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SIMDAX in Intensive Care Unit

 

SIMDAX COMPARED TO TRADITIONAL INOTROPES

Current data suggest that SIMDAX is superior to traditional inotropes (dobutamine, PDE inhibitors) when used in operative settings:

  • Sustained hemodynamic improvement1
  • Less myocardial injury2,3
  • Less renal impairment4
  • Lower need for IABP5
  • Improved survival on patients with preoperative low ejection fraction6

Early initiation of SIMDAX is preferable. In case of hypotension, vasopressors should be used concomitantly.

 

References: 1. De Hert SG et al. Anesth Analg. 2007;104:766–773. 2. Zangrillo A et al. J Cardiothorac Vasc Anesth. 2009;23:474–478. 3. Eriksson H et al. Ann Thor Surg. 2009;87:448. 4. Landoni G et al. J Cardiothorac Vasc Anesth. 2010;24:51–57. 5. Laitinen P et al. Crit Care Med 2011;39:1–8. 6. Sanfilippo F et al. Critical Care. 2017;21:252-62.

 

SIMDAX DOES NOT DISTURB RELAXATION...

In a study by Jörgenssen et al. SIMDAX not only improved contractility, but also decreased isovolumic relaxation time.1


SIMDAX has beneficial acute systolic and diastolic functional effects in experimental chronic pulmonary hypertension and right
ventricle afterload compared to dobutamine and milrinone.2

Effects of levosimendan on relaxation time 

References: 1. Jörgensen K et al. Circulation. 2008;117(8):1075–1081. 2. Tavares-Silva M et al J Cardiovasc Pharmacol Therap 2017 22(5) 485-95.

 

...IMPROVES RIGHT VENTRICULAR FUNCTION IN CARDIOGENIC SHOCK...

In a study by Russ et al.1, the investigators included 25 consecutive patients with cardiogenic shock due to myocardial infarction
who had not improved sufficiently with conventional therapy (including dobutamine and norepinephrine). All patients received
SIMDAX (as a bolus of 12 mcg/kg/min followed by 0.1 – 0.2 mcg/kg/min) as "bail-out" therapy for 24 hrs while invasive hemodynamic parameters were recorded.

Levosimendan decreased pulmonary vascular resistance and improved cardiac power index in both ventricles 

Reference: 1. Russ MA et al. Crit Care Med 2009;37:3017−23.

 

…AND IMPROVES SURVIVAL IN CARDIOGENIC SHOCK

When compared with enoximone in patients with refractory cardiogenic shock complicating acute myocardial infarction, the use of
SIMDAX resulted in a significantly higher survival1. In the recommendations for the management of shock for cardio-surgical
Intensive Care Unit patients, SIMDAX should be “…considered in patients with impaired cardiac contractility…”.2

30 day survival in patients with cardiogenic shock 

References: 1. Fuhrmann JT et al. Crit Care Med 2008;36:2257-66; 2. Hauffe T et al. Card Fail Rev 2016;2(1):56-62.

 

HELPS WEANING FROM CARDIO-PULMONARY BYPASS

SIMDAX helps patients to be successfully weaned from cardiopulmonary bypass. In the study by Eriksson et al., SIMDAX was
compared to placebo in 60 patients undergoing coronary artery bypass grafting.1

Weaning from cardiopulmonary bypass (CPB). First weaning attempt with levosimendan and placebo 

Reference: 1. Eriksson HI et al. Ann Thorac Surg. 2009;87:448–454.

 

...AND HELPS PREVENTING ECMO WEANING FAILURE

In a retrospective analysis (N=240) with ECMO after cardiac surgery, patients with SIMDAX showed improved ECMO-weaning and
reduced short- and long term mortality. The patients received SIMDAX during the first 24 h after ECMO implantation.1

Confouder-adjusted survival curves of long-term mortality (p=0.04) 

Reference: 1. Distelmeyer K et al Br J Anaesth 2016;117(1):52-8.

 

SIMDAX REDUCES LCOS

In the recent Phase III trial (LEVO-CTS1) SIMDAX, despite not meeting the primary endpoint, decreased significantly post-surgical
low cardiac output syndrome (LCOS). This was accompanied with increased cardiac index and lower need for secondary inotropes.

Incidence of LCOS and secondary inotrope use in the LEVO-CTS trial (N=882)1 

Reference: 1. Mehta RH et al. N Engl J Med. 2017;376(21):2032-2042.

 

...AND REDUCES THE RATE OF ACUTE RENAL FAILURE

In a meta-analysis of 4 randomized studies on the effect of SIMDAX in cardiac surgery a reduction of the rate of acute renal failure
was seen in favor of SIMDAX treated patients (OR = 0.26 [0.12–0.60], p for effect = 0.002, with 228 patients included).1

These data were corroborated by meta-analyses by Harrison et al.2 and Sanfilippo et al.3

Meta-analysis of 4 randomized studies on the effect of SIMDAX in cardiac surgery 

References: 1. Landoni G et al. J Cardiothorac Vasc Anesth. 2010;24:51–57. 2. Harrison RW et al. J Cardiothorac Vasc Anesth. 2013;27(6):1224–1232. 3. Sanfilippo F et al. Critical Care. 2017;21:252-62.

 

THE BENEFITS OF SIMDAX FOR RENAL FUNCTION

GFR improved in SIMDAX compared to dobutamine-treated patients with heart failure who required inotropic therapy.1

A placebo-controlled study in patients hospitalized for decompensated heart failure and renal dysfunction, showed a statistically significant improvement of GFR in SIMDAX-treated patients.2

The peak effect was seen at three days after a 24 hour infusion and the effects persisted up to 14 days.2

Effects of levosimendan on glomerular filtration rate 

References: 1. Yilmaz et al. Cardiovasc Drugs Ther. 2007;21:431–435. 2. Hou Z-Q et al. Cardiovasc Ther. 2013;31:108–114.

 

SIMDAX CONTRAINDICATIONS

Severe renal failure is a contraindication for SIMDAX use as no formal pharmacokinetic studies in heart failure patients with severe renal failure have been conducted.1

However, many heart failure patients in large regulatory studies such as REVIVE and SURVIVE had severe renal failure.2,3

The elimination of the SIMDAX metabolite OR‑1896 is prolonged 1.5-fold compared with healthy subjects in non-heart failure patients but with severe renal impairment, or undergoing chronic hemodialysis.4 The pharmacokinetics of SIMDAX is not altered.4

These results suggest that if SIMDAX was given to heart failure patients with severe renal impairment, the dose should be reduced.

References: 1. SIMDAX® SPC. 2. Mebazaa A et al. JAMA. 2007 May 2;297(17):1883-91. 3. Packer M et al. JCHF. 2013;1:103–111. 4. Puttonen J et al. Clin Pharmacokinet. 2007;46(3):235–246.

 

EASING THE CHALLENGE OF TREATING THE FAILING HEART WITH LONG LASTING HEMODYNAMIC STABILIZATION

SIMDAX GIVES YOU TIME BY PROVIDING:

  • Hemodynamic benefits1,2
  • Symptomatic benefits1,2
  • Sustained effects1
  • Protective effects on heart and other organs3,4
  • Stabilizing the patient for operation1

References: 1. De Hert SG et al. Anesth Analg. 2007;104:766–773. 2. Jörgensen K et al. Circulation. 2008;117(8):1075–1081. 3. Zangrillo A et al. J Cardiothorac Vasc Anesth. 2009;23:474–478. 4. Eriksson H et al. Ann Thor Surg. 2009;87:448.