Management of Sepsis

21/12/2017 Inotropes and Vasopressors • Medicines that do one or more of the following Management of Shock • Increase cardiac contractility and/or rate Inotropes and Vasopressors – positive inotrope John Dade • Alter cardiovascular tone Leeds Teaching Hospitals NHS Trust – vasodilator – vasopressor Shock Cardiovascular Features - Shock • Inadequate tissue perfusion Description Primary Secondary Example Defect Defect • Caused by one or more of Cardiogenic Low CO High SVR Post MI Shock Hypovolaemia Hypovolaemic Low CVP Low CO Dehydration, Inadequate cardiac output Shock High SVR hemorrhage Vasodilation Vasodilatory Low SVR High CO Septic Shock Shock CO : Cardiac Output SVR : Systemic Vascular Resistance CVP : Central Venous Pressure Treatment Options - Shock Description Primary Secondary Treatment Receptor Site Ligand Action Defect Defect 1 Arterial Noradrenaline Vasoconstriction (↑SVR) Vasculature 1 Myocardium Adrenaline Inotrope (↑CO) Cardiogenic Low CO High SVR Inotrope Dobutamine Chronotrope (↑HR) Shock vasodilator 2 Airways, Adrenaline Bronchodilation, Vasculature Salbutamol Vasodilation (↓SVR) Hypovolaemic Low CVP Low CO Fluid/Blood Shock High SVR products DA1 Kidney, Dopamine Vasodilation (↓SVR) splanchnic diuretic Vasodilatory Low SVR High CO Vasopressor DA2 Pre-synaptic Dopamine Vasodilation (↓SVR) Shock Fluid neurones inotrope 1 21/12/2017 Noradrenaline • 1st choice vasopressor vasodilatory shock, sepsis (SS) • Dose 0 to 1 microgram/kg/min (0-5mg/hr) 1 1 2 DA1 DA2 Adrenaline ++ +++ ++ - - • Can be used in conjunction with an inotrope Dobutamine + +++ ++ - - Dopamine + +++ + +++ ++ • Standard mix 4mg in 50mL / 8mg in 100mL (ICS) • Noradrenaline +++ ++ - - - Start at 2-5mL/hr – titrate to response • Aim for MAP ≥65mmHg Metaraminol +++ - - - - • Central Line only Phenylephrine +++ - - - - Dobutamine Adrenaline • Inotrope - ↑ CO with a smaller ↑heart rate than adrenaline • Increases CO, variable effects on SVR • May cause significant vasodilation – dose limiting • Doses up to 0.2 microgram/kg/min (1mg/hr) inotrope/inodilator • Limited role in sepsis, used with a vasopressor • Doses up to 1 microgram/kg/min (5mg/hr)- inotropic – Evidence of cardiac dysfunction e.g. echo, low Cardiac index and increasing vasopressor effect – Hypoperfusion despite adequate filling/MAP • Limited role in sepsis – induces lactic acidosis. • Usual mix 250mg in50mL or 500mg in 100mL • Start at 2-5ml/hr. Titrate to CO / MAP • Standard mix 4mg in 50ml / 8mg in 100mL (ICS) • Dose 0-20 microgram/kg/min (or higher) • Start at 2-5mL/hr – titrate to CO / MAP • Central Line • Central line only Metaraminol & Phenylephrine Vasopressin Agonists • Alternative α agonists • Vasopressin secreted normally to counteract vasodilation. • Less potent than noradrenaline • Response time limited as endogenous vasopressin becomes depleted • Maybe be given peripherally (short term) • Vasopressin therapy aims to mimic this effect • Limited role in severe sepsis – used in HDU setting • Aim for physiological replacement • Phenylephrine 10mg in 100mL • Typically used to minimise noradrenaline dose – Added when this exceeds 0.5mcg/kg/min – No improvement in survival – reduced AKI & need for renal replacement • Metaraminol 20mg in 40mL • Low doses only – Vasopressin – 0.01 to 0.04 units/min – Terlipressin – 0.25-0.5mg QDS or ≥0.1mg/hr infusion • Higher doses can cause ischaemic effects 2 21/12/2017 Prescribing Inotropes Monitoring patients Sepsis • High vs. Low BP Targets in Septic Shock NEJM • Review concurrent therapy - 2014:37;1583-93 – Sedation induced hypotension e.g. Propofol – MAP 80-85 vs. 65-70mmHg (776 pts. Multicentre) – Regular medicines – antihypertensives, tamsulosin – No difference in 28 or 90 days mortality • Is therapy appropriate – Is patient adequately filled. • Surviving Sepsis Campaign – Is there a role for other inotropes e.g. vasopressin, dobutamine – Can agents be stopped/started – Aim for Mean Arterial Pressure ~65mmHg – Addition treatments – steroids – Higher MAP in older or previous hypertension • Adverse effects • Also - Urine output (>0.5mL/kg/hr), lactate Adverse effects of inotropes 0000000000000000000000 • Tachyarrhythmias - may need to treat • Electrolyte effects - hypokalaemia. • Impaired glucose homeostasis - hyperglycaemia • Vasoconstriction - digits and feet, systemic circulation. • Lactic acidosis - adrenaline • Extravasation injury Administering “inotropes” • All catecholamines have vasoconstrictor activity. • Extravasation can cause tissue necrosis. • Very easy to observe effects in real time. • Infusions should be given via central line. • Will help you understand how each medicines works • Look at effects on parameters. • Administration via large antecubital maybe considered as – MAP short term option prior to central line placement – CVP, Pulse Pressure Variation • Phenylephrine or metaraminol often administered – Peripheral perfusion – hands/feet peripherally – at lower concentration – good safety record – Cardiac Index, Systemic Vascular Resistance, Stroke volume 3.

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