Inotropi och vasopressorer
Vasopressorer inducerar vasokonstriktion och ökar medelartärtrycket (MAP). Inotropa läkemedel ökar myokardiets kontraktilitet. Det finns flera syntetiska och endogena substanser med inotrop och vasopressoreffekt. Dessa behöver ofta kombineras för att optimera eller korrigera hemodynamiken. De flesta substanser utövar både vasopressiva och inotropa effekter (Figur 1). Nedan följer en lathund för användning på akutmottagning, intensivvårdsavdelning (IVA, HIA) eller operation. Noggrann elektrokardiografisk och hemodynamisk övervakning med EKG, central venkateter (CVK) och artärnål är nödvändigt för att nå optimalt resultat.
Översikt av vasopressorer och inotropa läkemedel
Indikationer, dosering och effekter för vasopressorer och inotropa läkemedel
| Läkemedel | Indikationer | Dosering | α1 effect | β1 effect | β2 effect | D1/D2 effect | Result | Side Effects |
|---|---|---|---|---|---|---|---|---|
| Dopamin – low dose | Rarely used | Low dose: 0.5-3.0 μg/kg/min | + | + | + | +++++ | Low dose dopamine stimulates D1 receptors and induces vasodilation in coronary, renal, cerebral and mesenteric vessels. | Few |
| Dopamin – medium dose | Cardiogenic shock Vasodilatory shock Heart failure (HF), acute Heart failure (HF), chronic Bradycardia (second-line alternative) | Medium dose: 3.0-10.0 μg/kg/min. | + | ++++ | + | +++++ | Medium dose dopamine activates β1, releases norepinephrine and thus increases contractility, chronotropy and mild increase in SVR. | Ventricular arrhythmias Myocardial ischemia Tissue ischemia (high doses or extravasation) |
| Dopamin – high dose | Cardiogenic shock Vasodilatory shock Heart failure (HF), acute Heart failure (HF), chronic Bradycardia (second-line alternative) | High dose: 10.0-20.0 μg/kg/min. | ++++ | ++++ | ++ | +++++ | Hig dose dopamine additionally induces α1 stimulation and thus vasoconstruction and pronounced increase in SVR. | As medium dose, and additionally severe hypertension (caution if patient on nonselective beta-blockers). |
| Dobutamin | Cardiogenic shock Bradycardia (second-line therapy) Stress testing (due to induced increase in myocardial O2 consumption) | Regular: 2.0–20 μg/kg/min Max: 40 μg/kg/min | + | +++++ | +++ | 0 | Potent inotrope with slight chronotropic effect. Doses <5 μg/kg/min induces mild vasodailation. Doses >5 μg/kg/min induces vasoconstriction, which dominates at dosease >15 μg/kg/min. | Tachycardia Increased ventricular rate in AF Ventricular arrhythmias Cardiac ischemia Hypertension (in patients on nonselective β-blocker) Tolerance after a few days |
| Noradrenalin (Norepinefrin) | Shock (any) Hypotension (any) | 0.01–3.0 μg/kg/min Safe for peripheral use | +++++ | +++ | ++ | 0 | Potent vasoconstrictor with mild inotropic effect. Increases systolic pressure, diastolic pressure and pulse pressure with minimal effect on CO. Minimal chronotropic effect. Increases coronary blood flow. | Atrial or ventricular arrhythmias Bradycardia Peripheral (digital) ischemia Hypertension (especially nonselective β-blocker patients) Prolonged use may be cardiotoxic. |
| Adrenalin (Epinefrin) | Shock (any) Cardiac arrest Bronchospasm Anaphylaxis Bradycardia (second-line alternative) | Infusion: 0.01 to 0.10 μg/kg/min Bolus: 1 mg IV every 3 to 5 min (max 0.2 mg/kg) IM: (1:1000): 0.1 to 0.5 mg (max 1 mg) Safe for peripheral use | +++++ | ++++ | +++ | N/A | Beta-effect more pronounced at low doses. Alpha-effect pronounced at higher doses. Coronary flow enhanced. Pulm vasoconstriction. Increased pulmonary blood flow. | Ventricular arrhythmias Severe hypertension resulting in cerebrovascular hemorrhage Cardiac ischemia Sudden cardiac death Prolonged use may be cardiotoxic. |
| Isoproterenol | Bradycardia (first-line therapy) Bradycardia causing torsade de pointes Brugada syndrome | 2.0–10.0 μg/min Safe for peripheral use | 0 | +++++ | +++++ | 0 | Powerful chronotropic and inotropic effect. Potent systemic vasodilation. Mild pulmonary vasodilation. No effect on CO. | Ventricular arrhythmias Cardiac ischemia Hypertension Hypotension |
| Fenylefrin | Typically used as emergency bolus to correct acute hypotension. Hypotension (any) Used to increase MAP during hypotension in aortic stenosis. Used to decrease LVOT gradient in HCM Used to correct hypotension caused by the simultaneous ingestion of sildenafil and nitrates | Bolus: 0.1 to 0.5 mg IV every 10 to 15 min Infusion: 0.4 to 9.1 μg/kg/min Safe for peripheral use | +++++ | 0 | 0 | N/A | Immediate and pronounced increase in MAP. | Reflex bradycardia Hypertension (especially with nonselective β-blockers) Severe peripheral and visceral vasoconstriction Tissue necrosis with extravasation |
| Milrinon | Heart failure, acute Heart failure, decompensated chronic. | Bolus: 50 μg/kg bolus over 10 to 30 min Infusion: 0.375 to 0.75 μg/kg/min. | 0 | 0 | 0 | 0 | PDI (Phosphodiesterase Inhibitor). Potent inotrope. Induces vasodialtion. Results in reduced preload, afterload and SVR. | Ventricular arrhythmias Hypotension Myocardial ischemia Torsade des pointes Accumulates in renal failure (dose adjustment necessary) |
| Amrinon | Heart failure, acute Heart failure, decompensated chronic | Bolus: 0.75 mg/kg over 2 to 3 min Infusion: 5 to 10 μg · kg−1 · min−1 | 0 | 0 | 0 | 0 | PDI (Phosphodiesterase Inhibitor). Rarely used due to side effects. | Arrhythmias, enhanced AV conduction Hypotension Thrombocytopenia Hepatotoxic |
| Vasopressin | Shock (any) Cardiac arrest | Infusion: 0.01–0.1 U/min (common fixed dose 0.04 U/min) Bolus (IV): 40 U | 0 | 0 | 0 | 0 | Vasopressin stimulates V1 receptors (vascular smooth muscle) and V2 (renal). V1 stimulation induces vasoconstriction, and V2 increases renal water reabsorption. Vasopressin increases SVR with no significant effect on CO. Vasopressin potentiates the vascular effect of norepinephrine. | Arrhythmias Hypertension Decreased CO (at doses >0.4 U/min) Cardiac ischemia Severe peripheral vasoconstriction causing ischemia (especially skin) Splanchnic vasoconstriction |
| Levosimendan (Simdax) | Heart failure, decompensated chronic | Loading dose: 12–24 μg/kg over 10 min Infusion: 0.05–0.2 μg/kg/min | 0 | 0 | 0 | 0 | Levosimendan is a calcium sensitizer that enhances ventricular contractility and induces peripheral arteriolar and venous vasodilation. | Enhanced AV conduction Hypotension |
Notera att plötsliga blodtrycksförändringar aktiverar autonoma reflexer som påverkar hemodynamiskt resultat. Reflextakykardi upkommer som regel vid hastig blodtryckssänkning.
Katekolaminreceptorer
- Alpha-1-adrenerga receptorer: uttrycks i glatt muskulatur i kärl. Aktivering resulterar i vasokonstriktion och ökad SVR (systemvaskulär resistans).
- Beta-1-adrenerga receptorer: uttrycks i myokardium. Aktiveringen resulterar i ökad kontraktilitet och ökad kronotropi (hjärtfrekvens).
- Beta-2-adrenerga receptorer: uttrycks i glatt muskulatur i kärl. Aktiveringen resulterar i vasodilatation.
- D1 och D2 (dopaminreceptorer): Aktiveringen av D1 och D2 i njurarna och splanknikuskärlbädd leder till renal och mesenteriell vasodilatation.
Dobutamin är en syntetisk katekolamin.
Referenser
- Overgaard, Dzavik et al. Inotropes and Vasopressors: Review of Physiology and Clinical Use in Cardiovascular Disease. Circulation 2011.
- Jentzer et al. Pharmacotherapy Update on the Use of Vasopressors and Inotropes in the Intensive Care Unit. J Cardiovasc Pharmacol Therap (2014).
- Müllner M, Urbanek B, Havel C, et al. Vasopressors for shock. Cochrane Database Syst Rev 2004
- Ballieu P, Besharatian Y, Ansari S. Safety and Feasibility of Phenylephrine Administration Through a Peripheral Intravenous Catheter in a Neurocritical Care Unit. J Intensive Care Med 2021; 36:101.
- Lherm T, Troché G, Rossignol M, et al. Renal effects of low-dose dopamine in patients with sepsis syndrome or septic shock treated with catecholamines. Intensive Care Med 1996; 22:213.
- Unverferth DA, Blanford M, Kates RE, Leier CV. Tolerance to dobutamine after a 72 hour continuous infusion. Am J Med 1980; 69:262.
- Gattinoni L, Brazzi L, Pelosi P, et al. A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group. N Engl J Med 1995; 333:1025.
- Gregory JS, Bonfiglio MF, Dasta JF, et al. Experience with phenylephrine as a component of the pharmacologic support of septic shock. Crit Care Med 1991; 19:1395.
- De Backer D, Creteur J, Silva E, Vincent JL. Effects of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in septic shock: which is best? Crit Care Med 2003; 31:1659.
- MacGregor DA, Smith TE, Prielipp RC, et al. Pharmacokinetics of dopamine in healthy male subjects. Anesthesiology 2000; 92:338.
- Löllgen H, Drexler H. Use of inotropes in the critical care setting. Crit Care Med 1990; 18:S56.
- Steel, A, Bihari, D . Choice of catecholamine: does it matter? Curr Opin Crit Care 2000; 6:347.
- Hannemann L, Reinhart K, Grenzer O, et al. Comparison of dopamine to dobutamine and norepinephrine for oxygen delivery and uptake in septic shock. Crit Care Med 1995; 23:1962.
- Al-Hesayen A, Azevedo ER, Newton GE, Parker JD. The effects of dobutamine on cardiac sympathetic activity in patients with congestive heart failure. J Am Coll Cardiol 2002; 39:1269.
- De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010; 362:779.
- Mutlu GM, Factor P. Role of vasopressin in the management of septic shock. Intensive Care Med 2004; 30:1276.
- Sharshar T, Blanchard A, Paillard M, et al. Circulating vasopressin levels in septic shock. Crit Care Med 2003; 31:1752.
- Tsuneyoshi I, Yamada H, Kakihana Y, et al. Hemodynamic and metabolic effects of low-dose vasopressin infusions in vasodilatory septic shock. Crit Care Med 2001; 29:487.
- Dünser MW, Mayr AJ, Ulmer H, et al. Arginine vasopressin in advanced vasodilatory shock: a prospective, randomized, controlled study. Circulation 2003; 107:2313.
- Kill C, Wranze E, Wulf H. Successful treatment of severe anaphylactic shock with vasopressin. Two case reports. Int Arch Allergy Immunol 2004; 134:260.
- Schummer C, Wirsing M, Schummer W. The pivotal role of vasopressin in refractory anaphylactic shock. Anesth Analg 2008; 107:620.
- McIntyre WF, Um KJ, Alhazzani W, et al. Association of Vasopressin Plus Catecholamine Vasopressors vs Catecholamines Alone With Atrial Fibrillation in Patients With Distributive Shock: A Systematic Review and Meta-analysis. JAMA 2018; 319:1889.
- Albanèse J, Leone M, Delmas A, Martin C. Terlipressin or norepinephrine in hyperdynamic septic shock: a prospective, randomized study. Crit Care Med 2005; 33:1897.
- Kam PC, Williams S, Yoong FF. Vasopressin and terlipressin: pharmacology and its clinical relevance. Anaesthesia 2004; 59:993.
- O’Brien A, Clapp L, Singer M. Terlipressin for norepinephrine-resistant septic shock. Lancet 2002; 359:1209.
- Leone M, Albanèse J, Delmas A, et al. Terlipressin in catecholamine-resistant septic shock patients. Shock 2004; 22:314.
- Rodríguez-Núñez A, Fernández-Sanmartín M, Martinón-Torres F, et al. Terlipressin for catecholamine-resistant septic shock in children. Intensive Care Med 2004; 30:477.
- Morelli A, Rocco M, Conti G, et al. Effects of terlipressin on systemic and regional haemodynamics in catecholamine-treated hyperkinetic septic shock. Intensive Care Med 2004; 30:597.
- Polito A, Parisini E, Ricci Z, et al. Vasopressin for treatment of vasodilatory shock: an ESICM systematic review and meta-analysis. Intensive Care Med 2012; 38:9.
- Gordon AC, Mason AJ, Thirunavukkarasu N, et al. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial. JAMA 2016; 316:509.
- Malay MB, Ashton JL, Dahl K, et al. Heterogeneity of the vasoconstrictor effect of vasopressin in septic shock. Crit Care Med 2004; 32:1327.
- Kahn JM, Kress JP, Hall JB. Skin necrosis after extravasation of low-dose vasopressin administered for septic shock. Crit Care Med 2002; 30:1899.
- Leather HA, Segers P, Berends N, et al. Effects of vasopressin on right ventricular function in an experimental model of acute pulmonary hypertension. Crit Care Med 2002; 30:2548.
- Dünser MW, Mayr AJ, Tür A, et al. Ischemic skin lesions as a complication of continuous vasopressin infusion in catecholamine-resistant vasodilatory shock: incidence and risk factors. Crit Care Med 2003; 31:1394.
- Russell JA, Walley KR, Singer J, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 2008; 358:877.
- Jeon K, Song JU, Chung CR, et al. Incidence of hypotension according to the discontinuation order of vasopressors in the management of septic shock: a prospective randomized trial (DOVSS). Crit Care 2018; 22:131.
- Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med 2021; 49:e1063.
- Landoni G, Lomivorotov VV, Alvaro G, et al. Levosimendan for Hemodynamic Support after Cardiac Surgery. N Engl J Med 2017.
- Mehta RH, Leimberger JD, van Diepen S, et al. Levosimendan in Patients with Left Ventricular Dysfunction Undergoing Cardiac Surgery. N Engl J Med 2017.
- Khanna A, English SW, Wang XS, et al. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med 2017; 377:419.
