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Sepsis

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sepsis

sepsis

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  • 1. by : Heba Abusaleem Abeer Alshare’
  • 2. Systemic inflammatory response syndrome (SIRS) A clinical syndrome that is a form of dysregulated inflammation. Noninfectious processes Infectious processes SEPSIS 1.Autoimmune disorder 2. Pancreatitis 3.Surgery 4.Vasculitis 5.Thromboembolism 6.burns
  • 3. • > 90 beats / minute • >38°C or <36°C. Temperat ure >20breaths /minute or PaCO2<32mm Hg Heart rate Respirator y rate leucocytes <4x109/L (<4000/mm³), >12x109/L (>12,000/mm³), or 10% band
  • 4. Infection : is the invasion of normally sterile tissue by organisms. Bacteremia : is the presence of viable bacteria in the blood. Sepsis: the clinical syndrome that results from a dysregulated inflammatory response to an infection. {the presence of infection together with systemic manifestations of infection}
  • 5. General variables :  Temperature >38.3 or <36ºC  Heart rate >90 beats/min.  Tachypnea, respiratory rate >20 breaths/min  Altered mental status  Significant edema or positive fluid balance (>20 mL/kg over 24 hours)  Hyperglycemia (plasma glucose >140 mg/dL or 7.7 mmol/L) in the absence of diabetes
  • 6. Inflammatory variables  Leukocytosis (WBC count >12,000 microL–1) or leukopenia (WBC count <4000 microL–1)  Normal WBC count with greater than 10 percent immature forms  Plasma C-reactive protein more than two standard deviations above the normal value  Plasma procalcitonin more than two standard deviations above the normal value
  • 7. Hemodynamic variables  Arterial hypotension (systolic blood pressure SBP <90 mmHg, MAP <70 mmHg, or an SBP decrease >40 mmHg in adults) Tissue perfusion variables Hyperlactatemia (>1 mmol/L)  Decreased capillary refill or mottling 
  • 8. Organ dysfunction variables        Arterial hypoxemia (arterial oxygen tension [PaO2]/fraction of inspired oxygen [FiO2] <300) Acute oliguria (urine output <0.5 mL/kg/hr for at least two hours despite adequate fluid resuscitation) Creatinine increase >0.5 mg/dL . Coagulation abnormalities (international normalized ratio [INR] >1.5 or activated partial thromboplastin time [aPTT] >60 seconds) Ileus (absent bowel sounds) Thrombocytopenia (platelet count <100,000 microL–1) Hyperbilirubinemia (plasma total bilirubin >4 mg/dL or 70 micromol/L)
  • 9. Severe sepsis : refers to sepsis-induced tissue hypoperfusion or organ dysfunction with any of the following thought to be due to the infection:  Sepsis-induced hypotension  Lactate above upper limits of laboratory normal  Urine output <0.5 mL/kg/hr for more than two hours despite adequate fluid resuscitation  Acute lung injury with PaO2/FIO2 <250 in the absence of pneumonia as infection source  Acute lung injury with PaO2/FIO2 <200 in the presence of pneumonia as infection source  Creatinine >2 mg/dL (176.8 micromol/L)  Bilirubin >2 mg/dL (34.2 micromol/L)  Platelet count <100,000 microL–1  Coagulopathy (INR >1.5) Sepsis-induced hypotension: (SBP) <90 mmHg or (MAP) <70 mmHg or a SBP decrease >40 mmHg in the absence of other causes of hypotension. Sepsis-induced tissue hypoperfusion : infection-induced hypotension, elevated lactate, or oliguria.
  • 10.  Septic shock : is defined as sepsis-induced hypotension persisting despite adequate fluid resuscitation. Adequate fluid resuscitation may be defined as infusion of 30 mL/kg of crystalloids .  Septic shock is a type of vasodilatory or distributive shock , it results from a marked reduction in systemic vascular resistance, often associated with an increase in cardiac output
  • 11. Multiple organ dysfunction syndrome (MODS)   refers to progressive organ dysfunction in an acutely ill patient, such that homeostasis cannot be maintained without intervention. It is at the severe end of the severity of illness spectrum of both SIRS and sepsis. MODS can be classified as primary or secondary: Primary MODS • is the result of a well-defined insult in which organ dysfunction occurs early and can be directly attributable to the insult itself (eg, renal failure due to rhabdomyolysis Secondary MODS • is organ failure that is not in direct response to the insult itself, but is a consequence of the host’s response (eg, acute respiratory distress syndrome in patients with pancreatitis)
  • 12. Incidence • racial and ethnic groups : highest among AfricanAmerican males . • Season : winter. • Age : patients ≥65 years of age account for nearly 60 percent of all episodes of severe sepsis . Gram positive bacteria are most frequently identified in patients with sepsis in the United States •The number of cases of Gram negative sepsis remains substantial. •Fungal sepsis has increased over the past decade, but remains lower than bacterial sepsis. • Pathogens Disease severity Mortality • The most common manifestations of severe organ dysfunction were acute respiratory distress syndrome, acute renal failure, and DIC. • Sepsis has a high mortality rate, with estimates ranging from 12 to 50 percent.
  • 13. Pathophysiology of sepsis Sepsis is the result of the interaction between the microorganism and their products and the host factors released on response (cytokines and other mediators).  This host response is an innate mechanism developed to protect the organism from harm but in sepsis the response is in excess, with negative effects, leading to organ dysfunction and frequently to death.  The amplitude of the host defense depends on: 1.the amount and virulence of the invading microorganism. 2.the genetic interindividual variability that governs the extent of the inflammatory response. 
  • 14. Initiation of the systemic response the microbial products are recognized by soluble or cell-bound recognition molecules or receptors, such as CD14 or the Toll-like receptors (TLRs).  This binding activates the nuclear factor K-B (NF-KB) with secondary macrophage activation and cytokine release. 
  • 15. The Inflammatory cascade
  • 16. The inflammatory cascade  If an imbalance develops between SIRS and CARS, homeostasis is violated. If SIRS predominates the result may be sepsis/ severe sepsis/ septic shock. If CARS predominates, the immune system may be suppressed, leaving the patient susceptible to life – threatening infections.
  • 17. Coagulation cascade  Tissue factor (TF) exposed on the surface of endothelial cells after stimulation by endotoxin or certain proinflammatory mediators (including TNF, IL-1, IL-6, PAF) activates the extrinsic coagulation pathway, resulting in the release of thrombin and the conversion of fibrinogen to fibrin. Here are a number of anticoagulant mechanisms that ensure the limitation of coagulation. These mechanisms include: a. Anticoagulation mechanisms: • Tissue factor pathway inhibitor (TFPI); • Antithrombin: blocks the activation of the thrombin and factor X; • Activated Protein C blocks thrombin generation; b. Fibrinolytic mechanism: • Tissue plasminogen activator (t-PA): activates plaminogen to plasmin, which realize the lysis of stable clots into soluble fibrin fragments; • Activated Protein C: inhibits Plasminogen activator inhibitor (PAI-1) and another inhibitor of fibrinolysis, Thrombin activatable fibrinolysis inhibitor (TAFI). In sepsis, these anticoagulant and profibrinolytic mechanisms are down regulated with a resultant procoagulant state.
  • 18.  There is usually an abscess or nidus of infection, which may be occult. Risk factors for developing sepsis include the following: 1. Age - elderly and very young at risk. 2. Instrumentation or surgery (including illegal abortion occurring in unhygienic circumstances). 3. Ethanol abuse. 4. Diabetes mellitus. 5. Burns. 6. Immunocompromise. 7. Medications, eg high dose corticosteroids, chemotherapy
  • 19.  1. 2. 3. 4.  • • • CLINICAL PRESENTATION / EVALUATION Patients may present a few days earlier with a focus of infection. Patients may then deteriorate rapidly despite having the appropriate oral antibiotics. Nonspecific symptoms are common, eg lethargy, nausea and vomiting, abdominal pain and diarrhoea. Also inquire about symptoms relating to a possible focus of infection, eg cough, recent travel. Cardiovascular changes are most significant physical findings in patients with septic shock; changes of heart rate – tachycardia / bradycardia, changes in perfusion are seen. Hypotension, when noted is a late finding and suggests decompensated shock.
  • 20.    1. 2. 3.   • Warm / Early shock: presentation is a febrile, warm, pink, wellperfused with tachycardia and tachypnea. The initial release of inflammatory cytokines causes a drop in systemic vascular resistance (SVR) which leads to low diastolic blood pressures. On physical exam, this causes a widened pulse pressure and bounding pulses. • Cold shock: describes a condition that resembles cardiogenic or severe hypovolemic shock. Pulses are poor, extremities are cool, and perfusion is severely diminished. The septic patient progresses to this state once the compensatory mechanisms are exhausted. Myocardial function is depressed and catecholamine response may be diminished due to relative cortisol and vasopressin deficiency.
  • 21.  Respiratory: Tachypnea is primarily due either to an inciting respiratory or metabolic acidosis. Patients often have a primary respiratory alkalosis on presentation and develop hypoxemia and respiratory acidosis as the sepsis progresses   Neurologic: Patients may present with agitation, which often progresses, to decreased mentation due to poor end organ perfusion.   Renal: Decreased urine output is noted for inpatients and elicited on history for outpatients. 
  • 22.  Skin: Palpable petechiae and purpura may be present if the patient presents in DIC.  Poor skin turgor and perfusion can also be noted.
  • 23. Clinical features 1. Looks unwell. 2. Fever (maybe spiking) and/or rigors. 3. Tachycardia, tachypnoea and cyanosis. 4. Hyperdynamic circulation with a bounding pulse (early on). 5. Poor capillary refill and cold peripheries occur later. 6. Hypotension with a postural drop (indicates septic shock). 7. Sweating. 8. Lymphadenopathy. 9. Hepatosplenomegaly. 10. Drowsiness or impaired consciousness (common in the elderly but a late sign in young children and young adults). 11. Features relating to actual infection, eg rash in meningococcal sepsis, dullness to percussion in pneumonia. These features may not be present in the very young, elderly and immunocompromised.
  • 24.  1. 2. 3. 4. 5. 6. Investigations should include: FBC - anaemia, neutrophilia or neutropenia,thrombocytopenia may be present (pancytopenia may indicate bone marrow involvement). In viral infections lymphocytosis predominates. Urine dipstick and sample for microscopy, culture and sensitivity. Renal function - looking at extent of dehydration or organ failure. Liver function tests - hypoalbuminaemia likely to be present. Glucose - hyperglycaemia can be present. Clotting screen, including D-dimer and fibrinogen testing, looking for disseminated intravascular coagulation (DIC).
  • 25. 7. Blood cultures - several sets from several sites are required. Cultures for mycobacteria should also be sent. Ideally these should be sent before antibiotics are given - but do not delay, especially if the patient is very ill. 8. Radiology - including CXR, abdominal ultrasound looking for a collection, and CT scan looking for source. 9. Measures of lactate and oxygen saturation of venous blood 10. Arterial blood gases - metabolic acidosis is common. 11. More invasive investigations looking for a source of infection for example, lumbar puncture, bronchoscopy, laparoscopy, lymph node biopsy, etc.
  • 26. 1. 2. 3. Disseminated intravascular coagulation (DIC). Adrenal failure, eg adrenal haemorrhage secondary to meningococcus (WaterhouseFriderichsen syndrome)*** Multiorgan failure, eg renal failure or cardiorespiratory failure.
  • 27.  Therapeutic priorities for patients with severe sepsis or septic shock include: 1- Early initiation of supportive care to correct physiologic abnormalities, such as hypoxemia and hypotension . 2- Distinguishing sepsis from systemic inflammatory response syndrome (SIRS) because, if an infection exists, it must be identified and treated as soon as possible .This may require a surgical procedure (eg, drainage), as well as appropriate antibiotics.
  • 28.  The first priority in any patient with severe sepsis or septic shock is stabilization of their airway and breathing. Next, perfusion to the peripheral tissues should be restored.  1-Stabilize respiration — Supplemental oxygen should be supplied to all pa tients with sepsis and oxygenation should be monitored continuously with pulse oximetry. Intubation and mechanical ventilation may be required to support the increased work of breathing that typically accompanies sepsis, or for airway protection since encephalopathy and a depressed level of consciousness frequently complicate sepsis.
  • 29.  2-Assess perfusion — Once the patient's respiratory status has been stabilized, the adequacy of perfusion should be assessed. Hypotension is the most common indicator that perfusion is inadequate (eg, systolic blood pressure (SBP) <90 mmHg, mean arterial pressure <70 mmHg, decrease in SBP >40 mmHg). Therefore, it is important that the blood pressure be assessed early and often. An arterial catheter may be inserted if blood pressure is labile or restoration of arterial perfusion pressures is expected to be a protracted process, because a sphygmomanometer may be unreliable in hypotensive patients.
  • 30. Critical hypoperfusion can also occur in the absence of hypotension, especially in:  1- during early sepsis(Common signs of hypoperfusion include cool, vasoconstricted skin due to redirection of blood flow to core organs, tachycardia >90/min, obtundation or restlessness, and oliguria or anuria).  2- elderly patients.  3-diabetic patients.  4-patients who take beta-blockers.  5-Patients with chronic hypertension .  ****An elevated serum lactate (eg, >1 mmol/L) can be a manifestation of organ hypoperfusion in the absence of hypotension and is an important component of the initial evaluation. 
  • 31.  3-Establish laboratory studies that help central characterize the severity of venous access: sepsis include : 1- platelet count. After initial assessment, a central 2- international normalized ratio. venous catheter (CVC) should be 3-creatinine, and bilirubin. 4- serum lactate>4mmol/l inserted in most patients with severe sepsis or septic shock. **** uses of CVC: 1- to infuse intravenous fluids, infuse medications, infuse blood products, and draw blood. 2- used for hemodynamic monitoring by measuring the central venous pressure (CVP) and the central venous oxyhemoglobin saturation (ScvO2).
  • 32. ***dynamic hemodynamic measures are: 1- radial artery pulse pressure. 2-aortic blood flow peak velocity. 3-brachial artery blood flow velocity. ***static hemodynamic measures are: 1-CVC. 2- PAC(Pulmonary artery catheter). You have to know there are two types of hemodynamic measures: 1-dynamic hemodynamic measures. 2-static hemodynamic measures. that dynamic measures are predictors of fluid responsiveness.
  • 33.       Once it has been established that hypoperfusion exists, early restoration of perfusion is necessary to prevent or limit multiple organ dysfunction, as well as reduce mortality. goals during the first six hours of fluid resuscitation, as suggested by the Surviving Sepsis Campaign Guidelines, include the following : 1-●Central venous pressure 8 to 12 mmHg. 2-●Central venous (superior vena cava) or mixed venous oxygen saturation 70 or 65 percent, respectively. 3-●Mean arterial pressure ≥65 mmHg (MAP = [(2 x diastolic) + systolic]/3). ●4-Urine output ≥0.5 mL/kg/hour.
  • 34. The best evidence favors targeting central venous oxygen saturation (ScVO2) ≥70 percent. However, following any or all of these goals, as valuable indicators of tissue perfusion, is reasonable.  ***** Lactate clearance — The lactate clearance is defined by the equation [(initial lactate lactate >2 hourslater)/initial lactate] x 100. The lactate clearance and interval change in lactate over the first 12 hours of resuscitation has been evaluated as a potential marker for effective resuscitation .  There is a trial show no difference in hospital mortality, length of stay, ventilator-free days, or incidence of multiorgan failure, suggesting that lactate clearance criteria may be an acceptable alternative to ScvO2 criteria. 
  • 35. Restoration of perfusion is predominantly focused on administration of intravenous fluids; additional modalities such as vasopressor therapy, inotropic therapy, and blood transfusion are added, depending on the response to fluid resuscitation, evidence for myocardial dysfunction, and presence of anemia.  ****Intravenous fluids : rapid, large volume infusions of intravenous fluids are indicated as initial therapy for severe sepsis or septic shock, unless there is coexisting clinical or radiographic evidence of heart failure. 
  • 36. Fluid therapy should be administered in welldefined (eg, 500 mL), rapidly infused boluses .Volume status, tissue perfusion, blood pressure, and the presence or absence of pulmonary edema must be assessed before and after each bolus. Intravenous fluid challenges can be repeated until blood pressure is acceptable, tissue perfusion is acceptable, pulmonary edema ensues, or fluid fails to augment perfusion. **** In our clinical practices, we generally use a crystalloid solution instead of albumin solution because of the higher cost of albumin. We believe that giving a sufficient quantity of intravenous fluids rapidly and targeting appropriate goals is more important than the type of fluid chosen. We do not use hydroxyethyl starch or pentastarch. 
  • 37.  **** Vasopressors: Vasopressors are second line agents in the treatment of severe sepsis and septic shock. However, intravenous vasopressors are useful in patients who remain hypotensive despite adequate fluid resuscitation or who develop cardiogenic pulmonary edema. ****** In severe septic shock, we prefer to use norepinephrine in most patients .However, we findphenylephrine (a pure alpha-adrenergic agonist) to be useful when tachycardia or arrhythmias preclude the use of agents with beta-adrenergic activity
  • 38. Prompt identification and treatment of the primary site or sites of infection are essential .This is the primary therapeutic intervention, with most other interventions being purely supportive.  *****Identification of the septic focus by: Taken gram stain and culture from : 1- urine(should be always taken:. 2-sputum(if there is prouducive cough) 3- intraabdminal collection (post op.) 4-blood(Blood should be taken from two distinct venipuncture sites and inoculated into standard blood culture media (aerobic and anaerobic). 
  • 39.  Prompt and effective treatment of the active infection is essential to the successful treatment of severe sepsis and septic shock .Source control should be undertaken since undrained foci of infection may not respond to antibiotics alone .As examples, potentially infected foreign bodies (eg, vascular access devices) should be removed when possible, and abscesses should undergo percutaneous or surgical drainage. Some patients require extensive soft tissue debridement or amputation; in severe cases, fulminant Clostridium difficile-associated colitis may necessitate colectomy.
  • 40. **The choice of antibiotics can be complex and should consider : 1-the patient's history(eg, recent antibiotics received ). 2-comorbidities. 3-clinical context(eg,community- or hospital-acquired). 4-Gram stain data. 5-local resistance patterns . ****When the potential pathogen or infection source is not immediately obvious, we favor broad-spectrum antibiotic coverage directed against both grampositive and gram-negative bacteria.
  • 41. Staphylococcus aureus is associated with significant morbidity if not treated early in the course of infection .There is growing recognition that methicillin-resistant S. aureus (MRSA) is a cause of sepsis not only in hospitalized patients, but also in community dwelling individuals without recent hospitalization . For these reasons, we recommend that severely ill patients presenting with sepsis of unclear etiology be treated with intravenous vancomycin (adjusted for renal function) until the possibility of MRSA sepsis has been excluded.  ***Potential alternative agents to vancomycin should be considered for patients with:1refractory or virulent MRSA, or 2-a contraindication to vancomycin.. Are:  1- daptomycin for non-pulmonary MRSA.  2- linezolid.  3- ceftaroline. 
  • 42.  In our practice, if Pseudomonas is an unlikely pathogen, we favor combining vancomycin with one of the following:  1-●Cephalosporin, 3rd generation (eg, ceftriaxone or cefotaxime).  2-●Beta-lactam/beta-lactamase inhibitor (eg, piperacillin-tazobactam, ticarcillinclavulanate).  3-●Carbapenem (eg, imipenem or meropenem).
  • 43. ***Alternatively, if Pseudomonas is a possible pathogen, we favor combining vancomycin with two of the following (see "Principles of In patients who are antimicrobial therapy of Pseudomonas neutropenic, aeruginosa infections"): antibiotic treatment should  1-●Antipseudomonal cephalosporin continue until the (eg, ceftazidime, cefepime). neutropenia has  2-●Antipseudomonal carbapenem resolved or the planned antibiotic (eg, imipenem, meropenem). course is complete,  3-●Antipseudomonal beta-lactam/betawhichever is lactamase inhibitor (eg, piperacillinlonger. tazobactam, ticarcillin-clavulanate).  4-●Fluoroquinolone with good anti-pseudomonal activity (eg, ciprofloxacin).  5-●Aminoglycoside (eg, gentamicin, amikacin).  ●6-Monobactam (eg, aztreonam). 
  • 44. CLINICAL SCENARIO ANTIMICROBIAL RATIONALE Meningitis – GPC on gram stain Meningitis – gram neg diplococci Neutropenia Vanco + 3rd gen cephalosporin 3rd gen cephalosporin Cover for resistant S.pneumo Likely N. meningitides Vanco + Double-coverage for GNR Pts are susceptible to Pseudomonas and other SPACE organisms Toxic shock Indwelling central venous catheters Clinda + Vanco Vanco + 3rd gen cephalosporin Deterioration despite broadspectrum antibiotics. Antifungals; also consider what possible resistant organisms may be involved Cover for MRSA/Strep Vanco is needed for Gram + organisms, most notably S.epi. Loss of normal bacterial flora increases susceptibility to fungus, particularly in patients on steroids, with hyperglycemia, or who are immunosuppressed
  • 45.  1-Glucocorticoids.  2-Nutrition.  3-Intensive insulin therapy.  4-External cooling( External cooling consists of using either an automatic cooling blanket, or ice-cold bed sheets and ice packs, to achieve a core body temperature of 36.5 to 37°C for 48 hours. It decreases the time to fever control without exposing the patient to potential adverse effects of antipyretic drug).  5-protocols.
  • 46.  http://www.uptodate.com/contents/evaluat ion-and-management-of-severe-sepsis-andseptic-shock-inadults?source=search_result&search=septice mia&selectedTitle=2~150  http://www.uptodate.com/contents/sepsisand-the-systemic-inflammatory-responsesyndrome-definitions-epidemiology-andprognosis?source=search_result&search=risk+ factors+of+sepsis&selectedTitle=1~150