3 SEPTIC SHOCK Multi-organ failure Infection SIRS Sepsis COMPLEX INTERACTIONTemp > 38.3°C or < 36°CHR > 90RR > 20 or PaCO2 < 32WCC > 12 or < 4+ other diagnostic criteriaBrain confusion, deliriumHeart SBP < 90 (> 40 decrease)Lungs acute lung injuryLiver LFTsGut ileusKidneys stop pee, CrBlood platelets, DICInfection SIRS Lactate CRTSepsis organ dysfunction , tissue hypoperfusionSevere SepsisVasopressors +/- Inotropesand more… hypotension despite adequate fluid resuscitationProinflammatory + antiinflammatory mechanismsComplex interaction between infecting pathogen and body’s inflammatory, immune and coagulation responsesSystolic BP less than 90mmHg (or fall 60mmHg)Sacrifice of perfusion to minor organs, skin, gut, kidneysTachycardia to correct systemic under-perfusionHyperventilation to improve oxygen availabilityMetabolic acidosis due to lack of oxygen (presence of lactic acid)Mental confusionSEPTIC SHOCKMulti-organ failureLevy et al SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003; 31 (4): 1250 – 56.Bone et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. CHEST 1992;101: 1644 – 55.
4 Bone et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. CHEST 1992;101: 1644 – 55.Pinsky. Septic shock. Medscape Reference: Drugs, Diseases & Procedures updated Oct 25, Available on [Accessed 29 March 2012]
8 58 year old female admitted to ICU after 1 day on the ward with respiratory failure requiring intubation. She was agitated and confused prior to intubation. HPC: 3 days of productive cough. SOB. General malaise. PMH: Hypertension, osteoarthritis, T2DM Meds: Ramipril 10 mg d, Atenolol 50 mg d, Panadol Osteo Metformin 1g nocte Prior to intubation: T 35.6°C BP 130/66 HR 98 RR 34 Results: Na 141 K 4 Ur 12.4 Cr 188 WCC 21 CXR left lower lobe consolidation
9 On ICU Day 3, she deteriorates with increased requirements for ventilatory support and profuse purulent tracheal aspirates. What further information would you require? What is the most likely cause of her deterioration? How will this affect her drug treatments?6. CXR changes, ?PCT, renal function7. VAP8. Change Abx
14 Further reading: “Surviving sepsis: going beyond the guidelines” NEW GUIDELINES 2012Dellinger et al. Surviving Sepsis Campaign: international guidelines for the management of severe sepsis and septic shock 2012.Crit Care Med 2013; 41: 580 – 637Further reading: “Surviving sepsis: going beyond the guidelines”Marik P. Annals of Intensive Care 2011; 1: 17. Available online:
15 SURVIVING SEPSIS CAMPAIGN BUNDLES Measure serum lactateBlood cultures before antibioticsBroad spectrum antibiotics30 mL/kg crystalloid for hypotension or lactate ≥ 4 mmol/LVasopressors (for hypotension despite initial fluid resuscitation) to maintain MAP ≥ 65 mmHgPersistent hypotension despite volume resuscitation (septic shock) or initial lactate ≥ 4 mmol/LMeasure central venous pressure (CVP) *controversial*Measure central venous oxygen saturation (Scvo2) *controversial*7. Re-measure lactate if initial lactate was elevatedTo be completed within 3 hours of presentation or diagnosisTo be completed within 6 hours of presentation or diagnosisBundles A "bundle" is a group of therapies for a given disease that, when implemented together, may result in better outcomes than if implemented individually. In a bundle, the individual elements included are built around best evidence-based practices. The science supporting the individual treatment strategies in a bundle is sufficiently mature such that implementation of the approach should be considered either best practice or a reasonable and generally accepted practice. The purpose of creating a bundle strategy is to clearly articulate a therapeutic framework that will function as a lever for change. We anticipate that making the Severe Sepsis Bundles standard practice will eliminate the piecemeal or chaotically applied of standards for sepsis care that characterize many clinical environments today. The Severe Sepsis Bundles have been designed with the hope to allow teams to follow the timing, sequence, and goals in the bundles, to achieve a 25 percent reduction in mortality due to severe sepsis or septic shock. Dellinger et al. Surviving Sepsis Campaign: international guidelines for the management of severe sepsis and septic shock Crit Care Med 2013; 41: 580 – 637
16 Recommendations: Initial Resuscitation and Infection Issues Initial resuscitation (first 6 hours) Goals: CVP 8-12 MAP ≥ 65 UO ≥ 0.5mL/kg/hr ScvO2 ≥ 70% normalise lactate Screening for sepsis and performance improvement Diagnosis Antimicrobial therapy Source control Infection prevention Fluid therapy Inotropic therapy Vasopressors Corticosteroids Blood product administration Renal replacement Immunoglobulins Bicarbonate (do not use..) Selenium DVT prophylaxis Mechanical ventilation (ARDS) Stress ulcer prophylaxis Sedation, analgesia, and NMB Nutrition Glucose control Setting goals of careRecommendations: Haemodynamic Support and Adjunctive TherapyRecommendations: Other Supportive Therapy of Severe Sepsis
18 But really includes all antimicrobials… ANtibiotics
19 Antibiotics Timing administer within 1 hour of diagnosis 79.9% survival rate when antibiotics administered within 1 hour.Each hour delay (over first 6 hours) 7.6% decrease in survival.Kumar et al. Critical Care Med 2006; 34 (6): 1589 – 96
20 Antibiotics Loading dose high to start with LD = V x Cp Volume of distribution (V): hydrophillic increase in sepsislipophillic increase in obeseRequired plasma concentration (Cp): MICsRenal function plays NO ROLE in calculation of loading doseMcKenzie. Antibiotic dosing in critical illness. J Antimicrob Chemother 2011; 66 Supp 2: ii25 – ii31LD = V x Cp
22 Adequate initial dosing important AntibioticsRoberts J and Lipman J. Pharmacokinetic issues for antibiotics in thecritically ill patient. Crit Care Med 2009; 37: 840 – 851.SEPSISIncreasedLeakyMulti-organcardiac outputcapillariesfailureIncreasedIncreasedDecreasedvolume ofclearanceclearancedistributionLow plasmaHigh plasmaconcentrationsconcentrationsAdequate initial dosing importantReassess and adjust
23 What initial dose would you give? VancomycinGentamicinTazocin
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