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Applied Bioscience for Health Complex Sepsis Learning outcomes ◼Define sepsis ◼Identify the risk factors of sepsis ◼Describe the pathophysiology of sepsis ◼Describe the signs and symptoms of sepsis ◼Describe the management of a patient with sepsis Definition of...

Applied Bioscience for Health Complex Sepsis Learning outcomes ◼Define sepsis ◼Identify the risk factors of sepsis ◼Describe the pathophysiology of sepsis ◼Describe the signs and symptoms of sepsis ◼Describe the management of a patient with sepsis Definition of terms ◼Sepsisis a life-threatening organ dysfunction caused by a dysregulated host response to infection” ◼Septic shock: Subset of sepsis with circulatory and cellular/metabolic dysfunction associated with higher risk of mortality ◼The quick Sequential Organ Failure Assessment (qSOFA) score is a bedside prompt that may identify patients with suspected infection who are at greater risk for a poor outcome outside the intensive care unit (ICU). It uses three criteria, assigning one point for low blood pressure (SBP≤100 mmHg), high respiratory rate (≥22 breaths per min), or altered mentation (Glasgow coma scale2 points Sequential Organ Failure Assessment (SOFA) score. ◼The new clinical criteria for septic shock include ◼sepsis with fluid-unresponsive hypotension, ◼serum lactate level greater than 2 mmol/L, and vasopressors to maintain mean arterial pressure > 65mmHg Abraham (2016), JAMA (Editorial): 315(8); 757-759 Sepsis, New definitions but… ◼Sepsis“…life threatening organ dysfunction caused by a dysregulated response to infection” ◼qSOFA does not replace systemic inflammatory response syndrome (SIRS) ◼qSOFA to help raise suspicion, not replace clinical judgement Vincent et al. (2016), Critical Care 2016: 20;210 Risk factors ◼Intensive care unit admission – Approximately 50 percent of intensive care unit (ICU) patients have a nosocomial infection and are, therefore, intrinsically at high risk for sepsis ◼Bacteremia– Patients with bacteremia often develop systemic consequences of infection. ◼Advanced age (≥65 years) – The incidence of sepsis is disproportionately increased in older adult patients and age is an independent predictor of mortality due to sepsis ◼Immunosuppression – Comorbidities that depress host-defense (eg, neoplasms, renal failure, hepatic failure, AIDS, asplenism) and immunosuppressant medications are common among patients with sepsis, or septic shock Risk factors ◼Diabetes and obesity – Diabetes and obesity may alter the immune system, resulting in an elevated risk for developing sepsis ◼Cancer – Malignancy is one of the most common comorbidities among patients with sepsis ◼Previous hospitalization – Hospitalization is thought to induce an altered human microbiome, particularly in patients who are treated with antibiotics ◼Genetic factors – Both experimental and clinical studies have confirmed that genetic factors can increase the risk of infection Pathophysiology ◼ Typically, a bacterial pathogen enters a sterile site in which resident cells can detect the invader and initiate the host response ◼ Thehost response is initiated by binding macrophages to microbial components resulting in the phagocytosis of invading bacteria, bacterial killing, and phagocytosis of debris from injured tissue ◼ These processes are associated with the production and release of a range of proinflammatory cytokines by macrophages. This response is highly regulated by a mixture of proinflammatory and anti-inflammatory mediators ◼ When a limited number of bacteria invade, the local host responses are generally sufficient to clear the pathogens. The end result is normally tissue repair and healing ◼ Sepsis occurswhen the release of proinflammatory mediators in response to an infection exceeds the boundaries of the local environment, leading to a more generalized response. Pathophysiology ◼ The cause is likely multifactorial and may include the direct effects of invading microorganisms or their toxic products, release of large quantities of proinflammatory mediators, and complement activation. ◼ The proinflammatory mediators, which include cytokines interact with endothelial causing injury to the endothelium and activation of the coagulation factors. ◼ In very small blood vessels the coagulation response, in combination with endothelial damage, may impede blood flow leading to blood vessels becoming leaky and clot formation ◼ As fluid and microorganisms escape into the surrounding tissues, the tissues begin to swell in the lungs can lead to pulmonary oedema, manifesting as shortness of breath ◼ If coagulation proteins become exhausted, bleeding may ensue. ◼ Cytokines also cause blood vessels to dilate (widen), producing a decrease in blood pressure. ◼ Nitric oxide which is key to blood pressure regulation is produced in an excessively, contributing to the widespread hypotension. Pathophysiology ◼ Inadequate tissue perfusion leads to cellular hypoxia and lactic acidosis. ◼ Widespread cellular injury may occur as a result of ischemia, cytopathic injury (direct cell injury) and an altered rate of apoptosis. Cellular injury is the precursor to organ dysfunction ◼ Thecellular injury, accompanied by the release of proinflammatory and antiinflammatory mediators, often progresses to organ dysfunction. No organ system is protected from the consequences of sepsis. Signs and symptoms Diagnostic signs ◼ Arterial hypotension (eg, systolic blood ◼ Leukocytosis (white blood cell [WBC] count >12,000 pressure [SBP] 38.3 or 20 breaths/minute. ◼ Thrombocytopenia (platelet count 4 mg/dL or 70 micromol/L). ◼ Hyperlactatemia Diagnosis ◼Aconstellation of clinical, laboratory, radiologic, physiologic, and microbiologic data is typically required for the diagnosis of sepsis ◼Imaging — There are no radiologic signs that are specific to the identification of sepsis other than those associated with infection in a specific site (eg, pneumonia on chest radiography, fluid collection on computed tomography of the abdomen). ◼Microbiology — The identification of an organism in culture in a patient who fulfils the definition of sepsis is highly supportive of the diagnosis of sepsis but is not necessary. The rationale behind its lack of inclusion in the diagnostic criteria for sepsis is that a culprit organism is frequently not identified in up to 50 percent of patients who present with sepsis. Recommendation for initial resuscitation During the first 6 hours of resuscitation, the goals of initial resuscitation should include all of the following as a part of a treatment protocol: ◼CVP 8–12mmHg ◼MAP ≥ 65mmHg ◼Urine output ≥0.5mL/kg/hr  Antibiotics ◼The administration of IV antimicrobials be initiated as soon as possible after recognition and within 1 hour for both sepsis and septic shock. With one or more antimicrobials to cover all likely pathogens. ◼Empiric combination therapy (using at least two antibiotics of different antimicrobial classes) aimed at the most likely bacterial pathogen(s) for the initial management of septic shock is recommended. Fluid Therapy ◼Crystalloidsis recommended as the fluid of choice for initial resuscitation and subsequent intravascular volume replacement in patients with sepsis and septic shock ◼albuminin addition to crystalloids when patients require substantial amounts of crystalloids ◼Young children may require up to 80 to 100 mL/kg of isotonic solution during their initial resuscitation phase. ◼Early aggressive fluid resuscitation in children may be required in the child with normal blood pressure. As children often maintain systolic blood pressure despite significant volume depletion. ◼The most useful clinical features for detecting dehydration in a young child are absence of tears, dry mucous membranes, prolonged capillary refill, and abnormal general appearance.  Vasoactive agents ◼ Norepinephrine as the first-choice vasopressor ◼ Norepinephrine (warm shock) and Dobutamine (cold shock) Mechanical Ventilation ◼Use of higher PEEP over lower PEEP in adult patients with sepsis- induced moderate to severe ARDS is recommended. Glucose control ◼A protocolized approach to blood glucose management in ICU patients with sepsis, commencing insulin dosing when 2 consecutive blood glucose levels are >7 mmol is recommended. ◼Blood glucose values should be monitored every 1 to 2 hrs until glucose values and insulin infusion rates are stable, then every 4 hrs thereafter in patients receiving insulin infusions.  Lactate can help guide resuscitation Guiding resuscitation to normalize lactate in patients with elevated lactate levels as a marker of tissue hypoperfusion is important Paediatric antibiotics ◼ Antimicrobialagents should be given as soon as possible, according to the most likely pathogens. The following therapies are commonly employed: ◼ Newborns and infants in the first 6-8 weeks of life: Ampicillin and gentamicin, ampicillin and cefotaxime, or ampicillin and ceftriaxone ◼ Older infants and children with sepsis of unclear etiology: A third-generation cephalosporin plus vancomycin. Add clindamycin if S aureus ◼ Patients who have indwelling catheters or those who are at high risk for methicillin-resistant Staphylococcus aureus (MRSA) infection: As above, with the addition of vancomycin. ◼ Patients who have fever and neutropenia: Broad-spectrum coverage with an emphasis on Gram-negative bacteria  Sepsis Treatment Conti…… ◼Surgical intervention(e.g. abscess drainage or venous access) is occasionally required. ◼Adjunctive therapies may be considered, including the following: - Corticosteroids?? - Intravenous immunoglobulin (IVIg) ◼Generally, these patients should not be fed until gut hypoxia and hypoperfusion have been excluded. Once feeding can safely begin, immune-enhancing nutrition may reduce mortality. References ◼Abraham, E. (2016). New Definitions for Sepsis and Septic Shock: Continuing Evolution but With Much Still to Be DoneNew Definitions for Sepsis and Septic Shock Editorial. JAMA, 315(8), 757-759. doi:10.1001/jama.2016.0290 ◼LeMone, P., Burke, K., Dwyer, T., Levett-Jones, T., Moxham, L., Reid-Searl, K., et al. (2020). Medical- Surgical Nursing: Critical Thinking in Client Care (4th ed.). Frenchs Forest, NSW: Pearson Australia ◼Vincent, J.-L., Martin, G. S., & Levy, M. M. (2016). qSOFA does not replace SIRS in the definition of sepsis. Critical Care, 20(1), 210. doi:10.1186/s13054-016-1389-z