|Year : 2017 | Volume
| Issue : 1 | Page : 188-194
Effect of dexmedetomidine infusion on desflurane requirement and perioperative hemodynamic changes during laparoscopic gastric sleeve operations: a study based on entropy
Khaled M Elnaghy1, Ibrahim Abd-Elsalam Nasr2
1 Department of Anesthesia and Intensive Care, Ain Shams University, Cairo; Department of Anesthesia, Dr Sulaiman Alhabib Hospital, Riyadh, Egypt
2 Ain Shams University, Cairo; Department of Anesthesia, Sultan Bin Abdul-Aziz Humanitarian City Hospital, Riyadh, Egypt
|Date of Web Publication||3-Aug-2018|
Khaled M Elnaghy
Department of Anesthesia, Dr Sulaiman Alhabib Hospital, Riyadh 11393
Source of Support: None, Conflict of Interest: None
Context Obese patients undergoing laparoscopic gastric sleeve operations are sensitive to the respiratory depressant effect of opioid analgesics. Alternative methods for analgesia may be beneficial for intraoperative management of those patients. Dexmedetomidine is a highly selective α2 agonist with anesthetic and analgesic sparing properties that makes it an adjuvant in general anesthesia.
Aim The aim of this study was to assess the effect of intravenous administration of dexmedetomidine during laparoscopic gastric sleeve operations on desflurane requirements, perioperative hemodynamic changes, and also postoperative recovery. This study was based on entropy to monitor the depth of anesthesia.
Patients and methods Eighty patients of American Society of Anesthesiologists II and III who were scheduled for laparoscopic gastric sleeve operations were randomly allocated to two groups of 40 patients each. Dexmedetomidine at a loading dose of 1 μg/kg was given over 10 min before anesthesia induction, followed by 0.5 μg/kg/h maintenance throughout the operation in group II, and saline (placebo) was given in group I at the same volume and rate. Routine induction with propofol, fentanyl, and cisatracurium was carried out. Anesthesia was maintained with desflurane that was adjusted to maintain adequate depth of general anesthesia with response entropy between 40 and 60 and a difference of less than 10 with the state entropy. Desflurane inspired fraction and desflurane expired fraction were monitored.
Results End-tidal concentration of desflurane was significantly low at 15, 30, 45, and 60 min of operation. End-tidal concentration of desflurane decreased by 13.2–21.8% with the use of dexmedetomidine in comparison with group I. Systolic blood pressure, diastolic blood pressure, and heart rate were significantly decreased with the use of dexmedetomidine at different time intervals throughout the operation in comparison with group I and in comparison with the baseline in group II. Perioperative fentanyl consumption was significantly low with the use of dexmedetomidine in group II in comparison with group I. It was 325±55 μg in group II in comparison with 178±45 μg in group I. There was no significant difference between the two study groups as regards the extubation time. Pain score was significantly higher in group I in comparison with group II on admission to the postoperative acute care unit, and at 1 and 2 hlater.
Conclusion In conclusion, the use of dexmedetomidine as preanesthetic medication followed by infusion during laparoscopic sleeve gastrectomy reduces desflurane requirement, maintains hemodynamic stability due to attenuation of stress response, and reduces the fentanyl requirement during intraoperative and early postoperative period, with decreased risk for respiratory depression in the postoperative acute care unit for morbidly obese patients who are at great risk for obstructive sleep apnea and oxygen desaturation.
Keywords: desflurane, dexmedetomidine, laparoscopic sleeve gastrectomy, morbidly obese
|How to cite this article:|
Elnaghy KM, Nasr IA. Effect of dexmedetomidine infusion on desflurane requirement and perioperative hemodynamic changes during laparoscopic gastric sleeve operations: a study based on entropy. Ain-Shams J Anaesthesiol 2017;10:188-94
|How to cite this URL:|
Elnaghy KM, Nasr IA. Effect of dexmedetomidine infusion on desflurane requirement and perioperative hemodynamic changes during laparoscopic gastric sleeve operations: a study based on entropy. Ain-Shams J Anaesthesiol [serial online] 2017 [cited 2018 Nov 20];10:188-94. Available from: http://www.asja.eg.net/text.asp?2017/10/1/188/238444
The frequency of laparoscopic gastric sleeve operations has increased worldwide due to the increased prevalence of obesity . Laparoscopic bariatric surgeries offer the advantage of early mobilization and reduced hospital stay, but the associated carboperitoneum may lead to intraoperative cardiac instability . Moreover, morbidly obese patients are liable to intraoperative respiratory problems such as reduced functional residual capacity and hypoxemia, in addition to development of sleep apnea and insufficient postoperative ventilation . New inhalational anesthetics such as desflurane and sevoflurane have a low blood–gas partition coefficient, and hence share the advantage of faster onset and faster offset of anesthesia ,. However, because of the effect of obesity on the proportion of different tissues, body composition, perfusion uptake, and solubility, this can not only potentially affect wash-in and wash-out kinetics of inhalational agents but also recovery time in obese patients . Moreover, the use of opioids for morbidly obese patients could cause respiratory depression and affect the respiratory time . Laparoscopic surgeries under general anesthesia are associated with unique hemodynamic changes in the form of increased systemic vascular resistance leading to hypertension that needs increasing anesthesia depth to be controlled, and hence alternative analgesics are needed to improve the anesthetic management for obese patients, reduce the requirements of inhalational anesthetics and opioids, and subsequently improve the recovery. Dexmedetomidine is a highly selective α2 adrenoreceptor agonist  possessing hypnotic, sedative, anxiolytic, and analgesic properties without producing significant respiratory depression and promotes hemodynamic stability when used as an adjuvant during general anesthesia . The aim of this study was to assess the effect of intravenous administration of dexmedetomidine during laparoscopic gastric sleeve operations on desflurane requirements, perioperative hemodynamic changes, and also postoperative recovery. This study was based on entropy to monitor the depth of anesthesia, as administration and studying of drugs known to decrease anesthetic requirement without monitoring the depth of anesthesia may lead to underdosing of anesthetic drugs, thus causing awareness under anesthesia.
| Patients and methods|| |
This prospective randomized double-blind study was conducted over a period of 8 months (from April 2015 to December 2015) after approval of our human ethical committee of doctor Suleiman Alhabib Hospital (Riyadh, Saudi Arabia) and obtaining signed informed written consent from patients. Eighty obese and extremely obese patients of American Society of Anesthesiologists (ASA) class II or III aged 20–50 years with BMI more than 40 kg/m2 who were scheduled for elective laparoscopic sleeve gastrectomy were included in the study. Exclusion criteria were as follows: diabetes and hypertension, age more than 50 years or less than 20 years, chronic obstructive pulmonary disease, cardiac diseases, atrioventricular block, hepatic and renal dysfunction, and preoperative hematocrit values of less than 25%. Patients were randomly allocated to the two study groups using the sealed envelope technique. Forty patients were allocated in group I (the control group), desflurane–fentanyl, and another 40 patients were included in group II (the test group) desflurane–fentanyl–dexmedetomidine. Patients and investigators who recorded data in the operating room were blinded to the test group whether I or II.
For all study group patients, low molecular weight heparin was started 12 h before operation as an antithrombotic treatment. All drug doses were determined according to the true patient weight. Upon arrival of patients in the holding area, midazolam 20 μg/kg and glycopyrrolate 0.2 mg were given intravenously after insertion of an intravenous cannula. Intravenous premedication consisted of 10 mg of metoclopramide, pantoprazole 40 mg, ranitidine 50 mg, and dexamethasone 8 mg.
Inside the operating room, standard anesthesia monitoring was applied and baseline readings were recorded: noninvasive blood pressure, ECG, pulse oximetry, end-tidal CO2 monitor, peripheral nerve stimulator, and temperature probe. For observation of desflurane requirements, desflurane inspired fraction and desflurane expired fraction were monitored. For monitoring the depth of anesthesia, entropy (state entropy and response entropy) analysis was used (Datex-Ohmeda S/5 Module, Aisys Workstation; GE Healthcare, Helsinki, Finland). Difficult airway cart was kept ready for all patients and C Mac (C Mac monitor, 8403ZX endoscope; Karl Storz, Berlin, Germany) was used for endotracheal intubation, with appropriately sized cuffed flexometallic endotracheal tubes passed orally.
Ringer lactate solution at a rate of 10 ml/kg, intravenous, was started and another 18 G intravenous cannula was inserted for infusion of dexmedetomidine only. Redial artery catheter was inserted for invasive blood pressure monitoring.
Patients in group II received dexmedetomidine 1 μg/kg, intravenous, over 10 min through infusion pump before induction. (200 μg of dexmedetomidine was diluted in 40 ml of saline to obtain a concentration of 5 μg/ml.). Patients in group I received normal saline in the same volume (ml) and rate (ml/h). During the period of infusion of the study drug, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), and ECG were closely monitored.
After 5 min of preoxygenation for all patients, anesthesia was induced with intravenous fentanyl 0.5 μg/kg, lidocaine 1 mg/kg, propofol 1.5 mg/kg, and cisatracurium 0.15 mg/kg. C Mac was used for tracheal intubation. Anesthesia was maintained with 50% oxygen in air and cisatracurium infusion, and desflurane was started with 4% concentration and then adjusted to maintain an adequate depth of general anesthesia with response entropy between 40 and 60 and a difference of less than 10 with the state entropy. In group II, dexmedetomidine infusion of 0.5 μg/kg/h was started with an infusion pump at a concentration of 5 μg/ml solution throughout the operation and stopped 30 min before the expected time of completion. A similar volume of normal saline was infused in group I with the same rate. Tidal volume and respiratory rate were adjusted to maintain end-tidal CO2 within 30–40 mmHg and arterial blood gases within normal limit.
Anesthetist was permitted to treat the hemodynamic events, defined as HR and blood pressure more or less than 25% of the baseline, first by changing the desflurane concentration. Hypotension (defined as an MAP value of <25% of the baseline on two consecutive readings within 2–3 min not responding to 2% decrease in the inspired desflurane concentration and 200 ml of saline bolus) was treated with intravenous phenylephrine 100 μg bolus, and the infusion study medication was discontinued if the hypotension persisted for more than 2 min after these interventions and resumed with 50% of the initial rate upon return of the MAP within 25% of the baseline value. Hypertension (defined as MAP value of more than 25% of the baseline on two consecutive readings within 2–3 min) and/or tachycardia (defined as HR value of more than 25% of the baseline more than 2 min) despite 2% increase in the inspired desflurane concentration were treated with intravenous fentanyl 0.5 μg/kg bolus, followed by intravenous labetalol 5 mg bolus if no response. Bradycardia (defined as HR less than 45 persisting more than 2 min) was treated with intravenous glycopyrrolate 0.2 mg bolus.
Similar amounts of intravenous crystalloids were administered to all patients intraoperatively on the basis of body weight 8 ml/kg/h. Ondansetron was administered at a dose of 8 mg, intravenous, after removal of the laparoscope to prevent postoperative nausea and vomiting. Diclofenac sodium 75 mg and paracetamol 1 g were given intravenously for postoperative analgesia. Before wound closure, bupivacaine 0.25% was infiltrated at the fascial level of all ports. Neostigmine 0.04 mg/kg with glycopyrrolate 4 μg/kg was given to reverse the residual neuromuscular blockade based on nerve stimulator response. Infusion of the study medication was discontinued at the start of wound closure. Desflurane was discontinued upon completion of wound closure and inspired oxygen concentration was increased to 100% and flow increased to 5 l. Times from discontinuation of desflurane to eye opening and obeying simple commands (open eyes and open mouth) and tracheal extubation were recorded. Immediately after extubation, sedation was assessed with sedation score as follows: 1, awake; 2, sleepy but arousable; and 3, sleepy but difficult to awake. All patients were transferred to the postoperative acute care unit (PACU) and standard monitoring was applied. In the PACU, patients were started on patient-controlled analgesia (PCA) with fentanyl in a protocol of 50 μg PCA bolus followed by 25 μg PCA dose with a lockout time of 15 min. All patients were kept in the PACU for 2 h for observation of hemodynamics and pain. The verbal rating scale was used for subjective assessment of pain from 0 to 10 (0=no pain and 10 worst pain).
End-tidal concentration of desflurane and entropy was recorded at 5, 10, 15, 30, 45, and 60 min after intubation. HR and invasive arterial blood pressure were recorded at 5 and 10 min after starting the study drug, at the time of induction, at the time of intubation, at 5, 10, 15, 30, 45, and 60 min after intubation, at the time of extubation, and at 30, 60, and 120 m after extubation. Time required for extubation was detected. Visual analog scale was used for assessment of postoperative pain. Perioperative fentanyl requirements were detected.
For statistical analysis, SPSS software (version 17; SPSS Inc., Chicago, Illinois, USA) was used. A power analysis of α=0.05 and β=0.90 showed that 40 patients were required per group to detect at least 30% difference in desflurane requirement and perioperative hemodynamics between the two study groups. Data were expressed as mean±SD, number, and percentage of patients or median (interquartile range). Fisher’s exact test was used for comparison of patient sex and ASA classification between the two study groups. The Mann–Whitney test was used for comparison of verbal rating scale data. Unpaired Student’s t-test was used for comparison of hemodynamic data, end-tidal concentration of desflurane, and perioperative fentanyl consumption. A P-value of less than 0.05 was considered significant.
| Results|| |
A total of 80 patients enrolled in the study were comparable as regards age, sex, BMI, ASA physical status, and duration of surgery ([Table 1]).
There was no significant difference between the two study groups as regards the depth of anesthesia, which was assessed using response entropy (RE) and state entropy (SE), and was maintained between 40 and 60 during the period of surgery. In the perioperative period, the RE value was 98–100 and the SE value was 90–91, which indicated that patients were fully conscious. Values dropped by around 20–25% after dexmedetomidine loading in group II to be 55–80, indicating good sedating effect (sedated but can be awakened with verbal commands).
A significant decrease in desflurane requirements in group II was found in comparison with group I. End-tidal concentration of desflurane was significantly low at 15, 30, 45, and 60 min of operation ([Table 2]). End-tidal concentration of desflurane decreased by 13.2–21.8% with the use of dexmedetomidine in comparison with group I ([Table 2]).
|Table 2 Comparison of the end-tidal concentration of desflurane in the two study groups at different time intervals|
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As regards hemodynamic parameters, measures of HR, SBP, and DBP were comparable in the two study groups before starting dexmedetomidine loading dose (baseline). After loading dose of dexmedetomidine, HR decreased by 12.5%, SBP decreased by 12.9%, and DBP decreased by 14% in comparison with baseline values in group II. During operation, there was a significant difference between the two study groups at different time intervals. SBP, DBP, and HR were significantly decreased with the use of dexmedetomidine at different time intervals throughout the operation, in comparison with group I and in comparison with the baseline in group II ([Table 3] and [Table 4]). The use of dexmedetomidine in group II decreased the HR by 13.4–23.6% during the surgery in comparison with group I. HR was less by 10–22.3% inside group II in comparison with baseline. SBP decreased by 8.3–20% in group II in comparison with group I during operation and by 5.4–20.5% in group II in comparison with the baseline before dexmedetomidine loading dose. In the recovery room, the hemodynamic parameters were significantly lower in group II in comparison with group I at different time intervals ([Table 3] and [Table 4]).
|Table 3 Comparison of systolic blood pressure, and diastolic blood pressure at different time intervals between the two study groups|
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|Table 4 Comparison of heart rate at different time intervals between the two study groups|
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Perioperative fentanyl consumption was significantly low with the use of dexmedetomidine in comparison with group I. It was 325±55 μg in group II in comparison with 178±45 μg in group I ([Table 5]). There was no significant difference between the two study groups as regards the extubation time ([Table 5]).
|Table 5 Comparison of the verbal rating scale on postoperative acute care unit admission, and 1 h and 2 h later|
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Pain score was significantly higher in group I in comparison with group II on admission to the PACU, and at 1 and 2 h later ([Table 5])
| Discussion|| |
Laparoscopic sleeve gastrectomy has become a popular choice for patients seeking excellent weight loss in a straightforward procedure with fewer complications compared with gastric bypass operations and more effective compared with the gastric band operation .
The results of the present study showed that the use of dexmedetomidine during laparoscopic sleeve gastrectomy reduced desflurane requirements, which was detected by decreased end-tidal concentration of desflurane, maintaining patients at an adequate depth of anesthesia, monitored with entropy, due to the anesthesia-sparing effect of dexmedetomidine. The anesthesia-sparing effect of dexmedetomidine in our study was consistent with earlier studies. A study was conducted on patients undergoing laparoscopic bariatric surgeries including gastric banding and gastric bypass . The design of the previous study was different from ours, as different concentrations of dexmedetomidine were used. We preferred to use dexmedetomidine at a concentration of 0.5 μg/kg/h for infusion during surgery, as higher concentrations were associated with more significant hemodynamic disturbances. Moreover, in our study, fentanyl was used for induction and our target was to evaluate the reduction in fentanyl need. Several previous studies detected reduction in sevoflurane requirements with dexmedetomidine infusion. However, in nonbariatric surgeries ,,, desflurane in our study has a faster wash-in and wash-out in comparison with sevoflurane in morbidly obese patients due to its low blood–gas partition coefficient, which suggests a more rapid kinetic profile. For the previous reason, desflurane could be more suitable for morbidly obese patients . In fact, it is safe and effective in maintaining general anesthesia, and its use is followed by rapid recovery . In another study conducted in 2012, isoflurane was used and its end-tidal concentration was reduced with the use of dexmedetomidine during laparoscopic surgeries, but extubation time was not detected in comparison with our study . Moreover, isoflurane has fallen out of favor for use in morbidly obese patients as its high lipophilicity coupled with increased fat mass in morbidly obese patients suggests increased peripheral tissue uptake, which may affect the recovery time .
The profound reduction in desflurane requirements with dexmedetomidine infusion was shown to be mediated through its agonist effect on the central α2 adrenergic receptors, which is eight times higher than that of clonidine as regards the affinity to the receptors with anxiolytic, analgesic, and sedative effect . Moreover, the use of dexmedetomidine potentiates anesthetic effects of all intraoperative anesthetics regardless of the method of administration. A study was conducted in 2013 and detected the role of dexmedetomidine in the reduction of the mean induction and maintenance dose of propofol . Another work was conducted during laparoscopic gastric bypass and detected a 33% reduction in propofol requirements with the use of dexmedetomidine .
Dexmedetomidine has a sympatholytic and hemodynamic stability effect due to its highly selective α2 agonist action . Results of the present study demonstrated a significant reduction in blood pressure and HR with the use of dexmedetomidine, mostly due to attenuation of the stress response to various noxious stimuli. After administration of the test drug, a significant decrease in SBP by 12.9%, DBP by 14%, and HR by 12.5% was found. This is different from the work conducted in 2012 by Chirag et al. , which showed a reduction in hemodynamic parameters by 6–9% in comparison with the control group. This may be attributed to the difference in the category of patients in our study, as it was conducted on morbidly obese patients. Reduction in hemodynamic parameters during induction of anesthesia with the use of dexmedetomidine was related to attenuation of the stress response effect of intubation by decreasing the central sympatholytic outflow with reduction in serum epinephrine and norepinephrine levels. This is in agreement with several earlier studies ,. The results of Tanskane et al.  were different from the results of the present study, as they detected a significant increase in hemodynamic parameters after intubation, with no significant difference between the control and dexmedetomidine groups. However, this may be attributed to the use of dexmedetomidine in two concentrations of 0.2 and 0.4 μg/kg/h without loading dose.
The use of entropy to evaluate the depth of anesthesia in our study gave a reliable indicator about the requirements of the inhalational agent with accurate adjustment of desflurane to keep adequate depth of anesthesia. Because of the sympatholytic action of dexmedetomidine that decreases HR and BP, dependence on hemodynamic parameters to evaluate the depth of anesthesia would be unreliable. Entropy was used to assess the depth of anesthesia by increasing and decreasing the sevoflurane concentration in several previous studies ,. Entropy is based on processing a raw electroencephalogram and facial electromyogram signals by using entropy algorithm . Response entropy is sensitive to activation of facial muscles due to painful stimulus that can be interpreted as inadequate analgesia, whereas state entropy indicates depth of hypnosis . Display of RE range from 0 to 100 and that of SE from 0 to 91, and values of SE is always lower than or equal to RE. In the present study, the use of dexmedetomidine guided by entropy allowed us to detect a reduction in desflurane requirements and fentanyl consumption, which runs with several previous studies ,,.
The use of dexmedetomidine in group II in the present study was associated with a reduction in fentanyl consumption by 45.3% during the intraoperative period and during the first 2 h in the postoperative period, with lower pain scores in comparison with group I, which supported the results of previous works ,. There was no significant difference between the two study groups as regards the extubation time. This is in agreement with the work of Poonam et al. . Extubation time in the work of Bakhamees et al.  was 5.1±0.7 min with the use of dexmedetomidine, which is significantly different from that in our work (7.8±1.5 min). This may be attributed to the difference in the design of the study by Bakhamees, as they used propofol infusion instead of the inhalational anesthetic for maintenance of anesthesia.
In conclusion, the use of dexmedetomidine as preanesthetic medication and then as an infusion during laparoscopic sleeve gastrectomy at a dose of 1 μg/kg, intravenous, loading, followed by infusion at a dose of 0.5 μg/kg/h throughout the operation, reduces the desflurane consumption, maintains hemodynamic stability due to attenuation of stress response, and reduces fentanyl requirements during intraoperative and early postoperative period, by decreasing the risk for respiratory depression in the PACU for morbidly obese patients, who are at great risk for obstructive sleep apnea and oxygen desaturation.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]