The clinical effect of dexmedetomidine combined with parecoxib sodium on sedation, antianxiety and prevention of intubation stress in patients undergoing functional endoscopic sinus surgery: a randomised controlled trial

Functional endoscopic sinus surgery (FESS) is a new technology rising in the field of nasal surgery, which has become the mainstream technology in the treatment of sinusitis. Because of the abundant blood vessels in the pathological part of the nasal cavity, it is easy to bleed. Therefore, in order to ensure the smooth operation of FESS, it is required that patients should be quiet and have less bleeding to keep the operation field clear. At the same time, keep the respiratory tract unobstructed to prevent the obstruction and aspiration of the respiratory tract [1]. Since the Department of Anesthesiology began to use DEX and parecoxib sodium in our hospital, it was found that the combination of the two drugs was worth further discussion in clinical practice. Therefore, we used dexmedetomidine combined with parecoxib sodium in patients undergoing FESS surgery. From the aspects of preoperative sedation, antianxiety and intubation stress, we evaluated the clinical effect of dexmedetomidine combined with parecoxib sodium in FESS surgery, in order to find a suitable preoperative anesthesia medication for FESS. It could provides a direct clinical basis and reference for anesthesiologists to implement comfortable and safe anesthesia.

According to the relevant medical data statistics, the incidence rate of sinusitis and nasal polyps in China has been increasing [3] in recent years. Surgery is an ideal method for the treatment of patients with sinusitis and nasal polyps. In early clinical practice, conventional sinus surgery is often used to treat the disease. However, it is found that this kind of surgery causes greater damage to the patients’ nasal mucosa, and postoperative complications such as nasal adhesion likely to occur, which is not conducive to the recovery of patients [4]. With the continuous progress of medical technology, functional endoscopic sinus surgery (FESS) has been widely used in the clinical treatment of patients with sinusitis and nasal polyps. Compared with conventional sinus surgery, endoscopic sinus surgery has the advantages of simple operation, small trauma, low postoperative complications, and is more and more trusted by the majority of patients [5].

Previous studies have shown that the incidence of preoperative anxiety in perioperative patients is generally about 60%, up to 80% [6]. When preoperative patients have emotional reactions of over tension and anxiety, it will directly affect the smooth operation and postoperative physical recovery [7, 8]. Therefore, the ideal anesthesia goal should be anxiety relief before operation, stable hemodynamics during operation with less bleeding and clear operation field, quick recovery after operation. Make the patient safe and comfortable during the whole perioperative period.

Dexmedetomidine is a highly effective and selective agonist of adrenergic α 2 receptor, which can stimulate the blue spots of brain stem in α 2 receptor in nervous system to play an analgesic role, and can also act on α 2 receptor in presynaptic membrane and postsynaptic membrane of spinal cord hind foot to produce a sedative effect similar to natural sleep [9, 10]. Compared with midazolam, it has its unique advantages: stable hemodynamics, inhibition of sympathetic activity and analgesia. It is a new sedative and analgesic drug [11‐14]. In addition, it is convenient to increase the depth of anesthesia during the operation, reduce the dosage of other anesthetics, and maintain a relatively stable vital signs [15]. When it acts on the nucleus tractus solitarius of medulla oblongata, it will produce sympathetic inhibition, resulting in hypotension and bradycardia [16]. The results of this study showed that Ramsay Sedation in group P and group N was 1–2 points, BIS value was greater than 89, this suggests that group P and group N patients were in awake state; Ramsay Sedation in group D and group DP was maintained at 2–4 points, BIS value was about 70–80, and this suggests that patients of group D and group DP were in shallow sedation state, showed calm, responded accurately to language instructions, and were in a sleep state without external stimulation, but they were easily awakened by language stimulation, cooperated and communicated with medical staff, and soon entered a sleep state after the stimulation disappeared.

Previous studies have shown that the application of DEX before anesthesia can reduce or eliminate the preoperative anxiety of patients to the greatest extent, so that they can actively cooperate and successfully pass the perioperative period [17]. The results of this study are consistent with the state anxiety score SAI. Therefore, We think that the preoperative application of DEX can not only calm the patients, but also reduce their anxiety response. It also provides the relevant basis for how to reduce the incidence of preoperative anxiety and the stress induced by preoperative anxiety. Good preoperative medication not only needs to relieve patients’ anxiety, fully calm and produce amnesia, but also needs to reduce the stress of nerve reflex and stabilize hemodynamics. Therefore, how to regulate stress response reasonably should be concerned by anesthesiologists. Perfect preoperative medication can make the hemodynamics induced by anesthesia stable, and reduce the stress response caused by placing laryngoscope and tracheal intubation [18]. Parecoxib sodium is a kind of water-soluble non steroidal anti-inflammatory drugs (NSAIDs). It is a new analgesic drug. It is a second generation selective inhibitor of cyclooxygenase-2 (COX-2). It can be injected intravenously or intramuscularly and then transformed into vardixib. The research shows that the analgesic effect is accurate, it can effectively control the acute pain caused by surgical trauma, reduce the postoperative pain score, and improve the patient satisfaction rate [19]. The analgesic mechanism is that it can effectively inhibit the activity of COX-2, inhibit the activation of ERK in spinal neurons, and play an analgesic and anti-inflammatory role. Previous studies have shown that preoperative administration of parecoxib sodium can reduce the production of various inflammatory mediators and cytokines, reduce the sensitivity of nerve center and peripheral to pain, and improve the quality of pain control [20]. According to the results of this study, the intubation was successful in four groups after induction of conventional anesthesia. The SBP, DBP, HR in the control group were significantly higher than those in the control group at 3 min (T6) and 5 min (T7) after intubation. The SBP, DBP in group P and N at the time of intubation (T5) and 3 min after intubation (T6) were significantly higher than before administration (T0), while the SBP, DBP in group DP and D at the time of intubation (T5) and 3 min after intubation (T6) kept the same level as the before administration (T0). Compared with before administration (T0), HR of group D and DP decreased significantly at the time of intubation (T5), 3 min after intubation (T6) and 5 min after intubation (T7), while HR of group N increased significantly at T5, T6 and T7. HR of group P did not change significantly at each time point. We speculate that DEX can reduce the self-regulation of sinoatrial node by selectively acting on renal α 2-adrenergic receptor of myocardium, so that the body does not have the increase of heart rate after stress.

Our results showed that the NE, E, Cor and BS of group D, DP and P decreased before anesthesia induction (T4), while the NE, E, Cor, BS of group DP decreased more significantly than those of group D. And compared with before T0, the NE, E, Cor, BS of group D, DP and P remained at the same level with T6. While compared with T0, the NE, E, Cor, BS of group N had no significant difference from T4, but the values significantly increased at T6.Compared with group DP, NE and E of group D, P and N were statistically significant at T6.The concentrations of NE, E, Cor and BS are good indicators of “alert period” of stress response, and the degree of increase is positively correlated with the stimulation intensity of stress. The results showed that the control group did not inhibit the stress response of tracheal intubation well, and group DP was more effective in inhibiting the stress response of tracheal intubation.

Since the anesthesiology department of our hospital began to use DEX and parecoxib sodium, through our continuous learning and clinical practice, our research group has confirmed in the early clinical research that the intranasal drip of DEX (1–1.5μg / kg) in 45 min before gynecological laparoscopic surgery can achieve the “wake-up” sedation and anti anxiety effect for patients before surgery [21]. Pre-injection of Dex in thyroid surgery can improve the stability of hemodynamics, reduce the stress response of patients, inhibit the over secretion of PRA, ANG-II and ALD, which is conducive to the stability of circulatory system in the recovery period of patients with general anesthesia in thyroid surgery, and does not extend the recovery time [22]. We found that these two drugs not only have good “sober and sedative”, analgesic and protective effects on organs such as heart and brain, but also have many beneficial effects such as stabilizing hemodynamics, inhibiting perioperative stress response, reducing the dosage of anesthetics and analgesics, and reducing postoperative discomfort of patients, which are worthy of further discussion in clinical practice. At present, there are few reports about it in the domestic and foreign literature, lacking of the corresponding clinical application standards, norms and the best dosage suitable for Chinese constitution. Jian Lu et al. [23] evaluate the effect of parecoxib sodium pretreatment combined with dexmedetomidine on early postoperative cognitive dysfunction in elderly patients after shoulder arthroscopy. But perhaps because of the different goals of the study, all of their patients were treated with parecoxib sodium without a control group. Niyogi S et al. [24] compared the efficacy of intranasal and intravenous DEX to attenuate the stress response of laryngoscopy and endotracheal intubation.they found that there was no significant differences between intranasal and intravenous DEX. However, the long effective time of intranasal administration should also consider the absorption of nasal mucosa at FESS operation site. Given the procedure short median time of FESS and considering the efficient administration of Dex via nasal route [25‐27], in order to minimize Operation occupation time, We used the intravenous route. Our results show that intravenous injection of dexmedetomidine combined with parecoxib sodium 30 min before FESS operation can not only achieve sedation and anti anxiety, but also better prevent tracheal intubation stress response. It is a safe and effective way of preoperative medication, providing a direct clinical basis and reference for anesthesiologists to implement comfortable and safe anesthesia.

Intravenous injection of dexmetomide combined with parecib sodium before functional endoscopic sinus surgery can not only calm and resist anxiety, but also better prevent stress response of endotracheal intubation. It is a safe and effective preoperative drug.