Dexmedetomidine Compared to Remifentanil Infusion as Adjuvant to Sevoflurane Anesthesia during Laparoscopic Sleeve Gastrectomy.

OBJECTIVES: Evaluation of postoperative (PO) analgesic effects of intraoperative (IO) Dexmedetomidine (DEX) compared to remifentanil (REMI) infusions during sevoflurane anesthesia for laparoscopic gastric sleeve surgery. PATIENTS AND METHODS: One hundred and thirty-two patients with body mass index >35 kg.m-2 and ASA Grades II or III were randomly divided into group R received REMI infusion (6-18 μg.kg-1.h-1) and Group D received DEX infusion (0.2-0.5 μg.kg-1.h-1) after tracheal intubation till before stoppage of inhalational anesthetic. Heart rate and mean arterial pressure were noninvasively monitored during and after surgery. Emergence time, time until postanesthetic care unit transfer, and total operating room (OR) time was recorded. PO shoulder-tip pain and wound pain scores were recorded and rescue analgesia was provided as 50 mg pethidine intramuscular injection. Occurrence of PO nausea and vomiting (PONV) and frequency of the need for antiemetic therapy were recorded. Primary study outcome was the ability of the study infusions to reduce consumption of PO pethidine down to one dose during 24-hr PO.
RESULTS: IO use of REMI or DEX infusion allowed hemodynamic control to surgical stresses with nonsignificant difference between both infusions. REMI infusion insured significantly rapid recovery and short OR times but required larger volume of sevoflurane during surgery and proper PO follow-up for pain and PONV. DEX infusion significantly improved control of PO pain with a larger number of patient requested rescue analgesia only once, reduced the dose of PO analgesia, reduced the frequency of PONV, and the need for antiemetic therapy.
CONCLUSION: REMI or DEX infusion as IO adjuvant to general anesthesia is appropriate option to achieve hemodynamic control of surgical stresses and to improve perioperative outcomes. REMI infusion may be preferred for its induced rapid recovery and short OR time, whereas DEX infusion may be chosen for its improved control of PO pain and reduction of PO analgesia and frequency of PONV. Copyright:

INTRODUCTION

Obesity has become a worldwide epidemic affecting adults, as well as children and adolescents.[1] The current obesity epidemic poses a major public health problem since obesity predisposes towards several chronic diseases.[2] Bariatric surgery is the most effective treatment for obesity.[3] Its effects go beyond weight loss, for achieving remission of co-morbidities associated with obesity and reducing mortality.[4]

Remifentanil (REMI) is a novel, synthetic short-acting mu-receptor opioid derivative with a unique modification of its chemical structure to include a methyl ester ring.[5] REMI undergoes widespread extrahepatic metabolism by blood and tissue nonspecific esterases.[6] The molecular configuration of REMI, resulting in its rapid metabolism and thereby provides a rapid onset, easy titration by continuous infusion,[5] and a short context-sensitive half-life with extremely rapid clearance of approximately 3 L.min-1.[6]

REMI was used as adjuvant to general anesthesia for its analgesic effect to reduce intraoperative analgesia,[7] its intraoperative hypotensive effect with subsequent reduced intraoperative blood loss.[8] Moreover, REMI used as adjuvant to sevoflurane does not cause acute opioid tolerance or hyperalgesia.[9]

Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist that uniquely maintains respiratory drive, produces arousable sedation[10] and reduces the incidence and shortened duration of postoperative (PO) delirium, especially in the elderly.[11] DEX produces sympatholytic effects and dose-dependent analgesia and sedation and attenuates neuroendocrine and hemodynamic responses related to surgery and anesthesia.[12] Commercially available DEX must be diluted before use and DEX admixtures of 200 μg/50 ml of 0.9% sodium chloride were stable for 2 days at room temperature and for 14 days in refrigerator.[13] DEX infusion improves oxygenation and lung mechanics in patients with chronic obstructive lung disease and morbidly obese patients with restrictive lung disease.[14]

Objectives

This study aimed to evaluate the PO analgesic effects of IO administration of DEX versus REMI infusion during sevoflurane anesthesia for bariatric surgery.

Design

Prospective comparative randomized clinical trial.

Setting

This study was conducted at Almoosa Hospital, KSA.

PATIENTS AND METHODS

All patients assigned for bariatric surgery since June 2017 till March 2018 were eligible for evaluation. Obese patients with body mass index (BMI) >35 kg.m-2, of ASA Grades II or III, were free of or had controlled obesity-associated comorbidities and assigned for laparoscopic gastric sleeve bariatric surgery were included in the study after approval of the Institutional Ethical Committee and obtaining a written informed consent. Exclusion criteria included obstructive sleep apnea syndrome, uncontrolled hypertension or diabetes mellitus, allergy to any of the drugs to be used, refusal of or the presence of contraindication for laparoscopic surgery, presence of synchronous pathology requiring open surgery, uncompensated cardiac lesion, advanced hepatic or kidney diseases or coagulopathies.

Preoperative assessment and preparation

Patients' demographic data, including age, weight, height, and presence of associated comorbidities, were obtained. BMI was calculated as weight (kg) divided by square the height (m2). Obesity is defined as BMI of >30 kg.m-2, morbid obesity as BMI >35 kg.m-2, and super obesity as BMI >55 kg.m-2.[15]

All enrolled patients received individualized perioperative management according to their preoperative history and physical examination. Diabetic patients were maintained on subcutaneous injection of regular insulin every 6 h with dose adjusted according to regular urine examination for glucose so as to maintain fasting blood glucose level at <160 mg.dL-1, with no ketonuria. Hypertensive patients were maintained on Ca-channel blockers and β-adrenergic agonists so as to maintain systolic and diastolic blood pressures at ≤130 and 90 mmHg, respectively. Patients receiving treatment for chronic obstructive pulmonary diseases maintained on bronchodilators and β-adrenergic agonists. All patients with medical diseases were continued postoperatively on the same lines of treatment applied preoperatively.

Patients' randomization and grouping

Randomization was performed using sealed envelopes containing cards carrying the group label, either R for REMI group or D for DEX group. Cards were previously prepared by an assistant not included as an author and did not know the significance of the letters: R and D. Cards were chosen by patient him/herself to determine the group to be included in.

Patients of Group R received REMI intravenous (IV) infusion at rate 6–18 μg.kg-1.hr-1 and patients of Group D received DEX IV infusion at rate of 0.2–0.5 μg.kg-1.hr-1.[16] IV infusion was started after intubation had commenced and maintenance anesthesia was started. Infusion of study medication was stopped at the time of completion of gastric sleeve and removal of the stomach through the trocar.

Preanesthetic preparation

All patients received anti-thrombotic prophylaxis and pantoprazole 40 mg IV routinely before shifting to the operating room (OR). Before induction of anesthesia, capillary hemoglobin oxygen saturation (SpO2) was measured using a Datex Cardiocap pulse oximeter (Datex, Helsinki, Finland) and were preoxygenated to maintain SpO2 at a range of 97%–99%. Baseline measurements of blood pressures, heart rate (HR), and respiratory rate were determined and noninvasively monitored during and after surgery. All patients received IV droperidol in a dose of 1 mg[17] and dexamethasone in a dose of 0.25 mg.kg-118 as prophylactic therapy against PO nausea and vomiting (PONV).

Anesthetic procedure

All patients were premedicated with midazolam (0.05 mg.kg-1), 2 min before induction of anesthesia. Anesthesia was induced using propofol 2 mg.kg-1, fentanyl 1–2 μg.kg-1, and cisatracurium 0.15 mg.kg-1 to facilitate orotracheal intubation. Balanced anesthesia was continued with 1.24% end-tidal sevoflurane in oxygen and air. After tracheal intubation, the lungs were ventilated with 100% O2 in air using a semi-closed circle system for a tidal volume of 6–8 mL.kg-1, and the ventilatory rate was adjusted to maintain an end-tidal carbon dioxide (paCO2) of 32–35 mmHg. Patients were continuously noninvasively monitored for mean arterial pressure (MAP) and HR, and changes were adjusted by changing the infusion rate or sevoflurane concentration. At the end of surgery, residual neuromuscular blockade was reversed with IV injection of neostigmine 0.05 mg.kg-1 with atropine 0.02 mg.kg-1 IV and patients were extubated. Following extubation, patients were transferred to the postanesthetic care unit (PACU). All surgeries were performed by the same team of surgeons using three-port approach.

Intraoperative monitoring

IO monitoring included recording HR and MAP, before (T1) and after induction of anesthesia (T2), 5 min after insufflation (T3) and exsufflation of CO2 (T4), and after extubation (T5). Duration of the surgery and occurrence of IO anesthetic or surgical problems were recorded. Emergence times to awakening, i.e., opening eyes on verbal command and orientation, i.e., correctly telling date, place, and person were determined at 1-min interval after discontinuation of the maintenance anesthetics. Time until, the patient was transferred to PACU was also recorded.

Postoperative monitoring

In PACU, patients were maintained in semi-sitting position throughout PO period and were noninvasively monitored for MAP and HR. Oxygen saturation was monitored using pulse oximetry, and oxygen (6 L.min-1) was administrated via a face-mask in the PACU if indicated.

The severity of PO shoulder-tip pain was assessed at 1, 3, 6, 12, and 24 h after PACU transfer. The pain was assessed using 11-points numeric rating scale (NRS) from 0 to 10 where 0 indicates no pain and 10 indicates the worst pain imaginable. NRS was more practical than the graphic visual analog scale, easier to perceive for most people, and does not need clear vision, pen, and paper.[19] When vital signs were stable, patients were allowed sips of water followed by a fluid diet of 60 mL.hr-1 and were asked to get off the bed and walk around the ward with the assistance. PO wound pain was assessed using 4-point verbal analog scale; 0: no pain, 1: mild, 2: moderate, and 3: severe pain[20] during rest and on mobilization. All patients received a dose of IV pethidine 20 mg on pain sensation, irrespective of its site or severity, as a baseline dose to allow painless immediate PO time to allow early ambulation. Further rescue analgesia was provided as an intramuscular injection of pethidine 50 mg that was given and repeated after 4 h if necessary.

The occurrence of PONV was recorded and the frequency of the need for antiemetic therapy, in the form of ondansetron 4 mg IV injection, was recorded. The occurrence of other PO complications either cardio-pulmonary, hypertensive or diabetic, the frequency of the need for intensive care unit (ICU) admission, and duration of hospital stay were also recorded.

Study outcomes

Primary outcome was the ability of the study infusions to reduce consumption of PO narcotic analgesia down to only one dose during 24-hr PO.

Secondary outcomes included:

Total dose of narcotic rescue analgesia consumed during 24-h PO

Duration of PO analgesia defined as time since cessation of IV infusion till first request of rescue analgesia

Frequency of PONV and the need for antiemetic therapy.

Sample size calculation

Based on the previous data obtained by Kontrimavičiūtė et al.[21] that PO pain scores and PO analgesic consumption after IO REMI infusion were similar to fentanyl during bariatric surgery under general anesthesia and by Abu-Halaweh et al.[22] that perioperative DEX infusion till 24-h following laparoscopic bariatric surgery, can decrease the overall morphine requirements during this period in comparison to morphine perioperative infusion, it was hypothesized IO DEX infusion could induce 3-fold increase in number of patients requested PO rescue narcotic analgesia once only during 24-h PO (primary outcome) and thereby significantly reduced PO narcotic consumption (secondary outcome) than IO REMI infusion. For a power of 0.85 and assuming α risk of 0.05, the sample size of 65 patients in each group was calculated to be appropriate.

Statistical analysis

Obtained data were presented as mean ± standard deviation, numbers, and percentages. Results were analyzed using the paired t-test, one-way ANOVA test and Chi-square test. Statistical analysis was performed using the IBM SPSS (Version 23, 2015; IBM, South Wacker Drive, Chicago, USA) for Windows statistical package. Value of P < 0.05 was considered statistically significant.

RESULTS

The study included 159 obese-morbid obese patients eligible for evaluation, 132 were included in the study and were randomly categorized into two equal groups [Figure 1].

Figure 1

Consort flow sheet

There were nonsignificant (P > 0.05) differences between patients of both groups as regards enrollment data [Table 1].

Table 1

Enrollment data of patients categorized into two study groups

Variables	Group R	Group D	P
Age (years)	38.7±7.5	38.1±6.1	0.603
Sex: male:female	18:48	13:53	0.305
Body weight (kg)	114.9±9.1	116.7±8.8	0.241
Body weight (cm)	169.6±2.2	169.4±2.2	0.581
BMI (kg/m2) (%)
Mean (±SD)	40±3.4	40.7±3.3	0.396
<40	41 (62.1)	34 (51.5)	0.219
>40	25 (37.9)	32 (48.5)
Associated comorbidities (%)
No	50 (75.8)	47 (71.2)	0.554
Yes	16 (24.2)	19 (28.8)
Type-2 diabetes mellitus (%)
Number	12 (18.1)	14 (21.2)	0.662
FBG (mg.dL1)	160.5±7.5	164.5±8.3	0.212
PP-BG (mg.dL-1)	242.8±18.9	255±16.6	0.089
Hypertension (%)
Number (%)	8 (12.1)	7 (10.6)	0.511
SAP (mmHg)	141.4±11.4	144.3±13.1	0.666
DAP (mmHg)	91.6±3.3	92±3	0.794
Chronic obstructive lung disease	4 (6)	6 (9.1)	0.511
ASA physical status class (%)
II	31 (47)	34 (51.5)	0.639
III	35 (53)	32 (48.5)

Data are presented as mean±SD, ratio, numbers and percentages. P value indicates significance of inter-group difference; P>0.05 indicates nonsignificant difference. BMI=Body mass index, FBG=Fasting blood glucose, PP=Postprandial blood glucose, SAP=Systolic arterial pressure, DAP=Diastolic arterial pressure, SD=Standard deviation, ASA=American Society of Anesthesiologists

Mean HR and MAP estimated in patients of both groups was significantly higher at T2 and T3 compared to T1, while was significantly lower at T4 compared to T1. On the other hand, mean HR and MAP estimated at T5 were nonsignificantly higher compared to T1 measures. Concerning inter-group difference, mean HR measures were nonsignificantly lower in patients of Group R at T1, T2, T3, and T5, while at T4 mean HR measures were significantly (P = 0.005) lower in patients of Group R compared to patients of Group D. On the contrary, mean estimates of MAP were nonsignificantly (P > 0.05) lower in patients of Group R compared to patients of Group D [Table 2].

Table 2

Heart rate and mean arterial pressure measures estimated in studied patients categorized into two study groups

Variables	Time	Group R	Group D	P
HR (beat/min-1)	T1	79.4±3.9	79.2±4.9	0.797
	T2	83.1±4.4	84.7±7.1	0.152
	T3	83±4	84±5.3	0.214
	T4	73.2±5.4	76.3±7	0.005
	T5	80.6±3.7	79.8±4.5	0.291
MAP (mmHg)	T1	90.9±4.9	91.5±5.7	0.475
	T2	92.7±5	93.6±6.4	0.341
	T3	94.3±5	94.9±6.1	0.546
	T4	89.5±4.8	90.9±6.5	0.174
	T5	91.9±4.9	92.2±5.3	0.777

Data are presented as mean±SD, HR, MAP, P value indicates significance of inter-group difference, P<0.05 indicates significant difference, P>0.05 indicates nonsignificant difference. HR=Heart rate, MAP=Mean arterial pressure

All surgeries were conducted uneventfully and no patient required conversion to open surgery and no IO anesthetic or surgical complications were encountered. The actual duration of the surgical procedure showed nonsignificant (P > 0.05) difference between studied groups. The consumed amount of sevoflurane was significantly (P = 0.006) smaller with DEX infusion than with REMI infusion. Emergence time till awakening, time till being ready for transfer to PACU and total OR time were significantly (P = 0.001, <0.001, and 0.003, respectively) shorter among patients of Group R who received REMI infusion compared to patients who received DEX infusion [Table 3].

Table 3

Intraoperative data of studied patients categorized into two study groups

Variables	Group R	Group D	P
Duration till stoppage of infusion (min)	64.7±11	67.5±9.5	0.118
The consumed amount of sevoflurane (mL)	25.7±6.4	23.1±3.8	0.006
Emergence time to awakening (min)	3.2±1	5±1.3	0.001
Time till being ready for transfer to PACU (min)	3.9±2	5.6±2.6	<0.001
Total OR time (min)	71.8±12.8	78.2±11.2	0.003

Data are presented as mean±SD; P<0.05 indicates significant difference; P>0.05 indicates nonsignificant difference. PACU=Postanesthetic care unit, OR=Operating room, SD=Standard deviation

The mean duration of PO analgesia was significantly (P < 0.001) shorter in patients of Group R than patients of Group D. Moreover, PO pain scoring for shoulder-tip pain was significantly higher at 3-h PO in patients of Group R compared to patients of Group D [Figure 2].

Figure 2

Mean postoperative numeric rating scale score for shoulder-tip pain determined throughout 24-h postoperative in patients of both groups

Wound pain was more manifested in patients of Group R, both during rest and mobilization with significantly lower pain scores compared to patients of Group D. All patients requested for additional analgesia, after that routinely administered, but number of patients requested rescue analgesia for one time only was significantly (P = 0.0036) higher [Figure 3] with significantly lower mean number of requests (P = 0.016) in Group D compared to Group R [Figure 4].

Figure 3

Patients' distribution according to the number of requests of rescue analgesia

Figure 4

Mean number of requests of rescue analgesia and dose used by patients of both groups

Moreover, the dose of pethidine (P = 0.025) was significantly higher in patients of group R compared to patients of Group D [Figure 4].

Twenty-four patients (18.2%) developed PO complications and 5 patients (3.8%) were admitted to ICU with nonsignificantly (P = 0.071 and 0.648, respectively) higher frequency among patients of Group R. Thirteen patients (9.8%) developed PONV of which 10 patients (15.2%) in Group R and 3 patients (4.5%) in Group D with significantly (P = 0.041) higher frequency of PONV among patients of Group R. Five patients (3.8%) required antiemetic therapy; 4 patients (6.1%) in Group R and only one patient (1.5%) in Group D with nonsignificantly (P > 0.05) higher frequency of the need for antiemetic therapy. The mean duration of hospital stay was 2.4 (±1) days with nonsignificant (P = 0.398) between both groups [Table 4].

Table 4

PO data of studied patients categorized into two study groups

Data	Group R	Group D	P
Duration of PO analgesia (h)	1.5±0.6	2.2±0.8	<0.001
Shoulder-tip pain
PO NRS pain score
1 h PO	2.21±0.8	2.24±0.4	0.788
3 h PO	2.6±0.7	2.29±0.5	0.008
6 h PO	2.7±0.9	2.56±0.88	0.341
12 h PO	2.36±1.4	2.73±1.1	0.101
24 h PO	2.44±1.58	2.68±1.3	0.336
Wound pain
Pain score during rest
1 h PO	0.27±0.45	0	<0.001
3 h PO	0.73±0.6	0.39±0.5	<0.001
6 h PO	1.7±0.6	1.05±0.37	<0.001
12 h PO	2.5±0.77	2.1±0.9	0.004
24 h PO	3.2±1.06	2.6±1.12	0.002
48 h PO	2.1±1.55	2.1±1.2	0.085
Pain score during mobilization
1 h PO	0.59±0.53	0.2±0.4	<0.001
3 h PO	1.89±0.68	1±0.53	<0.001
6 h PO	2.79±0.64	1.8±0.6	<0.001
12 h PO	3.2±1.28	2.88±0.7	<0.001
24 h PO	1.45±1.8	1.15±1.72	0.331
Rescue analgesia
Number of requests
Once (%)	4 (6.1)	16 (24.2)	0.0036
Two times (%)	32 (48.5)	28 (42.5)	0.484
Three times (%)	29 (43.9)	21 (31.8)	0.151
Four times (%)	1 (1.5)	1 (1.5)	0
Mean number	2.4±0.6	2.1±0.8	0.016
Dose of pethidine (mg)	120.5±31.6	106.4±39.4	0.025
PO events
Complications (%)
PONV	10 (15.2)	3 (4.5)	0.041
Others	6 (9.1)	5 (7.6)	0.753
Total	16 (24.2)	8 (12.1)	0.071
ICU admission (%)	3 (4.5)	2 (3)	0.648
Hospital stay (days)	2.5±1.1	2.3±0.9	0.398

Data are presented as mean±SD; P<0.05 indicates significant difference; P>0.05 indicates non-significant difference. SD=Standard deviation, PO=Postoperative, NRS=Numeric rating scale, PONV=PO nausea and vomiting, ICU=Intensive care unit, SD=Standard deviation

DISCUSSION

The nonsignificant differences between IO measurements of MAP and HR recorded with both REMI and DEX infusions indicated good hemodynamic control and anesthetic outcome of this group of patients by the use of either infusion as adjuvant to general anesthesia. In a similar study, Javaherforooshzadeh et al.[23] compared DEX versus REMI infusions with propofol and reported no significant difference regarding the volume of blood loss, MAP, and systolic and diastolic blood pressures.

Each of REMI and DEX infusions provided certain perioperative advantages; REMI infusion allowed more reduction of HR and MAP estimates, despite the nonsignificant difference compared to DEX infusion, a finding which is consistent with previous studies evaluated the effect of REMI on hemodynamic variables.[82425] Moreover, patients received REMI had significantly shorter emergence time and time till being ready for transfer to PACU with subsequent significantly shorter total OR time than those received DEX infusion. Similarly, Lee et al.[26] demonstrated that the quality of recovery for patients who underwent thyroid surgery is significantly better with propofol and REMI total IV anesthesia compared to desflurane inhalational anesthesia.

However, patients in the REMI group required frequent adjustments of the rate of REMI infusion and increases of sevoflurane concentrations to accommodate the vasopressor effects of IO manipulation and this could be attributed to the short duration of action of REMI. On the contrary, DEX infusion allowed reduction of HR and MAP in conjunction with reduction of sevoflurane concentration owing to its hemodynamic adjusting effect as well as its sedative and analgesic effects, and hence there was no need for re-adjustment of its rate.

In similar comparative studies, Chen et al.[27] demonstrated that DEX and REMI can reduce hemodynamic responses to surgery and coughing and agitation during the recovery period, but DEX can provide longer sedation time than REMI. Furthermore, Okello et al.[28] compared the risk of hypotension using REMI compared to DEX infusion under isoflurane anesthesia for patients undergoing elective surgeries and detected a significantly higher proportion of patients with hypotension with REMI, while episodes of hypotension were fewer with DEX.

The reported reduction of sevoflurane concentration with DEX infusion go in hand with that previously reported in the literature that DEX significantly reduced sevoflurane concentration and dosage than with REMI.[293031]

Furthermore, IO DEX infusion improved PO outcome as manifested by significantly longer duration of PO analgesia and lower pain scoring for shoulder-tip and wound pain. Moreover, mean number of requests of rescue analgesia and dose of pethidine was significantly lower in patients of Group D compared to patients of Group R. Concerning the primary outcome of the study, DEX infusion allowed significantly higher frequency of patients requested rescue analgesia only once (16 compared to. 4), so reduced the need for PO opiate analgesia by four-fold than REMI infusion.

These findings go in hand with Xu et al.[32] who reported that the combination of DEX and lidocaine significantly improved PO pain and enhanced recovery of bowel function after abdominal hysterectomy than lidocaine alone. Furthermore, Suhitharan et al.[33] found IO REMI infusion increases opioid consumption during the immediate PO period. Moreover, Elbakry et al.[34] reported that total IV anesthesia using propofol and DEX is a better anesthetic regimen than desflurane anesthesia for laparoscopic sleeve gastrectomy in morbidly obese patients for provision of better PO recovery with fewer analgesic requirements and PO side effects and Suero Molina et al.[35] found the use of DEX infusion during awake neurological surgeries sedates moderately and acting as anxiolytic can ensure more rapid surgery with reduction of doses of antihypertensive and vasoactive drugs as well as the length of hospitalization than propofol-REMI infusion.

During immediate PO period, more patients in REMI group developed PONV with significant difference compared to DEX group; regarding both the frequency of patients developed PONV and requirement for antiemetic therapy. Other PO morbidities showed nonsignificant difference between both groups. Similarly, Polat et al.[36] found the administration of PO analgesics and incidence of PONV was significantly lower after DEX than REMI infusion and Javaherforooshzadeh et al.[23] found DEX infusion improved PO outcome compared to REMI infusion.

CONCLUSION

The use of REMI or DEX infusion as IO adjuvant to general anesthesia for patients undergoing gastric sleeve bariatric surgery is appropriate option to achieve hemodynamic control to surgical stresses and improves perioperative outcomes. REMI infusion may be preferred for its induced rapid recovery and short OR time, while DEX infusion may be chosen for its improved control of PO pain and reduction of the dose of PO analgesia and frequency of PONV. Considering the advantage of each infusion, the choice of the used infusion may be modified according to patients' medical status, anesthetist's preference and drug availability.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.