13. [Infeksi Tropis] Sepsis - Dr. Budi Riyanto

Kuliah Sepsis Septik Syok November 2014 Dr.Budi Riyanto,MSc,SpPD,KPTI

INFECTION AND SEPSIS • Surrounded by pathogens • Infection is the exception • Protective from infection – Physical barriers – Chemical barriers – Immunological function

Physical and Chemical Barriers to Infection • Skin – stronger in hands and feet – sebaceous secretions lower pH

• Mucous membranes – ciliary function – mucous barrier – acid mileu in stomach

Immune Defense • Humoral defense – antibodies – complement

• Cellular defense • Cytokines – potential for deleterious effects

Interaction of mechanisms

Breakdown of Host Defense • Physical, chemical and immunological breakdown -act synergistically e.g. patient with – diabetes – immunosuppresion – surgery

• Potential for deleterious effects

Infection Manifestation • Local signs – pain,redness,swelling, warmth loss of function

• Systemic signs – Fever, somnolence, confusion, ileus, hypotension

• Lab tests – TW,polymorphs, Cultures

• Non infective- causes may manifest as infection

Sepsis and Septic Shock

Sepsis and Septic Shock

 Definitions  Epidemiology  Pathogenesis  Principles of management Budi Riyanto workshop PIT PAPDI 2009

Definitions  Infection: microbial phenomenon characterised by an inflammatory response to the presence of micro organisms or the invasion of normally sterile host tissue by these organisms  Bacteraemia: the presence of bacteria in the bloodstream  Septicaemia: no longer used ACCP/SCCM Consensus Conference: Bone et al, Chest 1992 101:1644

Definitions • Sepsis: systemic response to infection manifested by ≥ 2 of: – – – –

Temp > 38oC or < 36oC HR > 90 bpm RR > 20 bpm or PaCO2 < 32 mmHg WBC > 12 x 109/L, < 4 x 109/L or >10% band form

• Septic shock: sepsis with hypotension despite adequate fluid resuscitation, with perfusion abnormalities that could include, but are not limited to, lactic acidosis, oliguria, and/or acute mental status.

ACCP/SCCM Consensus Conference: Bone et al, Chest 1992 101:1644 Budi Riyanto workshop PIT PAPDI 2009

SIRS and Sepsis  SIRS: Systemic Inflammatory Response Syndrome  Fever, leucocytosis, organ failure  Recognises difficulty of always identifying infection, but…  As a result, high sensitivity but low specificity Budi Riyanto workshop PIT PAPDI 2009

Parasite

Virus

Infection

Fungus

Severe Sepsis shock

Bacteria

BSI

Adapted from SCCM ACCP Consensus Guidelines

SIRS

Sepsis

Severe SIRS Trauma

Burns Budi Riyanto workshop PIT PAPDI 2009

Budi Riyanto workshop PIT PAPDI 2009

Sepsis and septic shock Bacterial infection Excessive host response

Host factors lead to cellular damage Organ damage Death Budi Riyanto workshop PIT PAPDI 2009

Cohen, Nature: 2002 420:885

Management of Sepsis • • • • •

Recognition Supportive care Source control Antibiotics Specific (adjunctive) therapy Budi Riyanto workshop PIT PAPDI 2009

Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock

Dellinger RP, Carlet JM, Masur H, et al. for the Surviving Sepsis Campaign Management Guidelines Committee. Crit Care Med 2004; 32:858-873.

Initial Resuscitation 

Resuscitation should begin as soon as severe sepsis or sepsis induced tissue hypoperfusion is recognized



Elevated Serum lactate identifies tissue hypoperfusion in patients at risk who are not hypotensive



Goals of therapy within first 6 hours are -

Grade B

Central Venous Pressure 8-12 mm Hg (12-15 in ventilator pts) Mean arterial pressure > 65 mm Hg Urine output > 0.5 mL/kg/hr ScvO2 or SvO2 ≥ 70%; if not achieved with fluid resuscitation during first 6 hours: - Transfuse PRBC to hematocrit > 30% and/or - Administer dobutamine (max 20 mcg/kg/min) to goal Rivers E. N Engl J Med 2001;345:1368-77.

Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

Surviving Sepsis Campaign Guidelines

Early Goal-Directed Therapy Results 28-day Mortality 60 50

49.2%

40

P = 0.01* 33.3%

30 20

10 0

Standard Therapy EGDT n=133 n=130 *Key difference was in sudden CV collapse, not MODS Rivers E. N Engl J Med 2001;345:1368-77.

Diagnosis •

• •

Before the initiation of antimicrobial therapy, at least two blood cultures should be obtained Grade D • At least one drawn percutaneously • At least one drawn through each vascular access device if inserted longer than 48 hours Other cultures such as urine, cerebrospinal fluid, wounds, Grade D respiratory secretions or other body fluids should be obtained as the clinical situation dictates Other diagnostic studies such as imaging and sampling should be performed promptly to determine the source and causative organism of the infection Grade E • may be limited by patient stability

Weinstein MP. Rev Infect Dis 1983;5:35-53 Blot F. J Clin Microbiol 1999; 36: 105-109.

Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

Antibiotic Therapy •

Start intravenous antibiotic therapy within the first hour of recognition of severe sepsis after obtaining appropriate cultures

•

Empirical choice of antimicrobials should include one or more drugs with activity against likely pathogens, both bacterial or fungal – Penetrate presumed source of infection – Guided by susceptibility patterns in the community and hospital – Continue broad spectrum therapy until the causative organism and its susceptibilities are defined Kreger BE. Am J Med 1980;68:344-355. Ibrahim EH. Chest 2000;118:146-155. Hatala R. Ann Intern Med 1996;124-717-725. Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

Grade E

Grade D

Antibiotic Therapy • Reassess after 48-72 hours to narrow the spectrum of antibiotic therapy

Grade E

• Duration of therapy should typically be 7-10 days and guided by clinical response

Grade E

• Some experts prefer combination therapy for Pseudomonas infections or neutropenic patients • Stop antimicrobials promptly if clinical syndrome is determined to be noninfectious

Grade E

Grade E

Ali MZ. Clin Infect Dis 1997;24:796-809 Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

Source Control •

Evaluate patients for focus of infection amenable to source control measures • • • •

•

Grade E

Drainage of an abscess or local focus of infection Debridement of infected necrotic tissue Removal of a potentially infected device Definitive control of a source of ongoing microbial contamination

Source control methods must weigh benefits and risks of the specific intervention

Grade E

Jimenez MF. Intensive Care Med 2001;27:S49-S62. Bufalari A. Acta Chir Belg 1996;96:197-200. Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

Source Control (cont) •

Once a focus of infection has been identified, source control should be implemented as soon as possible following initial resuscitation

Grade E

• Especially important for patients with necrotizing soft tissue infection or intestinal ischemia

•

If intravascular access devices are suspected to be the source of infection, remove them promptly after establishing other vascular access

Grade E

• It may be reasonable to leave access devices in place when patients develop sepsis of unknown source, until the source of infection is determined

Moss RL. J Pediatr Surg 1996;31:1142-1146. CDC. MMWR 2002;51:1-29. Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

Fluid Therapy: Fluid Challenge • Fluid challenge in patients with suspected hypovolemia may be given • • • • •

500 - 1000 mL of crystalloids over 30 mins 300 - 500 mL of colloids over 30 mins Repeat based on response and tolerance Input is typically greater than output due to venodilation and capillary leak Most patients require continuing aggressive fluid resuscitation during the first 24 hours of management

Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

Grade E

Vasopressors •

Grade E

Initiate vasopressor therapy if appropriate fluid challenge fails to restore adequate blood pressure and organ perfusion •

•

Vasopressor therapy should also be used transiently in the face of lifethreatening hypotension, even when fluid challenge is in progress

Either norepinephrine or dopamine are first line agents to correct hypotension in septic shock • •

Grade D

Norepinephrine is more potent than dopamine and may be more effective at reversing hypotension in septic shock patients Dopamine may be particularly useful in patients with compromised systolic function but causes more tachycardia and may be more arrhythmogenic

LeDoux D. Crit Care Med 2000;28:2729-2732.

Regnier B. Intensive Care Med 1977;3:47-53.

Martin C. Chest 1993;103:1826-1831.

Martin C. Crit Care Med 2000;28:2758-2765.

DeBacker D. Crit Care Med 2003;31:1659-1667.

Hollenberg SM. Crit Care Med 1999; 27: 639-660.

Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

Vasopressors (cont) •

•

Low dose dopamine should not be used for renal protection in severe sepsis An arterial catheter should be placed as soon as practical in all patients requiring vasopressors

Grade B Grade E

• Arterial catheters provide more accurate and reproducible measurement of arterial pressure in shock states when compared to using a cuff

•

Vasopressin may be considered in refractory shock patients that are refractory to fluid resuscitation and high dose vasopressors

Grade E

• Infusion rate of 0.01-0.04 units/min in adults • May decrease stroke volume

Hollenberg SM. Crit Care Med 1999; 27:639-660. Bellomo R. Lancet 2000; 356: 2139-2143. Kellum J. Crti Care Med 2001; 29: 1526-1531. Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

Inotropic Therapy •

In patients with low cardiac output despite adequate fluid resuscitation, dobutamine may be used to increase cardiac output •

•

Should be combined with vasopressor therapy in the presence of hypotension

It is not recommended to increase cardiac index to target an arbitrarily predefined elevated level •

Grade E

Grade A

Patients with severe sepsis failed to benefit from increasing oxygen delivery to supranormal levels by use of dobutamine

Gattinoni L. N Eng J Med 1995;333:1025-1032. Hayes MA. N Eng J Med 1994;330:1717-1722.

Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

Steroids • Intravenous corticosteroids are recommended in patients with septic shock who require vasopressor therapy to maintain blood pressure

Grade C

• Administer intravenous hydrocortisone 200-300 mg/day for 7 days in three or four divided doses or by continuous infusion • Shown to reduce mortality rate in patients with relative adrenal insufficiency Annane, D. JAMA, 2002; 288 (7): 868

Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

THANK YOU