Clinical trial NCT01648777: Catheter Outcomes With Sternotomy Cardiac Operated
Official title: Cicatricial Analgesia Catheters Outcome on Bronchopulmonary Infection Number With Sternotomy Cardiac Operated
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumonia
Cardiac Surgery
Multiperforated Catheter
Analgesia
Critical Care Medicine
Keywords: Pneumonia
Postoperative infection
Cardiac surgery
Multiperforated catheter
Analgesia
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Baxter Healthcare Corporation
name: WYM France
name: Abbott
First posted: 2012-07-24
Enrollment: 1502
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Pneumonia occurs frequently in patients undergoing cardiac surgery and allows to increase their mortality. While chest physical therapy plays a crucial role to prevent postoperative pneumoniae, painful mobilization of the sternum after sternotomy limits chest physical therapy. The continuous local anesthetic infusion by multiperforated catheter decreases sternum pain. Because of this optimal pain management, early chest physical therapy could be more efficient and could contribute to decrease the rate of pneumonia.

The aim of this study is to test if management of sternotomy pain using continuous local anesthetic infusion by multiperforated catheter may contribute to decrease the rate of perioperative pneumonia.

Detailed description: Introduction:

Pneumonia occurs in 15 to 20% of patients undergoing cardiac surgery and allows to increase their mortality. Early non-invasive ventilation (NIV) after extubation and active and passive chest physical therapies have shown to diminish risk of respiratory failure and lowered 90-day mortality. Unfortunately, pain after cardiac surgery is mainly related to the median sternotomy. The mobilization of the sternum after sternotomy induces paroxysmal and periodical pain, sorely control by opioid treatment, regulated by the chest movements of ventilation or chest mobilization such during NIV or chest physical therapy. The continuous local anesthetic infusion by multiperforated catheter has been shown to be effective for decreasing paroxysmal sternum pain, opioid analgesic medication, length of intensive care medicine (ICU) and hospital stay. Because of this better pain management, early NIV and chest physical therapy could be more efficient and could contribute to decrease the rate of pneumonia in patients undergoing cardiac surgery with sternotomy.

Hypothesis: The aim of this study is to test if management of sternotomy pain using continuous local anesthetic infusion by multiperforated catheter may contribute to decrease the rate of perioperative pneumonia.

Primary end-point: Rate of post-operative pneumonia in hospital. Secondary end-points: post operative quality of Analgesia (total morphine consumption), 30-days all-cause mortality, mechanical ventilation free days, ICU free days, hospital stay, rate of ICU readmission, reintubation rate, septic shock rate, extrarenal epuration rate, cerebral vascular injury rate, Major Cardiac Adverse Events at 30-days, mortality at 30 days.

Method: This is a multicenter (5 french university centers) double blind randomized study compared to placebo. Patients are randomized the day before surgery (computer randomization) between L-bupivacaine and placebo which is infused with continuous local anesthetic infusion by multiperforated catheter at the end of cardiac surgery with sternotomy. Anesthesia protocol is pre-established (propofol and sufentanil with TCI and atracurium only at the induction), tranexamic acid (bolus of 20 mg/kg and 2mg/kg/h). Total dose of each agent is reported in the electronic case report (eCRF, cleanWeb®). Antibioprophylaxy is standardized in agreement with French guidelines in cardiac surgery. Analgesic treatment is standardized as well. During the first postoperative 48 hours: paracetamol (1g x4/day), morphine sulfate (intravenous titration and immediately after the end of titration, self pain management with morphine pump during 48 hours for all the patients included in the study. Total dose of morphine sulfate is reported in the eCRF. In addition, intravenous ketoprofen may be associated in addition if requested. Multiperforated catheter is introduced at the end of surgery above steel sternal bands. A bolus of 10 ml of L-bupivacain or placebo is infused into the catheter at the end of surgery when skin suture is done. Then, the elastomeric pump is connected to the catheter for 48 postoperative hours at 8ml/hour. Extubation is done ideally in the first 6 postoperative hours and chest kinesitherapy is performed at day 1 and 2, in postoperative period. Follow up is done during 30 days after surgery.

Statistical analysis: Rate of pneumonia is expected to be 18% in the placebo group, and 12.6% in the L-bupivacaine group. The number of patients needed (with alpha=0.05, beta= 0.80) is estimated to be 1500 patients (750 patients by group). Because 5 centers are expected to participate, 15% only of eligible patients in all these centers will be enough. Twenty four months would be necessary for the inclusion with 1 month more for the follow up. Thus, the study would last 25 months.

Ethical issue: The present study will be presented to pitie salpetriere Research Ethics Board for approval. An independent Safety Board will survey the study.

Conclusion: This study should decrease the rate of pneumonia in patients undergoing cardiac surgery with sternotomy.

Eligibility criteria: Inclusion criteria :

* all patient more than 18 years old
* planned cardiac surgery with sternotomy and bypass
* Informed consent written

Exclusion criteria :

* Refusal of patient to be included in the study
* Age less than 18 years old
* Pregnancy
* Emergency
* Prolonged sedation and ventilation more than 48h00 expected in teh postoperative period
* Moribund patient
* Palliative medicine
* Patient in the care of a guardian
* Preoperative pneumonia
* Patient randomized in an other randomized study
* Contraindication to L-bupivacain, morphine sulfate, paracetamol or tramadol
* Lack of national health care insurance

Primary outcomes:
measure: Rate of post-operative pneumonia in hospital
timeFrame: 30 days
Secondary outcomes:
measure: all-cause mortality
timeFrame: 30 days
measure: mechanical ventilation free days
timeFrame: 30 days
measure: ICU free days
timeFrame: 30 days
measure: Hospital stay
timeFrame: 30 days
measure: Rate of ICU readmission
timeFrame: 30 days
measure: Reintubation rate
timeFrame: 30 days
measure: Septic shock rate
timeFrame: 30 days
measure: Extrarenal epuration rate
timeFrame: 30 days
measure: Cerebral vascular injury rate
timeFrame: 30 days
measure: Major Cardiac Adverse Events
timeFrame: 30 days
Other outcomes:
Locations:
city: Paris
country: France
facility: Pitié salpetrière Hospital
Study officials:
affiliation: APHP
name: Julien Amour, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Amour J, Cholley B, Ouattara A, Longrois D, Leprince P, Fellahi JL, Riou B, Hariri S, Latremouille C, Remy A, Provenchere S, Carillion A, Achouh P, Labrousse L, Tran Dinh A, Ait Hamou N, Charfeddine A, Lafourcade A, Hajage D, Bougle A; STERNOCAT investigators. The effect of local anesthetic continuous wound infusion for the prevention of postoperative pneumonia after on-pump cardiac surgery with sternotomy: the STERNOCAT randomized clinical trial. Intensive Care Med. 2019 Jan;45(1):33-43. doi: 10.1007/s00134-018-5497-x. Epub 2019 Jan 7.