Sepsis with Septic Shock and its management.pptx

Sepsis and septic shock

1. subject seminar Septic shock and surviving sepsis campaign

2. shock Clinical condition of organ dysfunction resulting from an imbalance between cellular oxygen supply and demand Common in icu set up

3. Determinants of oxygen delivery DO2= CO X CaO2 DO2= HR X SV X CaO2 SV = PRELOAD X CONTTRACTILITY/ SVR CaO2=(Hb X 1.39 X SaO2) + (PaO2 X 0.03)

4. CLASSIFICATION OF SHOCK DISTRIBUTIVE CARDIOGENIC OBSTRUCTIVE HYPOVOLEMIC MIXED

5. DISTRIBUTIVE Sepsis Pancreatitis Severe burns Anaphylactic shock Neurogenic shock Endocrine shock Adrenal shock

6. Cardiogenic shock Myocardial infarction Myocarditis Arrhythmias Severe aortic and mitral valvular insufficiency

7. obstructive Tension pneumothorax Cardiac tamponade Restrictive cardiomyopathy Pulmonary embolism Aortic dissection

8. hypovolemic Hemorrhage Gi loss Burns Diabetic keto acidocis Diabetes insipidus

9. Stages of shock Compensated/ preshock Shock/decompensated shock Irreversible shock

10. body utilizes a variety of physiologic responses to counteract the initial insult and attempts to reestablish the adequate perfusion and oxygen delivery. there are no overt signs of organ dysfunction. Laboratory evaluation may demonstrate mild organ dysfunction or a mild elevation of lactate. In early sepsis with reduction in SVR, there is a compensatory rise in HR and CO. With early hemorrhagic volume loss, there will be a compensatory increase in SVR

11. As the host compensatory response gets overwhelmed, patient transitions into decompensated stage of shock In this stage, organ dysfunctions becomes evident Timely interventions during compensated and decompensated stages of shock can help in recovery of the patient If intervention was not done in time or was inadequate, patient progresses to irreversible shock where there will be permanent end organ damage and minimal or nil recovery

12. Shock index Shock index= HR/SBP To identify high risk population normalSI= 0.5-0.7 SI>0.9 indicative of transfusion requirement SI also indicative of postintubation hypotension

13. Bacteremia and septisemia Bacteremia- presence of bacterial pathogen in bloodstream Septicemia- presence of bacterial pathogens along with bacterial toxin in blood stream Associated with systemic symptoms of infection

14. sepsis Dysregulated host response to infection that leads to acute organ dysfunction Septic shock- a subset of sepsis cases in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality risk

15. Sepsis1/sepsis 2 criteria Sepsis- Suspected (or documented) infection plus ≥2 systemic inflammatory response syndrome (SIRS) criteria Septic shock- Suspected (or documented) infection plus persistent arterial hypotension (systolic arterial pressure, <90 mmHg; mean arterial pressure, <60 mmHg; or change in systolic by >40 mmHg from baseline)

16. Sepsis 3 criteria Sepsis - Suspected or documented infection and an acute increase in ≥2 sepsis-related organ failure assessment (SOFA) points Septic shock- Suspected or documented infection plus vasopressor therapy needed to maintain mean arterial pressure at ≥65 mmHg and serum lactate >2.0 mmol/L despite adequate fluid resuscitation

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18. SIRS heart rate >90 rr >20 temp <36 or >38 degree C wbc count <4k or >12k or bands>10%

19. quick Sequential Organ Failure Assessment ( qSOFA ) score SBP<100 RR>22 ALTERED MENTAL STATUS WITH GCS<15 >/=2 associated with significant risk of death and prolonged icu stay

20. etiology Pneumonia Intra abdominal and genitourinary infections Staphylococcus aureus and streptococcus pneumoniae most common gram positive E coli, pseudomonas and klebsiella most common gram negative

21. Risk factors Age- higher in extremes of age Sex-more in males Race- more in blacks Ethnicity Chronic diseases like HIV and COPD Immunosuppression

22. epidemiology Sepsis and septic shock are two among the major health care problems in the world It has a Mortality of 1 among 4 patients affected In 2017, an estimated 48.9 million cases of sepsis was reported worldwide and 11 million sepsis related deaths were reported It represents 19.7% of all global deaths

23. Age standardised incidence of sepsis according to the cause- Infections- 466.8 per 100000 population Injuries- 24.7 per 100000 population Non communicable diseases- 186.0 per100000 population Total- 677.5 per 100000 population The incidence of sepsis has come down from 60.2 million in 1992 to 48.9 million in 2017

24. Leading causes of sepsis are changing, from diarrheal disease and maternal disorders to 1. lower respiratory tract infections 2. diarrheal disease 3. neonatal disorders 4. stroke 5. cirrhosis 6. COPD 7. HIV 8. malaria 9. tuberculosis 10. diabetes

25. PATHOPHYSIOLOGY Cell no longer able to support aerobic mechanism Pyruvate metabolised into lactate with reduced atp production Na/k ATPase unable to function Cellular osmotic and ionic imbalance Ca influx leading to cell swelling and death Leakage of intracellular contents into extracellular space causing activation of inflammatory cascade and organ dysfunction

26. pathogenesis The inflammatory response is typically initiated by an interaction between pathogen-associated molecular patterns (PAMPs) expressed by pathogens and pattern recognition receptors expressed by innate immune cells on the cell surface Toll-like receptors [TLRs] and C-type lectin receptors [CLRs] in the endosome , or in the cytoplasm ,retinoic acid inducible gene 1 – like receptors and nucleotide-binding oligomerization domain – like receptors [NLRs]. The resulting tissue damage and necrotic cell death lead to release of damage-associated molecular patterns (DAMPs) such as uric acid, high-mobility group protein B1, S100 proteins, and extracellular RNA, DNA, and histones

27. These molecules promote the activation of leukocytes, leading to greater endothelial dysfunction They also promote expression of intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule 1 (VCAM-1) on the activated endothelium coagulation activation and complement activation also ensues This cascade is compounded by macrovascular changes such as vasodilation and hypotension, which are exacerbated by greater endothelial leak tissue edema, and relative intravascular hypovolemia.

28. Subsequent alterations in cellular bioenergetics lead to greater glycolysis (e.g., lactate production), mitochondrial injury, release of reactive oxygen species, and greater organ dysfunction .

29. pathogenesis

30. Coagulation abnormalities Frequently associated with DIC To isolate invading organisms and to prevent spread of inflammation Driven by coagulation via tissue factor, impaired anticoagulant mechanisms and depressed fibrinolytic systems

31. Organ dysfunction Several factors leading to reduced oxygen delivery Hypotension Reduced red cell deformability Microvascular thrombosis Dysfunction of vascular endothelium- loss of barrier integrity- subcutaneous and body cavity edema Release of NO- vasomotor collapse- pathologic shunting Mitochondrial damage

32. Anti inflammatory measures Phagocytes with anti inflammatory phenotype Regulatory T cells Myeloid derived suppressor cells Neuroinflammatory response via vagus nerve and splenic nerve of celiac plexus

33. IMMUNE SUPPRESSION Reduced responsiveness of leukocytes to pathogens Increased expression of ligand of t cell inhibitory receptors on parenchymal cells Enhanced apoptotic cell death of B cells, CD4+ T cells and follicular dendritic cells

34. Clinical manifestations In compensated phase, it is nonspecific- Tachycardia Tachypnoea When decompensated, it presents as shock Mean arterial pressure <65mm hg Alternatively, patients with systemic hypertension can present with end organ damage at higher blood pressures

35. Physical examination CNS,kidney and skin are considered as windows to identify end organ damage in shock It usually manifests as Confusion and encephalopathy Oliguria (<0.5ml/kg/hr) Decreased capillary refill and cold clammy skin

36. Evaluation of JVP and periphderal edema for right sided cardiac pressures- elevated in cardiogenic shock and reduced in hypovolemic shock Pulmonary auscultation for left sided cardiac pressures Distributive shock may present with warm peripheries, brisk capillary refill <2 sec and bounding pulse Weak pulse, delayed capillary refill and cold extremities indicate low cardiac output form of shock

37. Examination may demonstrate the site of an untreated infection like cellulitis, abscess, infected pressure injury. The examination may reveal a brady- or tachyarrhythmia leading to development of shock. large ecchymosis may indicate a significant bleed related to trauma or spontaneous retroperitoneal bleeding. The rectal examination may reveal GI hemorrhage. Pulsus paradox us and elevated JVP may suggest the presence of cardiac tamponade. Patients with a tension pneumothorax may have a paucity of breath sounds over the affected side, deviation of the trachea away from the affected side, or subcutaneous emphysema.

38. The shock index (SI) is defined as the HR/systolic blood pressure normal SI is 0.5–0.7. An elevated SI (>0.9) has been proposed to be a more sensitive indicator of transfusion requirement and of patients with critical bleeding among those with hypovolemic (hemorrhagic) shock than either HR or BP alone It can also be used to identify patients with post intubation hypotension

39. CARDIO RESPIRATORY FAILURE ARDS- hypoxemia and b/l infiltrates of non cardiac origin that arises within 7 days of suspected infection Mild- PaO2/FiO2=201-300mmHg Mod-PaO2/FiO2=101-200mmHg Severe-PaO2/FiO2=<100mmHg ACUTE PULMONARY EDEMA HYPOTENSION

40. KIDNEY INJURY ACUTE KIDNEY INJURY Oliguria, azotemia, rising serum creatinine levels NEUROLOGIC COMPLICATIONS Coma or delirium Secondary to inflammatory response to infection Critical illness polyneuropathy and myopathy

41. Laboratory investigations 1. Lactate 2. Renal function tests 3. Liver function tests 4. Cardiac enzymes 5. Complete blood count (with differential) 6. PT, PTT, and INR 7. Urinalysis and urine sediment 8. Arterial blood gas 9. ECG 10. 2d echo

42. laboratory findings leukocytosis leukopenia(<5%) thrombocytopenia deranged liver and renal function test metabolic acidocis with anion gap serum hypoalbuminemia elevated troponin levels hypoglycemia hypofibriogenemia

43. Elevated lactate levels Elevated cardiac markers in case of cardiac causes od shock Elevated aptt and pt inr due to coagulation abnormality Urine routine showing uti or sediments indicating urinary obstruction or upper urinary tract pathology Ecg indicating cardiac causes

44. echocardiography The basic echocardiographic assessment for the shock patient is transthoracic echocardiography (TTE) utilizing both the two-dimensional (2D) and M mode The 2D mode can evaluate LV size, wall thickness, and ventricular function. Ventricular size and thickness can suggest longer standing cardiac processes Evaluation of LV function through estimation of left ventricular ejection fraction (LVEF), and can identify shock with globally reduced LV function or regional wall motion abnormalities

45. the assessment of RV function also examines RV size and wall thickness to identify conditions such as elevated pulmonary pressures or suggest pulmonary embolism, and also evaluate the patient for pericardial tamponade Can also be used to assess valve function

46. treatment Adequate venous access- 16g or 18g venous catheterfor adequate fluid resuscitation If hypotension still persisting inspite of adequate volume resuscitation, central venous catheter(CVC) can also be considered Central venous pressures and ScvO2 status can also be measured through CVC ScvO2 is a surrogate of mixed venous oxygen saturation, and can provide insight into the adequacy of oxygen delivery

47. Central venous access using Swan Ganz catheter if more detailed assessment of hemodynamic measurements are required (PCWP, CO, and SVR). If patient presents in cardiopulmonary arrest or critically ill, an intra osseous route can be secured An intra arterial line can help in measurement of mean arterial pressures , spo2 and acid base status

48. A minimal volume resuscitation of 30ml/kg is required in patients with septic shock even patients with cardiogenic shock may benefit by cautious volume replacement Fluid resuscitation should begin with crystalloids. Since hemoglobin is a key determinant of CaCO2 red cell administration may be a part of volume replacement even without hemorrhage if hemoglobin content is <7 g/dL in order to optimize oxygen delivery.

49. Assessment of intravascular volume status and the adequacy of volume resuscitation begins with the physical examination. The passive leg raise (PLR) test can predict responsiveness to additional intravenous fluid (IVF) by providing the patient with an endogenous volume bolus While the patient is resting in a semi-recumbent position at a 45-degree angle, the bed is placed in trendelenburg such that the patient’s head becomes horizontal and the legs are extended at a 45-degree angle. There is then an immediate (within 1 min) assessment of changes in CO or pulse pressure variation as a surrogate if the shock patient is mechanically ventilated there is the option of looking at changes in SV variation or pulse pressure variation during the respiratory cycle to assess volume responsiveness. A >12% SV variation suggests a volume-responsive state

50. The most commonly used parameters to assess adequacy of volume resuscitation are inferior vena cava (IVC) diameter and IVC collapse serial assessments of LV function can be performed while volume is being administered Pressure measurements using swanz ganz catheter can also be used for guiding volume resuscitation Ports in the PAC (Swan Ganz catheter) allow for direct measurement of CVP, pulmonary artery (PA), and PCWPs.

51. Choice of fluid Crystalloid solutions are the fluids of choice for sepsis and septic shock Normal saline is the most commonly used crystalloid solution during septic shock However, balanced crystalloid solutions may improve patient centred outcomes and should be considered if available Use of albumin does not improve mortality in patients with septic shock

52. Phases of fluid therapy RESUSCITATION At this initial phase, usually during the first 3–6 h after the initiation of therapy, fluid resuscitation is commonly administered according to an  early, adequate, goal - directed, fluid management  strategy Fluid bolus should be administered first. The volume of fluid bolus is heterogeneous among clinicians , typically 500–1000 mL . The minimal fluid volume that is able to increase the backward pressure of venous return is 4ml/kg L/kg

53. OPTIMISATION In this phase, we use various measures like passive leg raising test, end expiratory occlusion test, 2decho and pulmonary pressures to assess the further need of fluid and adjust the dosage of fluids. STABILISATION Daily fluid balance is the sum of all fluid intakes and outputs over 24   h, and the cumulative fluid balance is the sum of daily fluid balances over a set period of time  

54. Maintenance fluids should be used only to cover daily needs, and their prescription should take other sources of fluids and electrolytes into account. When a patient already receives daily needs of water, glucose and electrolytes via other means (enteral or parenteral nutrition, medication solutions, etc.), specific intravenous maintenance fluids should be stopped.

55. EVACUATION It specifically refers to   late goal-directed fluid removal   and   late conservative fluid management. Late goal-directed fluid removal   involves aggressive and active fluid removal using diuretics and renal replacement therapy with net ultrafiltration. It is characterized by the discontinuation of invasive therapies and a transition to a negative fluid balance Late conservative fluid management   describes a moderate fluid management strategy following the initial treatment in order to avoid (or reverse) fluid overload. Recent studies showed that two consecutive days of negative fluid balance within the first week of the intensive care unit stay is a strong and independent predictor of survival  

56. vasopressors In patients with distributive shock, the aim is to increase the SVR. Norepinephrine is the first choice vasopressor: with potent α1 and β1 adrenergic effects. The α1 causes vasoconstriction while β1 has positive inotropic and chronotropic effects. At high doses, epinephrine has a similar profile as at lower doses the β effects predominate, but is associated with tachyarrhythmia, myocardial ischemia, decreased splanchnic blood flow, pulmonary hypertension, and acidosis. In distributive shock, vasopressin deficiency may be present. Vasopressin acts on the vasopressin receptor to reverse vasodilation and redistribute flow to the splanchnic circulation.

57. Dopamine does not have a role as a first line agent in distributive shock. A randomized control study in patients with all cause circulatory shock did not show a survival benefit, but did reveal an increase in adverse events mostly arrhythmias For patients with cardiogenic shock, dobutamine is the first line agent it is a synthetic catecholamine with primarily β-mediated effects and minimal α adrenergic effects. The β1 effect is manifest in increased inotropy and the β2 effect leads to vasodilation with decreased afterload it can be used with norepinephrine in patients with mixed distributive and cardiogenic shock

58. steroids O lder, traditional trials of corticosteroids in sepsis were unsuccessful, probably because of high dosages and poor patient selection More recent trials with low-dose dosages in select patient populations (those with vasopressor dependence and, possibly, relative adrenal insufficiency) may have resulted in improved outcome Corticosteroids (hydrocortisone) should be considered only for patients with vasopressor-dependent septic shock    ; wean steroid therapy when vasopressor therapy is no longer needed  

59. Consider moderate-dose corticosteroids in the management of patients with early severe ARDS ,as well as before day 14 in patients with unresolving ARDS    investigators still need to determine what role corticosteroid treatment may have in less severe ARDS A cortisol stimulation test may be performed to identify patients with relative adrenal insufficiency, defined as failure to increase levels by more than 9 µ g/dL Do not administer corticosteroids to treat sepsis when shock is not present  

60. Maintenance steroid therapy or stress-dose steroids may be continued as needed on the basis of the patient’s endocrine or corticosteroid-administration history  

61. OXYGENATION AND VENTILATION SUPPORT patients with shock may present with hypoxemia For patients with distributive shock, this may be related to a primary pulmonary process For patients with cardiogenic or obstructive shock, the hypoxemia may be related to LV dysfunction and elevations of PCWP. For patients with all types of shock, there can be development of ARDS and subsequent V./Q. mismatch and shunt. Supplemental oxygen should be initiated and titrated to maintain SpO2 of 92–95%. This may require intubation and initiation of mechanical ventilation.

62. Patients with shock may have high minute ventilatory needs to compensate for metabolic acidosis. If mechanical support is initiated, it is important to provide ventilation with lung-protective strategies focused on low tidal volume ventilation and optimization of positive end-expiratory pressure to minimize ventilator-induced lung injury. there should be daily sedation cessation to assess underlying neurologic function and minimize time on mechanical ventilation

63. respiratory support target tidal volume of 6ml/kg is recommended in sepsis induced ards A higher peep is required in moderate to severe sepsis induced ards conservative fluid strategy should be followed in sepsis induced ards to reduce fluid overload component

64. infection control iv antibiotics should be started within 1 hour- empirical broad spectrum antibiotics should be started as the sensitivity of the pathogen wont be known immediately microbiological cultures should be sent before starting antibiotics antibiotic therapy should be narrowed once pathogen is isolated daily assessment of antibiotic requirement and de-escalation of antibiotic therapy should be done accordingly

65. Initial antimicrobial therapy IMMUNOCOMPETENT ADULT Piperacillin tazobactum(4.5g q6h)/ meropenem(1g q8h)/imipenem-cilastatin(0.5g q6h) Allergic to beta lactam- aztreonam 2g q8h/ ciprofloxacin 400mg q12h)/levofloxacin (750mg q24h) Add vancomycin loading dose25-30mg/kg, f/b 15-20mg/kg q8h-q12h)

66. NEUTROPENIA Cefepime 2g q8h/ meropenem 1g q8h/ doripenem 500mg q8h/ imipenem-cilastatin 0.5g q8h/ piperacillin- tazobactum 3.375g q4h Add vancomycin if central line associated blood stream infection suspected Add tobramycin 5-7mg/kg q24h + vancomycin + caspofungin 70mg stat f/b 50mg q24h if patient is in septic shock

67. general supportive care arterial catheter as soon as possible insulin initiated when 2 glucose levels >180mg/dl continuos or intermittent renal replacement in sepsis with aki dvt and thromboembolism prophylaxis stress ulcer prophylaxis

68. RRT IN SA-AKI Renal Replacement Therapy (RRT) has been frequently used to support critically ill patients with SA-AKI. The optimal time to start Renal Replacement Therapy (RRT) in the setting of SA-AKI is still unknown The conventional indications for commencing RRT in patients with AKI -refractory acidosis, severe hyperkalemia, uremia, oliguria/anuria, and volume overload unresponsive to diuretic therapy However, many believe that awaiting those life-threatening complications to evolve before commencing RRT are too late or relatively delayed for the disease process

69. Despite conflicting results from observation studies on beneficial effects of early RRT approach , there are increasing trends toward earlier or pre-emptive use of RRT well before the development of advanced complications Hemodialysis (HD) and Peritoneal Dialysis (PD) have been primarily used to support SA-AKI patients for years. The current dialysis armamentarium has expanded to various modalities of Continuous Renal Replacement Therapy (CRRT), intermittent hemofiltration/hemodiafiltration, and Prolonged Intermittent Renal Replacement Therapy (PIRRT).  

70. Applying convective solute transport to dialysis therapy enhances middle to large molecule solute clearance, pro and anti-inflammatory cytokine removal that play significant roles in sepsis   CRRT may seem more suitable for unstable critically ill patients than intermittent HD because of its longer operating time allowing greater fluid control, and better hemodynamic stability anticoagulants usage to prolong circuit survival may aggravated bleeding in critically ill patients. Regional anticoagulant may be the alternative option

71. Retrospective and observational studies from Europe and the United States reported a beneficial effect of CRRT on promoting renal recovery   To date, the ideal modality to support SA-AKI remains controversial since prospective randomized controlled trials or meta-analysis trials have not shown a survival advantage with one particular modality  

72. Surviving sepsis campaign Europian society of intensive care medicine with society of critical care medicine came together in 2002 and began surviving sepsis campaign(SSC) To reduce mortality from Sepsis Recommendations for treatment of sepsis revised and released every 4 year 2015 saw recommendations in the form of 3 hour and 6 hour bundles In 2019, revised in thre form of 1 hour bundle to signify the importance of immediate action

73. Measurement of lactate levels Serum lactate is not a direct measure of tissue perfusion, but can act a surrogate , as increase may represent tissue hypoxia, accelerated aerobic glycolysis secondary to beta adrenergic stimulation, or other causes associated with worse outcomes If initial lactate levels are >2mmol/l, lactate should be reassessed after 2-4 hours to guide resuscitation and correction of lactate levels

74. The concept of lactate merely as a metabolic waste product (bad lactate) has now evolved towards lactate being viewed as an energy shuttle (good lactate). In most clinical critical-care situations,hyperlactataemia must be perceived as an adaptive response to an aggressive state and not as a marker of tissue hypoxia.

75. According to Brian Casserly et al, a lactate level of >4mmol/l qualifies for administration of early quantitative resuscitation therapy However, the advantage of using lactate over other parameters like ScvO2 as markers indicating the need for resuscitation is debatable(Jones et al)

76. Obtaining blood cultures prior to antibiotics Microbial cultures should be obtained in the form of Blood culture Urine culture Sputum culture Swab from local infection Suction tip culture if intubated

77. Cultures should be obtained prior to administering antibiotics to prevent sterile culture yield As per J T kanegaye et al, sterile cultures were obtained in meningococcal meningitis within 1 hour (as early as 15 mins) , within 4.3 hours in pneumococcal meningitis, and within 8 hours in group b streptococcal meningitis In study done by adhering strictly to the SSC 6 hour bundle, significant reduction in 28 day mortality was only found following obtaining microbial cultures prior to antibiotics The link between early administration of antibiotics and antibiotic stewardship remains an essential aspect of high quality sepsis management

78. Administration of iv fluids Early effective fluid resuscitation is crucial for the stabilisation of sepsis induced tissue hypoperfusion or septic shock Initial fluid resuscitation should start immediately on recognising patient with septic shock and should be completed within 3 hours Should comprise of a minimum of 30ml/kg of intravenous crystalloid fluids

79. There is an absence of clear benefit on administration of colloids compared to crystalloids in conjunction to albumin, supporting a strong recommendation for crystalloids Positive fluid balance was shown to have higher mortality in icu setup among patients with septic shock (Acheampong et al, Brotfain et al), urging the need for monitored fluid usage, especially on longer icu stays

80. Vasopressor usage Urgent resroration of perfusion pressure to vital organs is key to the management of shock If blood pressure is not restored after initial fluid resuscitation, vasopressors should be commenced within the 1 st hour to achieve mean arterial pressure >/=65mmhg

81. Noradrenaline(0.5-5micrograms/kg/min) is more effective than dopamine(2.5-25 microgram/kg/min) in reversing hemodynamic abnormalities in septic shock (Martin C et al) But noradrenaline on used in septic shock will increase lactic acidocis through beta adrenergic receptors in muscle tissues. Dopamine and noradrenaline has minimal effects on splanchnic circulation in septic shock but epinephrine impairs splanchnic circulation.(De Backer et al) Noradrenaline along with low dose of dobutamine can improve gastric mucosal perfusion((Shao Xia Zhou et al)

82. Thank you