Sirs

976 views
743 views

Published on

Published in: Education
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
976
On SlideShare
0
From Embeds
0
Number of Embeds
11
Actions
Shares
0
Downloads
41
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide
  • These clinical and laboratory markers of inflammation have all been associated with SIRS or sepsis. Procalcitonin is claimed to have reasonable diagnostic value for infection. Combinations of response markers may also be able to distinguish between sepsis and SIRS.
  • In simplified terms, sepsis can be conceptualized as a dysfunction of opposing mechanisms of coagulation/inflammation and fibrinolysis. In normal patients homeostasis is maintained because these mechanisms balance each other. Patients with severe sepsis have increased coagulation and increased inflammation. Manifestations of these include: Circulating proinflammatory mediators Endothelial injury Expression of tissue factor by monocytes and possibly a subset of endothelial cells Thrombin generation Patients with severe sepsis also have decreased fibrinolysis. Manifestations of these include: Increased levels of PAI-1 Increased levels of TAFI Carvalho AC, Freeman NJ. How coagulation defects alter outcome in sepsis: survival may depend on reversing procoagulant conditions. J Crit Illness. 1994;9:51-75. Kidokoro A, Iba T, Fukunaga M, et al. Alterations in coagulation and fibrinolysis during sepsis. Shock. 1996;5:223-8. Vervloet MG, Thijs LG, Hack CE. Derangements of coagulation and fibrinolysis in critically ill patients with sepsis and septic shock. Semin Thromb Hemost. 1998;24: 33-44.
  • Abnormalities in oxygen delivery in sepsis have been described at all levels of the circulation. The parameters that can be measured clinically (cardiac output, blood pressure) are indicative of the central circulation, but distribution between and within organs is altered. There are no reliable methods to monitor the microcirculation.
  • The result is a mismatch in oxygen delivery relative to tissue demand, similar to the mismatch that occurs in the lung between ventilation and perfusion. Factors that contribute to this mismatch include shunting (likely physiologic due to high flow rather than anatomic shunts). Decreased capillary perfusion and increased edema increase the diffusion distance for oxygen.
  • Mitochondrial injury and dysfunction has also been described, so even if oxygen delivery is adequate, the cell may not use it effectively to generate ATP. In experimental models, this can be monitored by measuring NADH or cytochrome c fluorescence.
  • Therapy that can interfere with this process has been described for each level. This combination of specific sepsis and general ICU treatment is expected to lead to better patient survival.
  • Sirs

    1. 1. Systemic Inflammatory ResponseSyndrome (SIRS) Dr. Madhu Aryal
    2. 2. SEPSIS and It’s Diseasespectrum Various stages of disease  Bacteremia  SIRS  Sepsis syndrome  Sepsis shock : early and refractory
    3. 3. Definition  Infection  Presence of microorganisms in a normally sterile site.  Bacteremia  Cultivatable bacteria in the blood stream.  Sepsis  SIRS criteria + suspected or proven infectionAmerican College of Chest Physicians/Society of Critical Care Medicine ConsensusConference Committee. Crit Care Med. 1992;20:864-874.
    4. 4. SIRS (Systemic Inflammatory Response Syndrome)  The systemic response to a wide range of stresses.  Temperature >38°C (100.4°) or <36°C (96.8°F).  Heart rate >90 beats/min.  Respiratory rate >20 breaths/min or PaCO2 <32 mmHg.  White blood cells > 12,000 cells/ml or < 4,000 cells/ml or >10% immature (band) forms.  Note  Two or more of the following must be present.  These changes should be represent acute alterations from baseline in the absence of other known cause for the abnormalities.American College of Chest Physicians/Society of Critical Care Medicine ConsensusConference Committee. Crit Care Med. 1992;20:864-874.
    5. 5. MODS (Multiple Organ Dysfunction Syndrome) multiorgan hypoperfusion Two or more of the followings:  SBP < 90 mmHg  Acute mental status change  PaO < 60 mmHg on RA (PaO /FiO < 250) 2 2 2  Increased lactic acid/acidosis  Oliguria  DIC or Platelet < 80,000 /mm3  Liver enzymes > 2 x normalAmerican College of Chest Physicians/Society of Critical Care Medicine ConsensusConference Committee. Crit Care Med. 1992;20:864-874.
    6. 6. Severe Sepsis  Sepsis with organ hypoperfusion one of the criteria of MODS  Septic Shock- Severe sepsis + Hypotension  Refractory septic Shock- shock not controlled by IV fluids and pressor agentsAmerican College of Chest Physicians/Society of Critical Care Medicine ConsensusConference Committee. Crit Care Med. 1992;20:864-874.
    7. 7. The Sepsis Continuum Severe Septic SIRS Sepsis Sepsis ShockA clinical response arising from a SIRS with a Sepsis with Refractory nonspecific insult, with presumed organ failure hypotension ≥2 of the following: or confirmed  T >38oC or <36oC infectious  HR >90 beats/min process  RR >20/min  WBC >12,000/mm3 or SIRS = systemic inflammatory <4,000/mm3 or >10% response syndrome bands Chest 1992;101:1644.
    8. 8. Mortality rate in SIRS Rangel-Frausto, et al. JAMA 273:117-123, 1995.
    9. 9. Organ Dysfunction Lungs  Adult Respiratory Distress Syndrome Kidneys  Acute Tubular Necrosis CVS  Shock CNS  Metabolic encephalopathy PNS  Critical Illness Polyneuropathy Coagulation  Disseminated Intravascular Coagulopathy GI  Gastroparesis and ileus Liver  Cholestasis Endocrine  Adrenal insufficiency Skeletal Muscle  Rhabdomyolysis Specific therapy exists
    10. 10. Response of body toinflamation Physiology  Markers of  Heart rate Inflammation  TNF  Respiration  IL-1  Fever  IL-6  Blood pressure  Procalcitonin  Cardiac output  PAF  WBC  Hyperglycemia
    11. 11. Normal Systemic Response to Infection and Injury (1) Leukocytosis Mobilizes neutrophils into the circulation Tachycardia Increases cardiac output, blood flow to injuried tissue Fever Raises core temperature; peripheral vasoconstriction shunts blood flow to injuried tissue. Occurs much more often when infection is the trigger for systemic responses Mandell et al. Principals and Practice of Infectious Diseases6th ed;906:906-926.
    12. 12. Normal Systemic Response to Infection and Injury (2) Acute-Phase Responses  Anti-infective  Increases synthesis of complement factors, microbe pattern-recognition molecules(mannose-binding lectin, LBP, CRP, CD14, Others) Haptoglobins, C-Reactive proteins, ESR Mandell et al. Principals and Practice of Infectious Diseases6th ed;906:906-926.
    13. 13. Normal Systemic Response to Infection and Injury (3) Anti-inflammatory  Releases anti-inflammatory neuroendocrine hormones (cortisol, ACTH, epinephrine, α-MSH)  Increases synthesis of proteins that help prevent inflammation within the systemic compartment  Cytokine antagonists (IL-1Ra, sTNF-Rs)  Anti-inflammatory mediators (e.g.,IL-4, IL-6, IL-6R, IL-10, IL-13, TGF-β)  Protease inhibitors (e.g.,α1-antiprotease)  Antioxidants (haptoglobin)  Reprograms circulating leukocytes (epinephrine, cortisol, PGE2, ?other) Mandell et al. Principals and Practice of Infectious Diseases6th ed;906:906-926.
    14. 14. Normal Systemic Response to Infection and Injury (4)  Procoagulant  Walls off infection, prevents systemic spread  Increases synthesis or release of fibrinogen, PAI-1, C4b  Decreases synthesis of protein C, anti-thrombin III  Metabolic  Preserves euglycemia, mobilizes fatty acids, amino acids  Epinephrine, cortisol, glucagon, cytokines  Thermoregulatory  Inhibits microbial growth  FeverMandell et al. Principals and Practice of Infectious Diseases6th ed;906:906-926.
    15. 15. Pathogenesis of sepsis andseptic shock Angus DC, et al. Crit Care Med 2001, 29:1303-1310.
    16. 16. Homeostasis Is Unbalanced in Severe SepsisCarvalho AC, Freeman NJ. J Crit Illness. 1994;9:51-75; Kidokoro A et al. Shock.1996;5:223-8; Vervloet MG et al. Semin Thromb Hemost. 1998;24:33-44.
    17. 17. Regulation of oxygen delivery Normal Abnormal Cardiac output BP=CO * SVR Cardiac Output regional distribution regional distributionIntra Organ Distribution Intra Organ Distribution Microcirculation Microcirculation QO2 = Flow * O2 content
    18. 18. Oxygen Delivery  Delivery:Demand mismatch  Diffusion limitation (edema)
    19. 19. Oxygen Consumption H+ H+ Cytc H+ H+ I Q III IVNADH + H+ H+ 1/2 O2 + H+ H2O NAD+ ADP + Pi ATP •Pyruvate Dehydrogenase (PDH) activity decreased •Decreased delivery of Acetyl CoA to TCA cycle •Mitochondrial dysfunction
    20. 20. Inflammatory Response toSepsis NEJM 2006;355:1699-1713.
    21. 21. Risk factors of sepsis aggressive oncological chemotherapy and radiation therapy use of corticosteroid and immunosuppressive therapies for organ transplants and inflammatory diseases longer lives of patients predisposed to sepsis, the elderly, diabetics, cancer patients, patients with major organ failure, and with granulocyopenia. Neonates are more likely to develop sepsis (ex. group B Streptococcal infections). increased use of invasive devices such as surgical protheses, inhalation equipment, and intravenous and urinary catheters. indiscriminate use of antimicrobial drugs that create conditions of overgrowth, colonization, and subsequent infection by aggressive, antimicrobial-resistant organisms. Angus DC, et al. Crit Care Med 2001, 29:1303-1310.
    22. 22. Patients at increased risks ofdeveloping sepsis Underlying diseases: neutropenia, solid tumors, leukemia, dysproteinemias, cirrhosis of the liver, di abetes, AIDS, serious chronic conditions. Surgery or instrumentation: catheters. Prior drug therapy: Immuno-suppressive drugs, especially with broad-spectrum antibiotics. Age: males, above 40 y; females, 20-45 y. Miscellaneous conditions: childbirth, septic abortion, trauma and widespread burns, intestinal u lceration. Angus DC, et al. Crit Care Med 2001, 29:1303-1310.
    23. 23. Source(usually an endogenous source of infection) intestinal tract oropharynx instrumentation sites contaminated inhalation therapy equipment IV fluids. Most frequent sites of infection: Lungs, abdomen, and urinary tract. Other sources include the skin/soft tissue and the CNS. Angus DC, et al. Crit Care Med 2001, 29:1303-1310.
    24. 24. Specific Infectious agents Splenectomy (traumatic or functional)  S pneumoniae, H influenzae, N meningitidis Neutropenia (<500 neutrophil/ml)  Gram-negative, including P aeruginosa, gram- positives, including S aureus  Fungi, especially Candida species Hypogammaglobulinemia (e.g.,CLL)  S pneumoniae, E coli Burns  MRSA, P aeruginosa, resistant gram-negatives MacArthur RD, et al. Mosby, 2001:3-10. Wheeler AP, et al. NEJM 1999;340:207-214. Chaowagul W, et al. J Infect Dis 1989;159:890-899.
    25. 25. Specific Infectious agents Aids  P aeuginosa (if neutropenic), S aureus, PCP pneumonia Intravascular devices  S aureus, S epidermidis Nosocomial infections  MRSA, Enterococcus species, resistant gram- negative, Candida species Septic patients in NE of Thailand  Burkholderia pseudomallei MacArthur RD, et al. Mosby, 2001:3-10. Wheeler AP, et al. NEJM 1999;340:207-214. Chaowagul W, et al. J Infect Dis 1989;159:890-899.
    26. 26. Surviving Sepsis CampaignGuidelines for Management ofSevere Sepsis and Septic Shock Dellinger RP, et al. Crit Care Med 2004; 32:858-873.
    27. 27. Case presentation 43-year-old male Flu-like symptoms for 1 day In ER  Temp 39.5  Pulse 130  Blood pressure 70/30  Respirations 32  Petechial rash  Chest, CV, Abdominal exam normal
    28. 28. Case presentation - 2 Laboratory  pH 7.29, PaO2 82, PaCO2 29 Investigations pending  Blood, urine cultures Orally intubated and placed on mechanical ventilation Central venous catheter inserted  Cefotaxime 2 g iv  Normal saline 2 litres initially, repeated Admitted to ICU
    29. 29. Case presentation - 3 In ICU:  Noradrenaline started to support blood pressure  Additional fluid (saline and pentastarch) given based on low CVP  Pulmonary artery catheter inserted to aid further hemodynamic management Despite therapy patient remained anuric  Continuous venovenous hemofiltration initiated
    30. 30. Case presentation - 4 Early gram stain on blood revealed gram negative rods Patient started on:  Hydrocortisone 100 mg iv q8h  Recombinant activated protein C 24µg/kg/hour for 96 hours  Enrolled in RCT (double-blind) of vasopressin vs norepinephrine for BP support  Enteral nutrition via nasojejunal feeding tube
    31. 31. Case Presentation - Resolution Patient gradually stabilized and improved with complete resolution of organ dysfunction over 5 days Final cultures confirmed diagnosis as meningococcemia
    32. 32. Severe Sepsis: Management of Our CaseEndothelial Dysfunction and rhAPC Microvascular Thrombosis Corticosteroids Fluids Hypoperfusion/Ischemia VasopressorsAcute Organ Dysfunction CVVHF (Severe Sepsis) Enteral nutrition Death Survival
    33. 33. Sepsis resuscitation bundle Serum lactate measured Blood cultures obtained before antibiotics administered Improve time to broad-spectrum antibiotics In the event of hypotension or lactate > 4 mmol/L (36 mg/dL)  a. Deliver an initial minimum of 20 mL/kg of crystaloid (or colloid equivalent)  b. apply vasopressors for ongoing hypotension In the event of persistent hypotension despite fluid resuscitation or lactate > 4 mmol/L (36 mg/dL)  a. achieve central venous pressure of > 8 mmHg  b. achieve central venous oxygen saturation of > 70% Hurtado FJ. et al. Crit Care Clin;2006; 22:521-9.
    34. 34. Sepsis management bundle  Fluid resuscitation  Appropriate cultures prior to antibiotic administration  Early targeted antibiotics and source control  Use of vasopressors/inotropes when fluid resuscitation optimizedSurviving Sepsis Campaign Management Guidelines Committee. Crit Care Med 2004; 32:858-873.
    35. 35. Sepsis management bundle  Evaluation for adrenal insufficiency  Stress dose corticosteroid administration  Recombinant human activated protein C (xigris) for severe sepsis  Low tidal volume mechanical ventilation for ARDS  Tight glucose controlSurviving Sepsis Campaign Management Guidelines Committee. Crit Care Med 2004; 32:858-873.
    36. 36. Infection Control  Appropriate cultures prior to antibiotic administration  Early targeted antibiotics and source controlSurviving Sepsis Campaign Management Guidelines Committee. Crit Care Med 2004; 32:858-873.
    37. 37. Antibiotic use in Sepsis (1) The drugs used depends on the source of the sepsis Community acquired pneumonia  third (ceftriaxone) or fourth (cefepime) generation cephalosporin is given with an aminoglycoside (usually gentamicin) Nosocomial pneumonia  Cefipime or Imipenem-cilastatin and an aminoglycoside Abdominal infection  Imipenem-cilastatin or Pipercillin-tazobactam and aminoglycoside Angus DC, et al. Crit Care Med 2001, 29:1303-1310.
    38. 38. Antibiotic use in Sepsis (2) Nosocomial abdominal infection  Imipenem-cilastatin and aminoglycoside or Pipercillin-tazobactam and Amphotericin B Skin/soft tissue  Vancomycin and Imipenem-cilastatin or Piperacillin- tazobactam Nosocomial skin/soft tissue  Vancomycin and Cefipime Urinary tract infection  Ciprofloxacin and aminoglycoside Angus DC, et al. Crit Care Med 2001, 29:1303-1310.
    39. 39. Antibiotic use in Sepsis (3) Nosocomial urinary tract infection: Vancomycin and Cefipime CNS infection:  Vancomycin and third generation cephalosporin or Meropenem Nosocomial CNS infection:  Meropenem and Vancomycin Drugs will change depending on the most likely cause of the patients sepsis Single drug regimens are usually only indicated when the organism causing sepsis has been identified and antibiotic sensitivity testing Angus DC, et al. Crit Care Med 2001, 29:1303-1310.
    40. 40. New Drug in Treating Severe Sepsis It is the first agent approved by the FDA effective in the treatment of severe sepsis proven to reduce mortality. Activated Protein C (Xigris) mediates many actions of body homeostasis. It is a potent agent for the:  suppression of inflammation  prevention of microvascular coagulation  reversal of impaired fibrinolysis Angus DC, et al. Crit Care Med 2001, 29:1303-1310.

    ×