sepsis with septic shock

2. • The term sepsis originatesfrom the ancient Greek word sêpsis
(“putrefaction” or “decay of organicmatter”

5. SOFA SCORE

6. The 2016 Task Force also introduced the quick SOFA, or q SOFA,score, composed of three
components that are easy to measure at the bedside:
• Respiratory rate of 22 breaths/min or greater
• Altered mentation
• Systolic blood pressure of 100 mm hg or less
.
Evidence indicated that suspected infection and a higher risk for poor outcomes typical of
sepsis can be rapidly identified by the presence of at least two qSOFA criteria.
qSOFA is not part of the new definition of sepsis.

7. Aetiology
• Sepsis can arise from both community-acquired and hospital-acquired infections.
• Pneumonia is the most common source, accounting for about half of cases; next most common are
intraabdominal and genitourinary infections.
• Blood cultures are typically positive in only one-third of cases, while many cases are culture
negative at all sites
• Staphylococcus aureus and Streptococcus pneumoniae are the most common gram-positive
isolates,
• 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

9. • Proinflammatory reactions (directed at eliminating pathogens) are responsible for
“collateral” tissue damage in sepsis, whereas anti-inflammatory responses are
implicated in the enhanced susceptibility to secondary infections that occurs later
in the course.
Host’s ability to resist as well as tolerate both direct and
damage will determine whether uncomplicated infection becomes sepsis

11. Coagulopathy
Sepsis is frequently complicated by coagulopathy. Abnormalities range from subclinical coagulation
disorders to prolongation of clotting times(most notably prothrombin time and partial thromboplastin
time), low platelet counts, and elevated D-dimer levels.
Clinically, severe DIC can be characterized by widespread thrombosis in small and midsizevessels with
simultaneous hemorrhage
In patients with sepsis the reported prevalence of the most severe form of coagulopathy, disseminated
intravascular coagulation (DIC), is 35%.

12. Abnormalities in coagulation are thought to isolate invading microorganisms and/or to prevent the spread of
infection and inflammation to other tissues and organs.
Excess fibrin deposition driven by coagulation via tissue factor, a transmembrane glycoprotein expressed by various
cell types; by impaired anticoagulant
mechanisms, including the protein C system and antithrombin; and by compromised fibrin removal due to
depression of the fibrinolytic system.
Coagulation proteases further enhance inflammation via protease-activated receptors. In infections with
endothelial predominance (e.g., meningococcemia), these mechanisms can be common and deadly

13. Commonly used screening assays for DIC include
(1) a reduced or downward trend in the platelet count (usually <100,000/mm3);
(2) the presence of fibrin-related markers including fibrin degradation products, D-dimers, or soluble fibrin in
plasma;
(3) prolongation of PT or APTT (>1.2 times the upper limit of normal);
(4) low plasma levels of endogenous anticoagulants such as antithrombin and protein C.
from various sites studies have shown that the development of DIC in patients with sepsis can double the risk
of death

14. Cardiovascular Dysfunction
The cardiovascular impact of sepsis has two components: myocardial
dysfunction and relative hypovolemia resulting from vasodilation.
Sepsis-associated myocardial dysfunction includes
1. Reduced left and right ventricular ejection fractions,
2. Increased left and right ventricular end-diastolic volumes,
3. Elevated heart rate and cardiac output.
In early shock, when volume status is reduced, systemic vascular
resistance may be quite high with low cardiac output; after volume
repletion, however, this picture may rapidly change to low systemic
vascular resistance and high cardiac output

15. 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
The underlying pathology is diffuse alveolar epithelial injury, with increased barrier permeability and
exudation of protein-rich fluid into the interstitial and airspace compartments. Neutrophils and monocytes
accumulate in the lungs and may form cellular aggregates in pulmonary vessels. Significant right-to-left
shunting occurs
A common competing diagnosis is hydrostatic edema secondary to cardiac failure or volume overload.
(identified by elevated pulmonary capillary wedge measurements from a pulmonary artery catheter(>18
mmHg)
cardiac failure can be objectively evaluated on the basis of clinical judgment or focused echocardiography.

16. RENAL DYSFUNCTION
Acute kidney injury (AKI) is documented in >50% of septic patients,
Increases the risk of in-hospital death by six- to eight-fold.
AKI manifests as oliguria, azotemia, and rising serum creatinine levels and frequently requires dialysis.
The mechanisms of sepsis-induced AKI are incompletely understood.
AKI may occur in up to 25% of patients in the absence of overt hypotension.
Current mechanistic work suggests that a combination of diffuse microcirculatory blood-flow abnormalities,
inflammation, and cellular bioenergetic responses to injury contribute to sepsis-induced AKI beyond just organ ischemia.

17. HEPATIC DYSFUNCTION
Hepatic dysfunction includes cholestatic jaundice characterized by elevations in conjugated and
unconjugated bilirubin, often seen in association with elevated levels of alkaline phosphatase and
aminotransferase levels.
A “shock liver” is unusual, but if the duration of septic shock is prolonged,a massive rise in serum
transaminases may follow hypoxic necrosis ofcentrilobular liver cells

18. GASTROINTESTINAL INJURY
Gastrointestinal tract injuries include disruption of the intact intestinal epithelium, which may lead to the translocation of
inflammatory mediators;
The gut microbiota of patients with sepsis are characterized by lower diversity, lower abundances of key commensal
genera, and in some cases overgrowth by one bacterial genus, a state otherwise known as dysbiosis.
Preclinical work underscores the role of the microbiota in maintaining gut-barrier function and suggests that impaired
communication across the gut-organ axes is associated with brain, lung, and kidney failure
The occurrence of erosions of the gastric and duodenal mucosa that predispose to upper gastrointestinal bleeding; and
the development of ileus, which may persist for several days after the resolution of septic shock

19. Neurologic Complications Typical central nervous system dysfunction presents as coma or delirium.
Imaging studies typically show no focal lesions, and electroencephalographic findings are usually consistent with non
focal encephalopathy.
Sepsis-associated delirium is considered a diffuse cerebral dysfunction caused by the inflammatory response to
infection without evidence of a primary central nervous system infection.
Consensus guidelines recommend delirium screening with valid and reliable tools such as the
Confusion Assessment Method for the Intensive Care Unit (CAM-ICU)
and the Intensive Care Delirium Screening Checklist (ICDSC).

20. Post sepsis syndrome, an emerging pathologic entity characterized by long-term cognitive impairment and functional
disability, affects 25−50% of sepsis survivors.
.
The mechanisms of the neurocognitive derangements in post sepsis syndrome are not fully understood; however, a
combination of cerebrovascular injury, metabolic derangements, and neuroinflammation is proposed
Critical-illness polyneuropathy and myopathy are also common, especially in patients with a pro-longed course.

21. • Tachycardia(heart rate, >90 beats/min) was present in >50% of encounters;
• Tachypnoea (respiratory rate, >20 breaths/min)
• Hypotension (systolic blood pressure,≤100 mmHg)
• Hypoxia (SaO2, ≤90%).
• Leucocytosis (WBC count,>12,000/μL) was present in fewer than one-third of patients and leukopenia (WBC
count, <4000/Μl)
DIAGNOSIS

22. APPROACH TO SEPSIS
Early identification of infected patients, the quick SOFA(qSOFA) and the National Early Warning Score
(NEWS) scores are pro-posed as clinical prompts to identify patients at high risk of sepsis outside the ICU,
whether on the medical ward or in the emergency department
Moreover, failure to meet
two or more SOFA or qSOFA criteria should not lead to a delay of diagnosis

23. INITIATING 1HOUR BUNDLE CARE
This management bundle includes five components:
1. Measurement of serum lactate levels,
2. Collection of blood for culture before antibiotic administration,
3. Administration of appropriate broad-spectrum antibiotics,
4. Begin 30 ml/kg crystalloid bolus for hypotension or lactate≥4 mmol/l
5. Apply vasopressors if hypotensive during or after fluid resuscitation to maintain MAP ≥ 65
mm Hg.
* Remeasure lactate if initial lactate is elevated (> 2 mmol/L).
For every 1-h delay among septic patients, a 3−7%increase in the odds of in-hospital death is reported

24. Antimicrobials

25. Septic shock(immunocompetent adult)
The many acceptable regimens include (1) piperacillin-tazobactam (4.5 g q6h), (2) cefepime (2 g q8h), or
(3)meropenem (1 g q8h) or imipenem-cilastatin (0.5 g q6h).
OR
If the patient is allergic to β-lactam antibiotics, use (1)aztreonam (2 g q8h) or (2) ciprofloxacin (400 mg q12h) or
levofloxacin (750 mg q24h).
+
Add vancomycin (loading dose of 25–30 mg/kg, then 15–20 mg/kg q8–12h) to each of the above regimens.
ANTIMICROBIAL REGIMEN INITIAL ANTIMICROBIAL THERAPY FOR SEVERE SEPSIS WITH NO
OBVIOUS SOURCE IN ADULTS WITH NORMAL RENAL FUNCTION

26. Empirical broad spectrum antibiotics should be given by syndromic approach
For adults with sepsis or septic shock at high risk of MRSA, using empiric
antimicrobials with MRSA coverage recommended
Empirical antifungal therapy should be administered only to septic patients at
high risk for invasive candidiasis(Quality of evidence: low}
Antiviral not recommened
For adults with sepsis or septic shock and low risk for multidrug-resistant
(MDR) organisms, it is suggested using 2 gram-negative agents for empiric
treatment, as compared to 1 gram-negative agent.
(Quality of evidence: low}

27. Neutropenia (<500neutrophils/μL)
Regimens include (1) cefepime (2 g q8h), (2) meropenem(1 g q8h) or imipenem-
cilastatin (0.5 g q6h) or doripenem(500 mg q8h), or (3) piperacillin-tazobactam (3.375 g
q4h).
Add vancomycin (as above)
if the patient has a suspected central line–associated bloodstream infection, severe
mucositis, skin/soft tissue infection, or hypotension.
Add tobramycin (5–7 mg/kg q24h) plus vancomycin (as above)plus caspofungin (one
dose of 70 mg, then 50 mg q24h) if the patient has severe sepsis/septic shock

28. Splenectomy
Use ceftriaxone (2 g q24h, or—in meningitis—2 g q12h).
If the local prevalence of cephalosporin-resistant pneumococci is high, add
vancomycin (as above).
If the patient is allergic to β-lactam antibiotics, use levofloxacin (750 mg q24h) or
moxifloxacin (400 mg q24h) plus vancomycin (as above)

29. Resuscitation with IV crystalloid fluid (30 mL/kg) should begin within the first 3
(Quality of evidence: low in 2021}
.Saline or balanced crystalloids are suggested for resuscitation
.If the clinical examination does not clearly identify the diagnosis, hemodynamic assessments (e.g., with focused cardiac
ultrasound) can be considered.
In patients with elevated serum lactate levels, resuscitation should be guided toward normalizing these levels when possible.

30. • In patients with septic shock requiring vasopressors, the recommended target mean arterial pressure is 65 mmHg.
• Norepinephrine is recommended as the first-choice vasopressor. Vasopressin should be used with the intent of
reducing the norepinephrine dose.
• The use of dopamine should be avoided except in specific situations—e.g., in those patients at highest risk of
tachyarrhythmias or relative bradycardia .
• Dobutamine use is suggested when patients show persistent evidence of hypoperfusion despite adequate fluid loading
and use of vasopressors.
• levosimendan use is not recommended.

31. Monitoring
PAC is no longer recommended for routine use. Instead, a variety of non-invasive monitoring tools, such as
arterial pulse contour analysis (PCA)or focused echocardiography, can provide continuous estimates of
parameters such as cardiac output, beat-to-beat stroke volume, and pulse pressure variation. These tools, along
with passive leg-raise maneuvers or inferior vena cava collapsibility on ultrasound, can help determine a patient’s
volume responsiveness

32. Support of organ function
Support of Organ Function The primary goal of organ support is to improve delivery of oxygen to the tissues as quickly as possib
Administration of IV fluids or vasopressors, blood transfusions, or ventilatory support
In general, crystalloids are recommended on the basis of strong evidence as first-line fluids for sepsis resuscitation, Their use is
guided by resolution of hypotension, oliguria, altered mentation, and hyperlactemia
5. There is insufficient evidence to make a recommendation on the use of restrictive versus
liberal fluid strategies in the first 24hr of resuscitation in patients with sepsis and septic
shock who still have signs of hypoperfusion
and volume depletion after the initial resuscitation.

33. Ventilation
For adults with sepsis induced hypoxemic Respiratory failure, it is suggested to use of high flow nasal oxygen over
noninvasive ventilation.
Mechanical ventilation with a target tidal volume of 6 mL/kg predicted bodyweight is recommended compared
with 12 mL/kg in adult patients withs epsis-induced ARDS.
An upper limit goal for plateau pressures of 30 cmH2O over higher plateau pressures is recommended in
patients with sepsis-induced severe ARDS.
The use of higher PEEP over lower PEEP is recommended in patients with sepsis-induced moderate-to-severe
ARDS

34. When using recruitment maneuvers, we recommend against using incremental PEEP titration/strategy.
Strong recommendation, moderate quality of evidence.
adults with sepsis-induced severe ARDS, we
suggest using venovenous (VV) ECMO when conventional mechanical ventilation fails in experienced centers with
the infrastructure in place to support its use.