Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04987372 |
| Other study ID # |
2019-000515-84 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
January 21, 2019 |
| Est. completion date |
December 3, 2021 |
Study information
| Verified date |
October 2023 |
| Source |
University Hospital, Ghent |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
To compare standard "Fentanyl - Tramadol - Paracetamol - Oxycodone" regimen to a multimodal
painmanagement "pregabalin- minimal fentanyl-ketamine-lidocain-dexmedetomidine- paracetamol"
to determine which therapy provides the most comfort, the fastest extubation time, the least
pain and the least delirium.
Description:
Cardiac surgery for the adult, performed by sternotomy is associated with moderate to severe
acute postoperative pain. Postoperative pain is the primary reason for prolonged
convalescence and one of the main concerns of the surgical patient in the Intensive Care Unit
(ICU). This pain is multifactorial and multifocal; and can be caused by incision,
intraoperative tissue retraction and dissection, surgical manipulation of the parietal
pleura, posterior rib dislocation or fracture, possible brachial plexus injury, chest tube
insertion and harvesting of the saphenous vein and internal mammarian artery.
The most common analgesic schemes for postoperative pain in cardiac surgery are based on
intravenous opioids by bolus, with patient- or nurse-controlled delivery systems. Although
there is no doubt they have a beneficial effect on pain, opioids are associated with
dose-related side effects including "over"sedation, ileus, urinary retention, nausea,
vomiting, pruritus, mental confusion and respiratory depression leading to a prolonged
extubation time.
In the last decades many has been written about the value of multimodal pain protocols to
treat acute postoperative pain in non-cardiac surgery. This is not only to reduce the dose
and side effects of opioids. By blocking both the central and peripheral pain mechanisms the
aim is to find a holy grale, by which the patient suffers the least, by which central neural
hyper-excitability that increases postoperative pain is minimized and by which the
transformation of acute into chronic pain is reduced to a minimum.
Pregabalin has his role in treating various neuropathic pain syndromes. It inhibits central
neuronal sensitization and prevents hyperalgesia by decreasing excitatory amino acid
neurotransmission in the spinal cord through a direct postsynaptic or presynaptic inhibition
of Ca²+ influx. It has been shown that gabapentin reduced pain scores and opioid requirements
in different surgical settings. Literature is not conclusive and because of conflicting
results the routine use of gabapentin and pregabalin to reduce opioid consumption in the
cardiac surgical patients is not yet recommended.
Dexmedetomidine is an alpha-2 adrenergic receptor agonist that can be directly applied to the
peripheral nervous system, causing a dose-dependent inhibition of C-fibers and Aα-fibers. It
is widely used for sedation and anxiolysis in ICU settings. The clinical efficacy has been
proven in non-cardiac surgery by augmenting anesthesia and analgesia, and allowing a
reduction in opioid requirements. Additionally, there was a significantly lower incidence of
postoperative delirium.
Ketamine isn't only an anesthetic agent but also has an analgesic effect. The exact mechanism
is not yet known but some of the pathways are already identified. It binds to the opioid
receptors κ(kappa) δ(delta) μ(mu) and it was proven that ketamine induces phosphorylation of
mitogen-activated protein kinases by 2-3 times that of traditional opioid drugs. Another way
of producing its analgesic effect is by the muscarinic acetylcholine receptors in the central
nervous system. Ketamine also effects other ion channels including sodium channels and
voltage sensitive calcium channels leading to local anesthetic and gabapentin like effects.
Because of the unique effect of keeping hemodynamic stability during induction, ketamine can
be useful in cardiac surgery. The analgesic effect, the absence of respiratory depression and
hemodynamic stability make it an excellent drug to use in the ICU.
Intravenous lidocain during the perioperative period has many beneficial effects in open
procedures, such as an earlier return of gastrointestinal tract function, less postoperative
opioid consumption, improvement of postoperative cognitive dysfunction and reduced stay in
the hospital. The exact working mechanism isn't 100% identified but the anti-inflammatory
effects of LA mediated through interactions with polymorphonuclear cells and the inhibition
of G protein-coupled receptors may play a crucial role for the observed effects in the
perioperative setting.
Magnesiumsulphate's analgesic mechanisms are also not fully identified, but it is thought
that the NMDA (N-methyl-d-aspartate) receptor is blocked by calcium regulation mechanisms.
Because the NMDA receptor plays a role in the transmission of pain, magnesium has become a
subject of interest as potential use in postoperative painschemes. It was proven that
peri-operative intravenous magnesium can reduce opioid consumption especially in the first
24h.
The investigator's goal is to compare standard "Fentanyl - Tramadol - Paracetamol - Oxycodon"
regimen to a multimodal painmanagement "pregabalin- magnesiumsulphate - minimal
fentanyl-ketamine-lidocain-dexmedetomidine- paracetamol" to determine which therapy provides
the most comfort, the fastest extubation time, the least pain and the least delirium.
