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Inotropes and Vasopressors.pptx

  1. Inotropes and Vasopressors Uppers, downers and squeezers
  2. 2 Aim of the session: • Overview of inotropes and vasoactive drugs • Discuss case examples • Hopefully feel more confident in their use.
  3. 3 Overview Inotropes are indicated in acute conditions where there is low cardiac output (CO), such as cardiogenic shock following myocardial infarction, acute decompensated heart failure and low CO states after cardiac surgery Different vasopressors work by a variety of means: The adrenergic group of vasopressors work by stimulating the sympathetic nervous system. Drugs in this group include noradrenaline, adrenaline and phenylephrine which work by narrowing blood vessels and dopamine which stimulates the heart. Vasopressin and terlipressin are called non-adrenergic vasopressors. They do not act upon the heart or blood vessels, but increase blood pressure by reducing water loss through urination. The main mechanism of action for most inotropes involves increasing intracellular calcium, either by increasing influx to the cell during the action potential or increasing release from the sarcoplasmic reticulum
  4. Inotropes Inotropes influence the contractility of the heart… • Positive inotropes – increase the force of contractility • Negative inotrope – reduce contractility(some calcium channel blockers) Positive inotropes mimic the sympathetic nervous system that increasing heart rate and contractility Application to cardiogenic shock, acute heart failure, ventricular fibrillation etc. *drugs influencing the heart rate referred to as chronotropes
  5. 5 Its all about the OXYGEN! For tissues to be oxygenated, 3 factors need to be considered: 1. Oxygen transfer across the alveolar-capillary membrane 2. Oxygen attachment to haemoglobin 3. Adequate cardiac output(CO) to move the oxyhaemoglobin compound to the tissues. This is what we are going to be talking about
  6. 6 Two Limbs to Oxygenation
  7. 7 To increase CO we can… 1. Enhance circulating volume through fluid resuscitation (increasing preload) 2. Enhancing myocardial contractility with inotropes(their inotropic effect) 3. Manipulating heart rate with inotropes(their chronotropic effect) REMEMBER: Cardiac output(CO)= Heart rate(HR) x Stroke Volume(SV)
  8. 8 Measuring cardiac output • How do we commonly evaluate? • How complex is this? Tissue perfusion is dependent on mean arterial blood pressure (MAP), which is the product of CO and systemic vascular resistance (SVR):* MAP = CO × SVR Reducing CO or SVR lowers the MAP and therefore reduces tissue perfusion. CO is dependent on the stroke volume (SV) and heart rate (HR): CO = HR × SV ……SIMPLE?
  9. 9 Remember this! Stroke Volume is a complex aspect! Affected by preload, afterload and contractility Preload (the degree to which ventricles are stretched before contracting) correlates with the end diastolic volume (the volume of blood in a ventricle at the end of filling). It is important to optimise preload by correcting fluid balance before starting inotropes, since there is little point in increasing the contractility of the heart if its chambers are not filled optimally. Central venous pressure (CVP) can be used as a surrogate measure of preload.
  10. 10 So how does this stay balanced? Parasympathetic nervous system down regulates Sympathetic nervous system up regulates
  11. 11 A&P
  12. 12 Lets talk drugs In the context of the SNS, drugs: • Mimic or impair(stimulate or block) • Directly(Agonist or antagonist) • Indirectly- releasing endogenous Norad(metaraminol,, ephedrine at a1) In the context of the PNS, drugs work on: • Nicotinic and muscarinic receptors with Ach as neurotransmitter • M2 muscarinic receptors- heart
  13. Autonomic control of heart rate
  14. Autonomic control of myocardial contractility Sympathetic Nervous System, adrenaline and certain drugs have positive inotropic effects- increase contractility Parasympathetic Nervous System, and certain drugs have negative inotropic effects- reduce contractility
  15. Receptor type Location Action a1 Peripheral, renal and coronary circulation Vasoconstriction Increase in Systemic Vascular resistance Decrease Insulin release A2 Peripheral circulation. Vasoconstriction Systemic Vascular resistance ß1 Heart, Sinoatrial node and myocardium Increase in contractility and heart rate ß2 Lungs-bronchial smooth muscle; peripheral and coronary circulation-coronary arteries, AV node Vasodilation, bronchodilation It’s all about the receptors…
  16. So how do we treat this stuff?
  17. 18 Atropine-PNS Anticholinergic drug- works as a competitive antagonist in muscarinic receptors(M2= heart) M2 muscarinic receptors are located in the heart, where they act to slow the heart rate down to normal sinus rhythm after negative stimulatory actions of the parasympathetic nervous system, by slowing the speed of depolarization Atropine therefore blocks and slows down signals to the heart, increasing the heart rate
  18. Adrenaline (Epinephrine)- SNS A1,A2,B1,B2 Agonist A non-selective b and a agonist A sympathomimetic drug emulating the action of sympathetic nervous system. Positive inotrope and chronotrope Boosts cardiac function by increasing heart rate (chronotropy) and contractility (ionotropy) – via β1 Agonist. Vasoconstrictor at high dose… effecting alpha receptors Vasodilator as low dose effecting β2 receptors resulting in bronchial smooth muscle relaxant Adrenaline 1mg/mL (1:1000) solution for injection.
  19. Noradrenaline. (Norepinephrine)-SNS Mainly an a1 Agonist Because it acts mainly via a1 receptors in the heart, it is usually used as a vasopressor (increasing Systemic Vascular Resistance(SVR) in order to maintain Mean Arterial Pressure) rather than an actual inotrope. Causes vasoconstriction(alpha-adrenergic action) and positive inotropic effect of the heart and dilation of coronary arteries(beta-adrenergic action) It is often used with other inotropes, such as dobutamine, to maintain adequate perfusion. Noradrenaline 1mg/mL concentrate for solution for infusion.
  20. Dobutamine-SNS Dobutamine is mainly a direct acting inotropic as a ß1 agonist and therefore increases cardiac contractility and with mild chronotropic effects on the heart rate. It also acts at ß2 receptors causing vasodilation and decreasing afterload. In order to ensure adequate MAP. Does not cause the release of noradrenaline and therefore to ensure adequate MAP dobutamine should be used in combination with a vasopressor (eg, noradrenaline). The main side effects are increased heart rate, arrhythmias and an increased myocardial oxygen demand. (These can cause myocardial ischaemia.) Used for heart failure for the above reasons 250mg vials
  21. Vasopressin(ADH) Increase reabsorption of water by the renal tubules Cause contraction of smooth muscle of the gastrointestinal tract and all parts of the vascular bed, especially the capillaries, small arterioles and venules with less effect on the smooth musculature of the large veins 20IU/ml
  22. Metaraminol-SNS Increases both systolic diastolic blood pressure The pressor effect begins one to two minutes after intravenous injection and lasts about 20 mins-1 hour Positive inotropic effect on the heart and has a peripheral vasoconstrictor action Potent sympathomimetic-alpha agonist effects, mild beta 1 effects Metaraminol 10mg/mL Solution for injection or infusion
  23. Ephedrine-SNS Stimulates both alpha and beta-adrenergic receptors indirectly and also releases endogenous noradrenaline from its storage site(substantia nigra) Often used in operating theatres due to strong direct evidence base for anaesthetic hypotension.
  24. Phenylephrine-SNS Also used mostly in operating theatres Produces vasocontriction that lasts longer than adrenaline and ephedrine Responses are more sustained tham those to adrenaline, lasting 20minutes after IV inj. and as long as 50mins after SC inj. Its action on the heart vs adrenaline/ephedrine, is that it slows the HR and increases the stroke output, producing no disturbance to the rhythm Powerful postsynaptic alpha-receptor stimulant with little effect on the beta- receptors of the heart Phenylephrine 10mg/mL Solution for injection or infusion
  25. GTN-Direct Vasoactive Glyceryl trinitrate produces a dose related dilation of both arterial and venous beds Decreases venous return to the heart, reducing left ventricular end diastolic pressure and pulmonary capillary wedge pressure(preload) Arteriolar relaxation reduces systemic vascular resistance and arterial pressure(afterload) Also dilates the coronary arteries, although this effect is short-lived.
  26. Dopamine This is a complicated inotrope because it’s effect is dose-dependent . At lower doses,(0.5–2 microgram/kg/min) it exerts mainly dopaminergic (Neurotransmitter…) effects and blood pressure does not change or decreases slightly. Causes renal and mesenteric vasodilation-renal plasma flow, GFR and Na+ excretion usually increase At medium strength doses (2–10micrograms/kg/min) the ß1 inotropic effects are more prominent and CO and Systolic BP increase. Total peripheral vasoconstriction is relatively unchanged due to vasoconstriction (alpha effect) and muscle vasodilation(beta effect) At high doses (10–20micrograms/kg/min) a1 vasoconstriction is the main action. Systolic and diastolic pressures increase 200 mg ampoules
  27. Some less frequently used drugs Isoprenaline- has a similar profile to dobutamine but tends to cause more tachycardia. It is sometimes used for bradycardic patients/ complete heart block requiring inotropic support. Milrionone- positive inotropic and vasodilatory activity, ventricular dysfunction by increasing SV and LV contractility producing pulmonary vasodilation Sodium Nitroprusside(SNP)-direct vasoactive, relaxation of vascular smooth muscle and dilation of peripheral arteries and veins, non- selective compared to GTN Levosimendan-decompensated heart failure, increases calcium sensitivity of myocytes by binding to cardiac troponin C, smooth muscle relaxation Terlipressin- similar profile to vasopressin, vasoconstriction on the splanchinic blood vessels and reduces blood flow to the portal vein
  28. Route of administration. ????
  29. Peripheral administration is emerging (as it is in anaesthetic practice in the perioperative period) with a recent systematic review of over 1300 patients suggesting the risk of doing so being lower than is anecdotally cited. D. H. Tian, C. Smyth, G. Keijzers, S. P. Macdonald, S. Peake, A. Udy and A. Delaney, “Safety of peripheral administration of vasopressor medications: A systematic review,” Emergency Medicine Australasia, vol. 32, no. 2, pp. 220-227, 2020. This review reported that extravasation events were uncommon (event rate 3.4%), with no reported incidents of tissue necrosis or limb ischaemia. The most common alternative to a PVC is the insertion of a central venous cannula (CVC) [2] [3]. Whilst the use of ultrasound-guided insertion will aid in the reduction of the incidence of such risks, many remain clinically significant (such as pneumothorax, arterial injury, arrhythmias and catheter- related infection) and so it seems sensible to consider circumstances wherein administration via PVC may be preferable when there is a need for: • stabilisation of critically unwell patients awaiting transfer to a critical care area; • short term post-operative use; • patient preference; • or where central venous access would prove problematic. The decision will ultimately come down to local policy and the responsible senior at the time.
  30. Monitoring Inotropes are usually only used in clinical areas where patients’ haemodynamics can be monitored adequately. Continuous monitoring of MAP, CO and CVP allows haemodynamic changes to be detected and addressed rapidly.
  31. Summary • Inotropic drugs are potentially dangerous so be very thorough in checking • Vascular access needs to be spot on • On central lines always endeavour to use distal, brown lumen(furthest) • Wear gloves when preparing/assisting • Know what the drug does and why we use it • Don’t EVER make a mistake with inotropes or disconnect them without direction
  32. Case 1 Type 1 anaphylactic reaction Type 1 anaphylactic reaction What will you need and why?…
  33. Case 2 Septic shock How would you approach this case ? Please explain why ?
  34. Case 3 Cardiac arrest (pre and post resuscitation)
  35. Case study 4 Cardiogenic shock Dobutamine Noradrenaline Management of cardiogenic shock article

Notas del editor

  1. M2 muscarinic receptors are located in the heart, where they act to slow the heart rate down to normal sinus rhythm after negative stimulatory actions of the parasympathetic nervous system, by slowing the speed of depolarization
  2. The circled area is where SYMP and PARA (&drugs) will have an effect on HR The sooner the drift line gets to TH – the sooner the HR
  3. Vasopressors are drugs that cause blood vessels to narrow, thereby increasing blood pressure and hence the flow of blood. They are used to treat patients with septic shock, helping to restore blood flow to the vital organs and the rest of the body. Think about preload and adequate fluid loading
  4.  SN located in the basal ganglia structure located in the midbrain that plays an important role in reward and movement
  5. Epinephrine- alpha-1-adrenergic agonist effects-increased vasoconstriction, peripheral resistance and decreased mucosal edema beta-1adrenergic agonist effects- increased inotropy and increased chronotropy beta-2-adrenergic agonist effects-increased bronchodilation, decreased release of mediators of inflammations from mast cells and basophils.
  6. Septic shock is when blood pressure drops to a dangerously low level after an infection. There is a high 02 demand to reduce cell death Noradrenaline- Causes vasoconstriction(alpha-adrenergic action) and positive inotropic effect of the heart and dilation of coronary arteries(beta-adrenergic action) Compared to dopamine, noradrenaline reduced deaths from any cause at 28 days by 11% (Relative Risk [RR] 0.89, 95% Confidence Interval [CI] 0.81 to 0.98). Forty-five percent of people treated with noradrenaline died, compared with 52% treated with dopamine. This result came from a meta-analysis of 11 trials. Noradrenaline reduced the risk of major adverse effects, such as irregular heart-beat, heart attack, stroke or reduction in blood supply (ischaemia) to the heart or limbs, by about two-thirds compared with dopamine (RR 0.34, 95% CI 0.14 to 0.84). This result came from a meta-analysis of just three trials. Meta-analysis of four trials found that noradrenaline reduced the risk of irregular heart beat by about a half compared to dopamine (RR 0.48, 95% CI 0.40 to 0.58). No reduction in all-cause mortality or major adverse effects was demonstrated for noradrenaline compared to adrenaline, phenylephrine, vasopressin or terlipressin as any difference in mortality were not statistically significant. Other outcomes, including length of stay in intensive care, were similar between the different vasopressors. However, noradrenaline did improve some other measures indicating stability of blood pressure and circulation, such as urine output.
  7. Give adrenaline 1 mg IV (IO) as soon as possible for adult patients in cardiac arrest with a non-shockable rhythm. Give adrenaline 1 mg IV (IO) after the 3rd shock for adult patients in cardiac arrest with a shockable rhythm. Repeat adrenaline 1 mg IV (IO) every 3-5 minutes whilst ALS continues. May consider vasopressin for treatment of asystole, but there is insufficient evidence to recommend for or against its use in PEA. Further studies are required. Epinephrine may be administered every 3 to 5 minutes during the attempted resuscitation; vasopressin may be substituted for the first or second epinephrine dose.
  8. Dobutamine may be given simultaneously to norepinephrine in an attempt to improve cardiac contractility which is often performed in clinical practice.7 Other inotropes such as levosimendan or phosphodiesterase-inhibitors are of interest in CS based on their improvement of myocardial contractility without increasing oxygen requirements and potential for vasodilation. However, as shown in a recent Cochrane review, the current evidence for inotropes and vasodilators in CS is very limited.
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