SepsisIan Turner

SepsisWhat it isWhat worksWhat doesn’tWhat’s next

Severe Sepsis and Septic Shock. N Engl J Med. 2013 Aug;369(9):840-51.

Language

Sepsis

Severe sepsis

Septic shock

Severity

More organ systems = more badness

~20% increase in mortality with each failing organ

6 major systems that fail

CVS : Resp : Renal : Hepatic : CNS : Haem

Australian Stats2000: 35% mortality

2012: 18.4% mortality

Sites: 50.3% pulmonary19.3% intra-abdominal

Mortality Related to Severe Sepsis and Septic Shock Among Critically Ill Patient in Australia and New Zealand. JAMA. 2014 Apr;311(13):1308-1316

Adult-population Incidence of Severe Sepsis in Australia and New Zealand Intensive Care Units. Intensive Care Med. 2004 Apr;30(4):589-96.

Emergency Role

We treat these patients

We are sometimes looking after them for longer

Text

Sepsis Six Pack

Antibiotics(+ airway)BroadCultureAvoid delayDe-escalateDuration of Hypotension Before Initiation of Effective Antimicrobial Therapy is the Critical Determinant of Survival in Human Septic Shock. CCM 2006 Jun;34(6): 1589-96

one

BreathingLow tidal volumesModest fluid resuscitationVentilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for ALI and the ARDS. N Enlg J Med. 2000; 342:1301-1308.Comparison of Two Fluid-management Strategies in Acute Lung Injury. N Enlg J Med. 2006 Jun;354(24):2564-75.

two

CirculationEnd-pointsEarly goal-directed therapyFluid choicesVasopressor choices

three

CirculationEnd-points:CVPMAPUO

threeLactateScvO2

CirculationEarly goal-directed therapy2001: 30.5% vs 46.5% mortality2014/15: No difference, lower mortalities (~20-29%)

Early Goal-directed Therapy in the Treatment of Severe Sepsis and Septic Shock. N Engl J Med. 2001 Nov;345(19):1368-77A Randomised Trial of Protocol-based Care for Early Septic Shock. N Engl J Med. 2014 May;370(18):1683-93Goal-directed Resuscitation for Patients with Early Septic Shock. N Engl J Med. 2014 Oct;371:1496-1506Trial of Early, Goal-Directed Resuscitation for Septic Shock. N Engl J Med. 2014 Apr;372:1301-1311

three

CirculationFluid choicesConflicting evidenceToo much = bad lungsToo little = reliance on vasopressorsAfrican experienceCrystalloid or colloidNo starches

Mortality After Fluid Bolus in African Children with Severe Infection. N Engl J Med 2011;364:2483-2495.A Comparison of Albumin and Saline for Fluid Resuscitation in the ICU. N Engl J Med. 2004 May;350(22):2247-56.Hydroxyethyl Starch 130/0.42 Versus Ringer’s Acetate in Severe Sepsis. N Engl J Med. 2012 Jul;367(2):124-34.Association of Hydroxyethyl Starch Administration with Mortality and Acute Kidney Injury in Critically Ill Patients Requiring Volume Resuscitation: a Systematic Review and Meta-analysis. JAMA. 2013 Feb;309(7):678-88.

three

CirculationVasopressor choicesNoradrenaline then maybe vasopressin

Comparison of Dopamine and Norepinephrine in the Treatment of Shock. N Engl J Med. 2010 Mar;362(9):779-89.Vasopressin Versus Norepinephrine Infusion in Patients with Septic Shock. N Engl J Med. 2008 Feb;358(9):877-87.

three

CirculationYou can start noradrenaline peripherallyArms obs

Central or Peripheral Catheters for Initial Venous Access of ICU Patient: a RCT. Crit Care Med 2013 Sep;41(9):2108-15.

three

DrugsInsulinCorticosteroidsActivated Protein C

four

DrugsInsulinTight control has been debunkedAim to keep <10mmol/LIntensive Insulin Therapy in Critically Ill Patients. N Engl J Med. 2001 Nov;345(19):1359-67.Intensive Versus Conventional Glucose Control in Critically Ill Patients. N Engl J Med. 2009 Mar;360(13):1283-97.

four

DrugsCorticosteroidsOften given when noradrenaline requirements are high (>20mcg/min)

Effect of Treatment with Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients with Septic Shock. JAMA. 2002 Aug;288(7):862-71.Hydrocortisone Therapy for Patients with Septic Shock. N ENGL J Med. 2008 Jan;358(2):111-24.

four

DrugsActivated Protein CAnti-inflammatoryAnti-thromboticPro-fibrinolytic2001: 24.7% vs 30.8% mortality

Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis. N Engl J Med. 2001 Mar;344(10):699-709.

four

DrugsActivated Protein C2012No mortality benefit at 28 or 90 days

Drotrecogin Alfa (Activated) in Adults with Septic Shock. N Engl J Med. 2012 May;366(22):2055-64.

four

Source controlClinicallyImagingDon’t delay ABs

five

Source controlIntervene within first 12 hours of diagnosis being madeThe least physiologically insulting interventionSurviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012. Crit Care Med. 2013 Feb;41(2):580-637.

five

SupportiveHead-upSedation and analgesiaDVT prophylaxisStress ulcer prophylaxisNutritionCare goals

six

SummaryWe are getting betterRecognise earlyGive fluid but not too much2014 trilogy of sepsis trialsRemember the 20% rule-of-thumb when talking to patient and familiesCarry a six-pack with you

Case73 F presents to you 8-bed rural ED

3/7 worsening abdo pain. Now vomiting with shakes and chills.

PHx – stage II NHL (completed 4th cycle of 4 of CHOP 1/52 ago), managed in the city. HPT. Hyperchol.

Meds – perindopril/HCT, metoprolol, atorvastatin

Allergies – penicillin (“whole body swelling”)

SHx – lives with husband, independent

O/E – in pain, 38.1C, 92/60, HR 92, SaO2 91%, RR 23, GCS 15, lower zone creps, RUQ tenderness, with positive Murphy’s

Red FlagsAge + abdo painImmunosuppressedAbnormal vitalsMedications masking vitalsLocation

Working Diagnosis?

Sepsis – probably severeSource – likely intra-abdominalPossible pulmonary component

Early Decisions

Stabilisation – how?Best location for treatment and ongoing careNeed for transfer – when, and by who?

StabilisationAttend to vitalsMonitoring – how extensive?IV access and fluids – how much?AnalgesiaAntiemeticsAntibiotics – choice?

InvestigationsVBG

pH 7.18CO2 39HCO3 14Na 132K 5.4Cl 99Glucose 7.1Lactate 4.1

Investigations

FBEHb 95WCC 8.1Plt 89

UECUr 16.8Cr 169

Investigations

LFTBili 26ALP 198GGT 154ALT 31AST 24TP 77Alb 34Lipase 58

Investigations

CoagsINR 1.6APTT 39Fibrinogen 1.1

Progress

Following 1.5L crystalloid, IV Abs, analgesia

HR 95, BP 84/60, SaO2 95% on 8L, RR 22

Next steps?

Next Steps

Maybe more fluid

Vasopressors

More monitoring

Do we need to control ventilation and oxygenation?

Source control

ProgressAnother 500mL crystalloid

Noradrenaline 8mcg/min

BP 101/65 (MAP 77), HR 90, SaO2 95% on 8L, UO 32mL/hr

Remains stable

Accepted for admission at regional centre ICU

Six PackEmpirical then adjusted ABs

Invasive ventilation not required (yet)

Fluids and vasopressors

Fancy drugs – no

Source control – yes, but needs transport

Supportive care