|Year : 2017 | Volume
| Issue : 1 | Page : 207-212
Dexmedetomidine infusion versus placebo for analgesia and prevention of emergence agitation in morbidly obese patients undergoing laparoscopic sleeve gastrectomy
Mostafa M Hussein, Raham H Mostafa
Department of Anesthesia, Intensive Care and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt
|Date of Web Publication||3-Aug-2018|
Mostafa M Hussein
5 Abdelazim Salama Street, Nasr City, Cairo 11727
Source of Support: None, Conflict of Interest: None
Background Emergence agitation (EA) can occur following recovery from general anesthesia. The patient may exhibit aggressive behavior, disorientation, agitation, and restlessness. If untreated, this complication may result in significant morbidity. EA has been poorly investigated in patients undergoing laparoscopic sleeve gastrectomy.
Aim The aim was to assess the efficacy of perioperative dexmedetomidine infusion on EA and quality of recovery after elective laparoscopic sleeve gastrectomy in morbidly obese adult patients.
Materials and methods A total of 60 patients undergoing laparoscopic sleeve gastrectomy were randomized into two groups (30 patients each). The dexmedetomidine group (group D, N=30) received dexmedetomidine infusion, whereas the control group (group C, N=30) received normal saline in the same volume and rate as placebo. Propofol, fentanyl, and atracurium were used for induction of anesthesia, and isoflurane was used for maintenance of anesthesia.
Postoperative hemodynamic variables, postoperative pain, the need for ‘rescue’ analgesics and antiemetics, and the incidence of agitation were recorded up to 2 h postoperatively. Pain was evaluated using the visual analog scale score in the postanesthesia care unit on arrival, at 5 min, and then every 15 min for 120 min. EA was evaluated at the same time intervals by Richmond agitation-sedation scale (RASS). Pethidine 50 mg intravenously was given for pain (if pain score >4) or severe agitation (RASS score >+1).
Results No patients in group D experienced postoperative EA during the second hour postoperatively (RASS ˂1). On the contrary, RASS scores of patients in group C were 2 (2–3) on arrival to postanesthesia care unit and greater than +1 during the remaining time up to 2 h postoperatively, indicating postoperative EA. In group C, 25 (92.5%) patients required rescue analgesia compared with only five (18.5%) patients in group D. Hemodynamic parameters were stable in group D.
Conclusion Dexmedetomidine infusion during laparoscopic sleeve gastrectomy for morbidly obese patients is beneficial and effective in preventing postoperative pain and postoperative EA.
Keywords: dexmedetomidine, emergence agitation, obesity, postoperative pain, sleeve gastrectomy
|How to cite this article:|
Hussein MM, Mostafa RH. Dexmedetomidine infusion versus placebo for analgesia and prevention of emergence agitation in morbidly obese patients undergoing laparoscopic sleeve gastrectomy. Ain-Shams J Anaesthesiol 2017;10:207-12
|How to cite this URL:|
Hussein MM, Mostafa RH. Dexmedetomidine infusion versus placebo for analgesia and prevention of emergence agitation in morbidly obese patients undergoing laparoscopic sleeve gastrectomy. Ain-Shams J Anaesthesiol [serial online] 2017 [cited 2018 Nov 20];10:207-12. Available from: http://www.asja.eg.net/text.asp?2017/10/1/207/238478
| Introduction|| |
Emergence agitation (EA) is a postanesthetic phenomenon that develops in the early phase of general anesthesia recovery and is characterized by agitation, confusion, disorientation, and possible violent behavior. Although agitation is observed more frequently in pediatric patients, the incidence in adults has been reported from 4.7 to 21.3% .
Emergence from general anesthesia can be an extremely challenging event. It involves cessation of drug administration, reversal of paralysis, and extubation. During this phase, patients may demonstrate hemodynamic instability, retching and vomiting, respiratory compromise, and occasionally, uncooperative or frankly aggressive behavior . If untreated, this complication may result in significant morbidity. It may lead to self-extubation or removal of catheters, which can cause serious complications such as hypoxia, aspiration pneumonia, bleeding, or reoperation .
The causes of agitation are multifactorial. 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. Moreover, it is common with the use of specific anesthetics like sevoflurane. Preoperative benzodiazepines, breast surgery, abdominal surgery, ophthalmology or otorhinolaryngology procedures, and surgery of long duration were shown to be risk factors for EA .
The immediate postoperative period after bariatric surgery is critical, because this surgery has specific complications associated with the patient morbidity being morbidly obese. Prophylaxis or treatment for EA after bariatric surgery should not have an unfavorable effect on airway. Although opioid sedatives are often used to reduce the incidence and severity of EA, anesthesiologists should always consider the risk of postoperative respiratory complications in morbidly obese patients .
Opioid drugs are better avoided for analgesia in the morbidly obese patients because of the risk of respiratory depression. This requires that alternative drugs be used in place of opioids to provide analgesia during surgery. Several drugs including ketamine, clonidine magnesium, ketorolac, lidocaine, and steroids have all been shown to be analgesic .
Dexmedetomidine is a highly selective α2-adrenoceptor agonist. It has hypnotic, sedative, anxiolytic, sympatholytic, and analgesic properties without significant respiratory depression. Dexmedetomidine infusion was proved to reduce agitation from general anesthesia in children. However, the data related to the effects of dexmedetomidine on reducing agitation from general anesthesia in adults are limited. This medication has not been associated with respiratory suppression but occasionally high levels of sedation .
α2-Adrenoceptor agonists have been used as an adjuvant to anesthetic agents in perioperative period for several beneficial actions. These drugs improve hemodynamic stability during endotracheal intubation and surgical stress by its central sympatholytic action, and thus reduce anesthetic and opioids requirements .
In this randomized, double-blind, placebo controlled study, we hypothesized that perioperative use of dexmedetomidine infusion until extubation would reduce EA in morbidly obese adult patients undergoing bariatric surgery. Moreover, we hypothesized that perioperative dexmedetomidine infusion would be a safe and effective substitute to opiates intraoperatively, reducing opiate requirements postoperatively.
| Materials and methods|| |
This was a prospective, randomized, comparative, controlled study conducted on 60 morbid obese patients (BMI: 35–45 kg/m2) on American Society of Anesthesiologist physical status II and III, aged between 20 and 50 years of either sex, undergoing elective laparoscopic sleeve gastrectomy under general anesthesia. The study was done in Ain Shams University Hospital during the period from December 2014 till November 2015. Patients randomization was done by using a computer-generated program.
Approval for the study was obtained from Ain Shams University’s ethical committee, and written informed consent was taken from the patients after explaining the nature of the study. Patients with history of hypertension (controlled or uncontrolled), cerebrovascular, cardiac, respiratory, hepatic or renal diseases, thyrotoxicosis, allergy to the study drugs, therapy with vasoactive medications, or positive pregnancy test were excluded from the study. Moreover, patients with allergy to eggs or soy were excluded. Patients who experienced major complications that may have contributed to a prolonged hospital stay or increased pain (intestinal leak or bleeding for example) were also excluded.
All patients in this study were subjected to a detailed preanesthetic evaluation. All basic investigations according to our hospital protocol (e.g. fasting blood sugar, serum hemoglobin, kidney function tests, liver function tests, chest radiographies, and ECG) were checked. In the operating room, standard monitoring [including ECG, heart rate (HR), blood pressure, pulse oximetry, and end-tidal CO2] was established. A peripheral intravenous cannula was inserted and secured. An anesthesiologist (who was not one of the observers for the study) prepared injectable solutions containing either dexmedetomidine or 0.9% saline. The dexmedetomidine was supplied in 2 ml ampoules of 100 µg/ml concentration. Only 100 µg was diluted with 99 ml of normal saline to yield a final concentration of 1 µg/ml. For each patient in group C, a 100 ml volume of 0.9% saline solution was prepared. This prepared solution was given over 20 min before induction of general anesthesia to the randomly selected patients. All baseline hemodynamic parameters were recorded.
Drug doses used during anesthetic procedure were calculated based on the 100 kg weight. After proper assessment of the airway and anticipation of difficult airway, preoxygenation with 100% O2 on 8 l/min for 3 min via face mask is started. Induction of anesthesia was achieved with propofol 2 mg/kg intravenouly and fentanyl 2 µg/kg intravenouly. Atracurium besylate 50 mg intravenouly was given to facilitate tracheal intubation, and anesthesia was maintained with 1–2% isoflurane. After orotracheal intubation, patients were kept under mechanical ventilation. For both groups, ventilation was initiated with tidal volumes of 10–12 ml/kg to avoid barotraumas and respiratory rates of up to 12–14 breaths/min to maintain normocapnia and positive end expiratory pressure of 5–10 cm H2O. Patients were placed in the semilithotomy position. Laparoscopic sleeve gastrectomy was performed through five abdominal trocars. Intra-abdominal pressure was maintained at 15 mmHg. All patients received a total volume infusion of 6 l of Ringer’s lactate solution during anesthesia. Supplemental boluses of atracurium besylate 0.1 mg/kg intravenously were administered as required to maintain muscle relaxation during surgery.
In each case, the aim was to maintain mean arterial blood pressure (MAP) within 80–120% of baseline values. MAP rise of more than 20% above baseline was treated by administering a 0.5 µg/kg intravenous bolus of fentanyl and raising the end-tidal isoflurane concentration to 2.5%. MAP decrease of more than 20% below baseline was treated initially with reduction of the end-tidal isoflurane concentration to 0.5%.
Each group D patient received an initial loading dose of dexmedetomidine 1 µg/kg lean body weight (LBW) over 20 min before induction, followed by an infusion started at 0.5 µg/kg/h. The infusion was discontinued when the laparoscopy ports were removed. Group C patients received the same volume of 0.9% saline, followed by a saline infusion.
On completion of surgery, each patient was extubated after fulfilling the extubation criteria. All participants were transferred to the postanesthesia care unit (PACU), where they were monitored for an extra 2 h and received nasal O2 supplementation.
Data for pain scores, HR, MAP, and agitation/sedation scores were recorded in the PACU on arrival, at 5 min, and then every 15 min for 120 min. Observers who recorded data were blinded with respect to patients’ group allocation. The observer was never the anesthesiologist providing clinical care to the patient.
Pain intensity was assessed using a 10-point visual analog scale (VAS), where 0 indicated no pain and 10 indicated the worst pain imaginable. Sedation/EA levels were also recorded at the same time intervals using Richmond agitation-sedation scale (RASS) score ([Table 1]) .
Moreover, the need for rescue analgesia, nausea, and vomiting incidence were recorded during the mentioned period.
The primary outcome measures were evaluation of the incidence of EA and the postoperative pain. The levels of agitation and sedation were evaluated by RASS. Agitation is defined as RASS score of +2 to +4. Postoperative pain was assessed by VAS. Pain score greater than 4 was considered significant and required rescue analgesia in the form of pethidine 50 mg intravenously.
The secondary outcome measures were postoperative hemodynamics, postoperative rescue analgesics, and postoperative nausea and vomiting.
Using PASS for sample size calculation, it was calculated that a sample size of 27 patients per group will achieve 80% power to detect a difference of 35% reduction in the incidence of emergency delirium between the two groups with a significance level (α) of 0.05 using a two-sided two-sample t-test.
The statistical analysis was performed using a standard SPSS software package version 17 (SPSS Inc., Chicago, Illinois, USA). Student’s t-test was used to analyze the parametric data and were expressed as mean±SD. Discrete (categorical) variables were analyzed using the χ2-test and were expressed as numbers (%), and nonparametric data were compared using Mann–Whitney test and were expressed as median (interquartile range). P values less than 0.05 were considered statistically significant.
| Results|| |
A total of 60 patients were enrolled in our study. However, six patients were excluded from the study (two patients refused to participate and four patients did not meet the inclusion criteria). So, the remaining 54 patients were divided randomly between the two groups (27 patients each).
There were no statistically significant difference between the two groups regarding demographic data and duration of anesthesia (P>0.05) ([Table 2]).
[Table 3] and [Table 4] showed comparison between the dexmedetomidine group and the control group regarding MAP and HR. From the time of arrival to PACU until 2 h postoperatively, MAP and HR were significantly lower in dexmedetomidine group compared with the control group (P<0.001). No hemodynamic instability was recorded in the group D, and all measures of HR and MAP were within 20% of baseline.
By using VAS for pain assessment, the pain score was found lower in group D compared with group C up to 2 h postoperatively ([Table 5]; P value <0.001).
|Table 5 Comparison of visual analog score for pain assessment between the two groups|
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The degree of EA was assessed by using the RASS score. The scale ranges from +4 to −5, with 0 grade referring to calm and oriented patient. Patients with RASS score greater than +1 in the PACU is considered to have EA. In group D, no patients experienced any degree of postoperative agitation, and most of patients were calm and oriented especially during the second hour postoperatively (RASS ˂1). On the contrary, RASS scores of patients in group C were two (2–3) on arrival to PACU and greater than +1 during the remaining time up to 2 h postoperatively indicating postoperative EA ([Table 6]; P value <0.001).
|Table 6 Comparison of Richmond agitation-sedation scale between both the groups|
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A total of 25 (92.5%) patients in group C required rescue analgesia compared with only five (18.5%) patients in group D up to 2 h postoperatively. Moreover, postoperative nausea and vomiting (PONV) were more common in group C (55.5%) compared with group D (22.2%) ([Table 7]).
|Table 7 Comparison of postoperative nausea and vomiting and rescue analgesia between both the groups|
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| Discussion|| |
The results of our study demonstrate the beneficial effect of dexmedetomidine in attenuating the postoperative EA in obese patients undergoing laparoscopic sleeve gastrectomy. Patients received dexmedetomidine infusion (started just before induction of general anesthesia and continued throughout the operation to be discontinued with removal of laparoscopic ports at the end of operation) showed decreased postoperative pain score, stable HR and MAP, decreased post-PONV, and postoperative rescue analgesia for up to 2 h postoperatively.
The sedative and analgesic effects of dexmedetomidine are caused by stimulation of α2-adrenergic receptors in the brain (i.e. locus coeruleus) and spinal cord (i.e. dorsal horn). Three subtypes of α2 adrenergic receptors were identified (i.e. α2A, α2B, and α2C). Dexmedetomidine effects are thought to be mediated through action on α2A receptors .
The lipophilic nature of dexmedetomidine is beneficial in morbidly obese patients. It results in prolonged elimination time as it is taken up by adipose tissues and hence more prolonged postoperative analgesia. This will decrease the need for postoperative rescue analgesia and opioid requirement. This is in agreement with the study done by Arain et al.  who concluded a 66% reduction of postoperative morphine requirements with the use dexmedetomidine.
Another study done by Feld et al.  demonstrated the narcotic-sparing effects of dexmedetomidine both intraoperatively and postoperatively. Their results showed the possibility of using dexmedetomidine in place of fentanyl for intraoperative analgesia and hemodynamic stability during open gastric bypass surgery. This will avoid the risk of using narcotics in morbidly obese patients, which are frequently associated with respiratory depression, airway obstruction, and hypoxemia .
A study done by Dresel et al.  showed a significant reduction in narcotics consumption and respiratory depression in patients who received dexmedetomidine infusion for acute pain management after Roux-en-Y gastric bypass surgery. Another study done by Hofer et al.  reported that dexmedetomidine infusion can entirely replace intraoperative narcotics in morbidly obese patients.
The predisposing factors for EA can be divided into either factors related to anesthesia, factors related to operation, and factors related to patients. Inhalational anesthetics with rapid emergence (like sevoflurane) are associated with higher incidence of EA than halothane. The ophthalmologic, otorhinolaryngologic surgeries are risk factors for EA. Patient-related factors include preoperative anxiety, young age, and no past surgical history.
Different scales are present to assess postoperative EA, like the RASS, the Riker agitation-sedation scale, the New Sheffield sedation scale, and the motor activity assessment scale . Although these scales are created primarily to be used for ICU patients, it can be applied also in PACU.
We found that there was a strong correlation between EA and postoperative pain. The analgesic property of dexmedetomidine decreased postoperative pain and hence postoperative EA. This finding was supported by many studies . Galinkin et al.  suggested that pain is considered the major factor responsible for postoperative EA. So, adequate analgesia results in reduction of agitation.
Laparoscopic procedures frequently associated with PONV owing to vagal stimulation resulting from peritoneal distension. Dexmedetomidine group showed decreased incidence of PONV to be 22.2% compared with 55.5% in control group. This can be explained by the beneficial antiemetic properties of α2 agonists. Moreover, reduced opioids consumption with the use of dexmedetomidine can decrease all opioid-related complications (e.g. PONV) ,.
There are three limitations to our study. First, the sample size was small, and the number of patients recruited was less. Second, patients were monitored for only 2 h postoperatively. Third, we did not monitor for signs postoperative respiratory depression.
| Conclusion|| |
Continuous intraoperative dexmedetomidine infusion in morbidly obese patients undergoing laparoscopic sleeve gastrectomy is a good option with reduced postoperative EA, adequate postoperative analgesia, and stable hemodynamics.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]