Surgery commonly causes postoperative pain that should be alleviated as soon and as effective as possible to reduce suffering, to promote the healing process and rehabilitation and to prevent complications. However, 80% of patients report their postoperative pain is not adequately treated, a metric unchanged for decades. Although debated [23], the utilization of opioid-free anesthesia (OFA) could be the answer, as it is associated with a reduction of postoperative morphine consumption, and better pain control in selected patient and selected procedure [27]. Inspired by promising results, our anesthesia regimen was adapted to avoid intraoperative opioid use. This retrospective study shows that OFA is feasible even after major abdominal surgery with good results.
Consistent with other published reports, we found that introduction of an OFA protocol for pancreatic resection resulted in a 60% reduction in opioids requirement and NRS scores. Indeed, in the OBA group the NRS was almost systematically above the NRS cut-off for opioid administration (> 4) while a NRS pain scores ≤ 4 in the OFA group was the standard (24h: 4.7 ± 1.8 vs 1.0 ± 1.4; 48h: 2.9 ± 1.5 vs 0.6 ± 1 respectively). However, there is large variation in how patients translate their pain to an NRS score. Therefore, without a pain assessment beyond the NRS, there is a risk of both undertreatment and overtreatment of the patient postoperative pain [28]. Since this was mitigated by the utilization of an IV-PCA, it allows us to assume that both these indicators give a fair picture of postoperative pain control. At least they should reduce the fear of more difficult postoperative pain control.
The time required until patients consistently report minimal postoperative pain is also key feature of pain control. It must be noted that NRS scores increased in the OBA group at 24 hours but not in the OFA group. This might be explained by the anti-hyperalgesic techniques included in the OFA regimen, and/or by an opioid-induced hyperalgesia induced by OBA. These non-mutually exclusive hypotheses are supported by the fact that movement-related pain is substantially more intense than pain at rest and seems to be more closely associated with pain-related functional impairment [29]. The 24h measurement correspond to the return to the ward. Therefore, pain intensity may have been influenced by activity such as sitting or standing. This movement-related pain, also called dynamic pain, has been suggested to be associated with opioid-induced hyperalgesia. Indeed, several laboratory and clinical studies have shown that hyperalgesia occurs after the administration of opioids (most of the time, after the termination of ultra-short-acting opioid remifentanil infusion) or intrathecal morphine, and could be prevented by the use of ketamine and alpha-2 agonists like dexmedetomidine [30]
Compared to OBA, with a discharge on median day 10, we report a shorter postoperative stay, indicating that OFA might be more than a feasible option but also a viable one. In our cohort, independent variables associated with extended LOS included, as expected, the presence of index complications mainly POPF ≥ grade B and DGE grade C [3]. This study confirms that index complications are important indicators of immediate postoperative outcomes. Indeed, the CCI known for its significantly stronger correlations with LOS and cost of complications [18], was the lowest in the OFA group and statistically different from the OBA group (24.9 ± 25.5 vs 14.1 ± 23.4, P = 0.03). This is of importance since the CCI at postoperative day 7 strongly predicts high 90-day morbidity (odds ratio 3.96 per 10 CCI points, P< 0.001) [31]. Although not significant, the fewest index complications, especially POPF and DGE, were seen in the OFA group. The reduction in DGE make sense, as drug-induced gastric emptying delay is commonly reported in patients receiving opioids for postoperative pain management. Moreover, numerous studies have shown the opioid-sparing effect of a multimodal approach combining regional analgesia, non-opioid analgesics, lidocaine infusions, and ketamine, as in the OFA group, resulted in an accelerated gastrointestinal recovery and improved outcomes [32]. A recent study identified an inverse correlation between LOS and readmission, prolonged length of hospital being protective for certain post-discharge complications requiring readmission, mostly surgical site infection [33]. In our setting, reduced LOS with OFA did not lead to the unintended consequence of increasing readmission rates, neither in an increased 30-day mortality or unexpected post-discharge complication. It is however too early to identify long-term benefit such as improved disease-free or overall survival due to the limited follow-up (upmost 13 months) [4, 34].
Recently, OFA with dexmetedomidine was associated with more adverse events such as bradycardia, asystole, hypoxemia delayed extubation, and prolonged PACU stay, despite a lower overall opioid consumption and less postoperative nausea and vomiting [23]. Most of these adverse events were not present in our setting. This might be explained by several factors. First, definition of bradycardia by Beloeil et al was rather liberal, while we only treated bradycardia, provide that the MAP was maintained, if heart rate was < 40 bpm, supported by data showing that a slower heart rate (< 55 bpm) has been associated with reduced risk for myocardial injuries in non-cardiac surgeries as well as mortality [35]. Second, according to the internal guidelines and published recommendations, we provided preemptive oxygen therapy [23]. Finally, the dosage of dexmedetomidine was much lower and began with a loading dose. Dose differences may be associated with different effects, sometimes even more important the medication choice. For instance, regarding the extubation delay and postoperative sedation, some studies reported a reduced delay [36], while other reported the opposite [37]. In this study, we report no difference between groups. This might be the consequence of a resulting mean dosage of the continuous infusion of dexmetedomidine at 0.5 ± 0.2 µg/kg/h, where the POFA study reported a median and a mean dose of respectively 0.9 and 1.2 µg/kg/h, but, importantly, without including any loading dose. Therefore, we could hypothesize that the absence of increased sedation, delayed extubation and the absence of severe bradycardia observed in our study are a consequence of this adequate loading dose conjointly with a low maintenance.
Limitations of these work are linked to the retrospective, single-institution cohort design with a relatively limited number of patients. Our sample size was one of convenience, chosen from the time of first OFA implementation. However, to limit selection bias, we analyzed consecutive patients. Also, based on the post hoc power calculation, it is unlikely that our findings can be attributed to the limited sample size. However, even if an inclusion bias is controlled, the non-blind assessment by nurses may have influenced results and other confounders cannot be formally excluded, including the anesthesiologist in charge, the day of the week, among others. Despite these limitations, we believe that our findings add information about feasibility, safety, and viability of OFA in major abdominal surgery. It shows that, in experienced hands, the technique is deemed appropriate, and potentially better than the others, even if demonstrating a direct effect of OFA will require a randomized-controlled trial.