Lecture 3.1 - Sepsis PDF

What is sepsis?: ◦Sepsis is defined as life-threatening organ dysfunction due to dysregulated host response to infection. ◦Organ dysfunction is defined as an acute change in total SOFA score greater than 2 points secondary to the infection cause. Definitions: ◦Bacteraemia?...

What is sepsis?: ◦Sepsis is defined as life-threatening organ dysfunction due to dysregulated host response to infection. ◦Organ dysfunction is defined as an acute change in total SOFA score greater than 2 points secondary to the infection cause. Definitions: ◦Bacteraemia? ◦Septic shock? ◦‘Septic shock’ is a subset of sepsis where particularly profound circulatory, cellular and metabolic abnormalities substantially increase mortality. ‣ Persistent hypotension requiring vasopressors to maintain Mean Arterial Pressure (MAP) greater than or equal to 65 mmHg ‣ Lactate greater than or equal to 2 mmol/L. Pathophysiology: ◦Normal physiologic response to localised infection includes: ‣ Activation of host defence mechanisms ‣ Influx of inflammatory cells ‣ Release of inflammatory mediators ‣ Local vasodilation and increased endothelial permeability ‣ Activation of coagulation pathways ◦Sepsis from exaggerated systemic inflammatory response induced by infecting organisms Aetiology of septic shock: ◦Respiratory tract and abdominal infections are the most frequent causes of sepsis, followed by urinary tract and soft-tissue infections Proposed mechanisms of injury: ◦Hypoxic hypoxia: ‣ CVD dysfunction and vascular redistribution ‣ Microvascular change; thrombosis, endothelial dysfunction ◦Direct cytotoxicity (leading to histotoxic anoxia): ‣ Endotoxin, TNF-alpha and NO ◦Coagulopathy:  ‣ Deficiencies of coagulation system proteins ‣ Cytokine effects ◦Immunosuppression ◦Apoptosis Organ failure: Pulmonary dysfunction: ◦The clinical and pathologic evolution can be categorised into the following 3 overlapping phases: ‣ Exudative phase (oedema and haemorrhage) ‣ Proliferative phase (organisation and repair) ‣ Fibrotic phase (end-stage fibrosis) ◦Direct/indirect injury to the endothelial and epithelial cells of the lung ‣ Increases alveolar capillary permeability, causing ensuing alveolar oedema ◦Surfactant problems enhance the surface tension producing diffuse microatelectasis ‣ Damage to pneumocytes ‣ Plasma proteins in alveolar fluid inactivate surfactant ◦Neutrophil entrapment initiates and amplifies the injury ◦After initial extravasation of intravascular fluid, inflammation and fibrosis of pulmonary parenchyma develop Cardiovascular dysfunction: ◦Derangement in autoregulation of the circulatory system ‣ Vasoactive mediators cause vasodilation and increase the microvascular permeability at the site of infection ◦Changes in systemic vasodilation ◦The microcirculation is the key target organ for injury in patients with sepsis ◦Hypotension: ‣ Redistribution of intravascular fluid volume from reduced arterial vascular tone ‣ Diminished venous return from venous dilation ‣ Release of myocardial depressant substances Central nervous system dysfunction: ◦Systemic inflammation ◦Hypoxemia ◦Hypotension ◦Haemorrhage  ◦Medications such as sedatives and analgesics Gastrointestinal dysfunction: ◦Barrier function may be affected, allowing translocation of bacteria and endotoxin into the systemic circulation ◦Interference with nutritional intake. Septic shock usually causes ileus, and the use of narcotics and sedatives delays the institution of enteral feeding Hepatic and renal dysfunction: ◦The hepatic reticuloendothelial system acts as a first line of defence in clearing bacteria and their products; liver dysfunction leads to a spillover of these products into the systemic circulation ◦Acute kidney injury (AKI): ‣ Associated with systemic hypotension ‣ Cytokines (e.g. TNF) ‣ Activation of inflammatory cells, which indirectly and directly contribute to renal tubular injury Sepsis risk groups: ◦Extremes of age ◦Impaired immune systems because of illness or drugs, including people being treated for cancer with chemotherapy (suspect neutropenic sepsis) ◦Recent surgery, or other invasive procedures ◦Breach of skin integrity (e.g. cuts, burns, blisters or skin infections) ◦IVDU ◦In dwelling liens or catheters ◦Women who are pregnant, have given birth or had a termination of pregnancy or miscarriage in the last 6 weeks ◦Neonates ◦Adapted from NICE guideline, sepsis: recognition, diagnosis and early management Common causes of sepsis: Examination: ◦Pale ◦Temp 36 degrees Celsius, pulse 110/min, BP 90/70 mmHg ◦Respiratory rate 30/min ◦Widespread purpuric (non-blanching) rash noted ◦Mentally alert, Glasgow Coma Scale 15 Clinical assessment: ◦Assess people with any suspected infection to identify:  ‣ Possible source of infection ‣ Factors that increase the risk of sepsis ‣ Any indicators of clinical concern, such as new onset abnormalities of behaviour, circulation or respiration ◦Use a structured set of observations/early warning score to assess people in a face to face setting to stratify risk ◦Assess: ‣ Temperature ‣ Heart rate ‣ Respiratory rate ‣ Blood pressure ‣ Level of consciousness ‣ Oxygen saturation ◦Ask the person, parent or carer about frequency of urination in the past 18 hours ◦Measurement should not cause a delay in assessment or treatment ◦Examine skin: ‣ Mottled or ashen appearance ‣ Cyanosis of the skin, lips or tongue ‣ Non-blanching rash of the skin ‣ Any breach of skin integrity (for example, cuts, burns or skin infections) or other rash indicating potential infection NEWS2 scoring system: Sepsis: ◦Narrative of sepsis is progressive organ failure - e.g. SOFA but this is not often practical clinically ◦Simplified clinically to red flag sepsis ◦Aggregate NEWS2 score of 7 or above ◦OR a patient with a lower NEWS2score (5 or 6) but also when any of the following apply: ‣ Lactate > 2 mmol/L ‣ Chemotherapy in last 6 weeks ‣ Other organ failure evident (e.g. AKI) ‣ Patient looks extremely unwell ‣ Patient is actively deteriorating  Risk stratification (NICE) >12 years: Risk stratification (NICE) children: Patient has red flag sepsis: ◦Immediate action required ◦Inform senior doctor for review ◦Send urgent investigations ◦Complete sepsis six bundle Sepsis 6 (sepsis trust): ◦Sepsis 6 works to minimise the increased mortality risk by restoring the circulation, assessing risk, monitoring the effect of treatment and switching off the infective trigger ◦The sepsis 6 should be delivered as quickly as possible, but for the sickest patients with red flag sepsis always within the first hour following recognition of sepsis Senior review:  ◦Sepsis is complex and dynamic ◦Often needs multidisciplinary input ◦Experience and authority to make things happen fast are key Oxygen: ◦Imbalance between oxygen demand and supply ◦If the patient is shocked or critically ill, the initial oxygen therapy is a reservoir mask at 15 l/min^2 ◦Adults: ‣ Give oxygen to target saturation of 94-98% ‣ 88-92% for those at risk of hypercapnic respiratory failure ◦Children: ‣ Given oxygen if (SpO2) 92%) ◦Any patient who is critically ill - for example, who is shocked or unconscious - should immediately receive high flow oxygen at 15 litres per minute via a non-rebreathe face mask with reservoir bag Bloods including cultures: ◦Glucose: ‣ Stress response causes gluconeogenesis, glycogenolysis and insulin resistance ‣ Increases risk of secondary infection ◦FBC: ‣ WCC: Trend Differential Aetiology ‣ Plt: Acute phase increase then sign of progressing organ dysfunction ‣ Hb: Helpful to maximise oxygenation Lactate: ◦In sepsis and in other pathological conditions, lactate is a marker of anaerobic respiration ◦A raised arterial lactate is usually because of one four types of problems: ‣ Insufficient oxygen delivery due to circulatory failure (the ‘macro circulation’) ‣ Insufficient oxygen delivery due to microcirculation (the capillary beds are not working properly) ‣ Inability of the tissue to use oxygen (e.g. mitochondrial dysfunction)  ‣ Excessive oxygen demand (e.g. tonic-clonic seizures, or excessive exercise) ◦Therefore, response to fluids gives an indication of severity and underlying Pathophysiology Antibiotic and considering suitable control: ◦Ensure mechanisms are in place to deliver antibiotics fast ◦Take microbiological samples before prescribing an antimicrobial (where possible) ◦For all people with suspected sepsis where the source of infection is clear use existing local antimicrobial guidance ◦If not clear - broad spectrum ◦Revise according to results ◦Think about the source: abscess; obstruction Consider IV fluids: ◦O2 delivery = O2 content of blood x cardiac output ◦Cardiac output = stroke volume x heart rate ◦The stroke volume is dependent on: ‣ Preload ‣ After load ◦The aims of fluid therapy are: ‣ To correct absolute and relative hypovolaemia ‣ To bring the patients pulse, blood pressure, mental state, lactate and urine output within target ‣ To do this judiciously, and to avoid pushing the patient into overload ◦Crystalloids are the preferred first line fluid for resuscitation. Monitor: ◦UO: ‣ In early stages this is key ‣ Easy to measure/ask about ‣ The urine output is an excellent window on the circulation. As blood flow (cardiac output) falls, so does urine output. This is essential in guiding further fluid challenges, and may identify a problem with the circulation before the blood pressure begins to fall ‣ However, the kidneys cannot auto regulate well for changes in blood flow. The relationship here is quite linear - as blood flow to the kidneys falls, so does renal blood flow and therefore urine output (gold line) ◦Serial lactate ◦NEWS2 After sepsis: ◦For around 40% of patients surviving sepsis, leaving hospital is not the end of their problems ◦Microvascular changes and disseminated intravascular coagulopathy can result in loss of digits or limbs ◦Acute lung injury can result in respiratory dysfunction ◦Acute kidney injuries can lead to a reliance on dialysis ◦Mental health impact