Preoperative levosimendán and Hip Fracture (OPL)

Preoperative Optimization Levosimendan in Heart Failure Patients Undergoing Hip Fracture

The purpose of this study is to evaluate whether preoperative optimization with levosimendan in heart failure patients undergoing hip fracture surgery improves haemodynamic and tissue perfusion parameters.

Study Overview

• Status: Completed
• Conditions: Ventricular Dysfunction, Left; Hip Fracture
• Intervention / Treatment: Drug: Levosimendan

Detailed Description

Hip fracture is a very predominant entity in elderly patients and it is one of the most frequent cause of admission in a hospital.

Elderly patients undergoing surgery for hip fracture have a high risk of morbidity and mortality in the postoperative. Several studies have shown that there is a high risk of cardiovascular complications in this group of patients and 3-months mortality is 15-20%. One of the causes of this high morbidity and mortality is the high incidence of chronic cardiac failure in this patients. The goal of the present study is to evaluate if the optimization of preoperative cardiac function with levosimendan in patients with left ventricular ejection fraction < 45% can improve haemodynamic and the tissue perfusion values, and reduce cardiac morbidity and mortality 3 months postoperatively.

Following written consent, the patients with left ventricular ejection fraction < 45% will be admitted in the resuscitation and anaesthesia room where they will receive a levosimendan intravenous injection undergoing a strict haemodynamic vigilance.

Before the levosimendan intravenous injection the patients firs have an echocardiography to evaluate myocardial function, NT-proBNP. Subsequently, an arterial line is inserted and optimization achieved by using this arterial line connected to a ProAQT sensor system ( PULSION , Edwards). The system uses pulse wave analysis to assess several parameters including: stroke volume index (SVI), cardiac index (CI), systemic vascular resistance index (SVRI), cardiac power index (CPI).The levosimendan will be administered like a continues injection during 24 hours (0,1 mcg/kg/min) without initial dose. Following the optimization the patients will be transferred to the operating room in the next 3 days and will come back to the resuscitation and anaesthesia room where they will stay 24 hours more if there is no any complication.

All the cardiac complications will be documented and follw-up will be done by after 30 days and 3 months postoperative.

The patients will be selected for more than 24 months.

• Study Type: Observational
• Enrollment (Actual): 19

Contacts and Locations

Study Locations

• Spain
  • S/C Tenerife
    • La Laguna, S/C Tenerife, Spain, 38320
      • Complejo hospitalario Universitario de Canarias

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All the patients with chronic heart failure of any etiology with hip fracture that present an acute descompendation of their chronic heart failure and need inotropes because of the conventional treatment is not enough

Description

Inclusion Criteria:

1. Patients due to undergo urgent of hip fracture.
2. Patients with cardiac failure (EF < 45 %).
3. Decompensated heart failure.
4. Informed consent provided by the patient.

Exclusion Criteria:

1. <18 years old
2. Emergency surgery
3. Serious aortic stenosis (< 1 cm2)
4. Sustained ventricular tachycardia or atrial fibrillation >140
5. Earlier episodes of "torsades depointes"
6. Systolic blood pressure < 85 mmHg
7. Serious kidney failure (GFR < 30 ml/min)
8. Serious liver failure (known class C Child-Pugh score)
9. Allergy levosimendan

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Levosimendan; At least 12 hours before surgery: Infusion of levosimendan (0,1 mcg/kg/min). 24 hours of infusion without a bolus.	Drug: Levosimendan; 24h preoperative infusion of levosimendan (0,1 mcg/Kg/min); Other Names: Simdax.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effects of Levosimendan on left ventricular function.	Changes of left ventricular function as assessed transthoracic.	Baseline and every 24 hours postoperative, 48 h postoperative, and 7 days and after 30 days postoperative.
Change in cardiac index	Measured through arterial pulse wave analysis. A baseline measurement is done before infusion is started	48 hours after start of iv infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in transport and tissue perfusion of oxygen	measured by arterial and venous blood gases	1 to 2 day postoperative
Changes in renal function	Proportion of subjects who develop AKIN stage 1 (increase > 0.3 mg/dl or > 25% in serum creatinine from previous visit)	1 to 7 days postoperative
Changes in NT-proBNP and troponin I	Plasma NT-proBNP levels were measured	24 hours postoperative, 48 h postoperative, 72 h postoperative, and 168 h postoperative
Number of patients with adverse.	Development of arrhythmias	30 days postoperative
Number of patients with adverse.	Occurence of nausea/vomiting	30 days postoperative
Number of patients with adverse event.	Occurence of headache	30 days postoperative
Use of high inotropes (dopamine, Norepinephrine)	during postoperative unit stay.	after 12 hours, after 48 hours and every 24 hours if still in the PO-Unit
morbidity	All cause	3 months
Major adverse cardiovascular events	Perioperative heart failure infarction, stroke	1st-30th postoperative day
Time on mechanical ventilation	Perioperative heart failure infarction, stroke	1st-30th postoperative day
mortality	All cause	measured at 3 months
Perioperative mortality	All cause	7 days postoperative

Collaborators and Investigators

• Sponsor: Hospital Universitario de Canarias
• Collaborators: Orion Corporation, Orion Pharma
• Investigators: Principal Investigator: María del Carmen Martín Lorenzo, MD, Hospital Universitario de Canarias

Publications and helpful links

General Publications

• Cauley JA, Thompson DE, Ensrud KC, Scott JC, Black D. Risk of mortality following clinical fractures. Osteoporos Int. 2000;11(7):556-61. doi: 10.1007/s001980070075.
• Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet. 1999 Mar 13;353(9156):878-82. doi: 10.1016/S0140-6736(98)09075-8.
• Pedersen SJ, Borgbjerg FM, Schousboe B, Pedersen BD, Jorgensen HL, Duus BR, Lauritzen JB; Hip Fracture Group of Bispebjerg Hospital. A comprehensive hip fracture program reduces complication rates and mortality. J Am Geriatr Soc. 2008 Oct;56(10):1831-8. doi: 10.1111/j.1532-5415.2008.01945.x.
• Ponschab M, Hochmair N, Ghazwinian N, Mueller T, Plochl W. Levosimendan infusion improves haemodynamics in elderly heart failure patients undergoing urgent hip fracture repair. Eur J Anaesthesiol. 2008 Aug;25(8):627-33. doi: 10.1017/S0265021508004080. Epub 2008 Apr 11.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2014
• Primary Completion (ACTUAL): September 1, 2018
• Study Completion (ACTUAL): April 1, 2019

Study Registration Dates

• First Submitted: November 14, 2016
• First Submitted That Met QC Criteria: November 21, 2016
• First Posted (ESTIMATE): November 25, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 5, 2020
• Last Update Submitted That Met QC Criteria: February 3, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Wounds and Injuries; Leg Injuries; Femoral Fractures; Hip Injuries; Fractures, Bone; Hip Fractures; Ventricular Dysfunction; Ventricular Dysfunction, Left; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Simendan
• Other Study ID Numbers: MML-LEV-2013-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED