MedPath

Reduce Nonsteroidal Antiinflammatory Drugs Doses for Analgesia After Sternotomy

Phase 2
Conditions
Cardiac Surgery
Post-operative Pain
Interventions
Registration Number
NCT02180087
Lead Sponsor
University Hospital, Clermont-Ferrand
Brief Summary

Currently, the management of pain after cardiac surgery is based on the concept of multimodal analgesia: Combined use of non-opioid analgesics associated with morphine intravenous analgesia by a system controlled by the patient (patient-controlled analgesia-PCA).

The combination of paracetamol and morphine PCA is very effective on pain at rest, but is limited on pain mobilization and causes the problem of side effects associated with opioid (overdose, sedation, respiratory depression, gastrointestinal intolerance, urinary retention ...) which are contributing factors to increase the length of stay in Intensive Care Unit, an additional cost of care and an increase postoperative morbidity and mortality.

Methods that have proved their effectiveness on pain and mobilization used in postoperative cardiac surgery are: anti-inflammatory drugs (NSAIDs) and / or loco-regional analgesia techniques. NSAIDs enhance analgesia produced by PCA Morphine and allow a reduction in morphine consumption, improved postoperative pain, decreased sedation and decreased postoperative morbidity and mortality.

Adverse effects of NSAIDs are commensurate with their time and exposure dose. Consequently, NSAIDs, in the absence of against-indications, should always be prescribed and used at the lowest effective dose and for the shortest possible time.

Some studies have suggested that lower doses of NSAIDs didn't appear to affect their effectiveness. At present, the investigators have no studies that address the hypothesis from which minimum dose of ketoprofen analgesic effect is obtained.

The investigators hypothesis is that lower dose ketoprofen may have efficacy on pain in the postoperative mobilization of cardiac surgery. The investigators want to find, in their study, this "optimal" ketoprofen dose which would be the minimum dose for clinical efficacy demonstrated dose.

This optimal dose could reduce the number of adverse effects of NSAIDs, but their study will probably not have enough power to prove it. NSAID use at these low doses, in postoperative cardiac surgery, could be extended to patient populations most at risk or for a duration longer than 48 hours.

Detailed Description

To answer this hypothesis the investigators will consider starting a study of four groups of patients where appropriate doses to patient weight gradually increasing ketoprofen will be used in seeking the minimum effective dose.

Four groups will be determined by randomization. In all these groups, analgesia will be supplemented by a systematic standard self-administered treatment with morphine and paracetamol.

* Group 1 : Placebo group (P). 0 mg/kg ketoprofen IV every 6 hours for 48 hours (or 0 mg/kg every 24 hours) for 48 hours.

* Group 2 : "Ketoprofen quarter dose" (K ¼). 0,125 mg/kg ketoprofen IV every 6 hours (0,5 mg/kg every 24 hours) for 48 hours.

* Group 3 : "Ketoprofen half-dose" (K ½). 0,25 mg/kg ketoprofen IV every 6 hours (1 mg/kg every 24 hours) for 48 hours.

* Group 4 : "Ketoprofen full dose" (KPD). 0,5 mg/kg ketoprofen IV every 6 hours (or 2 mg/kg every 24 hours) for 48 hours.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
100
Inclusion Criteria
  • Patients scheduled for a cardiac surgery (Coronary artery bypass graft, valve replacement)
  • Age over 18 years
  • Weight between 60 and 100 kg
  • Absence of criteria for non-inclusion
Exclusion Criteria
  • Age over 75 years
  • Renal insufficiency (MDRD <60 ml / min)
  • Hepatic Insufficiency
  • Congestive heart failure (EF <40%)
  • Insulin-requiring diabetes
  • Preoperative coagulation trouble
  • History of peptic ulcer or gastrointestinal bleeding
  • Allergy to NSAIDs
  • Surgery in emergency, aorta surgery, heart transplantation
  • Peptic ulcer scalable, history of peptic ulcer or recurrent bleeding (2 or more distinct episodes of bleeding or ulceration objectified)
  • Pregnant or lactating women
  • Major protected

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
placebo groupKetoprofenGroup 1 : Placebo group (P). 0 mg/kg ketoprofen IV every 6 hours for 48 hours (or 0 mg/kg every 24 hours) for 48 hours
Ketoprofen full doseKetoprofenGroup 4 : "Ketoprofen full dose" (KPD). 0,5 mg/kg ketoprofen IV every 6 hours (or 2 mg/kg every 24 hours) for 48 hours
ketoprofen half-doseKetoprofenGroup 3 : "Ketoprofen half-dose" (K ½). 0,25 mg/kg ketoprofen IV every 6 hours (1 mg/kg every 24 hours) for 48 hours.
ketopofen quarter doseKetoprofenGroup 2 : "Ketoprofen quarter dose" (K ¼). 0,125 mg/kg ketoprofen IV every 6 hours (0,5 mg/kg every 24 hours) for 48 hours.
Primary Outcome Measures
NameTimeMethod
Pain at the mobilizationAt the first 48 hours postoperatively

Pain at the mobilization of the first 48 hours postoperatively, measured every 4 hours by simple numerical scale or VAS (0: no pain to 10: unbearable pain)

Secondary Outcome Measures
NameTimeMethod
Time of removal of drains after surgeryat day 1
Effective Duration of stay in the Intensive Care Unitat day 1
Resumption of transit characterized by the first gas time after surgery.at day 1
Nausea occurrence (number of episodes) assessed every 4 hoursfrom H0 to H0 +48 hours
Vomiting occurrence (number of episodes) assessed every 4 hoursfrom H0 to H0 +48 hours
Demographic criteriaat day 1
Quantity of sufentanil administered intraoperativelyat day 1
Pain at rest measured by Visual Analogue Scaleat day 1

Pain at rest measured every 4 hours from H0+4 hours to H+48 hours by Visual Analogue Scale (H0 : sedation stop time, 1 hour before waking)

Total morphine consumptionfrom H0 to H0+48 hours
Blood gas monitoring 3 times a dayfrom H0 to H0+48 hours
Patient satisfaction for its first mobilization assessed by simple scale Likertat H0+ 48 hours
Occurrence of the following complications: Renal respiratory cardiac Neurological infectious HemorrhagicFrom H0 to H0+48 hours
Any readmission to the intensive care unit in the two weeks following the surgeryat day 7

Trial Locations

Locations (1)

CHU de Clermont-Ferrand

🇫🇷

Clermont-Ferrand, France

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