Pain Management After Cardiac Surgery - Opioids or NSAID

Aalborg University Hospital

Status and phase: Completed; Phase 4

Conditions: Postoperative Pain; Myocardial Infarction; Renal Insufficiency

Treatments: Drug: Oxycodone; Drug: Ibuprofene

Study type: Interventional

Funder types: Other

Identifiers

NCT02479165

The NSAID trial

Details and patient eligibility

About

The aim of this randomized controlled study is to shed light on the analgesic properties and side-effect profile of an opiod-based regimen as opposed to an Ibuprofene based regimen.

Full description

Background:

Postoperative pain following median sternotomy can represent a major postoperative problem as it can lead to reduced mobilization and shallow, restricted breathing and insufficient cough, which can lead to pulmonary complications.

However, pain management with opioids has frequent side-effects such as confusion, respiratory depression, sedation, nausea and obstipation/ paralytic ilieus. Non-steroid anti-inflammatory drugs (NSAIDs) can been used as opiod-sparing analgesics following cardiac surgery. However, this remains controversial, as NSAIDs has been linked to an increased risk of myocardial infarction, especially in patients with ischaemic heart disease, renal failure, gastrointestinal bleeding, and possibly impaired sternal healing.

The investigators wanted to investigate the analgesic properties of a opiod-based regimen with that of an ibuprofene-based, through randomization of patients to one of the two arms.

Intervention:

The participants were given analgesics in accordance to their randomization group upon return from the postoperative ICU stay.

The opioid regimen relied on a basic dose of slow-release oxycodone ("Oxycontin", Norpharma, Vedbaek, Denmark, 10mg two times daily) and paracetamol ("Panodil", GlaxoSmithKline, Copenhagen, Denmark, 1g four times daily). For "break-through pain" extra oxycodone was administered as injections or capsules (5mg pr. dose). Furthermore laxatives were co-administered to prevent obstipation.

In the ibuprofene regimen slow-release ibuprofen ("Brufen Retard", Abbott, Copenhagen, Denmark, 800mg two times daily) replaced oxycodone as the basic analgesic. In the ibuprofene regimen lansoprazol ("Lansoprazole", Actavis, Gentofte, Denmark, 30mg once daily) was co-administered to prevent development of gastric ulcers. These regimens were initiated the first postoperative day, when the patient was transferred from the ICU to the ward, and continued until the seventh postoperative day. Some patient

Outcome:

Please refer to the "outcome" chapter

Statistics:

Data are presented as number of patients, medians, and ranges. Patients are compared according to the ibuprofen or the oxycodone group, and statistics were done using "intention-to-treat"-design. Fischer's exact test, Mann-Whitney, and 95% confidence intervals were used as appropriate. Significance was defined as P-values below 0.05.

Enrollment: 182 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Cardiac surgery through median sternotomy
• Written consent
• Age over 18 years

Exclusion criteria

• Other forms of sternotomy (i.e. re-sternotomy or partial sternotomy)
• Preoperative creatinine over 110 µmol/L
• Preoperative use of opioids or NSAIDs in analgesic doses (aspirin in antithrombotic doses was accepted)
• Allergy to NSAIDs or opioids, and other contraindications to the used drugs

The postoperative exclusion criteria were:

• Staying more than one night at the intensive care unit
• Unacceptable side effects
• Exclusion at the patients request

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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182 participants in 2 patient groups

Opioid group

Active Comparator group

Description:

If randomized to the opiod group, the patient was given the following regimen for 1 week, upon return from the intensive care unit, after surgery. Tbl. Oxycodone (slow-release) 10mg, Twice daily for 1 week Tbl. Paracetamol 1000mg, Four times daily for 1 week Tbl.oxycodone 5mg Max 4 times daily, as needed, until discharge. Inj, oxycodone 2.5 mg, Max 4 times daily, as needed, until discharge Tbl. Magnesia 1g, Twice daily, for 1 week Sol. Sodiumpicosulfate 7.5mg/ml 10 drops daily, for 1 week

Treatment:

Drug: Oxycodone

Ibuprofene group

Active Comparator group

Description:

If randomized to the ibuprofen group, the patient was given the following regimen for 1 week, upon return from the intensive care unit, after surgery. Tbl. Ibuprofen (slow-release) 800mg, Twice daily, for 1 week Tbl. Paracetamol 1000mg, Four times daily, for 1 week Tbl.oxycodone 5mg Max 4 times daily, as needed. Until discharge. Inj, oxycodone 2.5 mg Max 4 times daily, as needed. Until discharge. Tbl. Lanzoprazole 40 mg, Once daily, for 1 week Tbl. Magnesia 1g, Twice daily, for 1 week Sol. Sodiumpicosulfate 7.5mg/ml, 10 drops daily, for 1 week

Treatment:

Drug: Ibuprofene