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