Effects of Lidocaine Infusion on Quality of Recovery and Agitation after Functional Endoscopic Sinus Surgery: Randomized Controlled Study ()
1. Introduction
Functional endoscopic sinus surgery (FEES) is a common surgical procedure in the otorhinolaryngology specialty for symptomatic improvement in patients with medically refractory chronic rhinosinusitis and chronic polypous rhinosinusitis [1].
The essential anesthesia requirements for FESS include airway management, considerations for facilitating surgical access, provision of a clear and still surgical field for precision surgery, assuring quick and non-stimulating emergence from anesthesia, and fast-tracking patients for discharge [2].
Postoperative recovery which is defined as the patients return to the normal state after a surgery is the key outcome in the perspective of anesthesiologists. In the past it has been referred in terms of pain scores, duration of hospital stay, and return to normal activities [3]. But now it involves several factors such as regain of physical, physiologic and social functions. Therefore, it is fundamental for the evaluation of health care and patient satisfaction after surgery [4] [5].
A valid and reliable measure of quality of recovery (QoR) after anesthesia and surgery was developed by Myles et al. It has shown superior content validity and constructs validity, when compared to other pre-existing questionnaires. The Quality of Recovery-40 (QoR-40) questionnaire is a reliable and accurate multidimensional assessment tool used to evaluate the status of patients after anesthesia [6]. QoR-40 is a global measure of quality of recovery incorporating five dimensions of health; psychological support, physical comfort, emotions, physical independence, and pain; each item is graded on a 5-point Likert scale, (none of the time, some of the time, usually, most of the time, and all of the time). The scores range from 40 (extremely poor quality of recovery) to 200 (excellent quality of recovery). QoR-40 is well suited to measure quality of postoperative recovery; poor quality of recovery can predict a poor quality of life after surgery [7] [8]. Prolonged recovery after surgery can lead to delayed hospital discharges and increased costs which can impact resource utilization and mitigate patient satisfaction [9].
Emergence agitation (EA) after nasal surgery is a common phenomenon [10] [11]. Patients undergoing nasal surgery commonly complain of a sense of suffocation due to intranasal packing and manifest agitation during emergence which can lead to several problems, such as injury to the patient or medical staff, unplanned removal of a catheter or endotracheal tube, re-bleeding at the operation site, and delayed discharge [12] [13]. There are many independent risk factors for EA such as pain, endotracheal intubation, duration of surgery, and history of treatment by antidepressant agents. It is commonly observed in younger patients with lower American Society of Anesthesiologist scores [14].
Several pharmacological methods have been used to mitigate EA, including opioid (fentanyl, remifentanil), propofol, benzodiazepine (midazolam), α2- aderenoreceptor agonist (clonidine, dexmedetomidine), and N-methy-d-aspar- tate (NMDA) receptor antagonist (ketamine, magnesium sulfate) administration [15] [16].
Lidocaine is an amino amide-type short-acting local anesthetic (LA). It has a short half-life, and a favorable safety profile, and is therefore the LA of choice for continuous IV administration [17]. Systemic lidocaine has been shown to be an effective adjunct strategy to reduce postoperative pain [18] [19] [20]. We hypothesized that systemic infusions of lidocaine may improve postoperative recovery by reducing postoperative pain. The main objective of the current study was to evaluate the effect of systemic continuous lidocaine infusion in patients undergoing FESS procedure as regards to quality of postoperative recovery, emergence agitation incidence and time to discharge from postoperative care unit (PACU).
2. Patients and Methods
2.1. Patients
This prospective, randomized, comparative, controlled study was conducted on 100 adult patients, of both sexes, admitted to Alexandria Main University Hospital, Department of ENT Surgery. Patients were scheduled for elective functional endoscopic sinus surgery, selected to be ASA class I-II., aged (20 - 50 years). The sample size was statistically approved by the biostatistics department of High Institute of Public Health, Alexandria University. The study was registered at ClinicalTrials.gov (NCT04472689). Patients with body mass index >35 kg/m2, history of allergic reaction to local anesthetic agents especially lignocaine, history of preoperative use of opioids, history of uncontrolled hypertension, A-V conduction block, Psychotropic drugs and history of obstructive sleep apnea were excluded from the study. Patients were randomly classified into two equal groups; fifty patients each using closed envelope technique. Lidocaine group, group (L), patients received a loading dose of IV lidocaine 1.5 mg/kg slowly just before induction of anesthesia, then the lidocaine infusion started at a rate of 2 mg/kg/h. Control group, group (C), patients received an equal volume of 0.9% sodium chloride as the Lidocaine group (both the loading, and the infusion). The infusion in both groups was started just after induction of anesthesia induction and continued until the end of the operation. Approval of Ethical Committee of the Faculty of Medicine, Alexandria University was taken and an informed written consent was taken from each patient.
2.2. Methodology
Every patient in the study was subjected to a careful pre-anesthetic assessment including history taking as regards current medical illnesses and drug therapy, thorough clinical examination, and routine laboratory investigations. Before induction of anesthesia, standard monitoring was implemented. A bolus of lidocaine in group (L) and bolus of 0.9 normal saline in group (C ) were given over 10 minutes, then anesthesia was induced with fentanyl 2 μg∙kg−1, propofol 2 mg∙kg−1 followed by atracurium 0.5 mg∙kg−1 to facilitate tracheal intubation and throat pack was inserted under vision with indirect laryngoscopy. Mechanical ventilation was started to maintain end-tidal carbon dioxide between 32 and 36 mmHg. Anesthesia was maintained with an inspired sevoflurane concentration of 1 - 2 MAC in AIR/O2 mixture (1/1 l∙min−1). Neuromuscular block was maintained with atracurium 0.2 mg∙kg−1∙h−1 as needed. Using multichannel (Dräger Infinity Vista XL; Drägerwerk AG & Co., Lübeck 23558, Germany) monitor, patients were continuously monitored for noninvasive arterial blood pressure, lead II electrocardiography, heart rate, arterial oxygen saturation, inspired and end-tidal concentrations of sevoflurane, end tidal carbon dioxide, inspired and end-tidal concentrations of oxygen. Also, ventilatory monitoring for mean airway pressure peak airway pressure and minute ventilation were monitored. Continuous infusions of lidocaine and normal saline were started in both groups as mentioned till the end of surgery.
Intravenous paracetamol 1 g was administered in all the cases 15 min before expected time for extubation for postoperative analgesia. After the completion of surgery, suctioning of airways and oral cavity were done and the throat pack was removed. Patients received neostigmine 50 μg∙kg−1, given intravenously with atropine 1 mg after testing of neuromuscular block by means of a nerve stimulator with a train-of-four ratio (TOF) more than 0.7. Infusions of lidocaine and saline were stopped, patients were extubated and transferred to the PACU.
Incidence of emergence agitation was evaluated at zero time then at 15 min. and 30 min. after arrival to PACU using the Richmond Agitation-Sedation Scale (RASS). (RASS: +4, combative; +3, very agitated; +2, agitated; +1, restless; 0, alert and calm; −1, drowsy; −2, light sedation; −3, moderate sedation; −4, deep sedation; −5, unarousable) [21] EA was defined as any RASS score ≥ +2. Observers who recorded data were blinded with respect to patients’ group allocation. Quality of postoperative functional recovery was assessed using the QoR-40 questionnaire; it was evaluated the day before surgery and 24 hours postoperatively through telephone by an investigator unaware of group allocation. Patients were questioned by using QoR-40 questionnaire that assess five dimensions of recovery: physical comfort (12 items), emotional state (9 items), physical independence (5 items), psychological support (7 items), and pain (7 items). Each item was rated on a five-point Likert scale: (none of the time, some of the time, usually, most of the time, and all of the time). The total score on the QoR-40 ranges from 40 (poorest quality of recovery) to 200 (best quality of recovery). The total score was calculated for each patient [22] [23].
2.3. Statistical Analysis
2.3.1. Sample size
Based on literature review, a total sample of 100 patients (50 per group) is required to assess an average difference at QOR-40 score of 13 ± 5 point (1 - 3). The sample size was estimated using PASS software at 95% confidence level and study power of 80% and 10% for attrition rate [24].
2.3.2. Data Analysis
After data was extracted, it was revised, coded, and fed to statistical software IBM SPSS version 22 (SPSS, Inc. Chicago, IL). All statistical analysis was done using two tailed tests. P value less than 0.05 was statistically significant. Scale data normality was assessed using Shapiro test. Descriptive analysis based on frequency and percent distribution for categorical data (demographics and agitation) was used where mean with standard deviation was used to describe scale data including time and QOR-40 scores. Discrete scores for different QOR-40 scale domain were summed to have an overall score for each of the five domains and the grand total for the scale. Comparing distribution of agitation among the study groups was assessed using exact probability test due to small expected frequencies. Time to discharge from PACU, and QOR-40 scores were compared between the study groups using parametric independent samples t-test. Paired t-test was used to compare means scores of QOR-40 within the same group before and 24 hours after operation [25] [26].
3. Results
A total of 120 patients were initially enrolled in the study, six of whom were excluded, and fourteen patients were unable to complete the scoring after surgery. Therefore, the final sample size was 100 patients (Figure 1). There were no clinically important differences in demographic data, ASA classification or duration of surgery between the two groups (Table 1).
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Table 1. Bio-demographic data of the study groups& surgery duration.
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Figure 1. Consort 2010 flow diagram of the study.
According to emergence agitation incidence as shown in Table 2, the RSAS during emergence differed significantly between the 2 groups, it was significantly lower in lidocaine group 30% (15 agitated and 35 non-agitated) compared with 50% (25 agitated and 25 non-agitated) in the control group at zero time on admission to PACU (P < 0.036), also, it was significantly lower in lidocaine group 14% (7 agitated and 43 non-agitated) compared with 30% (15 agitated and 35 non-agitated) in the control group at 15 minutes time on admission to PACU (P < 0.047) and no significant difference between both groups at 30 minutes after arrival to PACU (P < 0.125).
The distribution of pre- and postoperative global QoR-40 scores and the score of each dimension are shown in Table 3 . Preoperatively global QoR-40 score was comparable between the two groups without significant difference (P = 0.33). Postoperatively global QoR-40 scores were significantly decreased compared with preoperative scores in both groups (P = 0.001 in group L and group C). A significant difference (P = 0.037) in QoR-40 scores was observed between the two groups on POD1 with significant decrease in control group compared to lidocaine group. The patients in group L showed a significantly lesser decline in global QoR-40 in POD1. Among the five dimensions of the QoR-40, physical comfort, emotional status and pain scores were significantly higher in the lidocaine group compared with the control group on POD1 without significant difference preoperatively.
The distribution of PACU time is shown in Table 4, it was significantly shorter in lidocaine group compared to control group (P = 0.001).
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Table 2. Distribution of agitation among study groups.
P: Exact probability test. *P < 0.05 (significant).
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Table 3. Distribution of quality of recovery among study groups at different study phases.
P: independent samples t-test; #: Paired t-test; *P < 0.05 (significant); **P < 0.01 (significant).
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Table 4. Distribution of time to discharge from PACU (minutes) according to study groups.
P: independent samples t-test; **P < 0.01 (significant).
4. Discussion
Postoperative pain after nasal surgery could be as a result many factors as intraoperative tissue injury, inflammation, nerve stimulation, and postoperative swelling, many inter-related postoperative events may provoke agitation, including postoperative pain and hypoxemia, Pain not only causes postoperative complications but also causes psychological stress and anxiety, which further aggravate postoperative pain consequently causing delayed postoperative recovery [27]. The exact etiological mechanism of EA has yet to be elucidated as multiple pathophysiological abnormalities in dopaminergic, noradrenergic, serotonergic, and γ-aminobutyric acid pathways have been suggested to be associated with the etiology of agitation. In adults, endothelial dysfunction due to the release of inflammatory cytokines is a common perioperative event and a crucial factor influencing the incidence of delirium, A possible explanation is that NMDA postsynaptic potential-induced excitatory hyperactivity at the thalamolateral nucleus of the amygdala synapse enhances the uncomfortable stimuli-induced behavior [28] [29]. Although EA can occur after minimal or non-painful surgeries, pain is a major risk factor of EA [30].
Administration of intravenous lidocaine in perioperative period produces analgesia by different ways; as it may cause an increase in concentration of acetylcholine in cerebrospinal fluid, leading to exacerbation of inhibitory descending pain pathway, blocking of muscarinic receptors M3, inhibition of glycine receptors, release of endogenous opioids, reduction of the inflammatory response to tissue ischemia, and decreased release of cytokines in response to tissue damage. Lignocaine is also responsible for direct or indirect reduction of postsynaptic depolarization mediated by N-methyl-D-aspartate receptors [31] - [36].
Nasal surgery is significantly associated with a higher incidence of EA compared to other types of surgery, Kim et al. reported that the occurrence of emergence agitation could be as high as 55.4%, and the presence of nasal pack is likely to be the main trigger of agitation. Elseryreported an incidence of 68% following nasal surgery [37] [38].
The present study demonstrated a significant decrease in the incidence of emergence agitation in patients received lidocaine infusion compared with those received saline infusion during anesthesia for FEES.
Tauzin-Fin and Bernard studied the effect of adding lignocaine infusion to standard anesthesia protocol in a total of 47 patients planned for laparoscopic nephrectomy. Lignocaine infusion was continued for 24 h postoperatively and was associated with significant reduced morphine consumption and postoperative pain score [39]. Previous studies support this suggestion, adequate postoperative pain control using potent analgesics, such as fentanyl or remifentanil, showed efficacy in reducing EA, but weak analgesics and nonsteroidal anti-inflammatory drugs such as ketorolac alone did not reduce EA after anesthesia [40] [41] [42].
In a study carried out by Rahimzadeh et al. [43] propofol lidocaine anesthesia regimen reduced the incidence of sevoflurane-induced agitation in children with retinoblastoma. In against to our results, in a study was done by Christian P. Both et al. [44], there was a non-significant difference in the incidence of emergence delirium observed between lidocaine group and control group in pediatric patients scheduled for laparoscopic appendectomy under general anesthesia. Young Ho Jang et al. [45] founded that 1.5 mg/kg of IV lidocaine 5 minutes before extubation did not reduce the incidence of EA and the severity of postoperative pain After sevoflurane anesthesia and the time to discharge from the PACU was similar to that with placebo.
The postoperative quality of recovery-40 (QoR-40), developed and validated by Myles et al. in 2000, is one of the most commonly used instruments to assess postoperative quality of recovery in clinical practice. It was supposed that a 10-pointdifference or more represents clinically relevant improvement in the quality of recovery [6]. Recently, Myles et al. reported that a change of 6.3 in the global QoR-40 can signify a clinically important improvement or deterioration [46].
In the current study our results showed that the global QoR-40 scores were significantly lower in both groups at POD1 compared to preoperative measurements suggesting that the surgery and anesthesia had significant effects on the postoperative quality of life. However, the decline of scores in group L was significantly less than that in group C therefore the postoperative quality of life in group L was superior than in group C. Comparing both groups at POD1 the global QoR-40 score was significantly higher in group L than in group C. Meanwhile, among the five dimensions of the QoR-40, physical comfort, emotional state and pain scores were superior in group L compared to group C. Therefore, our results indicate that intravenous lidocaine leads to significantly better quality of recovery by preventing physiologic deterioration related to anesthesia and surgery. These results consistent with that done by Wang Q et al. [47], they assessed effect of intravenous lidocaine infusion on postoperative early recovery quality at POD1 and POD2 in upper airway surgery, they founded that global QoR-40 scores on POD1 and POD2 were significantly lower compared with the preoperative measurement in both groups. Global QoR-40 scores were significantly higher in lidocaine group on POD1 and POD2compared with control group. Among the five dimensions of QoR-40, the scores for physical comfort, emotional state, and pain were superior in group L compared to group C.
Lee et al. [48] reported that systemic infusion of lidocaine during bimaxillary surgery reduces postoperative pain and analgesic consumption and relieves facial swelling. Our results were similar to these findings, as the pain dimension score was superior in group L than in group C, similar results reported by Kim MH, et al. [49] where lidocaine administered intravenously during anesthesia for thyroid surgery in female patients led to better quality of postoperative recovery measured by QoR-40 compared with the control group. Systemic lidocaine improves postoperative quality of recovery in patients undergoing outpatient laparoscopy with less opioid consumption [23].
PONV is a common complication after general anesthesia, with an incidence of up to 20% to 30%. It can affect patient satisfaction and can even lead to serious complications, such as aspiration and asphyxia, reducing the quality of postoperative early recovery [50]. In our study physical comfort dimension that includes nausea and vomiting as sub-dimensions was superior in group L than in group C. Likewise, Kim et al. [50] found that in addition to reducing postoperative pain, lidocaine can also quickly restore gastrointestinal function and reduce PONV through both physical and psychological mechanisms. Lidocaine is known to induce fast return of bowel function and reduce nausea/vomiting. These effects can contribute to better postoperative recovery, both physically and emotionally [51].
Our study demonstrated shorter discharge to from PCAU with use of perioperative lignocaine than in the control group. This may be a result of pharmacological effects of lignocaine on inflammation, analgesic requirement, and nausea/vo- miting [48].
5. Conclusion
Systemic lidocaine infusion can improve QoR-40 scores and decrease incidence of emergence agitation in patients scheduled for FEES, also it reduces the duration of stay in PACU after surgery thus improving the quality of early recovery after surgery.
Acknowledgements
No external funding or competing interests declared. The study was supported from anesthesia department (Alexandria University, Egypt).