Sepsis overview. Dr. Tsang Hin Hung MBBS FHKCP FRCP

Transcription

1 Sepsis overview Dr. Tsang Hin Hung MBBS FHKCP FRCP

2 Epidemiology Sepsis, severe sepsis, septic shock Pathophysiology of sepsis Recent researches and advances From bench to bedside Sepsis bundle

3 Severe sepsis in US Today Future >750,000 cases of severe sepsis/year in the US * Sepsis Cases 1,800,000 1,600,000 1,400,000 1,200,000 1,000, , , , ,000 Severe Sepsis Cases US Population Incidence projected to increase by 1.5% per year 600, , , , , ,000 Total US Population/1, Year Angus DC. Crit Care Med. 2001;29(7):

4 Angus DC. Crit Care Med. 2001;29(7):

5 Comparable Global Epidemiology 95 cases per 100,000 2 week surveillance 206 French ICUs 95 cases per 100,000 3 month survey 23 Australian/New Zealand ICUs 51 cases per 100,000 England, Wales and Northern Ireland.

6 Comparison With Other Major Diseases Incidence of Severe Sepsis 300 Mortality of Severe Sepsis 250,000 Cases/100, CHF Severe 0 AIDS* Colon Breast Cancer Sepsis Deaths/Year 200, , ,000 50,000 0 AIDS* Breast Cancer AMI Severe Sepsis National Center for Health Statistics, American Cancer Society, *American Heart Association Angus DC et al. Crit Care Med. 2001;29(7):

7 What is Sepsis? Systemic inflammatory response syndrome Infection

8 Definition of sepsis Sepsis is considered present if infection is highly suspected or proven and two or more of the following systemic inflammatory response syndrome (SIRS) criteria are met Heart rate > 90 beats per minute (tachycardia) Body temperature < 36 C C (96.8 F) or > 38 C C (100.4 F) (hypothermia or fever) Respiratory rate > 20 breaths per minute or, on blood gas, a PaCO2 less than 32 mm Hg (4.3 kpa) ) (tachypnoea( or hypocapnoea due to hyperventilation) White blood cell count < 4000 cells/mm³ or > cells/mm³ or greater than 10% band forms (immature white blood cells).

9 Definition of sepsis Sepsis is a serious medical condition characterized by a whole-body inflammatory state (called a systemic inflammatory response syndrome or SIRS) caused by infection. Severe sepsis: sepsis + acute organ dysfunction(organ hypoperfusion) Septic shock: sepsis + refractory arterial hypotension (SBP <90mmHg)

10 Septic shock Severe sepsis Mortality Sepsis

11 Sepsis a systemic disease!!

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13 Infective agents

14 Cytokines soluble (glyco)proteins( nonimmunoglobulin in nature released by living cells of the host act nonenzymatically in picomolar to nanomolar concentrations through specific receptors to regulate host cell function.

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16 Cytokine storm

17 Cardiovascular changes in septic shock.

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20 Fluid Therapy Fluid resuscitation Colloids or crystalloids?

21 Crystalloids vs. colloids in fluid resuscitation: A systematic review. Crit Care Med 1999; 27:

22 NEJM 2004 The Saline versus Albumin Fluid Evaluation (SAFE) Study investigators 3497 patients were assigned to receive albumin and 3500 to receive saline Primary outcome: 28-day mortality

23 Kaplan-Meier Estimates of the Probability of Survival. P=0.96 for the comparison between patients assigned to receive albumin and those assigned to receive saline. NEJM 2004

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25 Which vasopressors? Noradrenaline is better than dopamine or adrenaline? Vasopressin is better?

26 Effects of Dopamine, Norepinephrine, and Epinephrine on the Splanchnic Circulation in Septic Shock Effects of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in septic shock: Which is best? Crit Care Med 2003; 31:

27 Low dose dopamine for renal protection?

28 Surviving sepsis campaign 2008

29 Use of steroid in sepsis

30 Effect of treatment with low doses hydrocortisone and fludrocortisone on mortality in patients with septic shock Annane et al, JAMA 2002

31 Hydrocortisone Therapy for Patients with Septic Shock CORTICUS NEJM 2008

32 Activated protein C

33 Mortality (%) Results: 28-Day All-Cause Mortality Primary analysis results 2-sided p-value Adjusted relative risk reduction 19.4% Increase in odds of survival 38.1% % Placebo (n-840) 24.7% Drotrecogin alfa (activated) (n=850) 6.1% absolute reduction in mortality 0 Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344:

34 Mortality (percent) Mortality and APACHE II Quartile Placebo Drotrecogin 26:33 57:49 58:48 1st (3-19) 2nd (20-24) 3rd (25-29) 4th (30-53) APACHE II Quartile *Numbers above bars indicate total deaths 118:80 Adapted from Figure 2, page S90, with permission from Bernard GR. Drotrecogin alfa (activated) (recombinant human activated protein C) for the treatment of severe sepsis. Crit Care Med 2003; 31[Suppl.]:S85-S90

35 Mortality and Numbers of Organs Failing Percent Mortality Placebo Drotrecogin Number of Organs Failing at Entry Adapted from Figure 4, page S91, with permission from Bernard GR. Drotrecogin alfa (activated) (recombinant human activated protein C) for the treatment of severe sepsis. Crit Care Med 2003; 31[Suppl.]:S85-S90

36 Recombinant Human Activated Protein C (rhapc( rhapc) High risk of death APACHE II 25 Sepsis-induced induced multiple organ failure Septic shock Sepsis induced ARDS No absolute contraindications Weigh relative contraindications

37 6 Hour Resuscitation Golden hours for sepsis resuscitation Early Identification Early Antibiotics and Cultures Early Goal Directed Therapy

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39 Early Goal Directed Therapy

40 The Importance of Early Goal-Directed Therapy for Sepsis Induced Hypoperfusion Mortality (%) 60 Standard therapy EGDT NNT to prevent 1 event (death) = 6-8 In-hospital mortality (all patients) 28-day mortality 60-day mortality Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:

41 Do not delay resuscitation pending ICU admission

42 Intensive insulin therapy

43 The Role of Intensive Insulin Therapy in the Critically Ill 100 At 12 months, intensive insulin therapy reduced mortality by 3.4% (P<0.04) In-hospital survival (%) Intensive treatment P=0.01 Conventional treatment Days after admission van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001;345:

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45 Intensive insulin therapy in medical ICU van den Berghe G, NEJM 2006

46 Multiple organ failure in sepsis Acute respiratory distress syndrome ARDS Circulatory failure Acute renal failure ARF Liver derrangement Coagulopathy Encephalopathy

47 ARDS Acute respiratory distress syndrome

48 Mechanical Ventilation of Sepsis-Induced ALI/ARDS

49 ARDSnet Mechanical Ventilation Protocol Results: Mortality % Mortality ml/kg 12 ml/kg The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000;342:

50 Renal failure in sepsis Renal replacement therapy Blood purification

51 Transfusion Strategy in the Critically Ill Hebert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999; 340:

52 Other supportive therapies in DVT prophylaxis sepsis Stress ulcer prophylaxis Sedation and weaning from ventilator..

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54 From Bench to Bedside

55 Surviving Sepsis Campaign A global program to: Evidence based guideline Implementation and education Reduce mortality rates Improve standards of care Sepsis Bundle Approach

56 6 - hour Severe Sepsis/ Septic Shock Bundle Vasopressors: Early Detection: Hypotension not Obtain serum lactate responding to fluid level. Titrate to MAP > 65 mmhg. Early Blood Cx/Antibiotics: within 3 hours of Septic shock or lactate > presentation. 4 mmol/l: CVP and ScvO 2 measured. Early EGDT: CVP maintained >8 Hypotension (SBP < 90, mmhg. MAP < 65) or lactate > 4 MAP maintain > 65 mmol/l: mmhg. initial fluid bolus ml of crystalloid (or colloid equivalent) per kg of body ScvO2<70%with CVP > 8 weight. mmhg, MAP > 65 mmhg: PRBCs if hematocrit < 30%. Inotropes.

57 24 - hour Severe Sepsis and Septic Shock Bundle Glucose control: maintained on average <150 mg/dl (8.3 mmol/l) Drotrecogin alfa (activated): administered in high risk patients and without contraindication Steroids: for septic shock requiring continued use of vasopressors for equal to or greater than 6 hours. Lung protective strategy: Maintain plateau pressures < 30 cm H 2 O, tidal volume 6-6 8ml/kg and optimal PEEP

58 Conclusion Severe sepsis is a common, expensive and frequently fatal condition Growing problem and leading cause of death A systemic disease Sepsis bundle improve standards of care and reduce mortality rate

59 Thank you

60 Mechanical Ventilation of Sepsis-Induced ALI/ARDS Reduce tidal volume over hrs to 6 ml/kg predicted body weight Maintain inspiratory plateau pressure < 30 cm H 2 0

61 Mechanical Ventilation of Sepsis-Induced ALI/ARDS Minimum PEEP Prevent end expiratory lung collapse Setting PEEP FIO2 requirement Thoracopulmonary compliance