In the present study, we found that OFA was associated with: (1) lower postoperative morphine consumption; (2) higher operative use of antihypertensive agents; (3) a decrease of orotracheal intubation time and the use of non-invasive respiratory support; and (4) shorter ICU stays.
To date, two published case reports and one retrospective study have reported on the use of OFA study in thoracic surgery [7, 24, 25], but no study has focused specifically on the use of OFA in cardiac surgery. In non-cardiac surgery with OFA, previous studies have demonstrated decreased postoperative pain scores and opioid consumption [6, 8, 9]. In cardiac surgery, the studies evaluating loco-regional analgesia have demonstrated a decrease in morphine consumption . Despite its retrospective design, the present study confirmed the feasibility of OFA in cardiac surgery. Because OFA is based on the opioid avoidance with a multimodal analgesic treatment, it is associated with lower postoperative morphine consumption and fewer of the adverse effects that result from opioid use. The postoperative pain score did not differ between groups, indicating that OA and OFA provided comparable analgesia.
Yet one important question remains: what is the analgesic/anaesthetic effect of OFA during surgery ? OFA is an anaesthesia strategy that replaces opioids (balanced general anesthesia) with non-opioid drugs (multimodal general anesthesia). Opioids are usually administered during anesthesia for their antinociceptive effects, to control the responses of the autonomic nervous system (ANS) to surgical stress, and for their hypnotic effect. Our approach to OFA was based on published literature which demonstrates that each of the effects associated with opioids can be obtained with lidocaine (analgesic, hypnotic, and ANS control), dexamethasone (analgesic) and ketamine (analgesic and hypnotic) [11–13]. The lidocaine dosing regimen was based on the literature published since the 1990s that has demonstrated a safety profile with continuous infusion of lidocaine during cardiac and non-cardiac surgeries [27, 28]. Lidocaine has effects that depend on the total dose, and detrimental effects can be seen with elevated doses of lidocaine . But lidocaine also has beneficial effects during surgery, providing (a) an anti-inflammatory effect; (b) an increase in the cardioprotective effect of cardioplegia; (c) a decrease in the risk of arrhythmias; and (d) a decrease in the risk of brain inflammation [15, 16, 28, 29].
OFA may be associated with certain adverse effects such as a higher incidence of blood pressure events or adverse effects resulting from toxic plasma levels. We observed a trend towards the use of norepinephrine and anti-hypertensive agents that may be the result of several factors: the increasing use of propofol, the half-life of urapidil/nicardipine (mostly used before CPB), and the vasoactive effect of lidocaine. Several studies have already underlined the growing incidence of hypertensive episodes and the higher use of anti-hypertensive agents [6, 7]. Bakan et al also found that a higher total dose of propofol was needed to maintain OFA . According to the literature, the dosage regimen used in the present study may be associated with low to moderate plasma values of lidocaine, which are associated with vasoconstriction . Because blood pressure may be high, physicians frequently use anti-hypertensive agents. On the contrary, because the hypnotic effect of lidocaine may be less marked than that of opioids, physicians increase propofol doses which can potentially cause arterial hypotension. Finally, the combination of high-dose propofol and the increasing use of anti-hypertensive agents may increase the need for vasopressors during CPB. Accordingly, we did not demonstrate a higher incidence of postoperative vasoplegic syndrome. To date, we do not have observed clinical signs of local anaesthetic toxicity (arrhythmia, atrial-ventricular block, seizure) with our protocol, which confirms the existing data on lidocaine plasma levels [27–29].
Though we did not use dexmedetomidine in our protocol because it is not available in our department, the uses of an alpha2 agent may have several advantages. First, the combination of dexmedetomidine and lidocaine was shown to provide better postoperative pain relief than the use of each agent individually . Also, in cardiac surgery, a recent meta-analysis confirmed that dexmedetomidine provided good hemodynamic stability during surgery with less tachycardia and arterial hypertension . Moreover, studies suggest a positive effect on confusion and atrial fibrillation, with a shorter time to extubation and a shorter ICU length of stay [31, 32]. According to the literature, the combination of lidocaine and dexmedetomidine should improve hemodynamic stability and decrease the need for antihypertensive agents.
We demonstrated that OFA resulted in lower intubation time and use of non-invasive ventilation. The respiratory effects may be explained by the avoidance of opioids and better pain relief. In our experience, patients anesthetized with OFA have a shorter period of respiratory inhibition during surgery than patients anesthetized with opioids. Spontaneous breathing returns sooner following OFA and patients seem to become alert more quickly after orotracheal extubation. In our results, oxygen requirements and non-invasive ventilation was lower in the OFA group. These effects may be associated with the respiratory depression and cognitive dysfunction that are well-known effects of opioid sedation [8, 33].
The present study had several limitations. Our study was a single retrospective study, which implies a certain number of design-related limitations. Despite protocol management for sedation and analgesia, bias may have been introduced by the attending physician and nursing staff. In addition, some patients received analgesia in addition to patient-controlled morphine analgesia, suggesting postoperative multimodal analgesia. Nevertheless, the protocol for postoperative intravenous analgesic use was similar in the two groups. Similar limitations should be mentioned for non-invasive ventilation and ICU stays, which were left to the discretion of the attending physician. Only controlled prospective randomized studies can confirm the present results. Moreover, further studies are needed to determine the optimal associations, dosages, and infusion protocols during cardiac surgery. We have included two types of surgery (sternotomy and thoracotomy) than could be not equivalent in term of pain. Because the matching was based on this aspect, the two groups did not differ in term of type of surgery. The relatively small number of patients in our population might also limit our study’s external validity. Nevertheless, we calculated a sample size based on morphine consumption, which has been demonstrated to be associated with OFA, and we included a mixed cardiac surgery population. We believe our results demonstrate the feasibility of OFA in several cardiac surgery subtypes. Our team currently uses OFA in cardiac surgery on a daily basis without any restrictions other than contraindications to lidocaine use.