Levosimendan
CLASS
- Calcium sensitizer (novel inotrope, also considered an inodilator like milrinone)
MECHANISM OF ACTION
- sensitizes cardiac muscle to Ca2+
- stabilises troponin C in a conformation that triggers and maintain contraction.
- does not impair diastolic relaxation
- also produces vasodilation by opening ATP-sensitive K+ channels in vascular smooth muscle
-> reduces preload, afterload, improves O2 supply to myocardium, increases coronary blood flow and renal blood flow. - increases: Q, SV, HR and coronary blood flow.
- decreases: SVR, SBP, PCWP, PAP, coronary vascular resistance, myocardial oxygen consumption.
- shown to improve symptoms, and BNP in cardiac failure (but, unfortunately not survival)
- can be used with beta-blockers (doesn’t compete with levos)
- also has anti-inflammatory and anti-apoptotic effects
- has weak cAMP-PDE inhibitory effects
PHARMACEUTICS
–
DOSE
- loading dose: 6-24mcg/kg over 10 min
- infusion for 24 hours of 0.05-0.2mcg/kg/min
INDICATIONS
- heart failure (acute and chronic)
- sepsis
- post resuscitation myocardial dysfunction
- peri-operative optimization of cardiac patients with cardiomyopathy
ADVERSE EFFECTS
- hypotension
- headache
- N+V
- dysrhythmias
PHARMACOKINETICS
- Absorption – IV or PO
- Distribution – highly protein bound, peak concentrations reached after 2 days of treatment
- Metabolism – hepatic, active metabolite with t1/2 of 70 hours
- Elimination – dose adjust in renal insufficiency, eliminated in urine and faeces.
EVIDENCE
Mebazza, (2007) SURVIVE – Levosimendan vs Dobutamine in patients with acute decompensated heart failure, JAMA (pubmed)
- n = 1320
- sought to prove an mortality reduction of 25%!
- -> no difference in 180 day mortality
- initial reduction in plasma B-type natriuretic peptide level in patients in the levosimendan group
- higher rates of AF, hypoK and headache in levosimendan group
De Keulenaer, B. L. (2008) – “The case for Levosimendan” Critical Care and Resuscitation, Volume 10 (3) page 180
- decreased arrhythmias
- decreased myocardial oxygen consumption
- inodilator
- ?prevention of apoptosis and preservation of mitochondrial function
- improved right ventricular function in ARDS and in acute PE
References and Links
CCC Pharmacology Series
Respiratory: Bosentan, Delivery of B2 Agonists in Intubated Patients, Nitric Oxide, Oxygen, Prostacyclin, Sildenafil
Cardiovascular: Adenosine, Adrenaline (Epinephrine), Amiodarone, Classification of Vasoactive drugs, Clevidipine, Digoxin, Dobutamine, Dopamine, Levosimendan, Levosimendan vs Dobutamine, Milrinone, Noradrenaline, Phenylephrine, Sodium Nitroprusside (SNiP), Sotalol, Vasopressin
Neurological: Dexmedetomidine, Ketamine, Levetiracetam, Lignocaine, Lithium, Midazolam, Physostigmine, Propofol, Sodium Valproate, Sugammadex, Thiopentone
Endocrine: Desmopressin, Glucagon Therapy, Medications and Thyroid Function
Gastrointestinal: Octreotide, Omeprazole, Ranitidine, Sucralfate, Terlipressin
Genitourinary: Furosemide, Mannitol, Spironolactone
Haematological: Activated Protein C, Alteplase, Aprotinin, Aspirin, Clopidogrel, Dipyridamole, DOACs, Factor VIIa, Heparin, LMW Heparin, Protamine, Prothrombinex, Tenecteplase, Tirofiban, Tranexamic Acid (TXA), Warfarin
Antimicrobial: Antimicrobial Dosing and Kill Characteristics, Benzylpenicillin, Ceftriaxone, Ciprofloxacin, Co-trimoxazole / Bactrim, Fluconazole, Gentamicin, Imipenem, Linezolid, Meropenem, Piperacillin-Tazobactam, Rifampicin, Vancomycin
Analgesic: Alfentanil, Celecoxib, COX II Inhibitors, Ketamine, Lignocaine, Morphine, NSAIDs, Opioids, Paracetamol (Acetaminophen), Paracetamol in Critical Illness, Tramadol
Miscellaneous: Activated Charcoal, Adverse Drug Reactions, Alkali Therapies, Drug Absorption in Critical Illness, Drug Infusion Doses, Epidural Complications, Epidural vs Opioids in Rib Fractures, Magnesium, Methylene Blue, Pharmacology and Critical Illness, PK and Obesity, PK and ECMO, Sodium Bicarbonate Use, Statins in Critical Illness, Therapeutic Drug Monitoring, Weights in Pharmacology
Toxicology: Digibind, Flumazenil, Glucagon Therapy, Intralipid, N-Acetylcysteine, Naloxone, Propofol Infusion Syndrome
- De Keulenaer, B. L. (2008) The case for Levosimendan. Critical Care and Resuscitation, Volume 10 (3) page 180 [pdf]
- Pathak A, Lebrin M, Vaccaro A, Senard JM, Despas F. Pharmacology of levosimendan: inotropic, vasodilatory and cardioprotective effects. J Clin Pharm Ther. 2013 Apr 18. PMID: 23594161.
Critical Care
Compendium
Chris is an Intensivist and ECMO specialist at The Alfred ICU, where he is Deputy Director (Education). He is a Clinical Adjunct Associate Professor at Monash University, the Lead for the Clinician Educator Incubator programme, and a CICM First Part Examiner.
He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. He was one of the founders of the FOAM movement (Free Open-Access Medical education) has been recognised for his contributions to education with awards from ANZICS, ANZAHPE, and ACEM.
His one great achievement is being the father of three amazing children.
On Bluesky, he is @precordialthump.bsky.social and on the site that Elon has screwed up, he is @precordialthump.
| INTENSIVE | RAGE | Resuscitology | SMACC
