laparoscopic cholecystectomy is one of the most commonly practiced surgeries for gall bladder diseases in the present era . due to its well - known advantages like less post - operative pain , shorter hospitalization and faster functional recovery , laparoscopic cholecystectomy is also termed as patient friendly surgery . however , like any other surgery , laparoscopic cholecystectomy is also associated with stress response induced by surgery and anaesthesia . moreover , the pneumoperitoneum and carbon dioxide insufflations , required in laparoscopic surgeries , lead to increase in plasma nor - epinephrine , epinephrine levels and plasma renin activity . all these changes lead to increase in heart rate , blood pressure , systemic and pulmonary vascular resistance , and reduced cardiac output . the reverse trendelenburg position required for surgery leads to diminished venous return and thereby , further reduction in cardiac output . the haemodynamic changes predispose the myocardium to ischemia that may be life threatening in a vulnerable patient . modern anaesthesia practices , therefore , plan to prevent sympathetic discharge and provide haemodynamic stability perioperatively . various agents in the form of opioid analgesics , benzodiazepines , beta blockers , calcium channel blockers and vasodilators have been used to achieve this objective with variable success . in last few years , a great enthusiasm has been shown toward the use of 2 agonists in anaesthesia practice because of their anxiolytic , sedative , sympatholytic and analgesic sparing properties . dexmedetomidine , introduced in 1999 for human use , is a selective 2 agonist with 8 times more affinity for 2 adrenergic receptors compared to clonidine and possesses all the properties of 2 agonist without respiratory depression . intravenous use of dexmedetomidine in the perioperative period had been found to decrease serum catecholamine levels by 90% , to blunt the haemodynamic response to laryngoscopy , tracheal intubation , pneumoperitoneum and extubation , to provide sedation without respiratory depression and to decrease post - operative analgesic requirements . the primary aim of this study was therefore , to evaluate the effects of low dose dexmedetomidine infusion on haemodynamic response to critical incidences like laryngoscopy , endotracheal intubation , creation of pneumoperitoneum and extubation in patients undergoing laparoscopic cholecystectomy . the secondary aims were to observe the effects on extubation time , sedation levels , post - operative analgesia requirements , and occurrence of adverse effects . the present study was carried out from august 2010 to july 2012 , after taking the permission and approval from the departmental ethical committee and the written informed consent from the patients . sixty asa physical grades i and ii patients between 18 and 65 years , of either sex and posted for laparoscopic cholecystectomy under general anaesthesia were included in the study . patients with decreased autonomic control such as the elderly , diabetic patients , patients with chronic hypertension or severe cardiac disease , patients on drugs like  blockers or calcium channel blockers , pregnant or lactating women , patients with history of allergy to egg proteins and drugs particularly 2 agonists were not considered for the study . the patients were randomly allocated by envelope method into three groups of 20 patients each , group ns ( patients receiving normal saline 0.9% infusion ) , group dex 0.2 ( patients receiving dexmeditomidine infusion 0.2 mcg / kg / h ) and group dex 0.4 ( patients receiving dexmedetomidine infusion 0.4 mcg / kg / h ) . infusion was prepared according to the group allotted in a separate o.t . to prepare the infusion , dexmedetomidine 0.5 ml containing 50 g of the drug syringe and was diluted up to 12.5 ml with normal saline resulting in the final concentration of 4 mcg / ml . depending on the weight of the patient , the pump was set so as to deliver the targeted infusion rate . after the setting the infusion pump , it was covered with blue cloth so that the assessor did not come to know about the grouping of the patient . thus , the syringe was same , volume of prepared solution was same , only the rate of injection was different according to the weight and group of patient . decoding of blinding to the assessor was done only at the time of tabulation and result analysis . after taking the patient on the operation table , a multipara monitor was attached and the baseline pulse rate ( pr ) , mean arterial pressure ( map ) and oxygen saturation were noted down . a wide bore intravenous cannula was inserted for giving the intravenous fluids , and another line was taken up for the infusion pump . premedication was administered 45 min before induction of anaesthesia to all the patients in the form of injection glycopyrrolate 5 mcg / kg i m and injection tramadol 1.0 mg / kg i m as per the institutional protocol . at the time of induction , all the patients received injection ranitidine 50 mg iv and injection ondansetron 4 mg iv . fifteen minutes after starting the drug infusion , pre - oxygenation was performed for 3 min . patients were induced with injection propofol 2 mg / kg intravenously followed by injection succinyl choline 1.5 mg / kg intravenously . anaesthesia was maintained with o2:n2o ( 50:50 ) , isoflurane and injection vecuronium bromide as a muscle relaxant on fabius plus work station . intra - abdominal pressure was maintained between 12 and 14 mmhg throughout the laparoscopic procedure . the patients were mechanically ventilated using circle system to keep the etco2 between 35 and 45 mm hg . all the patients were observed for vital parameters like pr , map and spo2 at regular intervals including before starting the infusion , 15 min after starting the infusion , after induction , after intubation , after creation and release of pneumoperitoneum and after extubation . patients were also observed for time to extubate trachea , post - operative sedation level , time to first rescue analgesic requirement ( time from completion of injection of drug to the time post- operatively , when pain reported by patient was  4 on visual analogue scale [ vas ] , total amount of analgesic drug required during the first 24 h post - operatively and the adverse effects . injection diclofenac sodium 1.5 mg / kg i m was used as rescue analgesic and thereafter whenever the vas score became 4 . extubation time was counted from stoppage of anaesthetic agent to time , when the extubation was done . sedation was assessed at 1 , 15 , 30 , 60 to 120 min post - operatively using ramsay sedation score ( rss ) . throughout the study , patients were observed for any adverse effects like bradycardia , tachycardia ( pr less than or more than 20% of pre - operative level respectively on two consecutive readings ) , hypo and hypertension ( map less than or more than 20% of pre - operative level respectively on two consecutive readings ) , sedation score more than rss 4 , respiratory depression ( sao2 < 90% ) and dryness of mouth and they were managed conventionally . ( medcalc software bvba , acacialaan 22 , 8400 ostend , belgium ) based on minimum mean difference of 25% in parameters with  = 0.01 and  = 0.20 , sample size for each group was estimated as 18 . rounding up this figure the results were tabulated and statistically analysed using spss ( statistical package for social sciences ) software version 15.0 , chi - square test was used for qualitative data ( sex , asa grade ) , pr , blood pressure , oxygen saturation , end tidal carbon dioxide etc . , were compared within the group against baseline values using paired t - test . anova test was used for three group comparisons of continuous variables ; if anova was found significant , tuckey post - hoc test was used for comparing two groups and the results were expressed as mean  standard deviation . p > 0.05 was considered insignificant , < 0.05 as significant and highly significant if < 0.001 . all the three groups under study were comparable to each other with respect to age , sex , weight , asa grading , duration of surgery and anaesthesia [ table 1 ] . there was no significant difference among the three groups in reference to the baseline pr and the map . demographic characteristics and duration of surgery and anaesthesia in group ns , after starting the infusion there was no significant change in pr and map but these increased highly significantly above pre - infusion level after intubation and extubation ( p < 0.01 ) and significantly after pneumoperitoneum [ p < 0.05 , tables 2 and 3 ] . changes in pr ( beats per minute ) ( meansd ) changes in map ( mm of hg ) ( meansd ) in both the dexmedetomidine groups , after starting the infusion , the pr decreased highly significantly below the pre - infusion level . the map decreased significantly in dex 0.2 group and highly significantly in dex 0.4 group . after intubation and extubation , the pr and map increased significantly above the pre - infusion level in dex 0.2 group , though , this increase was less compared to increase in group ns ( p < 0.05 ) . unlike these changes in dex 0.2 group , pr and map in dex 0.4 group remained below pre - infusion level after intubation and extubation ( p < 0.05 when compared with dex 0.02 ) . the mean sedation scores [ table 4 ] were more in dexmedetomidine groups compared to normal saline group patients . none of the patients in dexmedetomidine groups developed siginificant sedation levels and the patients were cooperative , oriented and tranquil all the time . in group ns sedation score , which was less initially , improved subsequently due to early requirement of analgesia in this group . changes in mean sedation score there was no significant difference among the three groups with reference to extubation time ( 7.15  1.20 , 6.55  1.27 and 6.40  1.04 min in group ns , dex 0.2 and dex 0.4 group respectively . the rescue analgesia was required early ( 55.5 min . ) in group ns compared to dexmedetomidine groups ( 173 min in dex 0.2 and 249 min in dex 0.4 group ) . all the patients in group ns , 15 patients in group dex 0.2 and 10 patients in group dex 0.4 group required rescue analgesia . total analgesic requirement of first 24 h post - operative period also decreased by 36.11% in group dex 0.2 and by 63.88% in group dex 0.4 [ table 5 ] . post - operative analgesic requirements tachycardia and hypertension were seen in 7 and 6 patients of group ns compared to 1 and 2 patients of group dex 0.2 . hypotension was noted in 1 patient of group dex 0.2 and bradycardia was seen in 1 patient of dex 0.4 group . it acts through three types of 2 receptors-2 a , 2 b and 2 c situated in brain and spinal cord . the resultant action is sedation , anxiolysis , analgesia and sympatholysis , the latter leading to hypotension and bradycardia . activation of 2 a receptors in brain stem vasomotor centre results in suppression of norepinephrine release , hypotension and bradycardia . stimulation of 2 a and 2 c in locus ceruleus causes sedation . in the spinal cord , activation of both 2 a and 2 c receptors directly reduce pain transmission by reducing release of substance p. looking at these pharmacological properties , it has been evaluated in the past to assess its effect on haemodynamic responses in patients undergoing laparoscopic surgeries . infusion rates varying from 0.1 to 10 mcg / kg / h have been studied . however , with higher dose infusion of dexmedetomidine , high incidence of adverse cardiac effects have been observed . stimulation of 2 b receptors in vascular smooth muscles is said to be responsible for this . low dose infusion of 0.250.5 mcg / kg / h results in a monophasic response of 1015% fall in mean arterial blood pressure and pr . furthermore , in low dose , dexmedetomidine exhibits linear kinetics , meaning that a constant amount of drug is eliminated per hour rather than a constant fraction of drug . hence , in a pilot study , we used low dose infusions of dexmedetomidine without any bolus . initially , we used dexmedetomidine 0.2 mcg / kg / h infusion . though it controlled the rise in pr and map at pneumoperitoneum , the control was not very effective at the time of tracheal intubation and extubation , and the pr and map both increased above pre - infusion levels . hence , we increased the dose to 0.4 mcg / kg / h infusion in our next two patients . we also studied few cases with dex 0.6 mcg / kg / h dose but the hypotension was seen in greater number of patients , and the sedation was more ( rss 45 ) . hence , we decided to have three groups in our study , which were group ns , group dex 0.2 and group dex 0.4 . our study confirms the fact that critical incidences like laryngoscopy and intubation , pneumoperitoneum and extubation do significantly increase the map and pr in patients undergoing laparoscopic cholecystectomy as seen in group ns . the effective attenuation dose with minimum side effects noted in our study was 0.4 mcg / kg / h infusion . apart from providing stress response attenuation , the added effects of dexmedetomidine are sedation and analgesia . sedation produced by 2 agonists is unique in the sense that the patients can be easily aroused to co - operate during procedures and also respond to the verbal commands and then can return to sleep like state when not stimulated . we observed patients for 120 min as elimination half - life of dexmedetomidine is 2 h. initially , the sedation score was more in group dex 0.4 compared to group ns or group dex 0.2 . over a period of time mean sedation score settled around 2 in group dex 0.2 and group dex 0.4 , while in group ns , score improved from 1 to 2 because of early administration of analgesia 3040 min post - operatively . it may be hypothesised that due to its sedative effect , response to verbal command and extubation time may be delayed with dexmedetomidine . however , in our study the mean extubation time did not show any significant difference between three groups . bhattacharjee et al . also observed no significant effect of dexmedetomidine on response to verbal command and extubation time . dexmedetomidine has been found to reduce the intra and post - operative requirement of opioids . we also observed an increase in the time to receive first rescue analgesia and a decrease in total analgesic requirements in first 24 h post - operatively in both dexmedetomidine groups . low dose infusion of dexmedetomidine at the rate of 0.4 mcg / kg / h without any bolus dose serves as a very useful anaesthesia adjuvant to control haemodynamic stress response to intubation , pneumoperitoneum and extubation in patients undergoing laparoscopic cholecystectomy . it also provides lighter sedation and reduces the post - operative analgesic requirements without any significant adverse effects .