
Sepsis = SIRS + Infection SIRS = 2/4 of
Temp >38 or <36 HR >90 Respiratory Rate >20 or PaCO2 <32 (4.3kPa) WCC >12 or <4 or >10% bands

Infection = either
Bacteraemia (or viraemia/fungaemia/protozoan) Septic focus (abscess / cavity / tissue mass)
Department of Emergency Medicine Auckland City Hospital

Definitions Cont.
Severe sepsis = Sepsis + Organ Dysfunction Organ Dysfunction = Any of
SBP <90 or 40 <usual or inotrope to get MAP 90 BE <-5mmol/L Lactate >2mmol/L Oliguria <30ml/hr for 1 hour Creatinine >0.16mmol/L Toxic confusional state FIO2 >0.4 and PEEP >5 for oxygenation
Department of Emergency Medicine Auckland City Hospital

Definitions Cont.
Septic Shock = Severe sepsis + Hypotension
Hypotension = either
SBP <90 or 40<usual Inotrope to get MAP >90

Department of Emergency Medicine Auckland City Hospital

Dear SIRS I dont like you...

Department of Emergency Medicine Auckland City Hospital

Definitions Cont.

Department of Emergency Medicine Auckland City Hospital

High Risk Patients

For Sepsis

Post op / post procedure / post trauma Post splenectomy (encapsulated organisms) Cancer Transplant / immune supressed Alcoholic / Malnourished Genetic predisposition (e.g. meningococcus) Delayed appropriate antibiotics Yeasts and Enterococcus Site Cultural or religious impediment to treatment

For Dying

For Both

Department of Emergency Medicine Auckland City Hospital

Case 1 54yr Samoan male

24 hr Fever and delirium, Arrive 1300hr Initial Obs

HR 162, RR 30, sats 95% on 15l, BP 116/82, GCS 13/15 Migratory abdominal pain and fever 1/7

History

Examination

GCS 15, CNS, CVS, RS, GIT normal 160kg

Department of Emergency Medicine Auckland City Hospital

Differential Diagnosis (this list is not exhaustive)

Pancreatitis Ischeamic Gut Hypovolaemic shock

GI bleed / AAA rupture / ectopic / dehydration AMI / Myocarditis / Tamponade

Cardiogenic shock

PE Toxic Shock Syndromes

Staph Aureus Group A Strep

Addisonian crisis (note relative adrenocorticoid insufficiency in many septic patients) Thyroid Storm Toxidromes

Anticholinergic / serotoninergic

Department of Emergency Medicine Auckland City Hospital

Investigations
Basic
WBC Platelets Coags Renal function Glucose Albumin LFT ABG

Specific ?Source
Urine CxR Blood Cultures x 2 LP Aspirate Biopsy

May all be normal early on!

Department of Emergency Medicine Auckland City Hospital

Treatment
Specific

Antibiotics
Empiric based on source Know local pathogens Use the RMO guidelines / pharmacy handbook for best guess treatment Ideal to get cultures 1st but do not delay antibiotics

Surgery
Get the pus out! All of it! Early definitive care will improve survival

Department of Emergency Medicine Auckland City Hospital

Treatment
Supportive

Oxygenate / Ventilate (6ml/kg) Volume

Will need more than maintenance + replace losses with like fluid Colloid v Chrystalloid (SAFE trial awaited know the results!)

Inotropes
Noradrenalin is inotrope of choice, dopamine next

Early ICU referral

Department of Emergency Medicine Auckland City Hospital

Treatment
Supportive

Electrolyte homeostasis
THAM for pH <7.2 1-2mL / kg over 20min

Address co-morbidities
-Blocker & reduced inotropy DM / COAD Alcoholism / malnutrition / steroids Stop nephrotoxins (NSAIDs)

Early ICU referral

Department of Emergency Medicine Auckland City Hospital

Case 1 54yr Samoan male

Investigations

FBC, U and E, BC, MSU ABG IV Fluids

3l 0.9% Saline in 1.5 hours 1l Gelofusin in 1.5hrs

Treatment

IDUC Antibiotics
Gentamicin 320mg, Augmentin 1.2gm

Past History

April 2003 Left ureteric stone, 6mm Referred urology, discharge next day GP FU for US

Department of Emergency Medicine Auckland City Hospital

Case 1 54yr Samoan male

Results

Urine Dip: 500wbc, no nitirites, 200rbc FBC: wcc 4.67, pmn 3.85 (0.47bands) plt 177 Coag: Inr 1.1, Aptt 26, fibrinogen >7g/L U and E: Na 132, K 4.6, U 10.6, C 0.26 CRP 301.9 ABG: pH 7.36, po2 23, pco2 5.3, hco3 22, be -2.7 Lactate: 3.0 CXR

Department of Emergency Medicine Auckland City Hospital

Case 1 54yr Samoan male

Progress 15:10 hours

Urology referral (accepted) DCCM referral (declined) Renal imaging booked : CT 1 2 Progressively hypotensive 55mL urine over 7 hours

Declined all treatment

Department of Emergency Medicine Auckland City Hospital

Case 2 59 Male
29/10 Back pain, lifting fridge
Temp 37.3, HR 60 BP 130/60 Tender lumbar area with slight reduction SLR / R leg power PR normal Rx Analgesia, mobilised, discharged home

1/11

Represents 1400
Was getting better then worse again on mobilising Temp 35.8, HR 112 BP 150/80 Asleep when reviewed Findings as above Treated with analgesia, handed over Kept overnight Urine test done

Department of Emergency Medicine Auckland City Hospital

Case 2 59 Male
Urine: Trace blood +ve nitrites LFT: because patient thought he was jaundiced Bili 23, GGT 167, ALP 157 (40-120) AST 60 (< 40), ALT 72 (< 45) U and E: Na 131. K 3.1, U8.4, C0.09 FBC: Normal (lympho 0.88) Reviewed: Mobilising
Discharged with GP Follow up urine
Department of Emergency Medicine Auckland City Hospital

Case 2 59 Male
2/11/03 Self presented to White Cross

Temp 38.8c, GP rang lab Staph Aureus Referred medical ?pyelonephritis ?Discitis BC done

Progress

S/B med reg, Rx Flucloxacillin, stop NSAID

Delirium / L elbow bursitis MRI: 4/11/03 L2-3 discitis, L psoas abscess, epidural collection - decided not for drainage Discharge with ongoing PICC antibiotics 6 weeks

Department of Emergency Medicine Auckland City Hospital

Local Susceptibilities
There are current hospital recommendations based on local susceptibilities and presumed site of infection on the intranet USE THEM! Look under Pharmacy, antimicrobial guidelines, best guess therapy

Department of Emergency Medicine Auckland City Hospital

Department of Emergency Medicine Amoxycillin Clavulanic Acid Nitrofurantoin Norfloxacin Cefuroxime Ceftriaxone Gentamicin Aztreonam Trimethoprim / Sulfamethoxazole Auckland City Hospital

Case 1 54yr Samoan male

Microbiology results

Urine WCC >1000: RCC 310 million/L Bacteria : Present COLONY COUNT : 10 to 100 million/L CULTURE Mixed growth predominantly: (1) E. coli (1) (1) Amoxycillin R Cephalothin S Cefuroxime S Trimethoprim R Gentamicin S Cotrimoxazole R Norfloxacin S Amoxycillin/clav. S Nitrofurantoin S PERIPHERAL BLOOD CULTURE (1) E. coli (1) (1) Amoxycillin R Cephalothin S Cefuroxime S Ceftriaxone S Ceftazidime S Aztreonam S Trimethoprim R Gentamicin S Amikacin S Cotrimoxazole R Norfloxacin S Ciprofloxacin S Amoxycillin/clav. S Ticarcillin/clav. S Meropenem S Nitrofurantoin S

Department of Emergency Medicine Auckland City Hospital

Trimethoprim Tetracyclines Erythromycin Flucloxacillin Gentamicin Amoxycillin Penicillin Sulfamethoxazole

Department of Emergency Medicine Auckland City Hospital

Case 2 59 Male
URINE MICROSCOPY WCC 170 RCC 30 Epithel. cells <10 million/L Bacteria Present Granular casts 2 million/L CHEMISTRY Protein : Moderate amount COLONY COUNT : > 100 million/L CULTURE (1) Staphylococcus aureus (1) (1) Penicillin R Flucloxacillin S Cotrimoxazole S Doxycycline S Nitrofurantoin S Trimethoprim S PERIPHERAL BLOOD CULTURE (1) Staphylococcus aureus (1) (1) Penicillin R Erythromycin S Flucloxacillin S Doxycycline S
Department of Emergency Medicine Auckland City Hospital

Metronidazole Clindamycin Augmentin

Department of Emergency Medicine Auckland City Hospital

Department of Emergency Medicine Auckland City Hospital

Amphotericin

Local Organisms 1999-2000

ED / AAU / DCCM Positive BC 18/12, n=428
80 70 60 50

Pathogens
E.Coli S Aureus S Pneumoniae Viridans Strep Klebsiella N Men S Pyo E Cloacae

Number

40 30 20 10 0
vs M IC S P KL E C B O RS P N M EN E PR U O PS AS B EC LO SP YO PA C N PA E ST R AS P M R SA

Department of Emergency Medicine Auckland City Hospital

Organsim

IL st yp H FL U KO XY AC IS P PM I SA R G B

PI N S

EC

SE

SA

SF

PN

SM

Local Organisms
Approx 45-55% positive ED BC are skin organism contaminants Similar across the hospital This is approx 5% all BC done Always get at least 2 blood cultures

Help sort out ?contaminants

Department of Emergency Medicine Auckland City Hospital

Case 1 54yr Samoan male

Subsequently declared incompetent by pyschiatry, then consented to treatment

Nephrostomy 21:30 DCCM admission (3 days)

Noradrenalin CPAP (OSA) Creatinine 0.10

Discharged 2/12/03
Department of Emergency Medicine Auckland City Hospital

Local Outcomes
Mortality from sepsis varies (Age, co-morbidity, illness severity) DCCM data Auckland Hospital

5-15% for meningitis / brain abscess / pid 20-35% for pneumonia / uti / abdominal 45-50% for mediastinum / joints Data varies from other hospitals
? Due to Policies of DCCM for example

Early tracheostomy Admission criteria

Department of Emergency Medicine Auckland City Hospital

Novel Therapies
Steroids
JAMA. 2002 Aug 21;288(7):862-71

Many (>50%) septic patients have relative adrenocortical insufficiency. Physiological hydrocortisone improves mortality in this group (63% 53%, p=0.02 in this study, n=229) Antiinflammatory

Department of Emergency Medicine Auckland City Hospital

Novel Therapies
Activated Protein C (Drotrecogin )
N Engl J Med. 2001 Mar 8;344(10):699-709

Antithrombotic, antiinflammatory, profibrinolytic 1690 patients, Mortality 30.8% 24.7% p<0.01 Increased bleeding 2% 3.5% p=0.06

Caution in meningococcal sepsis / trauma / ICH / pregnant! $17181 / patient Consensus in NZ is restricted last resort use in selected ICU patients

Department of Emergency Medicine Auckland City Hospital

Novel Therapies
Tight glucose control with insulin
N Engl J Med. 2001 Nov 8;345(19):1359-67.

Mortality reduction 84.6% (p<0.04) all icu patients Biggest reductions in severe sepsis / long stayers Also reduced bacteraemic episodes / icu neuropathy Aim 4.4-6.1mmol/L
Department of Emergency Medicine Auckland City Hospital

Novel Therapies
rBacteriocidal/Permeability-increasing protein

In neutrophil granules Binds to and inactivates endotoxin

Lancet. 2000 Sep 16;356(9234):961-7.

393 Children with clinical meningococcaemia Mortality 9.9% 7.4% p=0.48 Amputations 7.4% 3.6%, p=0.067 Better functional outcome 66.3% 77.3% p=0.019
Department of Emergency Medicine Auckland City Hospital

Reducing mortality in sepsis: new directions Critical Care 2002, 6(Suppl 3):S1-S18 (http://ccforum.com/content/6/S3/S1 )
This is highly recommended reading, concise reviews of

Novel Therapies Summary

Low tidal volume ventilation Early goal directed therapy Drotrecogin alfa (activated) Moderate dose corticosteroids Tight control of blood sugar

Department of Emergency Medicine Auckland City Hospital

Novel Therapies
NAC Crit. Care. Med. 2003 31 (11) 2574-78

Nuclear factor-B controls expression inflammatory mediators NAC inhibits NFKB in vitro Pilot trial
20 patients, randomised 72 hrs NAC or placebo IL-8 suppressed (may be implicated in lung injury) Recommend larger human trials

Department of Emergency Medicine Auckland City Hospital

Summary
Sepsis may be obvious or subtle early There is a high mortality and morbidity Have a high index of suspicion Know local organisms / susceptibilities Take appropriate cultures Treat early and aggressively Investigate early and aggressively Refer early and aggressively Be aware of new developments
Department of Emergency Medicine Auckland City Hospital

Antimicrobial Therapy
http://ahsl85_gl/FormularyGuide/ Best Guess

Department of Emergency Medicine Auckland City Hospital

More References
Streat S Orientation Lectures for Medical Staff DCCM 12/1/2004 This hospitals approach Bone RC Chest 101: 1644, 1992 (Definitions) Vincent JL Crit Care med 1997 25(2) 372-74 Dear SIRS -editorial Angus DC Crit Care med 2001 29 (suppl) 7 s109-s116 epidemiology Klinzing S Crit Care med 2003 31 (11) 2626-50 inotropes

Department of Emergency Medicine Auckland City Hospital