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  1. Sepsis in surgical patients, its biomarkers and Surviving sepsis Campaign 2021 Presenter : Dr Samrat Shrestha
  2. DAY 1 Sepsis in surgical patients SOURCE CONTROL Biomarkers  DAY 2 Recent advances and recent biomarkers Surviving sepsis Campain 2021 MANAGEMENT
  3. SEPSIS •Schottmuller,in 1914 defines sepsis as “A state which is caused by microbial invasion from a local infectious source into the blood stream which leads to sign of systemic illness in remote organ.” • Early diagnosis and treatment influence the morbidity and mortality • Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection.
  4. • SIRS was diagnosed clinically by the presence of at least two features; -Temp >38C or <36C -HR > 90bpm -RR>20 breaths/m or PaCO2 <32 mmHg -WBC >12000/mm3 or <4000/mm3 or immature forms (bandemia)>10% • This definition was neither sensitive nor specific for sepsis. • These features can be seen in postoperative patient , many non infectious conditions like burns , pancreatitis , trauma , ischemia-reperfusion.
  5. • Sepsis life threatening organ dysfunction caused by dysregulated host response to infection. • Focus has been shifted from inflammation to organ dysfunction in presence of infection.
  6. Septic Shock: A subset of sepsis in which underlying circulatory and cellular/ metabolic abnormalities are profound enough to increase mortality. Clinical criteria identifying such condition include: • Persisting hypotension requiring vasopressors to maintain MAP≥65 mm Hg • Blood lactate >2 mmol/L despite adequate volume resuscitation
  8. • Organ dysfunction is defined in term of sequential organ failure assessment (SOFA) score increase in two or more from baseline in the presence of infections. • For identification of pathogens such as blood culture take time and are not helpful for rapid recognition. • Early and rapid recognition could lead to early institution of therapy, reduce morbidity and mortality and improve outcome.
  9. SOFA Score
  10. Pathophysiology
  11. qSOFA score Use three criteria; • An alteration in mental status • Systolic BP <100 mm Hg • RR> 22 breaths/min Significance • Presence of at least 2 qSOFA criteria is predictor of both increased mortality and ICU stays of >3 days for non ICU patients.
  12. “PqSOFA” score combined the qSOFA score with procalcitonin Combining PCT and the qSOFA score can facilitate an early assessment of acute sepsis severity and prognosis among adult patients, although its predictive ability is less than ideal. PqSOFA score can independently identify critically ill patients with sepsis, predict their short-term adverse events, and their 28-day prognosis. PqSOFA score had superior predictive value than qSOFA score, although its performance was comparable to SOFA or APACHE II scores.
  13. • qSOFA score revealed sufficient prediction for mortality in the IMCU. • SOFA score showed best results regarding mortality in IMCU/ICU patients, its predictive quality depended on the severity of the disease. • Summarizing, it remains unclear whether qSOFA or SOFA score should be used in surgical IMCU patients for risk stratification.
  14. • Regarding hospital mortality, SIRS criteria and qSOFA score revealed only poor predictive validity, whereas the SOFA score was predictive for the patients’ death • SIRS criteria and qSOFA score reached high sensitivity but low specificity regarding mortality, whereas SOFA score performed adequately.
  16. • Source control may include drainage of an abscess, debriding infected necrotic tissue, removal of a potentially infected device, or definitive control of a source of ongoing microbial contamination Foci of infection readily amenable to source control include • Intra-abdominal abscesses • Gastrointestinal perforation, • Ischemic bowel or volvulus • Cholangitis • Cholecystitis, • Pyelonephritis associated with obstruction or abscess • Necrotizing soft tissue infection • Deep space infection (e.g., empyema or septic arthritis) • Implanted device infections
  17. • Source control should be achieved as soon as possible following initial resuscitation • Limited data to conclusively issue a recommendation regarding timeframe in which source control should be obtained • Smaller studies suggest that source control within 6 to 12 hours is advantageous • Studies generally show reduced survival beyond that point • Clinical experience suggests that without adequate source control, many severe presentations will not stabilize or improve despite rapid resuscitation and provision of appropriate antimicrobials
  18. • Selection of optimal source control methods must weigh benefits and risks of specific intervention, patient’s preference, clinician’s expertise, availability, risks of procedure, potential delays, and probability of procedure’s success. • Least invasive option that will effectively achieve source control should be pursued. • Open surgical intervention should be considered when other interventional approaches are inadequate or cannot be provided in a timely fashion. • Surgical exploration may also be indicated when diagnostic uncertainty persists despite radiologic evaluation, when probability of success with a percutaneous procedure is uncertain, or when undesirable effects of a failed procedure are high.
  19. MULTIDISCIPLINARY APPROACH FOR SOURCE CONTROL • Procedures for source control should be tailored to infection site and extent, and degree of derangement of patient physiology • Well-balanced decision as to the timing and methodology for source control is mandatory. • Multidisciplinary approach involving surgeons, infectious disease physicians, interventional radiologists, interventional endoscopists, anaesthesiologists, and intensivists to ensure selecting best source control strategy for the individual patient.
  20. • Conclusions: • For patients of GI perforation with associated septic shock, time from admission to initiation of surgery for source control is a critical determinant, under condition of being supported by hemodynamic stabilization. • Target time for a favorable outcome may be within 6 hours from admission. • We should not delay in initiating early goal-directed therapy assisted surgery if patients are complicated with septic shock.
  21. Conclusions: • Our data provide important clinically based evidence for the beneficial effects of surgical treatment within 12 hours of admission for V vulnificus-related NF.
  22. Biomarkers Of SEPSIS • Biomarkers are naturally occurring molecules , genes or other characteristics by which physiological and pathological processes can be identified. • Characteristics of ideal biomarker:- It should be an objective parameter Easy to measure Reproducible Inexpensive Fast kinetics High sensitivity and specificity Short turn around time Show Appropriate response to therapy(Decline In response with therapy)
  23. • Differentiate local infection, disseminated infection and sepsis. • Differentiate viral and fungal infection from bacterial infection. • Determine response of antibiotics , response to therapy , prediction of organ dysfunction and complications.
  24. • Initial biomarkers investigated in sepsis were WBC count Lactate ESR C-reactive protein Pro calcitonin . • WBC : leucocytosis can be seen in both noninfectious and infectious cause hence it is not specific. • ESR is an indicator of inflammation and its utility in sepsis is limited as it can be influenced in presence of anemia , immunoglobulins , change in erythrocyte size , shape and number ,malignancy , tissue injury.
  25. • Lactate: a byproduct of glycolysis is a marker of sepsis, hypoperfusion leading to anaerobic glycolysis causes hyperlactatemia . • Lactate level is high in hypovolemia and haemorrhage during trauma and surgery. • Lactate clearance is used as a marker of adequate resuscitation. • Lactates are not a good marker of sepsis but a important indicators of severity of shock , hypoperfusion and adequacy of resuscitation. LACTATE
  26. • Association of lactate level with mortality in patients with suspected infection and sepsis is well established • Currently recommended as part of the SSC Hour-1 sepsis bundle for those patients with sepsis • Lactate cutoffs determining an elevated level ranged from 1.6−2.5 mmol/L, although diagnostic characteristics were similar regardless of the cutoff. • Presence of an elevated or normal lactate level significantly increases or decreases, respectively, likelihood of a final diagnosis of sepsis in patients with suspected sepsis. • Lactate alone is neither sensitive nor specific enough to rule-in or ruleout the diagnosis on its own
  27. • CONCLUSION • The evidence reviewed suggested that whole blood, plasma or serum lactate measurement could not provide specific prognostic information for individual patients. • There may be a role for monitoring for normalization of serum D- or L- lactate concentrations during goal-directed therapy in ICU but further good- quality studies are needed. • Measurement of the D-lactate stereoisomer shows promise, such that further studies are warranted.
  28. • C-reactive protein is an acute phage reactant which is synthesized in liver(hepatocytes) in response to inflammation or tissue injury and upregulated by interleukin 6. • Normal level: Less then 0.3 to 0.5 mg/dl. • Level can rise upto 1000times in response to acute phase stimulus. • Starts to rise after 6 hours and peak at about 48 hours with half life of 20 hours. CRP
  29. • Elevated in both infectious and noninfectious conditions • Modest elevation can be seen in low grade inflammatory conditions such as atherosclerosis, obesity , hypertension, diabetes and obstructive sleep apnea. • Marked elevation is associated with bacterial infections. • It has good sensitivity but poor specificity. • It is a good marker of inflammation rather then infection.
  30. Results: • CRP had a sensitivity and specificity of 84.3% and 46.15%, respectively. Area under the receiver operating characteristics curve was calculated to be 0.683 (±0.153, P < 0.05). The cutoff value with the best diagnostic accuracy was found to be 61 mg/L. Conclusion: • CRP is a sensitive marker of sepsis, but it is not specific.
  31. Conclusion • An admission CRP level >100 mg/L is associated with an increased risk of ICU and 30-day mortality as well as prolonged Length Of Stay in survivors, irrespective of morbidity. • Thus, CRP may be a simple, early marker for prognosis in ICU admissions for sepsis.
  32. • Procalcitonin a precursor of calcitonin , produced by C –cells of thyroid under the control of calcitonin gene related peptides (CALC-1) gene. • During infection there is increase of CALC-1 gene expression in various extrathyroid tissue like parenchymal tissue such as lungs , liver , kidney which is mediated by proinflammatory cytokines such as TNF-a and IL-6. PROCALCITONIN
  33. • Both microbial toxins and host response by humoral or cell mediated can lead to release of PCT. • PCT starts rising by 2 hours after stimulus , peaks at 6 hours , plateau at 8-24 hours and decrease to base line by 2 days. • Half life is around 20 hours. • Low or negligible amount is seen in healthy individuals however it can be increased to 1000 folds during active infection and sepsis.
  34. • Interferon gamma released during the viral infections suppress PCT. • High level of PCT is seen in systemic infections therefore local bacterial colonization , encapsulated abscess , localised and limited infections may shows normal level of PCT. • Some condition where PCT can be elevated are : Neonate less then 48 hours of age First day after major surgery Trauma, Burns Pancreatitis Invasive fungal infections Malaria Severe cardiogenic shock Malignancies eg . Medullary carcinoma of thyroid ,small cell carcinoma of lungs.
  35. Interpretation of procalcitonin level Procalcitonin values(ng/ml) interpretation Less then 0.05 normal 0.05-0.5 Localized infection possible. Retest after 6-24 hours. 0.5 -2.0 Systemic bacterial infection possible. Retest after 6-24 hours. 2.0-10 Systemic bacterial infection highly likely. High risk of severe sepsis Greater then 10 Severe sepsis
  36. • An early diagnosis and the initiation of an appropriate antibiotic treatment are still the cornerstones of effective sepsis care. • In this respect, PCT has shown promising results for the treatment of patients with sepsis. • However, it should be noted that PCT values are not intended to replace good clinical practice, but should be used as a complementary tool combined with available clinical and diagnostic parameters. • The prognostic information derived from PCT kinetics can influence further procedure with regard to diagnostic testing, but also therapeutic decisions and timing of patients discharge • In high risk situation the use of PCT should not delay or inhibit the start of empirical treatments, but should rather be used for treatment termination in case PCT is <0.5 µg/L or decreased by 80–90% of the peak level. • To date, integration of the host-response marker PCT into a comprehensive clinical assessment seems to be a promising approach to reduce diagnostic uncertainties and antibiotic overuse. • Still, further research is needed to understand optimal use of PCT, also in combination with other remerging diagnostic tests for most efficient sepsis care.
  37. • Objective: To evaluate the prognostic value of C-reactive protein (CRP), procalcitonin (PCT), and their combination for mortality in patients with septic shock. • Combination matrix of CRP and PCT was compared to determine the 28-day mortality. • OR of both CRP and PCT elevated was 1.552 (95% CI 1.184–2.035), mortality rate was 26.9%. • 28-day mortality of both CRP and PCT elevated was signifcantly higher than that of only PCT elevated (17.8%) and both CRP and PCT not elevated (18.1%). • However, the 28-day mortality of patients with only CRP elevated was 21.5% which was not signifcantly different from those with both CRP and PCT elevated. • Nevertheless, in the multivariate logistic regression analysis, both CRP and PCT elevated was not an independent predictor of 28-day mortality.
  38. • Sabiston textbook of surgery -20th edition • Bailey & Love’s short practice of surgery- 27th edition • Roshan Lall Gupta’s Recent Advances in SURGERY, Volume 17. • Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2021 • Pubmed recent articles • Source Control: A Guide to the Management of Surgical Infections
  39. To be continued…………………………….. THANK YOU