
 hemodynamic monitoring and maintaining the heartbeat and blood pressure of patients undergoing spinal surgery is of prime importance .
it leads to better control of bleeding in the surgical field , particularly in congested , small and limited areas such as spine .
considering the nature of the spinal fusion surgery as a major surgery with a possibility of bleeding and the fact that this surgery is performed on the elderly or traumatic patients in many circumstances , the goal is to choose a drug with appropriate hemodynamic effects while providing good anesthetic depth and short recovery state . using a potent and short acting opioid such as
remifentanil has been used successfully as an analgesic - sedative drug in the recent years .
we chose remifentanil because it is an ultra - rapid opiod with safe and convenient tapering effects . on the other hand ,
another sedative - hypnotic - analgesic drug with an acceptable effect is dexmedetomidine ( dex ) .
dex has been known as a highly selective 2-adrenoreceptor agonist and has been used as a sedative agent in some operative and clinical situations ( 1 - 3 ) .
some investigators reported that dex could reduce the propofol requirement in remifentanil - based anesthesia for faster postoperative recovery and more stable intraoperative hemodynamics ( 4 , 5 ) .
however , the exact propofol sparing impact of dex during remifentanil - based anesthesia has not been well investigated . 
 

previous studies have found that dex had complex vasodilative and vasoconstrictive hemodynamic effects on pre and postsynaptic 2 -receptors .
the effect of dex in a lower dose was vasodilation and its vasoconstriction effects have been presented in higher doses .
reduction of blood pressure and heart rate decreased after long - term dex usage ( 6,7 ) . 
 

controlling hemodynamic state of patients who have spinal operation is very important , and maintaining their heart rate and blood pressure in normal or low- normal levels can reduce their bleeding loss . to increase anesthesia depth and minimize serious side effects ,
this study was designed to compare the effect of dex as an analgesic and sedative drug with remifentanil as an adjuvant drug in anesthesia regiment in spinal operation . 


 in the present randomized clinical trial with a parallel design , 60 patients in the age range of 15 - 65 years who were candidates for posterior spinal fusion operation were included .
this study was approved in the research ethical committee of iran university of medical sciences ; written informed consent was obtained from all the participants . the clinical trial was registered in the iranian clinical trial registry system as irct2012081410336n3 .
a pilot study of pain reported by patients after spinal fusion surgery revealed that the average vas score for pain was 3 with a standard deviation of 1.4 .
the sample - size calculation was based on a maximum allowable difference of 1 in vas scores .
inclusion of 30 patients in each group provided a power of 0.80 when alpha was set at 0.05 .
samples were gathered using random sampling method and sample size was calculated based on the following formula : 
 
 considering alpha= 0.05 , beta= 20% and the calculation power 80% ; the sample size was 60 patients .
eligibility criteria for the patients included in the trial were : patients with asa class i or ii , candidates for posterior spinal fusion surgery in maximum 3 levels , surgical time between 2 - 5 hours , participation agreement , and without cardiovascular , pulmonary , neurological , nephrology and coagulopathy abnormality in their history and physical examination .
all the operations were performed in rasool- akram hospital complex affiliated to iran university of medical sciences . 
 

patients were randomized using block randomization method and were equally divided into two trial groups with 30 patients .
the monitoring device was massimo ( saadat company , iran ) and we also used electrocardiography , pulsoxymetry , nibp and capnograph for these patients .
induction of anesthesia was performed for all the patients using fentanyl 3 microgram/ kilogram , midazolam 0.1 milligram / kilogram as premedication and was continued with 0.2 milligram / kilogram cis - atracurium and sodium thiopental 5 milligram / kilogram .
this study was double blinded and patients and their surgeons were both blind to the intervention and an unknown person of research team prepared encrypted codes separately . both groups received isoflurane 1% during the surgery as a maintenance regiment .
it has been observed that dex can decrease the heart rate and induce bradycardia in special doses ; propofol has this effect as well .
so we chose isoflurane which does not have this effect and was a suitable inhalation anesthetic agent for this study . 
 

as an intervention in one group , remifentanil ( ultiva , abbott , ca ) was injected firstly using infusion pump with a dose of 1 microgram / kilogram in 15 minutes and then injected with continuous infusion with a dose of 0.2 microgram / kilogram / min . in the other group , patients received dex ( precedex , hospira , usa ) firstly via infusion pump with a dose of 1 microgram / kilogram in 15 minutes continued followed by an infusion of 0.5 microgram / kilogram / hour .
dex was prepared as 4 microgram / milliliters in 0.9% sodium chloride infusion . for the postoperative pain control ,
an infusion pump containing 1000 micrograms of fentanyl was used in the first day followed by a rate of four milliliters per hour . 
 
 as trial outcomes
, heart rate and mean arterial blood pressure ( map ) was measured before and after induction and every 15 minutes during the surgery . in patients with bradycardia ( heart rate<40 bits / minute ) and map<50 mmhg ,
five milligrams of ephedrine was injected and recorded ; and in non - responded cases , patients were excluded from the trial . in patients with increased or decreased blood pressure , 10% increase or decrease in isoflurane dosage was used .
if blood pressure or heart rate were still elevated , fentanyl 50 microgram was used . in hypertensive patients who were non - responder to isoflourane or fentanyl ,
nitroglycerine infusion was used and they were then excluded from the study . at the end of the surgery ,
all the drugs were discontinued and patients were extubated and transferred to the recovery room . in order to provide a similar condition ,
50 microgram of fentanyl was injected for patients at the end of operation just after anesthetic drug cessation .
awakening time after anesthetic drugs cessation , time of discharge from recovery , surgeon satisfaction score from surgical field ( good , moderate , poor ) and bleeding loss were recorded .
pain score , sedation score and the need to analgesic therapy were recorded in first 30 , 60,120 and 360 minutes after entrance to the recovery room ; so patients were evaluated in the ward . in case of analgesic need ( vas>4 ) in the recovery and ward , 15 mg intravenous ketorolac
quantitative variables were presented as mean  standard deviation , and qualitative variables were presented as count and percentages .
independent sample t - test and chi - square were used for statistical analysis to compare numerical and categorical data , respectively between the two groups if they had a normal distribution .
repeated - measures analysis of variance ( anova ) was used to review the results at different time points .

 in the present randomized clinical trial with a parallel design , 60 patients in the age range of 15 - 65 years who were candidates for posterior spinal fusion operation were included .
this study was approved in the research ethical committee of iran university of medical sciences ; written informed consent was obtained from all the participants . the clinical trial was registered in the iranian clinical trial registry system as irct2012081410336n3 .
a pilot study of pain reported by patients after spinal fusion surgery revealed that the average vas score for pain was 3 with a standard deviation of 1.4 .
the sample - size calculation was based on a maximum allowable difference of 1 in vas scores .
inclusion of 30 patients in each group provided a power of 0.80 when alpha was set at 0.05 .
samples were gathered using random sampling method and sample size was calculated based on the following formula : 
 
 considering alpha= 0.05 , beta= 20% and the calculation power 80% ; the sample size was 60 patients .
eligibility criteria for the patients included in the trial were : patients with asa class i or ii , candidates for posterior spinal fusion surgery in maximum 3 levels , surgical time between 2 - 5 hours , participation agreement , and without cardiovascular , pulmonary , neurological , nephrology and coagulopathy abnormality in their history and physical examination .
all the operations were performed in rasool- akram hospital complex affiliated to iran university of medical sciences . 
 

patients were randomized using block randomization method and were equally divided into two trial groups with 30 patients .
the monitoring device was massimo ( saadat company , iran ) and we also used electrocardiography , pulsoxymetry , nibp and capnograph for these patients .
induction of anesthesia was performed for all the patients using fentanyl 3 microgram/ kilogram , midazolam 0.1 milligram / kilogram as premedication and was continued with 0.2 milligram / kilogram cis - atracurium and sodium thiopental 5 milligram / kilogram .
this study was double blinded and patients and their surgeons were both blind to the intervention and an unknown person of research team prepared encrypted codes separately . both groups received isoflurane 1% during the surgery as a maintenance regiment .
it has been observed that dex can decrease the heart rate and induce bradycardia in special doses ; propofol has this effect as well .
so we chose isoflurane which does not have this effect and was a suitable inhalation anesthetic agent for this study . 
 

as an intervention in one group , remifentanil ( ultiva , abbott , ca ) was injected firstly using infusion pump with a dose of 1 microgram / kilogram in 15 minutes and then injected with continuous infusion with a dose of 0.2 microgram / kilogram / min . in the other group , patients received dex ( precedex , hospira , usa ) firstly via infusion pump with a dose of 1 microgram / kilogram in 15 minutes continued followed by an infusion of 0.5 microgram / kilogram / hour .
dex was prepared as 4 microgram / milliliters in 0.9% sodium chloride infusion . for the postoperative pain control ,
an infusion pump containing 1000 micrograms of fentanyl was used in the first day followed by a rate of four milliliters per hour . 
 
 as trial outcomes
, heart rate and mean arterial blood pressure ( map ) was measured before and after induction and every 15 minutes during the surgery . in patients with bradycardia ( heart rate<40 bits / minute ) and map<50 mmhg ,
five milligrams of ephedrine was injected and recorded ; and in non - responded cases , patients were excluded from the trial . in patients with increased or decreased blood pressure , 10% increase or decrease in isoflurane dosage was used .
if blood pressure or heart rate were still elevated , fentanyl 50 microgram was used . in hypertensive patients who were non - responder to isoflourane or fentanyl ,
nitroglycerine infusion was used and they were then excluded from the study . at the end of the surgery ,
all the drugs were discontinued and patients were extubated and transferred to the recovery room . in order to provide a similar condition ,
50 microgram of fentanyl was injected for patients at the end of operation just after anesthetic drug cessation .
awakening time after anesthetic drugs cessation , time of discharge from recovery , surgeon satisfaction score from surgical field ( good , moderate , poor ) and bleeding loss were recorded .
pain score , sedation score and the need to analgesic therapy were recorded in first 30 , 60,120 and 360 minutes after entrance to the recovery room ; so patients were evaluated in the ward . in case of analgesic need ( vas>4 ) in the recovery and ward , 15 mg intravenous ketorolac
quantitative variables were presented as mean  standard deviation , and qualitative variables were presented as count and percentages .
independent sample t - test and chi - square were used for statistical analysis to compare numerical and categorical data , respectively between the two groups if they had a normal distribution .
repeated - measures analysis of variance ( anova ) was used to review the results at different time points .

 in this study , baseline variables such as age , gender , body mass index , having diabetes mellitus and hypertension were significantly different between the two trial groups .
female / male ratio in the remifentanil group was 9/21 , and it was 12/18 ( p=0.401 ) in the dex group . 
 

four patients in the remifentanil group , and 2 patients in the dex group had diabetes ( p= 0.890 ) , and 5 patients had hypertension ( p<0.001 ) .
the mean of blood pressure ( p = 0.005 ) and heart rate ( p<0.001 ) had significant changes in patients who received remifentanil and dex as study intervention compared to the baseline time . in the study patients ,
dex had a significant lowering impact on intraoperative blood pressure and heart rate compared to remifentanil ( p<0.01 ) . 
 
time series of mean arterial pressure ( map ) and pulse rate ( pr ) among study participants 
 the mean of sedation scores after extubation in patients who received dex was significantly higher than sedation scores in patients who received remifentanil ( p<0.01 ) . 
 

awakening time in patients of the remifentanil group was significantly lower than patients of dex group ( 3.1115.75 vs. 4.8932.93 ; p<0.001 ) .
there was a significant difference between the two groups in term of need to fentanyl at 105 minutes during the operation ( p= 0.010 ) .
in other measured times during operation , the need to fentanyl injection had no significant difference between the patients of the two groups .
in the first 30 and 60 minutes of entrance to the recovery room , the need to analgesic therapy in the remifentanil group was significantly higher than the dex group ( p<0.05 ) ; but there were no significant differences between the two groups in the other measured times in recovery .
discharge time in patients of the remifentanil group was significantly lower than the patients in the dex group ( 3.3933.25 vs. 5.3648.54 ; p<0.001 ) .
the mean of post - extubation pain score of patients in the remifentanil group was significantly higher than the patients in the dex group ( 0.42.1 vs. 0.31.8 ; p=0.03 ) .
the mean pain scores one and two hours after entering the recovery ward in was significantly higher in the remifentanil group comparing the dex group ( p<0.001 ) .
six hours after extubation , the mean pain score was not significantly different between the two groups ( 0.42.9 vs. 0.82.7 ; p=0.2 ) . surgeons were more satisfied with the observed outcomes in patients of the dex group compared to the patients of the remifentanil group ( 100% vs. 78.6% ; p=0.01 ) .

 although in this present study the mean blood pressure ( bp ) and heart rate ( hr ) revealed significant difference in both drugs , dex had a significant lowering impact on intra - operative bp and hr compared to remifentanil .
sedation after extubation was significantly higher in patients who received dex compared to patients who received remifentanil .
in addition , in the dex group lower need to analgesic was observed in some intra - operative times and more specifically in postoperative period .
some previous studies found relatively similar trial findings and reported that dex can make 30 - 50% reduction in the propofol requirement in concomitant use of dex in adolescent patients and healthy volunteers ( 1 , 2 ) .
it seems that the sedative impact of dex in patients is mediated by locus ceruleus in the brain stem . in this region
laryngoscope insertion and endotracheal intubation can induce the sympathetic nervous system and cause severe tachycardia , hypertension or arrhythmia ( 10 ) .
dex is a very effective alpha-2 agonist and has more impact on stabilizing cardiovascular system after intubation and reduces the need to analgesic and sedative drugs preoperatively ( 11 ) .
some investigators such as segal et al . reported a decrease in requirement for halothane , and aho et al .
reported a decrease in a requirement for isoflurane up to 90% ( 12 , 13 ) .
moreover , in one study , the dosage of thiopental sodium was significantly decreased after using dex in anesthesia ( 14 ) .
dex can decline the serum level of catecholamine and norepinephrine against some of the stressful stimuli such as intubation ( 15 ) . 
 

some other studies reported that dex have complex of vasodilation and vasoconstriction impacts , by activating pre - synaptic 2-receptors on sympathetic and post - synaptic 2 -receptors of the central nervous system medicates vasodilation , and by effects on post - synaptic 2 -receptors on vascular smooth muscle cells can mediate vasoconstriction impacts ( 16 - 18 ) .
some previous studies reported a biphasic and dose - dependent impact for dex on the blood pressure and heart rate of patients ( 17 , 18 ) . on the other hand ,
dex increases bp in the short - term usage and decreases bp in patients in the long time usage .
dex in low dosage ( plasma concentrations , 0.7 - 1.2 ng / ml ) causes reduction in the release of norepinephrine release and an inhibition of sympathetic neurotransmission by activating 2a receptors ( 6 , 8 , 19 ) .
the high dosage of dex ( i.e. , plasma concentrations , > 1.9 ng / ml ) produces 2b receptor - mediated vasoconstriction ( 6 , 8) .
most previous studies confirmed cardiovascular depressive effects of dex and reported an increase in the incidence of hypotension and bradycardia ( 7 , 14 , 19 ) .
the propofol - sparing effect of dex may be beneficial for the reduction of the propofol dosage and may avoid the adverse effects such as myocardial depression , metabolic acidosis , impaired platelet aggregation and extended recovery caused by prolonged and large - dose administration of propofol ( 20 - 24 ) . 
 

this study had some limitations that should be considered for the future studies in this filed .
firstly , our study was performed in one hospital and with patients with one type of operation .
secondly , some of the disease characters in spinal regions might have effects on their hemodynamic changes .
for the future studies , it is recommended to match the study variables and randomly select the participants while excluding patients with previous history of hemodynamic changes . 


 dexmedetomidine in patients with spinal operation is associated with lower postoperative pain score and intraoperative bleeding ; hemodynamic effects are also significantly better in the dex group . 


 the authors would like to thank the neurosurgery operation room staff for their cooperation . 

 
 background : controlling the hemodynamic situation of patients who have spinal operation is of 
 prime importance , and maintaining the heart rate and blood pressure in normal or low- normal levels 
 in these patients can reduce their bleeding loss . 
 one of the commonly used drugs for this purpose is 
 remifentanil . 
 another sedative - hypnotic - analgesic drug , with acceptable effects is dexmedetomidine . 
 
 the aim of this study was to compare the effect of dexmedetomidine with remifentanil in spinal operation . 

 
 methods : in a double blind randomized clinical trial , using random sampling method , 60 patients 
 with the age range of 15 - 65 years who were candidates for posterior spinal fusion operation were 
 included . 
 induction of anesthesia was performed , and both groups received isoflurane 1% during the 
 surgery . 
 remifentanil was injected via infusion pump in one group . 
 the patients in the trial group 
 received dexmedetomidine . 
 as trial outcomes , heart rate and blood pressure were measured before , 
 after induction and during the operation . 
 pain score , sedation score and the need to analgesic therapy 
 were recorded in the recovery room and the ward . 
 independent sample t - test and chi - square were 
 used for statistical analysis . 

 
 results : dexmedetomidine had a significant lowering impact on intraoperative blood pressure and 
 heart rate compared to remifentanil ( p<0.001 ) . 
 the mean of sedation scores after extubation in patients 
 who received dexmedetomidine was significantly higher than the sedation scores in patients 
 who received remifentanil ( p<0.001 ) . 
 the mean of post - extubation and recovery pain score in patients 
 taking remifentanil was significantly higher than patients taking dexmedetomidine ( p<0.05 ) . 

 
 conclusion : dexmedetomidine in patients with spinal operation is associated with lower postoperative 
 pain score and intraoperative bleeding . 
 hemodynamic effects are significantly better in patients 
 received dexmedetomidine . 
 