Feasibility and Postoperative Opioid Sparing Effect of an Opioid-free Anaesthesia in Adult Cardiac Surgery

A Retrospective Study

Clément Aguerreche; Gaspard Cadier; Antoine Beurton; Julien Imbault; Sébastien Leuillet; Alain Remy; Cédrick Zaouter; Alexandre Ouattara

Disclosures

BMC Anesthesiol. 2021;21(166) 

In This Article

Discussion

The major findings of our study are that dexmedetomidine-based OFA: 1) appears to be feasible, 2) has a statistically significant opioid sparing effect without obviously altering pain relief and 3) could be associated with better postoperative outcomes including less new onset of atrial fibrillation, a lower rate of postoperative need for non-invasive ventilation and perhaps less incidence of postoperative delirium.

Feasibility

Only one previous study evaluated the feasibility of OFA based on lidocaine and ketamine in cardiac surgery.[15] Despite a higher intra operative use of esmolol and urapidil, these authors reported that OFA reduces significantly postoperative morphine consumption.[15] A large opioid sparing effect was also observed in patients receiving an OFA protocol.[15] However, the OFA protocol used in our patients was substantially different and was based on a pre-induction mixture of intravenous infusion of dexmedetomidine, magnesium sulfate and lidocaine. Dexmedetomidine has been well studied as an adjunct in balanced anaesthesia for cardiac surgery but no previous study has ever evaluated the benefit of dexmedetomidine-based OFA strategy.[16,17] A safety and an efficient analgesic effect of dexmedetomidine in cardiothoracic surgery has been previously reported.[16] The hemodynamic effects of lidocaine have been previously investigated in cardiac surgical patients.[26] A 1.5 mg.kg− 1 intravenous bolus of lidocaine effectively limits increase in arterial pressure during aortic canulation.[26] Concerning the use of ketamine, its sympathomimetic effect could potentially lead to an increase in myocardial oxygen consumption.[27] Even if our OFA patients received a larger intraoperative amount of ketamine, no significant difference in postoperative hs-cTnI level was observed. Magnesium sulfate has a vasodilator effect and could potentiate the hypotensive effects of propofol.[28] For this reason, we have administered magnesium intravenously slowly over a period of 15 min. Because magnesium sulfate reduces intraoperative hemodynamic variability, some authors proposed its intraoperative use to control sympathetic response to surgery during OFA.[29] Moreover, magnesium sulfate significantly reduces requirement for anesthetic drugs and may potentiate neuromuscular blockade in cardiac surgery patients.[30,31] Additionally, a high incidence of postoperative residual curarisation in patients undergoing long duration non-cardiac surgery intervention and for whom the block is not antagonized.[32] In accordance with our daily clinical practice, absence of postoperative residual curarization was systematically eliminated before to stop propofol infusion and perform tracheal extubation. Our findings suggest that dexmedetomidine-based OFA is feasible. Although, dexmedetomidine has been discontinued in 10 (25%) patients, the intraoperative use of vasopressors was comparable between groups. This finding confirms results obtained from a meta-analysis conducted in non-cardiac surgery.43 In addition, we did not observe a higher incidence of postoperative vasoplegia in the OFA-group. Previous studies conducted in cardiac surgical patients reported an increased risk of bradycardia with dexmedetomidine. However, it should be pointed out that in these studies dexmedetomidine was used as an adjunct to an opioid based-anaesthesia strategy.

Opioid Sparing Effect and Analgesia

Dexmedetomidine analgesic and opioid-sparing effects are dose-dependent and trigger at spinal cord sites as well as through non-spinal mechanisms.[34] It has been suggested that alpha-2 agonist receptors activation, inhibition of the C and A delta fibres signals conduction, and the local release of encephalin are the underlying non-spinal mechanisms of dexmedetomidine to provide anti-nociception effects.[35] Grant et al.[7] showed that with an enhanced recovery program for cardiac surgery, the intraoperative opioid sparing effect was greater when preoperative acetaminophen, gabapentin, intraoperative ketamine and dexmedetomidine infusions, and regional analgesia (via a serratus anterior plane block) were combined. In the analysis of each individual intervention effect, dexmedetomidine was the molecule associated with the best intra operative opioid sparing effect.[7] For non-cardiac surgery, lidocaine combined with dexmedetomidine infusion significantly improve postoperative pain and lower opioid-related side effects such as bowel function or nausea.[36,37] Ketamine via its anti N-methyl-D-aspartate (NMDA) effect reduces postoperative hyperalgesia, provides analgesia, hypnosis and amnesia.[38] Ketamine as an analgesic adjunct reduces opioid consumption after cardiac surgery and reduces variability of blood pressure.[29,39] Some studies suggest an anti-inflammatory effect attenuating the inflammatory response to cardiopulmonary bypass and a delirium preventing effect.[40] By its antagonistic effect of NMDA receptor, magnesium sulfate minimizes postoperative pain, reduces requirement for analgesics and thus may have opioid sparing effect.[41,42] Maximal NPRS scores at rest were similar between the two groups but NPRS scores were lower during coughing in the OFA-group in accordance with a study conducted in thoracic surgery.[43] Our present data seem to indicate that an OFA protocol designed for cardiac surgery could further decrease perioperative opioid consumption compared to the OBA group that received a multimodal analgesia using opioid intraoperatively. The present study shows that OFA could lower by half the postoperative opioid consumption. A such reduction should be considered as clinically relevant regarding to most of the patients undergoing cardiac surgery are elderly and to when a cardiac ERAS program is sought to be implemented.[6]

Secondary Outcomes

The shorter extubation time in patients receiving OFA may appear to be surprising. No previous study reported similar result when dexmedetomidine was compared to remifentanil. However, the fact that surgical re-exploration for excessive bleeding was 5 times more frequent in the opioid anesthesia group must have confounded significantly the length of mechanical ventilation.

The OFA protocol was associated with better relevant outcomes in the post-operative course such as new onset of atrial fibrillation, a common event after cardiac surgery source of great morbidity and mortality.[44] Magnesium sulfate can have a preventive anti-arrhythmic effect on AF.[45] Dexmedetomidine can also have a protective effect in on-pump CABG[18] by decreasing myocardial ischemia-reperfusion and improving myocardium perfusion, anti-inflammatory,[46,47] sympatholytic and parasympathomimetic effect.[48] Lidocaine has anti-inflammatory effect, increases the cardioprotective effect of cardioplegia and decreases the risk of arrythmias but only of ventricular fibrillation.[49] Nevertheless, the incidence of ventricular arrythmias was too low in our study to show any benefit.

Interestingly, patients receiving OFA trend to present less postoperative delirium. Even if this difference was not significant, this beneficial effect may be explained by the opioid sparing effect observed and/or intrinsic effect of dexmedetomidine.[50] Moreover, intraoperative use of lidocaine could be protective against postoperative cognitive dysfunction modulating the cerebral inflammation secondary to cardiopulmonary bypass.[51]

Our findings suggest the synergistic effect and multiple action site of the drugs used in the OFA-group could improve post-operative pain lowering the incidence of the side effects of each drug. Moreover, the additive anti-inflammatory effects of each drug may lower the most frequent postoperative complications.

Limitations

The present study had several limitations, and the following points must be considered in the assessment of the clinical relevance of our study. First, our work is a single-centre retrospective observational study which did not control for any variables between the groups. Consequently, several differences between the two groups could be observed in baseline patients' characteristics, mostly EuroSCORE II, non-elective surgery, LVEF, diabetes, dyslipidaemia and Apfel score; but all disadvantaging the OFA-group. Thus, in light of these drawbacks it could be claimed that a dexmedetomidine-based OFA for cardiac surgery could offer a good hemodynamic stability even in more fragile cardiac surgery patients. Second, at the moment of the study, OFA was an anesthetic protocol starting to be implemented within our department of anesthesia. Consequently, the thought process behind one patient being in the OFA group versus the OBA group was mainly conditioned by the attending anesthesiologist. This aspect could highlight the benefit of a clinically well conducted OFA-protocol. This also explains the long period of time necessary to obtain this relatively low number of patients and limits its external validity. Third, in the OBA group the intraoperative use of anti-hyperalgesic medications such as ketamine and/or magnesium sulfate and/or lidocaine was left at the discretion of the attending anesthesiologist. It would have been easier to compare the OFA and the OBA group if all patients in the OBA group have received these anti-hyperalgesic medications. Fourth, remifentanil use for the opioid-based approach may make this medication a poor choice when designing a trial that compares an opioid-free to an opioid based approach because of the potential for this medication could lead to postoperative hyperalgesia.[52] Fifth, ketamine boluses used for postoperative analgesic management could not be converted to a morphine equivalent dose, thus this analgesic administration was not taken into account for the total morphine consumption. Finally, because all of the multimodal agents being simultaneously administered it appears difficult to clearly determine the specific role of dexmedetomidine acting as an opioid-sparing agent. However, the present study offers central clinical hints on the potential of a dexmedetomidine-based OFA protocol designed for cardiac surgery patients. Nevertheless, only controlled prospective randomized studies will confirm the present results. Further studies are needed to determine the optimal associations, dosages, and infusion protocols for cardiac surgery patients.

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