SEPSIS AND SEPTIC SHOCK.pptx

For surgical residents presentation

1. SEPSIS AND SEPTIC SHOCK Dr. Olofin K. E Dept. Of Surgery Maitama District Hospital

2. OUTLINE Introduction Aetiology Risk factors Pathogenesis Clinical features Investigation Treatment Complications Prognosis Prevention Future trends Conclusion References

3. INTRODUCTION DEFINATION OF TERMS : Bacteremia : transient invasion of circulation by bacteria Infection: 100,000/g of tissue or per milliliter of exudates Septicemia: prolonged presence of bacteria in the blood accompanied by systemic reaction ( this term is currently not in use)

4. SIRS (systemic inflammatory response syndrome ) American College of chest physicians and critical care in 1991 It is a syndrome characterized by the presence of two or more of the following clinical criteria : Temperature(core ) >38°C or<36°C Heart rate >90beats/min Respiratory rate >20b/min or PaC02 <32mmHg WBC >12000cells/ml or <4000cells/ml or >10% immature band forms.

5. Sepsis: When SIRS is known or suspected to arise from infection the patient is said to have sepsis SEPSIS = Infection + SIRS “ Sepsis is a deregulated host response to a severe infection resulting in some degree of organ dysfunction”

6. Diagnostic Criteria for Sepsis Infection, documented or suspected, and some of the following : General variables Fever (> 38.3°C) Hypothermia (core temperature < 36°C) Heart rate > 90/min–1 or more than two sd above the normal value for age Tachypnea Altered mental status Significant edema or positive fluid balance (> 20 mL/kg over 24 hr ) Hyperglycemia (plasma glucose > 140 mg/ dL or 7.7 mmol /L) in the absence of diabetes

7. Inflammatory variables Leukocytosis (WBC count > 12,000 μ L–1) Leukopenia (WBC count < 4000 μL –1) Normal WBC count with greater than 10% immature forms Plasma C-reactive protein more than two sd above the normal value ( < 10mg/L) Plasma procalcitonin more than two sd above the normal value ( < 0.15ng/ml) Hemodynamic variables Arterial hypotension (SBP < 90 mm Hg, MAP < 70 mm Hg, or an SBP decrease > 40 mm Hg in adults.

8. Organ dysfunction variables Arterial hypoxemia ( PaO 2 /FiO 2 < 300) Acute oliguria (urine output < 0.5 mL/kg/ hr for at least 2 hrs despite adequate fluid resuscitation) Creatinine increase > 0.5 mg/ dL or 44.2 μmol /L Coagulation abnormalities (INR > 1.5 or aPTT > 60 s) I leus (absent bowel sounds) Thrombocytopenia (platelet count < 100,000 μL –1) Hyperbilirubinemia (plasma total bilirubin > 4 mg/ dL or 70 μ mol /L )

9. Tissue perfusion variables Hyperlactatemia (> 1 mmol /L) Decreased capillary refill or mottling

10. Diagnostic criteria for sepsis in the pediatric population S igns and symptoms of inflammation plus infection hyper- or hypothermia (rectal temperature >38.5° or < 35°C ), T achycardia (may be absent in hypothermic patients) A t least one of the following indications of altered organ function: altered mental status , hypoxemia , increased serum lactate level, bounding pulses.

11. Severe sepsis: sepsis associated with organ dysfunction or hypoperfusion . Sepsis-induced tissue hypoperfusion is defined as infection-induced hypotension, elevated lactate, or oliguria. Sepsis-induced hypotension is defined as a systolic blood pressure (SBP ) < 90 mm Hg or mean arterial pressure (MAP) < 70 mmHg or a SBP decrease > 40 mm Hg in the absence of other causes of hypotension . Multiple organ dysfunction syndrome (MODS) - Altered function of more than one organ system in an acutely ill patient requiring medical intervention to maintain homeostasis

12. SHOCK It is the clinical manifestation of failure of cellular function due to inadequate tissue perfusion and consequent cellular hypoxia resulting from a reduction in the effective circulating blood volume . CLASSIFICATION The most common and clinically applicable way of classifying shock is that based on the initiating mechanism HYPOVOLEMIC –reduction in effective circulating volume CARDIOGENIC- failure of cardiac pump DISTRIBUTIVE – vasodilation and peripheral pooling of blood SEPTIC ANAPHYLACTIC NEUROGENIC

13. SEPTIC SHOCK T his can be defined as severe sepsis which is not responsive to intravenous fluid infusion for resuscitation and requires inotropic or vasopressor agent to maintain systolic blood pressure

14. EPIDEMIOLOGY 4.6 cases/1000 persons in a study in US 200,000 cases annually with 50% mortality M>F(most studies M=52-66%) Extreme of ages are more affected 13th leading cause of death in US Leading cause of death in ICU

15. Where’s the infection ?

16. Infection Parasite Virus Fungus Bacteria Trauma Burns Sepsis SIRS Severe Sepsis Severe SIRS Adapted from SCCM ACCP Consensus Guidelines shock

17. AETIOLOGY BACTERIA : G ram – ve nearly 2/3, gram + ve 1/3, o f the gram – ve , E.coli is the commonest. Gram - ve Klebsiella , Entrobacter , Serratia , Proteus , Mirabillis/ Vulgari , Pseudomonas and Bacteroides

18. GRAM +VE Streptococci Staphylococci Clostridia Pneumococci Viruses , Fungi and Parasites in a few especially the immuno-compromised.

19. SOURCE Endogenous – Skin- SSI urinary tract- UTI respiratory tract- LRTI GIT- bowel surgery, perforations Exogenous. surgical instruments drapes imaging machines staff

20. RISK FACTORS Age (<10 >70years) Malnutrition Anemia Primary disease: malignancies, DM, CLD, CRF Immunosuppression, immunosuppressive agents, Necrotic tissue Hematoma Poor surgical technique Catheterization Prolong hospitalization Major surgeries, trauma, extensive burns

21. PATHOGENESIS Micro-organisms or products of tissue damage stimulates production of pro-inflammatory cytokines which in turn stimulate production of secondary mediators of inflammation in order to localize infection and limit proliferation. Anti-inflammatory and immunosuppressive cytokines such as IL-10 aided by IL-4 inhibits the activity of the pro-inflammatory cytokines to limit damage. In severe sepsis they become immunosuppressive to patient. However in poorly controlled sepsis or extensive tissue damage, there is excessive inflammatory response which is poorly regulated .

22. PATHOGENESIS cont …

23. PATHOGENESIS cont … VIRUSES PRODUCTS OF TISSUE DAMAGE BACTERIA GRAM-VE GRAM+VE LIPOPOLYSACCHARIDE LIPOTEICHOIC ACID ( ENDOTOXIN) ( PEPTIDOGLYCAN) FACTOR XII (MACROPHAGE,MONO,NEU,LYM,END) COMPLEMENT COMPONENT PRO-INFLAMMATORY CYTOKINES

24. PATHOGENESIS cont … PRO-INFAMMATORY CYTOKINE TNF- α, IL-1 β, IL-6, IL-8 CELL MEMBRANE PHOSPHOLIPID PHOSPHOLIPASE A2 ARACHIDONIC ACID CYCLO-OXYGENASE LIPO-OXYGENASE SECONDARY MEDIATORS OF INFLAMMATION PGI2 , PGE2, TXA2, LT, PAF,NO, KININS, IL-1,IL-6, OXYGEN FREE RADICALS, PROTEASES .

25. PATHOGENESIS cont … COMPLIMENT COMPONENT C3a , C5a(ANAPHYLACTOXINS) Causes release of histamine from basophil and mast cells DAMAGE OF VASODILATION ACTIVATION OF DIC VASCULAR OF MICROCIRCULTION NEUTROPHILS ENDOTHELIUM

26. PATHOGENESIS cont … FACTOR XIIa ENDOTHELIAL CELLS MACROPHAGES. KININOGEN FACTOR XI ( intrinsic pathway) TISSUE FACTOR ( extrinsic pathway) BRADYKININ COAGULATION HYPOTENSION DIC

27. PATHOGENESIS cont … Effects of secondary mediators Damage of vascular endothelium Vasodilation of microvasculature Activation of neutrophils ( aggravates endothelial damage ) Diminished force of cardiac contraction Effect of compliment component vasodilatation and increase permeability Endothelial damage C5a causes aggregation of platelet and leucocytes thereby acting as procoagulant leading to DIC These ultimately lead to peripheral pooling of blood, extravasation of fluid, hypotension, hypoxia and shock

28. PATHOGENESIS cont … Pro-inflammatory cytokines reduces plasma levels of thrombomodulin, coagulation inhibitors like protein S, protein C, and Antithrombin III . Microvascular coagulation results which worsens DIC . Hence there is acute inflammation, vasculitis, haemorrhage, capillary thrombosis and necrosis seen in several vital organs. Net effect: Maldistribution of blood flow at the microvasculature Arteriovenous shunting O2 utilization Interstitial loss effective vol. Hypovolemia Myocardial depression

29. PATHOGENESIS cont … Vasodilatation of microcirculation Damage to vascular endothelium permeability Peripheral pooling of blood Extravasation of fluid Bradykinin Cardiac depression Arteriovenous shunt

30. CLINICAL FEATURES It could be in inpatients receiving treatment for another condition EARLY STAGE ( compensated/warm shock ) Not associated with hypovolemia febrile (38.2-41°C ) Shivering and malaise warm dry and flushed skin. hyperventilation rapid bounding pulse wide pulse pressure

31. CLINICAL FEATURES cont … LATE STAGE ( decompensated / cold shock ) Hypovolemia with superimposed sepsis altered sensorium cold clammy skin Feeble pulse hypothermia , hypotension Oliguria Jaundice upper GI bleeding DIC

32. INVESTIGATION NOTE THAT RESUSCITATION TAKES PRECEDENCE OVER INVESTIGATIONS , WHICH SHOULD NOT DELAY INTERVENTION INVESTIGATION GOES HAND-IN-HAND WITH RESUSITATION 1. FBC : there is leukocytosis after initial leucopenia. Thrombocytopenia 2. Septic work up Blood culture Sputum m/c/s Urine m/c/s Wound swab m/c/s Endocervical swab m/c/s or any exudate

33. INVESTIGATION cont … Based on suspected source Chest X-ray Plain Abd X-ray Abd -pelvic USS CT Scan of various sites

34. TREATMENT Septic shock is a medical emergency that requires prompt and efficient resuscitation If possible patient should be admitted to ICU AIMS : Improve haemodynamic state Restore tissue perfusion thereby increasing O 2 delivery to tissue. Combat the bacteria and cytokines Eliminate septic focus

35. TREATMENT cont … RESUSITATION 1. VOLUME REPLACEMENT IV access with 2 wide bore cannulas are secured, samples taken for FBC, E/U/Cr , GXM Crystalloids started(readily available ): 1L in 30-45min . Then re-assess, and repeat as appropriate. Urethral catheter is passed to empty the bladder then to monitor the hourly urine output 0.5mls -1 ml/kg/ hr (30-50ml/ hr ) Central venous catheter is inserted(10-15cmH20 )

36. TREATMENT cont. After adequate fluid resuscitation or about 4L, with signs of fluid overload(basal crepitation, high CVP) and persistent hypotension. Vasopressor agents for use in septic shock: Agent Typical Intravenous Dose Range Dopamine Epinephrine Norepinephrine Phenylephrine vasopressin 6-25ug/kg/min 1-10ug/kg/min 1-30ug/kg/min 40-180ug/kg/min 0.01-0.04 units/min

37. 2 . OXYGEN ADMISTRATION In a cleared and patent airway, O2 is delivered via a face mask to increase O2 saturation. Increasing uptake and delivery to tissue. 3 . ANTIBIOTIC Antibiotics to be given based on: Efficacy Spectrum of activity Pharmacokinetics & pharmacodynamics Patterns of resistance

38. TREATMENT cont … TOXICITY COST There is no, single, “best” regimen Consider the site of the infection Consider which organisms most often cause infection at that site Choose antibiotic(s) with the appropriate spectrum After obtaining cultures, give antibiotics quickly and empirically at appropriate dose

39. TREATMENT cont … 4. STEROIDS : Inhibits conversion of membrane phospholipid to arachidonic acid hence inhibiting release of secondary mediators. Hydrocortisone 200mg daily in 4 divided doses is beneficial if given at the onset. 5 . NSAIDS : e.g. Ibuprofen inhibits the COX pathway there by PG and TBX synth. Prevent neutrophil aggregation and activation ↓ production of superoxide radicals Stabilizes lysozomal membranes enzymes

40. 6. O2 Free radical scavengers superoxide dismutase Vitamin C, allopurinol, α- tocopherol They have been shown to decrease tissue damage and MOD in septic shock if given prophylactically. 7. Glycemic control- soluble insulin (GKI) to maintain blood sugar – 80- 120mg/dl has been found to ↓ morbidity/mortality .

41. 8 . NALOXNE : it raises the blood pressure 9. PREVENTION OF FURTHER COAGULATION Antithrombin iii and C₁ -esterase inhibitor Recombinant human activated protein C inhibits thrombosis and inflammation, promotes fibrinolysis , and modulates coagulation and inflammation. 10 . SURGERY resuscitative & therapeutic If septic focus is responsible for the shock it should be dealt with as soon as possible especially if response to therapy is poor. E.g. debridement, drainage of abscess

42. MONITORING Clinical signs: Sensorium- consciousness regained, calm. Conjunctiva becomes pink venous /capillary feeling warm dry skin. Urine output (best indicator): Hourly urine output(0.5-1ml/kg /h) PR and BP : Quarterly pulse and BP Central venous pressure (10-15cmH2O) Lung and jugular veins Arterial blood gases/ pulse oximeter ( oxygen saturation :90-100%)

43. COMPLICATION ARDS ARF DIC Encephalopathy Liver failure MODS Death

44. PROGNOSIS Poor prognostic factor Advanced age Immunosuppression Infection with resistance organism, level of IL -6 Need for inotrophs for > 24hrs MODS despite treatment

45. PREVENTION Early recognition Prompt treatment of infection Meticulous surgical technique Pre-op antibiotics Aseptic technique Sterilization of surgical equipment Optimization of patient – e.g. DM

46. FUTURE TREND Monoclonal antibodies to IL-1, IL-6, TNF Clinical trials have not been rewarding . Recombinant activated protein C – inhibits Va & V iiia also TNF- ά, IL-1,IL-6 although it is associated with high risk of bleeding. Research has focused on modifying the host response to sepsis via a number of approaches , including the following: Antibodies against gram-negative endotoxin Gamma globulins

47. Monoclonal antibodies against tumor necrosis factor Blockade of eicosanoid production Blockade of interleukin (IL)–1 activity Inhibition of nitric oxide (NO) synthase These approaches have met with modest success in animal experiments, but at present, they cannot be recommended for general use in humans.

48. Surviving Sepsis Campaign It is a joint collaboration of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM ) C ommitted to reducing mortality and morbidity from sepsis and septic shock worldwide. Initiated in 2002 at the ESICM’s annual meeting with the Barcelona Declaration

49. CONCLUSION Septic shock is an emergency with high mortality even in the best centers Early recognition and energetic treatment is the key to good outcome Early detection of those at risk and prevention is the safest and cheapest way of reducing the morbidity and mortality associated with it .

50. REFERENCES Baja’s Principles and practice of surgery E. A.Badoe .et al 5th edition. Bailey and L ove’s Short Practice of Surgery, 26th Edition Surviving Sepsis Campaign; International Guidelines for Management of Severe Sepsis and Septic Shock: 2017 Sabiston textbook of surgery 18th edition PubMed.gov US national library of med. Wikipedia , encyclopedia. Septic shock Medscape e-medicine. Septic shock

51. Thank you for your attention. .