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ORIGINAL ARTICLE
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Opioid-free total intravenous anesthesia improves postoperative quality of recovery after ambulatory gynecologic laparoscopy


 Department of Anesthesia, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Correspondence Address:
Karim Youssef Kamal Hakim,
Department of Anesthesia, Faculty of Medicine, Ain Shams University, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aer.AER_74_19

   Abstract 

Background: Gynecological laparoscopic surgery is commonly performed on an ambulatory basis under general anesthesia. The postoperative quality of recovery (QOR) should be considered one of the principal endpoints after ambulatory surgery. Total intravenous anesthesia (TIVA) with opioids is known to improve postoperative QOR after ambulatory surgery. However, opioids can be associated with an increased incidence of postoperative complications, which can affect postoperative QOR. The primary aim of this study was to compare the patient recovery using the QOR-40 at 24 h postoperative in ambulatory gynecological laparoscopy between opioid-free (OF) TIVA and opioid-based TIVA. Settings and Design: A prospective, randomized, controlled, comparative study was conducted at the day surgery center. Patients and Methods: Eighty females were included in the study. They were randomized into two equal groups: OF TIVA group with dexmedetomidine and propofol or opioid-based TIVA (O) group with fentanyl and propofol. The primary outcome was QOR-40 at 24 h postoperative, and the secondary outcomes were postoperative numerical rating scale (NRS), time to first rescue analgesia, number of rescue tramadol analgesia, and the incidence of postoperative nausea and vomiting. Results: A statistically significant difference in total QOR-40 score at 24 h postoperative was observed between the groups (median [range] QOR-40 of 182.0 [164.0–192.0] in the OF TIVA group and 170.0 [156.0–185.0] in the O group; P = 0.03). OF group had significantly lower time to first rescue analgesia, maximum NRS pain scores, number of rescue tramadol analgesia, and ondansetron use. Conclusions: OF TIVA significantly improves postoperative QOR in patients undergoing ambulatory gynecological laparoscopic surgery.

Keywords: Ambulatory surgery, gynecological laparoscopy, opioid free, quality of recovery, total intravenous anesthesia



How to cite this URL:
Hakim KY, Wahba WZ. Opioid-free total intravenous anesthesia improves postoperative quality of recovery after ambulatory gynecologic laparoscopy. Anesth Essays Res [Epub ahead of print] [cited 2019 May 26]. Available from: http://www.aeronline.org/preprintarticle.asp?id=257936


   Introduction Top


Gynecologic laparoscopic surgeries under general anesthesia are currently done in the form of ambulatory surgery for fast discharge from the hospital with reduced costs and rapid return of daily activities.[1] Adequate recovery from anesthesia is important to have successful ambulatory surgery. Satisfactory recovery is being defined as an improvement of overall quality of recovery (QOR), which speeds the resumption of normal activities.[2] However, the assessment of patient QOR is not easy with conventional recovery indices such as awakening time, duration of stay, or adverse events. Instead, the -QOR-40 questionnaire has been used to assess the difference in QOR depending on the type of anesthesia or the use of adjuvant agents.[3]

Opioids used as the part of a balanced anesthesia are known to have a lot of side effects, such as respiratory depression, postoperative nausea and vomiting (PONV), pruritus, difficulty in voiding, and ileus. These side effects prolong the patient's hospital stay.[4] The use of opioid-free (OF) analgesia using nonsteroidal anti-inflammatory drugs, dexamethasone, tramadol, and/or ketamine has been shown to either decrease or avoid intraoperative and postoperative opioid use. Dexmedetomidine, on the other hand, has shown to be an adequate analgesic therapy in a few recent studies in patients undergoing laparoscopic surgery.[5]

In this study, we compared patient QOR using the QOR-40 at 24 h postoperative using OF total intravenous anesthesia (TIVA) and opioid-based TIVA in ambulatory gynecological laparoscopic surgery.


   Patients and Methods Top


This prospective, double-blinded, randomized, parallel-group study enrolled eighty healthy females with the American Society of Anesthesiologists physical status (ASA-PS) Classes I and II, aged 21–50 years, and who were scheduled for gynecological laparoscopic surgery at the Day Surgery Units of Ain Shams University Hospitals in Cairo, Egypt, from December 2017 to January 2019.

The study was approved by the local ethics committee. All the patients gave written consent. Exclusion criteria included patients with ASA-PS Class ≥III, history of chronic use of opioids, and body mass index ≥35 and uncooperative patients.

The patients were allocated to OF group (OF) (n = 40) or opioid group (O) (n = 40), receiving dexmedetomidine or fentanyl, respectively, using a computer-generated randomization table. An anesthesia technician who was not involved in the study prepared the study drugs in a 50-mL syringe mixed with normal saline of either dexmedetomidine (OF group) or fentanyl (O group). The patient and the investigator were also blinded to the study drugs.

The baseline mean arterial blood pressure, heart rate (HR), and peripheral oxygen saturation values were obtained using standard monitors. Twenty-two-gauge intravenous (IV) line was inserted, and lactated Ringer's solution IV infusion was started at a rate of 40 mL/h in all patients. Before the induction of anesthesia, the OF group received IV dexmedetomidine 0.6 μg/kg loading over 5 min, whereas the O group received IV fentanyl 1 μg/kg loading over 5 min. After preoxygenation, anesthesia was induced with propofol 2 μg/kg and cisatracurium 0.1 mg/kg followed by endotracheal intubation. After securing the airway, patient's lungs were mechanically ventilated using air in O2 mixture (50%:50%) with an end-tidal CO2 between 30 and 35 mmHg in both the groups. In both the groups, anesthesia was maintained with propofol infusion at 5–10 mg/kg/h. To maintain the bispectral index between 40 and 60, dexmedetomidine infusion at 0.2 μg/kg/h in the OF group or fentanyl infusion at 0.5 μg/kg/h in the O group was administered. Both the drugs were titrated up by 0.1μg/kg/h to maintain HR and mean arterial pressure (MAP) changes within 20% of the baseline values in both the groups.

Dexmedetomidine, fentanyl, and propofol were stopped at the end of the surgery. Atropine 10 μg/kg and neostigmine 50 μg/kg were administered to reverse muscle relaxation. Tracheal extubation was performed once the patient was conscious and spontaneous ventilation of the patient was adequate, and the patients were transferred to the postanesthesia care unit (PACU).

Postoperative pain was assessed at 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 12 h, and 24 h postoperatively using the numerical rating scale (NRS) of <3 (0 = no pain and 10 = worst pain).

Postoperative pain was treated with IV ketorolac (30 mg) and acetaminophen (1000 mg) every 8 h for the first 24 h. Tramadol 0.5 μg/kg IV was used as rescue analgesia during the first 24 h postoperatively if NRS >3 and repeated after 30 min if required. PONV was recorded in the first 24 h after surgery and treated with metoclopramide 10 mg IV, followed by ondansetron 4 mg IV.

At 24 h postoperatively, a researcher who was unaware of the group allocation assessed the QOR, via interviews using the QOR-40 questionnaire, which includes five general quality of life dimensions: physical independence (five items), pain (seven items), emotional state (nine items), psychological support (seven items), and physical independence (five items). Each item was graded with a 5-point score: 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 questionnaire ranges from 40 to 200, representing extremely poor to excellent, respectively.[2]

The primary outcome was QOR 24 h postoperatively. The secondary outcomes were hemodynamics, propofol consumption, time to first analgesia, postoperative pain scores, and the incidence of adverse events.

Statistical analysis

Sample size calculation was performed using Power and Sample Size Calculation software (version 3.1.6). Based on the previous study,[6] the mean and standard deviation (SD) of postoperative QOR-40 were 170 and 15, respectively. A sample size of 35 patients per group was needed to detect the difference of 15 points in the global QOR-40 score, with a Type 1 error of 5% and a power of 80%. Finally, 80 patients were included to allow for a dropout rate of 10%.

Data were analyzed using SPSS version 20. Variables were expressed as counts mean ± SD or as median (interquartile range). Comparisons between the two groups were made using the Student's t-test, the Chi-square test, and the Mann–Whitney rank-sum test, as appropriate. Repeated-measures ANOVA was used to analyze the MAP and HR over time between the two groups. P < 0.05 was considered statistically significant.


   Results Top


One hundred female patients undergoing laparoscopic gynecological surgeries were identified. Twelve of them were not fulfilling the inclusion criteria, eight refused to participate in the study, and the remaining eighty patients were equally randomized to either OF group (n = 40) or O group (n = 40) [Figure 1].
Figure 1: Flowchart of the study

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The demographic and perioperative data of the two study groups are summarized in [Table 1]. Statistical analysis revealed nonsignificant differences between the two study groups as regards age, weight, height, ASA physical status, the duration of surgery, duration of anesthesia, extubation time, and PACU discharge time. However, propofol dose for the maintenance of anesthesia was significantly higher in the O group than OF group.
Table 1: Demographic characteristics and perioperative data

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As regards changes in the mean arterial blood pressure and HR, they were significantly lower on OF group [Figure 2] and [Figure 3].
Figure 2: Changes in heart rate between groups during perioperative period. P < 0.05 was considered statistically significant. *Significant to the opioid group. PACU = Postanesthesia care unit

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Figure 3: Changes in the mean arterial pressure between groups during perioperative period. P < 0.05 was considered statistically significant. *Significant to the opioid group. PACU = Postanesthesia care unit

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The QOR-40 questionnaire was statistically significant higher in the OF group (P < 0.05) [Table 2].
Table 2: 40-item quality of recovery questionnaire scores for both the groups at 24 h postoperative

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As regards NRS, time of first analgesia, and number of rescue analgesia required, there was a statistically significant difference between the two studied groups where O group was high than OF group (P < 0.05) [Table 3].
Table 3: Time to first analgesic need, maximum numerical rating scale, and number of rescue tramadol analgesia required in the first 24 h postoperative

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The incidence of nausea and vomiting was statistically significant in the O group, whereas shivering and bradycardia showed no significant difference between the studied groups [Table 4].
Table 4: Incidence of adverse events

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   Discussion Top


Our study showed a significant improvement in the global QOR at 24 h postoperative in the OF TIVA compared to those with opioid-based TIVA in patients undergoing ambulatory gynecological surgery. In particular, OF TIVA had significantly higher scores for physical comfort, emotional status, physical independence, and pain subcomponents of the QOR questionnaire. Another important finding of our study is a significant reduction in postoperative pain and incidence of PONV. These findings are particularly important in the day surgery, as patients expected to have fast discharge with reduced costs and rapid return of daily activities.[1],[7]

TIVA with opioids are known to improve QOR after ambulatory surgery.[8],[9],[10] However, opioids can be associated with an increased incidence of postoperative complications,[4] which can affect patient's QOR. The avoidance of opioids seems to improve the QOR. It is unclear in the literature whether the OF TIVA can improve the QOR in ambulatory surgery.

De Oliveira et al. found a significant improvement in QOR by 11.8% (from 156.5 to 170) in patients who received less opioid under sevoflurane in ambulatory gynecological laparoscopy.[11]

In the present study, OF TIVA led to a significant improvement in QOR by 8.5% (from 175 to 190) and by 21.7% (from 156.5 to 190) compared to De Oliveira et al.' s study. TIVA has been reported to improve the QOR by 8%.[2] The reduction in our study may have been related to the avoidance of both intraoperative opioids and volatile anesthetics.

TIVA has relied on the pharmacodynamic interaction between the propofol and short-acting opioids for their success.[12] However, dexmedetomidine has been used successfully as a component of OF TIVA during laparoscopic cholecystectomy.[13]

By its opioid-sparing properties, dexmedetomidine can reduce the postoperative pain and the incidence of PONV.[14],[15],[16],[17] Other benefits include improvement of hemodynamic stability and reduced anesthetic consumption.[18]

Our study found that the OF TIVA delayed request for the first analgesic, decreased pain scores and tramadol rescue analgesia. Mulier et al. used OF anesthesia and found improved pain scores and lower requirement of rescue tramadol analgesic, similar to the observation in our study.[19]

Increased use of inhalational agents and opioids has been associated with higher incidence of PONV.[20],[21]

Ziemann-Gimmel et al. found that OF TIVA is associated with a large reduction in relative risk of PONV in patients undergoing bariatric operations.[22] This is comparable to our finding, which showed a significant reduction in PONV by 75%. However, the comparison of reduction has to be interpreted with caution because of the different patient populations observed.

The requirement of propofol was found to be significantly less in the OF group. This is similar to previous studies that also noted significantly lower requirements of intraoperative anesthetics with dexmedetomidine.[23]

In our study, we found a significant fall in HR and MAP after dexmedetomidine. This is similar to previous studies that also noted that dexmedetomidine infusion attenuates stress response to various noxious stimuli and maintains hemodynamic stability.[24]


   Conclusions Top


We observed that OF TIVA during ambulatory gynecological laparoscopy improves QOR on the following day, prolonged postoperative analgesia, and lower incidence of PONV. In addition, it reduced the requirement for propofol and maintained stable intraoperative hemodynamics without delay in extubation time or PACU discharge time.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Lee JH. Anesthesia for ambulatory surgery. Korean J Anesthesiol 2017;70:398-406.  Back to cited text no. 1
    
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Lee WK, Kim MS, Kang SW, Kim S, Lee JR. Type of anaesthesia and patient quality of recovery: A randomized trial comparing propofol-remifentanil total i.v. Anaesthesia with desflurane anaesthesia. Br J Anaesth 2015;114:663-8.  Back to cited text no. 2
    
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Bowyer A, Jakobsson J, Ljungqvist O, Royse C. A review of the scope and measurement of postoperative quality of recovery. Anaesthesia 2014;69:1266-78.  Back to cited text no. 3
    
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White PF. The role of non-opioid analgesic techniques in the management of pain after ambulatory surgery. Anesth Analg 2002;94:577-85.  Back to cited text no. 4
    
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Tufanogullari B, White PF, Peixoto MP, Kianpour D, Lacour T, Griffin J, et al. Dexmedetomidine infusion during laparoscopic bariatric surgery: The effect on recovery outcome variables. Anesth Analg 2008;106:1741-8.  Back to cited text no. 5
    
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Myles PS, Weitkamp B, Jones K, Melick J, Hensen S. Validity and reliability of a postoperative quality of recovery score: The qoR-40. Br J Anaesth 2000;84:11-5.  Back to cited text no. 6
    
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Gornall BF, Myles PS, Smith CL, Burke JA, Leslie K, Pereira MJ, et al. Measurement of quality of recovery using the QoR-40: A quantitative systematic review. Br J Anaesth 2013;111:161-9.  Back to cited text no. 9
    
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Abdallah FW, Morgan PJ, Cil T, McNaught A, Escallon JM, Semple JL, et al. Ultrasound-guided multilevel paravertebral blocks and total intravenous anesthesia improve the quality of recovery after ambulatory breast tumor resection. Anesthesiology 2014;120:703-13.  Back to cited text no. 10
    
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De Oliveira GS Jr., Fitzgerald P, Streicher LF, Marcus RJ, McCarthy RJ. Systemic lidocaine to improve postoperative quality of recovery after ambulatory laparoscopic surgery. Anesth Analg 2012;115:262-7.  Back to cited text no. 11
    
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Egan TD, Minto CF. Pharmacodynamic drug interactions in anesthesia. In: Evers AS, Maze M, Kharasch ED, editors. Anesthetic Pharmacology: Basic Principles and Clinical Practice. 2nd ed. Cambridge University Press; 2013. p. 147-65.  Back to cited text no. 12
    
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Bakan M, Umutoglu T, Topuz U, Uysal H, Bayram M, Kadioglu H, et al. Opioid-free total intravenous anesthesia with propofol, dexmedetomidine and lidocaine infusions for laparoscopic cholecystectomy: A prospective, randomized, double-blinded study. Braz J Anesthesiol 2015;65:191-9.  Back to cited text no. 13
    
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Blaudszun G, Lysakowski C, Elia N, Tramèr MR. Effect of perioperative systemic α2 agonists on postoperative morphine consumption and pain intensity: Systematic review and meta-analysis of randomized controlled trials. Anesthesiology 2012;116:1312-22.  Back to cited text no. 14
    
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Schnabel A, Meyer-Frießem CH, Reichl SU, Zahn PK, Pogatzki-Zahn EM. Is intraoperative dexmedetomidine a new option for postoperative pain treatment? A meta-analysis of randomized controlled trials. Pain 2013;154:1140-9.  Back to cited text no. 15
    
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Turgut N, Turkmen A, Gökkaya S, Altan A, Hatiboglu MA. Dexmedetomidine-based versus fentanyl-based total intravenous anesthesia for lumbar laminectomy. Minerva Anestesiol 2008;74:469-74.  Back to cited text no. 16
    
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Thornton C, Lucas MA, Newton DE, Doré CJ, Jones RM. Effects of dexmedetomidine on isoflurane requirements in healthy volunteers 2: Auditory and somatosensory evoked responses. Br J Anaesth 1999;83:381-6.  Back to cited text no. 18
    
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Mulier JP, Wouters R, Dillemans B, De Kock M. A randomized controlled, double-blind trial evaluating the effect of opioid-free versus opioid general anaesthesia on postoperative pain and discomfort measured by the QoR-40. J Clin Anesth Pain Med 2018;2:015.  Back to cited text no. 19
    
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Apfel CC, Heidrich FM, Jukar-Rao S, Jalota L, Hornuss C, Whelan RP, et al. Evidence-based analysis of risk factors for postoperative nausea and vomiting. Br J Anaesth 2012;109:742-53.  Back to cited text no. 20
    
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Gan TJ. Mechanisms underlying postoperative nausea and vomiting and neurotransmitter receptor antagonist-based pharmacotherapy. CNS Drugs 2007;21:813-33.  Back to cited text no. 21
    
22.
Ziemann-Gimmel P, Goldfarb AA, Koppman J, Marema RT. Opioid-free total intravenous anaesthesia reduces postoperative nausea and vomiting in bariatric surgery beyond triple prophylaxis. Br J Anaesth 2014;112:906-11.  Back to cited text no. 22
    
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Aho M, Lehtinen AM, Erkola O, Kallio A, Korttila K. The effect of intravenously administered dexmedetomidine on perioperative hemodynamics and isoflurane requirements in patients undergoing abdominal hysterectomy. Anesthesiology 1991;74:997-1002.  Back to cited text no. 23
    
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Patel CR, Engineer SR, Shah BJ, Madhu S. Effect of intravenous infusion of dexmedetomidine on perioperative haemodynamic changes and postoperative recovery: A study with entropy analysis. Indian J Anaesth 2012;56:542-6.  Back to cited text no. 24
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