Please select the eligibility criteria that correspond to the clinical trial below.
Title: Reduce Nonsteroidal Antiinflammatory Drugs Doses for Analgesia After Sternotomy
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.


Options:
A: 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
B: Inclusion Criteria:

1. Are undergoing noncardiac surgery;
2. Are ≥ 45 years of age;
3. Are expected to require at least an overnight hospital admission after surgery; AND
4. Fulfill one or more of the following 5 criteria:

   * History of coronary artery disease
   * History of peripheral vascular disease
   * History of stroke
   * Undergoing major vascular surgery
   * Any 3 of the following 9 criteria:

     * undergoing major surgery (i.e. intraperitoneal, intrathoracic, retroperitoneal or major orthopedic surgery
     * history of congestive heart failure
     * transient ischemic attack
     * diabetes and currently taking an oral hypoglycemic agent or insulin
     * age ≥ 70 years
     * hypertension
     * serum creatinine \> 175 µmol/L (\> 2.0 mg/dL)
     * history of smoking within 2 years of surgery
     * undergoing urgent/emergent surgery

Exclusion Criteria:

1. Consumption of ASA within 72 hours prior to surgery
2. Hypersensitivity or known allergy to ASA or clonidine
3. Systolic blood pressure \< 105 mm Hg
4. Heart rate \< 55 beats per minute in a patient who does not have a permanent pacemaker
5. Second or third degree heart block without a permanent pacemaker
6. Active peptic ulcer disease or gastrointestinal bleeding within previous 6 weeks
7. Intracranial hemorrhage documented by neuro-imaging, in the 6 months prior to randomization. This does not include petechial hemorrhagic transformation of a primary ischemic stroke
8. Subarachnoid hemorrhage or epidural hematoma unless the event occurred more than 6 months prior to randomization and the offending aneurysm or arterial lesion has been repaired
9. Drug-eluting coronary stent in the year prior to randomization
10. Bare-metal coronary stent in the 6 weeks prior to randomization
11. Thienopyridine (e.g., clopidogrel, ticlopidine, prasugrel) or ticagrelor within 72 hours prior to surgery; or intent to restart a thienopyridine or ticagrelor during the first 7 days post-op; or currently taking an alpha-2 agonist, alpha methyldopa, monoamine oxidase inhibitors or reserpine;
12. Planned use - during the first 3 days after surgery - therapeutic dose anticoagulation or a therapeutic subcutaneous or intravenous antithrombotic agent
13. Undergoing intracranial surgery, carotid endarterectomy, or retinal surgery
14. Not consenting to participate in POISE-2 prior to surgery
15. Previously enrolled in POISE-2 Trial
C: Inclusion Criteria:

1. Scheduled for elective abdominal hysterectomy surgery with anticipated need for post-operative I.V. morphine analgesia with anticipated use of ≥ 24 hours.
2. Adequate IV access
3. Anticipated hospital stay ≥ 24 hours

Exclusion Criteria:

1. Be unable to make a reliable self-report of pain intensity to pain relief
2. Less than 18 years of age
3. Greater than 70 years of age
4. Use of NSAIDs within 12 hours prior to dosing
5. Use of analgesics, muscle relaxants and sedatives less than 24 hours prior to CTM administration with the following exceptions: paracetamol (acetaminophen) can be administered until 6 hours prior to surgery; tramadol can be administered until midnight the evening prior to surgery; muscle relaxants working at the neuromuscular junction used for intubation and/or anesthesia administration for the surgical procedure prior to CTM administration; and sedatives (i.e., midazolam) used as a co-induction agent for the surgical procedure prior to CTM administration
6. Patients taking warfarin, lithium, combination of ACE-inhibitors and furosemide
7. Patients with anemia (active clinically significant) and/or a history or evidence of asthma or heart failure
8. History of allergy or hypersensitivity to any component of Caldolor, aspirin (or aspirin related products), NSAIDs, or COX-2 inhibitors
9. Pregnant or nursing
10. History of severe head trauma that required current hospitalization, intracranial surgery or stroke within the previous 30 days, or any history of intracerebral arteriovenous malformation, cerebral aneurysm or CNS mass lesion
11. Weigh less than 30kg
12. Have a history of congenital bleeding diathesis (eg hemophilia) or any active clinically significant bleeding, or have underlying platelet dysfunction including (but not limited to) idiopathic thrombocytopenic purpura, disseminated intravascular coagulation, or congenital platelet dysfunction
13. Have GI bleeding that required medical intervention within the previous 6 weeks (unless definitive surgery has been performed)
14. Have a platelet count less than 30,000mm3 determined within the 28 days prior to surgery
15. Pre-existing dependence on narcotics or known tolerance to opioids
16. Inability to understand the requirements of the study, be willing to provide written informed consent (as evidenced by signature on an informed consent document approved by an Institutional Review Board \[IRB\]), and agree to abide by the study restrictions and to return for the required assessments
17. Refusal to provide written authorization for use and disclosure of protected health information
18. Be on dialysis, have oliguria or calculated creatinine clearance of less than 60 mL/min (calculated using the Cockcroft and Gault formula) determined within the 28 days prior to surgery
19. Inability to achieve hemostasis or inability to close surgical incision, prior to Operating Room discharge
20. Operative procedure includes organ transplant
21. Pre or intra-operative procedure utilized for the prevention of pre- or post-operative pain (i.e. epidural or nerve blocks)
22. Be receiving full dose anticoagulation therapy or Activated Protein C within 6 hours before dosing (Prophylaxis with subcutaneous heparin is acceptable)
23. Have received another investigational drug within the past 30 days
24. Be otherwise unsuitable for the study in the opinion of the investigator
D: Inclusion Criteria:

* age\>18
* any cardiac procedure with sternotomy
* able to give informed consent

Exclusion Criteria:

* cardiac surgery without sternotomy
* peripheral neuropathy
* neurological disease
* psychiatric illness
* history of GI bleeding
* chronic pain (i.e. back pain, cancer, arthritis)
* serum creatinine \>150 μmol/l
* hepatic disease with elevated liver enzymes (SGPT and SGOT elevated to 1.5 times maximum normal value)
* allergic to study medication
* alcohol abuse
* abuse of narcotics or medication
* pregnancy
* participation in other clinical trials
* insufficient language skills
* In addition intensive care unit (ICU) stay for more than 24 hours was used as a pre-defined post randomization exclusion criteria, because prolonged ICU stay and ventilator treatment would interfere with study analgesic protocol.

Answer: A