The Challenge of Opioid-Free Anesthesia

  • Maher Khalife
  • Graziela Biter
  • Marco Cascella
  • Raffaela Di Napoli
Part of the Neuromethods book series (NM, volume 150)


The introduction of opioids in the clinical practice of anesthesia was a revolution. By blocking the sympathetic response to surgical stimuli and obtaining a reduced requirement of hypnotic agents, a safer and a more stable hemodynamically perioperative period was made possible. However, administration of opioids can be associated with several side effects that can be responsible for delayed patient recovery and hospital discharge, as well as leading to increased health service costs. Furthermore, opioid use is related to a wide range of side effects including gastrointestinal (nausea, vomiting, ileus), respiratory (decreased central respiratory drive impacting respiratory rate, and tidal volume), central nervous system effects (sedation, delirium, dysphoria, catalepsy, hallucinations) effects, as well as urinary retention, pruritus, bradycardia, and dizziness. Another undesired effect of opioids as primary pain therapy in the perioperative period, is the development of “acute tolerance” to the analgesic effect of these drugs. This diminished analgesic effect may also be the result of the “opioid-induced hyperalgesia” (OIH) phenomenon. Again, some evidence has suggested that opioids may interfere with the immune system. Numerous studies have shown that opioids can influence the progression of cancer, metastasis, and cancer recurrence. In the 1990s, in the light of experience and studies conducted on opioids and their effects within the broader context of multimodal analgesia, their use came into question. New anesthesia techniques started to be developed that aimed to achieve the sparing use of opioids. These approaches culminated, in the 2000s, with the development of opioid-free anesthesia (OFA) pathways. The strategy of OFA is a realistic alternative that can lead to enhanced recovery and increased patient satisfaction by reducing important opioid related side effects; it can also facilitate the use of lower doses of opioids postoperatively in order to achieve a pain-free recovery and reduce pain scores while providing faster and safer mobilization and rehabilitation. The drugs used are hypnotics, N-methyl-d-aspartate (NMDA) antagonists (ketamine, magnesium sulfate), sodium channel blockers (local anesthetics), anti-inflammatory drugs [nonsteroidal anti-inflammatory drugs (NSAIDs), dexamethasone, local anesthetic], and alpha-2 agonists (dexmedetomidine, clonidine). The association of OFA and locoregional anesthetic techniques is very common. Several types of patients can benefit from this technique including narcotic history patients, obese patients with obstructive sleep apnea, patients with hyperalgesia and history of chronic pain, immune deficiency individuals, patients undergoing oncologic surgery as well as those affected by inflammatory conditions, chronic obstructive pulmonary disease, and asthma. While different OFA protocols have been reported in the literature, the publications rely mostly on case reports and small size investigations. More studies are necessary to assess what the interactions between these drugs are. Clinical researchers must design studies with rigorous methodology in order to correctly assess the risks and benefits of OFA for patients in different surgical settings.

Key words

Opioid-free anesthesia Opioids Opioid-related side effects Ketamine Dexmedetomidine Magnesium Lidocaine 


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Maher Khalife
    • 1
  • Graziela Biter
    • 2
  • Marco Cascella
    • 3
  • Raffaela Di Napoli
    • 1
  1. 1.Department of Anesthesiology, Institut Jules BordetUniversité Libre de BruxellesBruxellesBelgium
  2. 2.Department of Anesthesiology, CHU Saint-PierreUniversité Libre de BruxellesBruxellesBelgium
  3. 3.Istituto Nazionale Tumori - IRCCS - Fondazione PascaleNapoliItaly

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