Multimodal Versus Opioid aNalgesia in carDiAc Surgery
Condition: Postoperative Pain; Postoperative Delirium
MeSH terms: Emergence Delirium
Study type: Interventional
Phase: Phase 4

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.
    

Detailed 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.
    

Intervention name(s): Dexmedetomidine
Intervention type(s): Drug
Intervention description(s): The use of multimodal painkillers pre, per and postoperative
Other intervention name(s): pregabaline; ketamine; lidocaine; magnesium sulfate
Intervention MeSH terms: Lidocaine; Magnesium Sulfate; Pregabalin; Dexmedetomidine; Ketamine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment