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Year : 2016  |  Volume : 10  |  Issue : 3  |  Page : 649-654  

Effect of dexmedetomidine bolus dose on isoflurane consumption in surgical patients under general anesthesia

Department of Anesthesiology, M.S. Ramaiah Medical College, Bengaluru, Karnataka, India

Date of Web Publication27-Sep-2016

Correspondence Address:
Geetha C Rajappa
Department of Anesthesiology, M.S. Ramaiah Medical College, MSRIT Post, Bengaluru - 560 054, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0259-1162.191122

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Background and Objective: Various adjuvants have been introduced to decrease the dose of volatile agents and their side effects. Dexmedetomidine a potent alpha-2 adrenoreceptor agonist is one such agent. Our objective is to assess the effect of preanesthetic dexmedetomidine on isoflurane consumption and its effect on intraoperative hemodynamic stability and recovery profile.
Setting and Design: This prospective, randomized controlled, double-blind study was done in a tertiary care hospital.
Materials and Methods: One hundred patients were randomly allocated into two groups. Group 1 received saline infusion and Group 2 received dexmedetomidine infusion in a dose of 1 μg/kg over 10 min given 15 min before induction. Vital parameters and bispectral index (BIS) values were noted throughout the surgery. Patients were induced and intubated as per the standard protocol and maintained with N2O: O2 = 1:1 mixture at 2 L/min and isoflurane concentration adjusted to achieve BIS values of 45–60. Demographic profile, hemodynamic variables, total isoflurane consumption, and recovery profile data were collected.
Statistics: Independent t-test and Mann–Whitney U-test were used to compare the average anesthetic consumption, hemodynamics, and recovery profile between two groups.
Results: End-tidal concentration and total isoflurane consumption in Group 2 were 0.56 ± 0.11 and 10.69 ± 3.01 mL, respectively, with P< 0.001 which was statistically significant compared to Group 1 which were 0.76 ± 0.14 and 13.76 ± 3.84 mL. Postintubation and intraoperative mean arterial pressure values were significantly lower in dexmedetomidine group with P< 0.001.
Conclusion: Preanesthetic bolus dose of dexmedetomidine is a useful adjuvant to reduce isoflurane consumption.

Keywords: Bispectral index, dexmedetomidine, general anesthesia, isoflurane

How to cite this article:
Muniyappa RB, Rajappa GC, Govindswamy S, Thamanna PP. Effect of dexmedetomidine bolus dose on isoflurane consumption in surgical patients under general anesthesia. Anesth Essays Res 2016;10:649-54

How to cite this URL:
Muniyappa RB, Rajappa GC, Govindswamy S, Thamanna PP. Effect of dexmedetomidine bolus dose on isoflurane consumption in surgical patients under general anesthesia. Anesth Essays Res [serial online] 2016 [cited 2023 Jan 31];10:649-54. Available from:

   Introduction Top

Volatile anesthetics have been used since decades for the maintenance of general anesthesia. Various adjuvants have been introduced to reduce the dose of inhalational agents and also produce better sedation, hypnosis, and analgesia.[1] Agents such as benzodiazepines and opioids have already proven such effects.[1],[2],[3] Alpha-2 adrenergic agonists produce sedation, anxiolysis, and analgesia and have been reported to reduce the anesthetic requirement and produce intraoperative hemodynamic stability.[4],[5]

Dexmedetomidine is a potent alpha-2 adrenoreceptor agonist and decreases the use of volatile anesthetics with better hemodynamic stability in surgical patients.[6],[7] Dexmedetomidine administration before the induction of anesthesia caused decreased sevoflurane requirement during gynecological surgeries.[6] We hypothesized that similar results would be seen with isoflurane requirement; hence, this prospective, randomized, double-blind study was designed with the primary objective to assess the effect of preanesthetic dexmedetomidine on isoflurane requirement and also to assess its effect on hemodynamic stability and recovery profile.

   Materials and Methods Top

After obtaining the Institutional Ethics Committee clearance, the study was conducted over a period of 2 years from August 2013 to July 2015. Written informed consent was obtained from all patients. Patients aged between 20 and 60 years belonging to the American Society of Anesthesiologist (ASA) Grade 1 and 2 having surgery under general anesthesia were included in the study. Patients allergic to study drug, undergoing laparoscopic surgeries, with the history of psychiatric illness, alcohol abusers, altered mentation, epilepsy, with body mass index (BMI) >35 kg/m 2, on beta blockers, sedative or stimulant drugs, with uncontrolled hypertension, and diabetes mellitus were excluded from the study.

This prospective, randomized, double-blind, comparative two group study was done on one hundred patients. Patients satisfying the inclusion criteria were selected during the study period from the operation register on a daily basis and after obtaining a written informed consent, they were allocated into two groups of fifty each by computer generated randomization technique. All the patients were premedicated with oral pantoprazole 40 mg the previous night and on the morning of surgery; oral ondansetron 0.15 mg/kg was given on the morning of surgery.

The patient monitoring included electrocardiogram, noninvasive blood pressure (NIBP), heart rate (HR), oxygen saturation (SPO2), and bispectral index (BIS). The baseline HR, NIBP, SpO2, and BIS scores were recorded. Infusion pump containing dexmedetomidine 100 µg in saline 25 mL (4 µg/mL) or saline 25 mL was setup.

A computer-based randomization was done and sealed in an envelope. An anesthesiologist not involved in the management of the case opened a sealed envelope and setup either infusion dose of dexmedetomidine by diluting dexmedetomidine 100 µg/mL using saline in a 25 mL unlabeled syringe to obtain a concentration of 4 µg/mL or saline in 25 mL syringe based on the drug in the envelope.

  • Group 1 (normal saline): Received 25 mL of saline at 0.25 mL/kg over 10 min, 15 min before induction
  • Group 2 (dexmedetomidine): Received dexmedetomidine in a dose of 1 µg/kg over 10 min, 15 min before induction.

An anesthesiologist in the theater blinded to the test drug conducted the intraoperative anesthetic management and monitoring. Vitals were recorded during the infusion at 5th and 10th min after the infusion of the study drug, and BIS values were also noted. Patients were preoxygenated for 3 min with 100% oxygen at 8 L/min. All patients received propofol 2 mg/kg and fentanyl 1 µg/kg followed by atracurium 0.5 mg/kg to facilitate tracheal intubation. Anesthesia was maintained with isoflurane 1% until tracheal intubation. After 3 min, intubation was performed using appropriate size endotracheal tube; correct placement was confirmed by end-tidal carbon dioxide (ETCO2) and auscultation. In addition to the preinduction monitors, postinduction ETCO2 concentration, fraction of inspired and end-tidal isoflurane concentrations, fraction inspired and end-tidal nitrous oxide, fraction of inspired oxygen, and train of four (TOF) monitoring were also done. All patients were mechanically ventilated with fresh gas flow of 2 L/min (N2O: O2 = 1:1), FiO2-50% with minute volume adjusted to maintain ETCO2 between 30 and 35 mmHg using circle system and CO2 absorber. Parameters were recorded after intubation, then every 5 min interval for half an hour and subsequently every 15 min till the end of surgery and at extubation.

Isoflurane concentration was increased or decreased step by step by 0.2% to reach the predetermined values of BIS 45–60. Atracurium 0.1 mg/kg was given when TOF stimulus showed two twitches. Body temperature was maintained at 35.5–36.5°C.

If there was increase in HR and blood pressure more than 20% baseline, fentanyl 1 µg/kg was given. If fall in blood pressure more than 20% baseline, ephedrine intravenous (i.v.) 3–6 mg was given and if HR decreased <40 bpm, atropine 0.6 mg IV injection was given. In both the groups, additional intraoperative analgesic was provided in the form of paracetamol 20 mg/kg IV injection. After skin closure, all anesthetics were discontinued and patients were ventilated with 6 L/min oxygen. Neuromuscular blockade was reversed with neostigmine 50 µg/kg and glycopyrrolate 10 µg/kg. Extubation was done once the patients fulfilled subjective and objective criteria for extubation. The time duration from the discontinuation of isoflurane to extubation was noted.

Total isoflurane consumption was calculated using Dion's formula [8],[9] = PFTM/2412 × d.

Where P- Dialed vaporizer concentration; F - Fresh gas flow- 2 L/min; T - Duration of the anesthesia; M - Molecular weight of Isoflurane-184.5 g; d - Density of Isoflurane - 1.496 g/mL.

Recovery profile was assessed using modified Aldrete score (MAS), postoperative pain by Visual analogue scale (VAS), and postoperative nausea and vomiting (PONV) was monitored in the recovery room.

Statistical analysis

Descriptive statistics of anesthesia consumption, hemodynamics, sedation, and recovery profile were analyzed and presented in terms of mean with standard deviation. Independent t-test and Mann–Whitney U-test were used to compare the average consumption of the drug, duration of surgery, and demographic data between two groups. Repeated measures of ANOVA were used to compare the hemodynamic parameters between groups and within the group considering different time points. McNemar's test was used to compare pain score and sedation score at 0 and 30th min postoperatively. Chi-square test was used to compare the difference in proportion between categorical data like gender. SPSS Version 17.0. Chicago, 2008: SPSS Inc. was used for statistical analysis. P < 0.05 was considered as statistically significant.

   Results Top

Demographic profile in both the groups was similar with respect to age, gender, ASA grade, weight, height, and BMI distribution [Table 1]. Surgical procedures done were comparable in both the groups with no statistical difference. Duration of surgery was 126.79 ± 26.72 min in Group 1 and 136.79 ± 6.5 min in Group 2; it was similar between the groups with P = 0.40.
Table 1: Demographic data

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Hemodynamic data

HR [Graph 1]: No much variation was noted at different time intervals throughout the surgery among the groups, but Group 2 showed lower HR values than Group 1. After extubation, HR increased in both groups; rise was higher in the saline group, but it was not statistically significant. None of the patients from either group had bradycardia requiring atropine.

Mean arterial pressure (MAP) [Graph 2]: There was a rise in mean arterial blood pressure following intubation in both groups with a lesser increase in dexmedetomidine group with P < 0.001 which was statistically significant. Intraoperatively, MAP was lower in dexmedetomidine group compared to control group with P < 0.001 which was statistically significant. Similar changes in MAP were noted in both the groups during induction and after extubation which was not statistically significant. Ephedrine boluses were given to ten patients in Group 2 out of which seven patients received single bolus dose and three patients received two bolus doses. In Group 1, two patients received a single bolus dose of ephedrine with P = 0.014 suggesting statistical significance.

Rescue fentanyl: 32 patients in Group 1 and 11 patients in Group 2 required supplemental fentanyl for analgesia, P < 0.001 suggests that values are statistically significant. In Group 1, three patients required supplemental fentanyl doses twice and in Group 2, two patients required doses twice.

Isoflurane consumption [Table 2]: The values of fraction of inspired, dialed concentration, end-tidal isoflurane concentration, and total isoflurane consumption were statistically significant between the groups with P < 0.001.
Table 2: Isoflurane concentration - inspired, end-tidal, dialed concentration

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Consumption of isoflurane per hour: Using Dion's formula, results were extrapolated to obtain isoflurane consumption per hour. In Group 1, consumption per hour was 6.61 ± 1.20 mL and in Group 2, it was 4.84 ± 1.08 mL with P < 0.001 which was statistically significant.

Time to extubation: The time taken for extubation was 7.67 ± 2.62 and 6.20 ± 2.76 min, respectively, in Group 1 and 2 with P < 0.001 which was statistically significant.

PONV: Postoperatively, 11 patients in Group 1 and ten patients in Group 2 complained of nausea, P = 0.806 which was not statistically significant. None of the patients in either group had vomiting.

Recovery score - MAS: The immediate postoperative period MAS scores were better in Group 2 than Group 1 with 74% patients having MAS score of ≥9 in Group 2 as compared to 68% patients of MAS score ≥9 in Group 1. Patients were discharged from postoperative recovery room once they reached MAS score of ≥9. P =0.23 suggests that recovery profiles were similar between the groups.

Pain scores by visual analog scale (VAS): 18 patients in Group 1 and 12 patients in Group 2 had VAS of >4. Fentanyl 1 µg/kg was given for analgesia. P = 0.57 suggests that pain scores postoperatively was statistically insignificant.

   Discussion Top

In this study, the hypothesis that preanesthetic single loading dose of dexmedetomidine reduces the dose of inhalational anesthetics was evaluated. There are studies [6],[7],[8] which have shown the role of dexmedetomidine both loading and maintenance dose, reducing the dose of inhalational anesthetics. Our study used only loading dose of dexmedetomidine and dialed concentration of isoflurane was adjusted to achieve BIS of 45–60.

Dexmedetomidine is a more selective alpha-2-agonist, has a shorter duration of action than clonidine,[10] and produces hypnosis similar to normal sleep, without respiratory depression, making it a near ideal sedative.[11],[12] It suppresses nociceptive neurotransmission, terminating propagation of pain signals leading to analgesia. Its sympatholytic effect causes hypotension and bradycardia; effect judiciously used to attenuate the stress response of surgery. Other useful effects include decreased salivation, increased glomerular filtration rate, reduced intraocular pressure, and reduced shivering threshold.[13]

Attenuation of sympathoadrenal effects due to tracheal intubation has been reported in earlier studies.[14],[15],[16] Our study showed that dexmedetomidine group had partial blunting of response to intubation with statistically significant lower MAP values but not significant lower mean HR values.

Patel et al.[17] reported statistically significant lower values of HR, systolic, and diastolic pressure throughout the intraoperative period. During the maintenance of anesthesia, we observed significant lower MAP values requiring treatment in ten patients, and lower HR values which were statistically insignificant. This is probably due to the combined effect of vasodilatation and myocardial depression with volatile agents.

Shin et al.[6] have seen that patients undergoing gynecological surgeries have the end-tidal concentration and total sevoflurane consumption which were significantly lower in dexmedetomidine group than in control group. Ozcengiz et al.[18] noted in children undergoing minor surgeries that end-tidal sevoflurane concentration was significantly higher in control group at before incision, after incision, and at the end of the surgery than in dexmedetomidine group. Ohtani et al.[19] studied patients undergoing lower abdominal surgeries and noted that dexmedetomidine reduced the anesthetic requirements to maintain BIS of 45 by 20–30%, reducing sevoflurane from 1.1 ± 0.2% to 0.8 ± 0.2% and propofol from 4.4 ± 0.8 mg/kg/h to 3.1 ± 1 mg/kg/h. Our study showed that the use of dexmedetomidine and intraoperative BIS-guided isoflurane alteration led to decrease in the fraction of inspired concentration and end-tidal concentration. Thus, dexmedetomidine causes a decrease in maintenance inhalational consumption, especially when BIS monitoring is also being used.

Keniya et al.[16] demonstrated that the intraoperative requirement of fentanyl in dexmedetomidine decreased from 100 ± 10 to 60 ± 10 µg. Our study revealed that dexmedetomidine has an analgesia sparing action. The likely explanation is that the continued analgesic and sedative effects of dexmedetomidine during the perioperative period making it possible for patients in dexmedetomidine group to reach target BIS value at a lower end-tidal isoflurane concentration.

Studies have observed better postoperative analgesia in the recovery room.[20],[21] Patel et al.[17] in their study observed that postoperatively dexmedetomidine group showed a significant sedation at 2 h compared to control group. Our study showed that there were no differences noted in postoperative recovery profile and pain scores. Patients from both the groups had MAS scores of >9 and ready for discharge by half an hour following surgery. Similar findings were also noted in the study conducted by Shin et al.[6] The possible explanation can be due to 2 h elimination half-life of dexmedetomidine.[11]

One limitation of our study was the inclusion of varied surgical procedures. Hence, the requirement of inhalational agents and analgesics would differ depending on the invasiveness of the procedure.

Our study has demonstrated that a single preanesthetic i.v. dose of dexmedetomidine 1 µg/kg reduced the total isoflurane consumption from 6.61 ± 1.2 to 4.84 ± 1.08 mL with P < 0.001 which was statistically significant proving dexmedetomidine to be a useful adjuvant. More number of patients in Group 1 required supplemental analgesia suggesting analgesia sparing action of dexmedetomidine. However, there was a higher incidence of hypotension noted in dexmedetomidine group which could be easily treated. Dexmedetomidine group showed earlier emergence; however, recovery profile and pain scores postoperatively were similar between the two groups.

   Conclusion Top

We conclude that single preanesthetic 1 µg/kg dexmedetomidine loading dose with the BIS monitoring is a good anesthetic adjuvant for general anesthesia which reduces intraoperative isoflurane consumption, provides analgesic-sparing effect without affecting postoperative recovery profile.

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Conflicts of interest

There are no conflicts of interest.

   References Top

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  [Table 1], [Table 2]

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