Seminar - Sepsis and septic shock in medicine

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1. Sepsis and Septic Shock Moderator: Dr. Eshetu Wijira (Professor of Internal Medicine) Presenter: Daniel Angamo (C-I)

2. Outline Introduction Etiology Epidemiology Clinical manifestation Diagnosis Management

3. Objectives To define sepsis and septic shock; To describe the clinical presentation of sepsis and septic shock, hemodynamic measures, and laboratory tests; Describe the microbial pathogens of sepsis;

4. Question Who are at risk of developing sepsis? What is a gold-standard method for determining sepsis?

5. Introduction and Definition Sepsis : Life-threatening organ dysfunction caused by a ‘’ dysregulated ’’ host response to infection. Septic shock: Sepsis with circulatory and cellular/metabolic abnormalities profound enough to substantially increase mortality.

6. Introduction and Definition Sepsis can affect anyone, but people who are older, very young, pregnant or have other health problems are at higher risk. Common signs of sepsis include fever, fast heart rate, rapid breathing, confusion and body pain. It can lead to septic shock, multiple organ failure and death.

7. Introduction and Definition Sepsis and infection are two words that should not be confused. Although the terms infection and sepsis are sometimes used interchangeably, they do not refer to the same condition. Sepsis is the most severe form of infection, when host response becomes dysregulated, so that organ dysfunction develops.

8. Introduction and Definition Sepsis is fundamentally a systemic response to infection that results in organ dysfunction, however it is characterized by: complex underlying pathophysiology, and r epresents a broad spectrum of disease. Sepsis is a common and deadly disease which is usually caused by bacterial infections but may be the result of other infections such as viruses, parasites or fungi.

9. Introduction and Definition Criteria for septic shock include sepsis plus the need for vasopressor therapy to elevate mean arterial pressure to ≥65 mmHg(in absence of hypovolemia) with a serum lactate concentration >2.0 mmol /L despite adequate fluid resuscitation (hypotension persisting after a 30 mL/kg fluid bolus ); Standards have been proposed for emergency medicine and critical care providers in both basic and advanced POCUS techniques. The use of POCUS can improve care of septic patient by providing real-time clinical information.

10. Introduction and Definition The Sepsis Definitions Task Force in 2016 proposed the ‘’Third International Consensus Definitions’’ specifying that sepsis is a dysregulated host response to infection that leads to acute organ dysfunction. Pro- and anti-inflammatory responses (of the host against developing infection) result in a dysregulated reaction in sepsis. In the pathology of sepsis, the intracellular signaling process leads to expressional changes of genes contributing to adaptive immunity & inflammation .

11. Introduction and Definition For more than 25 years, t he defined based on physiologic derangements of vital signs and laboratory values suggestive of infection (Sepsis-1 and Sepsis-2 ); Recently , an international collaboration suggested a new definition based on end-organ dysfunction (Sepsis-3); In resource-poor areas where laboratory values are not easily available, hospitals may continue to use Sepsis-2;

12. Sepsis … Etiology Sepsis can arise from both community-acquired and hospital-acquired infections . Pneumonia is the most common infection accounting for about 50% of cases of sepsis, and intraabdominal and genitourinary infections are next most common infections. Blood cultures are typically positive in only 30% of cases, while many cases are culture negative at all sites.

13. Sepsis … Etiology Staphylococcus aureus and S. pneumoniae are the most common gram-positive isolates, while Escherichia coli, Klebsiella species , and Pseudomonas aeruginosa are the most common gram-negative isolates. In recent years, gram-positive infections have been reported more often than gram-negative infections, yet a 75-country point-prevalence study of 14,000 patients on intensive care units (ICUs ) found that 62% of positive isolates were gram-negative bacteria, 47 % were gram-positive bacteria, and 19% were fungi.

14. Sepsis … Pathogenesis Initiation of inflammation Coagulation a bnormalities Organ dysfunction Anti-inflammatory mechanisms Immune suppression

15. Sepsis … Pathogenesis Generally , proinflammatory reactions (directed at eliminating pathogens) are responsible for “collateral” tissue damage, Whereas anti-inflammatory responses are implicated in the enhanced susceptibility to secondary infections that occurs later in the course. These mechanisms can be characterized as an interplay between two “fitness costs”: direct damage to organs by the pathogen and damage to organs stemming from the host’s immune response .

16. Sepsis … Pathogenesis … Initiation of i nflammation: Host response to infection is initiated when pathogens are recognized and bound by innate immune cells, particularly macrophages. The interaction of Pathogen Recognition Receptors (PRRs) present on the surface of immune cells and pathogen-associated molecular patterns ( PAMPs) results in upregulation of inflammatory gene transcription and activation of innate immunity.

17. Sepsis … Pathogenesis … Initiation of i nflammation: Four main PRR classes are: Toll-like receptors (TLRs), RIG-I-like receptors, C-type lectin receptors, and NOD-like receptors; the activity of the last group occurs partially in protein complexes called inflammasomes .

18. Sepsis … Pathogenesis … Initiation of i nflammation: PAMPs include lipopolysaccharide (LPS), viral RNAs and flagellin . A common PAMP is the lipid A moiety of LPS (endotoxin) found in the outer membrane of gram-negative bacteria. LPS first attaches to the LPS-binding protein on the surface of monocytes, macrophages , and neutrophils.

19. Clinical manifestation The specific clinical manifestations of sepsis are quite variable, depending on: the initial site of infection, the offending pathogen, the pattern of acute organ dysfunction, the underlying health of the patient, and the delay before initiation of treatment. Signs of both infection & organ dysfunction may be subtle.

20. Clinical manifestation … Once sepsis has been established and the inciting infection is assumed to be under control , the temperature and white blood cell (WBC) count often return to normal. However , organ dysfunction typically persists. Two of the most commonly affected organ systems in sepsis are the respiratory and cardiovascular systems .

21. Clinical manifestation … Respiratory compromise classically manifests as acute respiratory distress syndrome (ARDS), defined as: Hypoxemia, and bilateral infiltrates of noncardiac origin that arise within 7 days of the suspected infection . ARDS can be classified by Berlin criteria as mild ( Pao2/Fio2, 201–300 mmHg), moderate (101–200 mmHg), or severe (≤100 mmHg).

22. Clinical manifestation … Acute kidney injury (AKI) is documented in >50% of septic patients, increasing the risk of in-hospital death by 6 – 8 folds. AKI manifests as oliguria, azotemia, and rising serum creatinine levels and frequently requires dialysis. The mechanisms of sepsisinduced AKI are incompletely understood. AKI may occur in up to 25% of patients in the absence of overt hypotension.

23. Clinical manifestation … Typical CNS dysfunction presents as coma or delirium. Brain imaging typically show no focal lesions, and electroencephalographic findings are usually consistent with non-focal encephalopathy. Sepsis-associated delirium is a diffuse cerebral dysfunction due to inflammatory response to infection without evidence of a primary central nervous system infection.

24. Clinical manifestation … Critical-illness polyneuropathy and myopathy are also common, especially in patients with a prolonged course. For survivors of sepsis, neurologic complications can be severe. Post-sepsis syndrome, an emerging pathologic entity characterized by long-term cognitive impairment and functional disability, affects 25−50% of sepsis survivors.

25. Additional manifestations Many other abnormalities including – ileus, elevated aminotransferase levels, altered glycemic control, thrombocytopenia and disseminated intravascular coagulation, adrenal dysfunction, and sick euthyroid syndrome. Adrenal dysfunction – related more to reversible dysfunction of the hypothalamic-pituitary axis or tissue glucocorticoid resistance than to direct damage to the adrenal gland .

26. DIAGNOSIS Laboratory and Physiologic Findings tachycardia (heart rate, >90 beats/min) present in >50% of encounters; the most common accompanying abnormalities: tachypnea (respiratory rate, >20 breaths/min), hypotension (systolic blood pressure, ≤100 mmHg), and hypoxia (SaO2, ≤90%). M Leukocytosis

27. Diagnosis … Laboratory and physiologic findings … Features that may identify acute organ dysfunction, such as platelet count, total bilirubin, or serum lactate level, are measured in only a small minority of at-risk encounters. Other , less common findings include serum hypoalbuminemia, troponin elevation, hypoglycemia, and hypofibrinogenemia .

28. Diagnostic criteria

29. Diagnostic criteria … In all sepsis definitions, the diagnosis of sepsis hinges on whether the patient has “suspected infection.” Unfortunately , there is little discussion about exactly how to determine whether infection is “suspected.” Indeed , for most patients presenting with an unclear problem, infection is somewhere on the differential diagnosis .

30. Diagnostic criteria …

31. Diagnostic criteria … In order to sort through these complex details, clinicians need simple bedside criteria to operationalize the logic statement. The Sepsis Definitions Task Force, with the introduction of Sepsis-3, has recommended that, once infection is suspected, clinicians consider whether it has caused organ dysfunction by determining a SOFA score.

32. Diagnostic criteria … Six distinct scores, one for each of the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems ( CNS ) make up the final result. Each organ system received a score ranging from 0 (normal) to 4 (most abnormal), with a minimum SOFA score of 0 and a maximum SOFA score of 24 .

33. Diagnostic criteria …

34. Diagnostic criteria … The SOFA score ranges from 0 to 24 points, with up to 4 points accrued across six organ systems. The SOFA score is widely studied in the ICU among patients with infection, sepsis, and shock. With ≥2 new SOFA points , the infected patient is considered septic and may be at ≥ 10% risk of in-hospital death.

35. Diagnostic criteria … A SOFA score from 0 to 1 is associated with 100% survival, while a SOFA score greater than 11 is associated with 100% mortality.

36. Diagnostic criteria …

37. Diagnostic criteria … The qSOFA score is a bedside evaluation that may identify patients with suspected infection who are at greater risk for a poor outcome outside the intensive care unit (ICU). The qSOFA score ranges from 0 to 3 points. The presence of 2 or more qSOFA points near the onset of infection was associated with a greater risk of death or prolonged intensive care unit stay.

38. Diagnostic criteria … Subsequent studies have shown that qSOFA may have low sensitivity to detect sepsis, which may potentially limit its role as a screening tool. NEWS2 adds to qSOFA's three key parameters with  oxygen saturation, pulse rate and temperature, as well as adding a score if the patient is dependent on oxygen therapy.

39. Diagnostic criteria … These extra variables enhance the ability of NEWS2 to identify patients at risk compared with qSOFA . A NEWS2 score of 5 or above is a critical marker, signaling an urgent need for response in sepsis cases. In EDs, NEWS2 outperforms the quick qSOFA in identifying sepsis accompanied by organ dysfunction, the need for intensive care, and mortality due to infection.

40. Diagnostic criteria … The National Early Warning Score (NEWS2)

41. Advice The NEWS2 (and any early warning score) should be used as an adjunct to clinical judgment, not to replace it. Any concern about a patient’s clinical condition should prompt urgent investigation regardless of early warning scores.

42. Management Resuscitation – C rystaloids , Vasopressors, C olloids; Infection control – IV antibiotics should be initiated as soon as possible; Respiratory support 'Sepsis Six' – a set of six tasks including oxygen, cultures, antibiotics, fluids, lactate measurement and urine output monitoring.

43. Management … The goals of resuscitation in sepsis and septic shock are to restore intravascular volume, increase oxygen delivery to tissues, and reverse organ dysfunction. A crystalloid bolus of 30 mL/kg is recommended within 3 hours of detecting severe sepsis or septic shock.

44. Management … Resuscitation with IV crystalloid (30 mL/kg) should begin within the first 3 h. Saline or balanced crystalloids are suggested for resuscitation. If clinical examination does not clearly identify the diagnosis, hemodynamic assessments (e.g., with focused cardiac ultrasound) can be considered.

45. Management … Vasopressors – recommended target mean arterial pressure is 65 mmHg. Vasopressors ( Norepinephrine, Adrenaline , V asopressin [ADH ] ) aim to optimize coronary and cerebral perfusion. Norepinephrine is recommended as the first-choice vasopressor. The use of dopamine should be avoided except in specific situations—e.g., in those patients at highest risk of tachyarrhythmias or relative bradycardia.

46. Management … Dobutamine use is suggested when patients show persistent evidence of hypoperfusion despite adequate fluid loading and use of vasopressors. Red blood cell transfusion is recommended only when the hemoglobin concentration decreases to <7.0 g/dL in the absence of acute myocardial infarction, severe hypoxemia , or acute hemorrhage.

47. Prevention In light of the persistently high mortality risk in sepsis and septic shock , prevention is the best approach to reducing avoidable deaths , but preventing sepsis is a challenge. The aging of the population, the overuse of inappropriate antibiotics, the rising incidence of resistant microorganisms, and the use of indwelling devices and catheters contribute to a steady burden of sepsis cases. Adoption of infection control in high-risk settings and could guide appropriate care .

48. Thank you

49. References Harrison’s Principles of Internal medicine 21st Edition AASLD 2021 guideline on diagnosis, evaluation and mgt of Ascites Davidson's principle and practice of Medicine 24th Edition