alpha ( )2-adrenoceptor agonists have been used as adjuvant to anesthetic agents in peri - operative period for its 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 .
dexmedetomidine , the pharmacologically active d - isomer of medetomidine , is highly selective and specific 2-adrenoceptor agonist .
the analgesic effect of dexmedetomidine is qualitatively different as compared to opioids and can be used as an alternative to opioids in general anesthesia .
the anesthetic sparing effect of dexmedetomidine demonstrated in earlier studies is confounded by the use of opioids .
opioids , when used as analgesic in general anesthesia , are known to decrease mac value of sevoflurane .
inhalation agents were titrated based on either hemodynamic criteria and/or bispectral index values in studies done earlier , and none of them demonstrated the effect of dexmedetomidine alone on requirement of sevoflurane with the use of entropy as a measure of depth of anesthesia .
the primary objective of our study was to evaluate the effect of continuous infusion of dexmedetomidine alone , without use of opioids , on sevoflurane requirement during general anesthesia with continuous monitoring of depth of anesthesia by entropy analysis .
the study protocol was approved by ethical committee of the institute , and written informed consent was obtained from all patients included in the study .
the study population comprised of 60 patients , aged 18 - 55 years , with american society of anesthesiologists ( asa ) status of 1 and 2 , undergoing major elective surgical procedures .
we excluded patients older than 55 years , those with a history of psychiatric / neurological illness , cardiovascular disease , hypertensive patients , morbid obese patients , pregnant and nursing women , with known allergic reaction to any of the study medication , recent use of sedatives or analgesics , and with significant laboratory abnormalities .
the consenting patients were randomly allocated into one of the two anesthetic groups based on the simple randomization table generated : group a ( control group ) : sevoflurane - fentanyl and group b ( test group ) : sevoflurane - dexmedetomidine .
after arrival in the operating room , glycopyrrolate 0.004 mg / kg and ondansetron 0.15 mg / kg intravenous ( iv ) were given as pre - medication in both the groups .
the patients in group b received dexmedetomidine(2 ml diluted in 48 ml of saline ) iv in a dose of 1 mcg / kg over10 minutes through infusion pump prior to induction .
monitoring consisted of continuous electrokardiogram ( ekg ) , non - invasive blood pressure ( nibp ) , pulse oximetry ( spo2 ) , co2 expired fraction ( etco2 ) , sevoflurane inspired fraction ( fisevo ) , sevoflurane expired fraction ( etsevo ) , and electroencephalograph ( eeg ) analysis by entropy ( response and state entropy ) . after the start of drug infusion , heart rate ( hr ) , blood pressure
( bp ) , respiratory rate ( rr ) , spo2 , and entropy were measured at 5 and 10 minute .
patients in group a received fentanyl 2 g / kg intravenous slowly , 2 minutes prior to induction .
after pre - oxygenation for 10 minutes , general anesthesia was induced with thiopentone sodium 5 mg / kg iv slowly .
, dexmedetomidine infusion was continued between 0.2 and 0.8 mcg / kg / h depending on hr , bp , and entropy value changes .
anesthesia was maintained with sevoflurane to a maximum of 2.5% end tidal to maintain heart rate and blood pressure within 20% of baseline value and entropy value between 40 and 60 .
the anesthesiologist was permitted to treat hemodynamic events , defined as heart rate and blood pressure more than 20% of baseline , in spite of increasing sevoflurane concentration to 2.5% and dexmedetomidine infusion to 0.8 mg / kg with supplemental analgesia in the form of fentanyl 1 mcg / kg . if rise in heart rate and blood pressure persisted further after supplementation with fentanyl , anesthesiologist was permitted to administer incremental doses of metoprolol 2 - 5 mg .
ephedrine 5 mg iv was given for fall in heart rate and blood pressure more than 20% of baseline .
in the group b , dexmedetomidine was stopped approximately 15 - 20 minutes before completion of surgery , diclofenac sodium aqueous 1 mg / kg was given iv in both groups at the time of skin closure .
reversal of neuromuscular blockade was achieved with neostigmine 0.05 mg / kg and glycopyrrolate 0.008 mg / kg iv slowly .
tracheal extubation was done when respiration was satisfactory and adequate muscle tone was achieved . 

hr and bp were recorded before induction , at the time of induction , intubation , and then at 5 , 10 , 15 , 30 , 45 , and 60 minute after intubation and at extubation.depth of anesthesia was evaluated by entropy ( state entropy , response entropy ) analysis ( datex - ohmeda s/5 avance workstation , ge healthcare , helsinki , finland ) at 5 , 10 , 15 , 30 , 45 , and 60 minute after intubation and at extubation.end tidal concentration of sevoflurane was assessed with anesthesia gas assessment module e - caiovx at same interval as entropy analysis . 
 
hr and bp were recorded before induction , at the time of induction , intubation , and then at 5 , 10 , 15 , 30 , 45 , and 60 minute after intubation and at extubation .
depth of anesthesia was evaluated by entropy ( state entropy , response entropy ) analysis ( datex - ohmeda s/5 avance workstation , ge healthcare , helsinki , finland ) at 5 , 10 , 15 , 30 , 45 , and 60 minute after intubation and at extubation .
end tidal concentration of sevoflurane was assessed with anesthesia gas assessment module e - caiovx at same interval as entropy analysis .
statistical analysis was conducted with epi info software ( version 3.5.3 , 2011 , centers for disease control and prevention , atlanta , ga , usa ) for windows statistical package using unpaired t - test for continuous variables with normal distribution .
the non - parametric kruskal - wallis test was used for variables not normally distributed . for categorical variables , chi - square test was used .
the two groups were similar regarding age , sex , weight , and asa physical status [ table 1 ] .
pre - induction heart rate , systolic and diastolic blood pressures were similar between two groups ( p > 0.05 ) .
the depth of anesthesia as assessed by response entropy ( re ) and state entropy ( se ) was comparable between two groups at all time points during maintenance period ( p > 0.05 ) .
the re and se was maintained between 40 and 60 during the period of observation .
the fisevo concentration was significantly less in group b as compared to the group a at all time points ( p < 0.05 ) [ figure 1 ] .
the average etsevo concentration during anesthetic maintenance was 1.35% and 1.72% in the group b and a , respectively .
a significant decrease of 13% to 33% of etsevo concentration was seen with group b from 5 min to 60 minutes post - intubation ( p < 0.05 ) during surgery [ figure 2 ] .
fraction of inspired sevoflurane at different time interval ( pi - post - intubation , fi - fraction of inspired ) end tidal sevoflurane at different time intervals ( pi - post - intubation ) during anesthesia maintenance , group b showed a statistical significant decrease in heart rate , systolic and diastolic blood pressure from baseline at all time points as compared to the group a ( p < 0.05 ) .
an average 6.5% fall in heart rate from baseline in group b as compared to 3.7% rise in the group a , 8% fall in systolic blood pressure from baseline as compared to 3.6% rise in the group a , and 8.16% fall in diastolic blood pressure from baseline as compared to 3.3% rise in the group a was observed [ figures 3 and 4 ] .
changes in sbp and dbp at various time points post - intubation ( pi - post - intubation , sbp - systolic blood pressure , dbp - diastolic blood pressure ) changes in hr at various time points post - intubation ( pi - post intubation , hr - heart rate ) in our study , none of the patients in either group required supplemental analgesia or anti - hypertensive drugs intra - operatively .
bradycardia was observed in 2 patients in group b within 10 mins post - extubation , which promptly responded to atropine 0.6 mg iv .
the major observation in our study was that dexmedetomidine infusion as an adjuvant in general anesthesia causes decreased requirement of sevoflurane without compromising adequate depth of anesthesia , thus it has anesthetic - sparing property .
a study done on patients undergoing hysterectomy showed a 30% reduction of maintenance concentration of isoflurane .
similarly , a reduction in 35% to 50% in isoflurane concentration with low or high dose of dexmedetomidine was found in a study on healthy human volunteers .
this larger reduction in isoflurane requirement seen as compared to our study might be due to difference in study population ( healthy human volunteers vs. patients posted for elective surgery ) and the type of stimulus ( tetanus nerve stimulus vs. surgical stimulus ) .
the results of our study results are consistent with that of the study done by fragen , et al . in elderly patients , which showed a 17% reduction .
dexmedetomidine by its sympatholytic action decreases heart rate and blood pressure , thus assessing the depth of anesthesia by hemodynamic parameters would be unreliable in evaluating its effect on requirement of inhalational agent . several electroencephalogram - dependent indices such as bispectral index and entropy have been used to measure the depth of anesthesia .
entropy is a useful monitor for measuring the electroencephalographic effects of increasing and decreasing sevoflurane concentration and assessing the depth of anesthesia .
analogous to the bispectral index , entropy displays a high degree of specificity and sensitivity in assessing consciousness during anesthesia . using bispectral index to assess the depth of anesthesia , magalhes et al
. showed decreased requirement of sevoflurane with continuous infusion of dexmedetomidine during general anesthesia . in our study , we used entropy to measure the depth of anesthesia , thereby eliminating the bias of evaluation by hemodynamic parameters as in earlier studies .
use of dexmedetomidine produces intra - operative and post - operative opioids - sparing effect .
dexmedetomidine by its sympatholytic action attenuates symapthoadrenal response to tracheal intubation . in patients undergoing laparoscopic tubal ligation , a 33% decrease in morphine
use post - operatively was observed when dexmedetomidine was used at a dose of 0.4 mcg / kg .
dexmedetomidine when administered as infusion at a dose of 0.5 mcg / kg / h has specific analgesic effect and provides visceral pain relief . in morbidly obese ,
dexmedetomidine produces a greater decrease in sympathovagal balance intra - operatively than fentanyl along with better post - operative analgesia .
dexmedetomidine , when used as sole substitute for remifentanil in ambulatory gynecologic laparoscopic surgery , provides better peri - operative hemodynamic stability and post - operative analgesia .
dexmedetomidine provides similar intra - operative hemodynamic response and better post - operative analgesia compared to remifentanil in patients undergoing supratentorial craniotomy .
use of opioids along with dexmedetomidine would confound its effect on requirement of inhalation agent .
hence , in our study , fentanyl was not administered in dexmedetomidine group b , and we found a 21.5% decrease in the etsevo , in contrast to 33.12% decrease in study done by magalhes e et al . where fentanyl was used .
one limitation of our study was that we included both laparoscopic as well as open surgeries .
to conclude , the continuous infusion of dexmedetomidine , as adjuvant in general anesthesia , significantly decreases the requirement of sevoflurane for maintaining adequate depth of anesthesia .
studies measuring plasma concentration of dexmedetomidine should be undertaken to establish the precise correlation between its dose and inhalational agent 's requirements .
 background : dexmedetomidine , a 2 agonist as an adjuvant in general anesthesia , has anesthetic and analgesic - sparing property.aims:to evaluate the effect of continuous infusion of dexmedetomidine alone , without use of opioids , on requirement of sevoflurane during general anesthesia with continuous monitoring of depth of anesthesia by entropy analysis.materials and methods : sixty patients were randomly divided into 2 groups of 30 each . in group 
 a , fentanyl 2 mcg / kg was given while in group b , dexmedetomidine was given intravenously as loading dose of 1 mcg / kg over 10 min prior to induction . 
 after induction with thiopentone in group b , dexmedetomidine was given as infusion at a dose of 0.2 - 0.8 mcg / kg . 
 sevoflurane was used as inhalation agent in both groups . 
 hemodynamic variables , sevoflurane inspired fraction ( fisevo ) , sevoflurane expired fraction ( etsevo ) , and entropy ( response entropy and state entropy ) were continuously recorded . 
 statistical analysis was done by unpaired student 's t - test and chi - square test for continuous and categorical variables , respectively . 
 a p - value < 0.05 was considered significant.results:the use of dexmedetomidine with sevoflurane was associated with a statistical significant decrease in etsevo at 5 minutes post - intubation ( 1.49  0.11 ) and 60 minutes post - intubation ( 1.11 0.28 ) as compared to the group a [ 1.73 0.30 ( 5 minutes ) ; 1.68 0.50 ( 60 minutes ) ] . 
 there was an average 21.5% decrease in etsevo in group b as compared to group a.conclusions:dexmedetomidine , as an adjuvant in general anesthesia , decreases requirement of sevoflurane for maintaining adequate depth of anesthesia . 
Introduction
Materials and Methods
Results
Discussion