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Sepsis

Sepsis. Dr. Peter Jones Emergency Medicine Specialist. 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. Definitions. Sepsis = SIRS + Infection

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Sepsis

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  1. Sepsis Dr. Peter Jones Emergency Medicine Specialist

  2. 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

  3. 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)

  4. 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

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

  6. Dear SIRS I don’t like you...

  7. Definitions Cont.

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

  9. Case 154yr 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 • History • Migratory abdominal pain and fever 1/7 • Examination • GCS 15, CNS, CVS, RS, GIT normal • 160kg

  10. Differential Diagnosis(this list is not exhaustive) • Pancreatitis • Ischeamic Gut • Hypovolaemic shock • GI bleed / AAA rupture / ectopic / dehydration • Cardiogenic shock • AMI / Myocarditis / Tamponade • PE • Toxic Shock Syndromes • Staph Aureus • Group A Strep • Addisonian crisis (note relative adrenocorticoid insufficiency in many septic patients) • Thyroid Storm • Toxidromes • Anticholinergic / serotoninergic

  11. Basic WBC Platelets Coags Renal function Glucose Albumin LFT ABG Specific ?Source Urine CxR Blood Cultures x 2 LP Aspirate Biopsy Investigations May all be normal early on!

  12. 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 Treatment

  13. 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

  14. Treatment • Supportive • Electrolyte homeostasis • THAM for pH <7.2 1-2mL / kg over 20min • Address co-morbidities • ß-Blocker & reduced inotropy • DM / COAD • Alcoholism / malnutrition / steroids • Stop nephrotoxins (NSAIDs) • Early ICU referral

  15. Case 154yr Samoan male • Investigations • FBC, U and E, BC, MSU • ABG • Treatment • IV Fluids • 3l 0.9% Saline in 1.5 hours • 1l Gelofusin in 1.5hrs • IDUC • Antibiotics • Gentamicin 320mg, Augmentin 1.2gm • Past History • April 2003 Left ureteric stone, 6mm • Referred urology, discharge next day “GP FU” for US

  16. Case 154yr 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

  17. Case 154yr Samoan male • Progress 15:10 hours • Urology referral (accepted) • DCCM referral (declined) • Renal imaging booked : CT 12 • Progressively hypotensive • 55mL urine over 7 hours • Declined all treatment

  18. Case 259 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

  19. Case 259 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

  20. Case 259 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

  21. 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

  22. Amoxycillin / Clavulanic Acid Cefuroxime Ceftriaxone Gentamicin Norfloxacin Nitrofurantoin Aztreonam Trimethoprim / Sulfamethoxazole

  23. Case 154yr 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

  24. Trimethoprim Sulfamethoxazole Erythromycin Flucloxacillin Gentamicin Penicillin Tetracyclines Amoxycillin

  25. Case 259 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

  26. Metronidazole Augmentin Clindamycin

  27. Amphotericin

  28. Local Organisms 1999-2000 Pathogens E.Coli S Aureus S Pneumoniae Viridans Strep Klebsiella N Men S Pyo E Cloacae

  29. 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

  30. Case 154yr 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

  31. 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

  32. 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

  33. Novel Therapies • Activated Protein C (Drotrecogin α) 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

  34. Novel Therapies • Tight glucose control with insulin N Engl J Med. 2001 Nov 8;345(19):1359-67. • Mortality reduction 8→4.6% (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

  35. 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

  36. Novel TherapiesSummary Reducing mortality in sepsis: new directionsCritical Care 2002, 6(Suppl 3):S1-S18 (http://ccforum.com/content/6/S3/S1 ) • This is highly recommended reading, concise reviews of • Low tidal volume ventilation • Early goal directed therapy • Drotrecogin alfa (activated) • Moderate dose corticosteroids • Tight control of blood sugar

  37. Novel Therapies • NAC Crit. Care. Med. 2003 31 (11) 2574-78 • Nuclear factor-κB 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

  38. 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

  39. Antimicrobial Therapy • http://ahsl85_gl/FormularyGuide/ • Best Guess

  40. More References • Streat S Orientation Lectures for Medical Staff DCCM 12/1/2004 – This hospital’s 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

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