sedation is often required in young children in order to obtain good diagnostic cross - sectional imaging like computed tomography scan ( ct scan ) and magnetic resonance imaging ( mri ) .
sometimes sedation is also needed for older children with complex neurodevelopmental disorders , such as autism and attention deficit hyperactivity disorder .
moderate sedation is unable to guarantee patient compliance ; therefore , a deeper level of sedation is required [ 1 , 2 ] .
the success of sedation for mri has typically been measured by two factors : the safety of sedation procedure ( lack of adverse events ) and its effectiveness ( completion of diagnostic examination ) .
it can be challenging to obtain the deep sedation level required to prevent the patient 's movement while maintaining respiratory and hemodynamic stability .
therefore , it is very important to select the appropriate drugs and dosage to achieve those objectives .
dexmedetomidine is a highly selective adrenoceptor agonist with a distribution half - life of six minutes and an elimination half - life of two hours .
five prospective trials have evaluated the efficacy of dexmedetomidine for sedation during noninvasive radiologic imaging [ 812 ] .
dexmedetomidine can be associated with side effects of hypotension , bradycardia , and transient hypertension with loading dose .
dexmedetomidine has been used at our institution since 2006 for mri and other noninvasive radiologic procedures .
the purpose of this retrospective study is to present our institutional experience with dexmedetomidine in relation to efficacy and related side effects .
collection of quality assurance data includes patient demographics , adverse events , physiologic variables , drug dosages , the time required to sedate the patient , time needed to obtain the imaging study , and recovery time .
after approval by the institutional review board , we conducted a retrospective analysis of all patients who received sedation for mri from july 2007 to december 2012 .
institutional sedation policies are based on guidelines by the joint commission on accreditation of health care organization and american academy of pediatrics and were closely followed [ 13 , 14 ] .
vital signs including pulse oximetry , heart rate , noninvasive blood pressure monitoring , and nasal capnography ( with concomitant oxygen delivery via the nasal cannula ) are continuously monitored and documented every five minutes throughout sedation . at the start of sedation
, intravenous dexmedetomidine was bolused at 2  g / kg over 10 minutes followed by a continuous infusion of 1  g / kg / h . most of the patients were sedated by the end of the bolus ; if not , a second bolus of 2  g / kg was repeated over another 10 minutes prior to the start of the maintenance infusion .
patients who continue to move after the second bolus or while the procedure is in progress , can compromise the quality of imaging and were given additional medications like midazolam or fentanyl as per physician discretion .
mg / kg to a max of 2  mg and for fentanyl was 0.5  mcg / kg1  mcg / kg to a max of 50  mcg .
the goal was to achieve a minimum ramsay sedation score ( rss ) of 4 as assessed by a sedation nurse .
rss is a clinically derived sedation score generally accepted as a tool for assessing the depth of sedation .
usually , a score of 4 - 5 is targeted to ensure appropriate sedation for diagnostic imaging studies [ 11 , 16 ] .
peak onset of the sedation was defined as the time from the start of the loading dose to achievement of a ramsay score of 4 .
procedure time was the time of achieving the required ramsay score to the end of the procedure ( stoppage of drug administration ) .
discharge time was defined as time from the end of the procedure to actual time when the patient was discharged home .
normal ranges for heart rates , blood pressure , and respiratory rates for data analysis were based on the published normal of fleming et al . [ 17 , 18 ] .
a trained registered nurse provided continuous assessment and monitoring while the procedure was in progress under the direct supervision of a pediatric intensivist .
monitoring was continued until the patient was awake with a minimum aldrete score of 9 points , and the patient has tolerated clear liquids prior to discharge [ 19 , 20 ] . all the parents were provided with written discharge instructions and a direct phone number for further assistance or to report any adverse effects .
database records were analyzed using dedicated statistical software sas v9.3 ( sas institute , cary , nc ) .
changes in the vital signs associated with the use of dexmedetomidine from the baseline were evaluated and compared using student 's t - test and mann - whitney rank - sum test , depending on the distribution of the data .
the entire study cohort was divided into three groups depending on dexmedetomidine bolus and additional medications received .
dexmedetomidine group a received one bolus ; dexmedetomidine group b received two boluses ; dexmedetomidine group c received one or two boluses and additional medications .
three groups were compared with respect to age , weight , blood pressure , heart rate , procedure time , and discharge time using analysis of variance .
incidences of bradycardia and hypotension were analyzed with fisher 's exact test , due to low cell counts .
discharge time of bradycardia and hypotensive patients was compared with normal cohorts using the t - test .
the most common indications included seizure disorder , developmental delay and behavioral disorder , autism , and neoplasia .
382 ( 70.2% ) of the total patients received one - time bolus , while two boluses were given to 162 patients ( 29.8% ) . in the population of 544 patients , additional medications ( fentanyl or midazolam )
were required in 117 ( 21.5% ) for spontaneous movements to avoid motion artifacts that can compromise mri quality ( 54 patients with one - time bolus and 43 patients with two boluses ) .
dexmedetomidine - induced vital sign changes from baseline for the whole group are shown in figure 1 .
hypotension ( systolic blood pressure 20% below the normal limits ) was observed in 100 patients ( 18.4% ) and transient hypertension ( systolic blood pressure > 20% above age - specific high limits ) was observed in 137 of the patients ( 25.2% ) .
there were 210 ( 38.6% ) patients who had a significant decrease in respiratory rate , that is , > 20% from the baseline , but no desaturation , upper airway obstruction , or apnea events were observed and the decrease was minimal in 403 patients ( 74% ) .
most of the patients received prophylactic supplemental oxygen to maintain oxygen saturation > 95% as per protocol , which makes it impossible to determine the actual incidence of desaturation at room air .
patients were divided into three groups based on numbers of dexmedetomidine boluses and additional medications received .
comparisons of blood pressure , heart rate , and other clinical measures between these groups of patients are shown in table 2 .
procedure time was significantly shorter in dexmedetomidine group a ( 40.31  19.40  min , p < 0.0001 ) compared to the other two groups .
oxygen , dose , maximum dbp , maximum respiration rate , and initial spo2 had statistically significant ( but clinically insignificant ) differences between groups .
the occurrence of hypotension among all three groups did not reach a statistically significant value ( p = 0.82 ) .
decrease in blood pressure from the baseline was frequently observed ; however , medical intervention was not needed to correct it .
the incidence of hypotension was usually noticed to be towards the completion of procedure or after stopping the infusion , with a mean procedure time of 48.73  25.46 minutes .
initial transient hypertension occurred in 137 patients approximately 20 minutes after the dexmedetomidine bolus and lasted for < 15 minutes . in the population of 544 patients , 165 children ( 30.9% ) had heart rates below the age - specific normal awake range during sedation ( based on the published normal of fleming et al . ) . only in 21 children ( 3.9% of total cohort ) did the lowest recorded heart rate fall > 20% below the given baseline average range .
bradycardia ( hr < 60/min ) , as defined according to pediatric advance life support ( pals ) guidelines , was observed in 10 children ( 4.5% ) mostly in the age range of 13 years ( figure 2 ) .
all the patients with bradycardia were continuously monitored and assessed by the supervising intensivist for normal blood pressure and oxygen saturation of 95% or above . no patient required treatment .
the incidence of bradycardia was high in patients in the age range of 13 years compared with the rest of the cohort .
the precise etiology of the bradycardia observed in this analysis can not be delineated as electrocardiogram monitoring is known to be significantly distorted by the magnetohydrodynamic ( mhd ) effect and is nondiagnostic within the bore of any mri magnet .
time to discharge when dexmedetomidine was used alone was 92  25 versus 94  37  min when additional medications were used ( p = 0.46 ) .
average discharge time among 165 children with bradycardia was longer and statistically significant compared to the other 372 children in the study population without bradycardia ( 99.08  32.57  min versus 89.74  25.54  min , p = 0.0012 , student 's t - test ) .
gender was not associated with any change in discharge time ( p = 0.30 ) ( table 3 ) .
the ideal drug would allow optimal imaging , while maintaining hemodynamic and respiratory stability . as reported in previous studies ,
this occurred more frequently in hyperactive , uncooperative , and older children [ 4 , 22 ] .
dexmedetomidine , a selective alpha 2 adrenoceptor agonist , has a very safe therapeutic window with respect to respiratory depression .
this quality offers a distinct advantage in procedural sedations , where the patient is not immediately accessible to the medical team .
there are various studies demonstrating that dexmedetomidine is a good option for procedural sedation [ 10 , 12 ] .
interestingly , the dose used varies greatly indicating an open debate regarding the best dosage .
previous studies indicate that infusion of relatively low dose dexmedetomidine 0.10.7  /kg / h provides effective sedation [ 2327 ] . in a study conducted on eight healthy volunteers receiving dexmedetomidine infusion of 0.20.6  /kg / h , the visual analog sedation scores and bispectral index scores dropped by 3060% . however , this level of sedation will likely not be conducive to pediatric mri sedation , where higher doses of dexmedetomidine will be needed to accomplish the necessary sedation level .
while dosing started low in initial reports , a recent one found that higher doses are required and have been well tolerated .
a comparison of pentobarbital and chloral hydrate was performed by rooks et al . in 498 children for mri sedation .
several clinical trials have compared dexmedetomidine to propofol for pediatric procedural sedation . in a trial of 60 children undergoing mri ,
onset , recovery , and discharge time were all significantly shorter in the propofol group .
adverse effects such as lower blood pressure and heart rate and respiratory rate were also found more in the propofol group .
dexmedetomidine safety and efficacy for sedation during noninvasive radiologic procedures have been evaluated in four prospective trials [ 1 , 810 ] .
all of these studies reported that the use of high dose dexmedetomidine as a sole sedative resulted in high quality radiologic imaging with less use of additional rescue medicines .
our study also demonstrated that the use of high dose dexmedetomidine as sole agent is effective for mri sedation .
we used fentanyl and midazolam as rescue medicines in 117 ( 21.5% ) of our patients to avoid imaging artifacts , suggesting that these agents make a significant contribution to the sedation strategy for a sizeable minority of patients . in our study , the heart rate decreased significantly from baseline during sedation .
this is an expected effect of anxiolysis and reflects higher baseline heart rate values from anxiety .
other studies reported a decrease in heart rate < 20% from the baseline that was considered to be clinically insignificant in 86 ( 26% ) patients .
to have a true comparison with previously published data , we use the same definition of bradycardia ; that is , the lowest recorded heart rate during sedation fell > 20% below the given baseline average range . using that definition ,
the incidence of bradycardia in our study was 3.9% ( 21 children ) in total cohort comparable to 4% as reported by mason et al .
more importantly , during those periods of bradycardia , all patients maintained normal blood pressure and normal oxygen saturation ( 95% or higher ) .
treating bradycardia in normotensive children with glycopyrrolate has been reported to be associated with hypertensive episode , which could be beneficial to children who are hypotensive and bradycardic at the same time .
similar to our findings , previous investigators have also reported the occurrence of transient hypertension with bolus administration of dexmedetomidine . in our study ,
the occurrence of hypotension associated with high doses of dexmedetomidine was about 18% , observed immediately after stopping the infusion or towards the end of the procedure .
none of the children needed any intervention , consistent with observation reported in other studies [ 12 , 31 ] .
respiratory events make up a large proportion ( 5.5% ) of sedation complications in children . in some studies
, rapid administration of large loading doses has been described to cause respiratory complications [ 3234 ] .
a loading dose of dexmedetomidine given over 2 minutes has been reported to cause irregular respiration , apnea , slight hypoxemia , and hypercapnia .
however , similar to ours , several other studies have reported trivial effect of dexmedetomidine on respiration [ 12 , 34 , 36 ] which is consistent with the notion that the risk of respiratory depression is minimal with careful dexmedetomidine sedation . despite these supporting lines of evidence , monitoring of respiratory function during the administration of dexmedetomidine in those receiving midazolam or fentanyl , which may depress respiratory function , appears warranted .
our reported discharge time of 92 minutes with dexmedetomidine only and 94 minutes when additional medicines were used is comparable to the 90 minutes ' discharge time of heard et al . .
observed a recovery time of 47 minutes   and mason et al .   reported recovery times ranging from 24.8 minutes to 35.2 minutes , depending on the dose of dexmedetomidine used .
in some studies , recovery time is the time lapsed until the patient meets the discharge criteria , while in our study , like few others , discharged time is defined as the actual time of leaving the recovery room to go home .
discharge time of children experiencing bradycardia was longer than that for those who did not .
in our study , 165 children with bradycardia had a mean discharge time which was statistically significant and longer than the other 372 children in the study without bradycardia ( 99.08 minutes versus 89.74 minutes ; p = 0.0012 ) .
this probably could be due to the prolonged monitoring of these patients until the bradycardia resolved .
recovery time previously reported after sedation with propofol for mri has been 17  8 minutes , almost half of the recovery time when dexmedetomidine was used as a sole agent . in a second trial
, forty children between the ages of 1 and 10 years were randomized to receive either a combination of midazolam + dexmedetomidine or propofol only for sedation during mri .
the fast recovery times of propofol must be weighed against the fact that it induced deeper sedation with significant hypotension and oxygen desaturation . taking the results of these comparison trials as a whole
, dexmedetomidine appears to provide a useful alternative to propofol for procedural sedation in children , with a longer time of recovery but a lower incidence of adverse effects .
this is a good alternative to propofol for patients with soy and egg white allergy and also in institutions where use of propofol is strictly limited to be used by anesthesiologists .
it could be asserted that the reported efficacy is due to the use of an intensivist based specialized sedation team rather than to dexmedetomidine itself .
this is reasonably true to some extent as specialization and experience should increase both success and efficiency . in spite of that , this can be stated with confidence ; much of the reported success is specifically a function of dexmedetomidine .
this is a descriptive study and few , if any , conclusions can be drawn about safety because the occurrence of serious sedation related side effects is fortunately rare .
additional prospective studies of the sedation for mri in children using a greater number of patients are warranted to provide a true idea of safety . in summary ,
high dose dexmedetomidine is an attractive and effective medication in children for mri sedation . when using high dose dexmedetomidine as the only agent for pediatric mri , it is not unusual to observe heart rate and blood pressure outside the established 
awake  normal values . in our experience , these changes were pretty benign and were not associated with any adverse event .
we conclude and recommend that , from hemodynamics and respiratory perspective , higher dose dexmedetomidine was well tolerated and is effective to use for successful completion of mri , in the majority of pediatric patients .
 
 objective . to determine the efficacy and safety of high dose dexmedetomidine as a sole sedative agent for mri . 
 we report our institution 's experience . design . a retrospective institutional review of dexmedetomidine usage for pediatric mri over 5.5 years . 
 protocol included a dexmedetomidine bolus of 2  g / kg intravenously over ten minutes followed by 1  g / kg / hr infusion . 
 544 patients received high dose dexmedetomidine for mri . 
 a second bolus was used in 103 ( 18.9% ) patients . 
 117 ( 21.5% ) required additional medications . 
 efficacy , side effects , and use of additional medicines to complete the mri were reviewed . 
 data was analyzed using student 's t - test , fisher 's exact test , and analysis of variance ( anova ) . 
 main results . 
 dexmedetomidine infusion was associated with bradycardia ( 3.9% ) and hypotension ( 18.4% ) . 
 none of the patients required any intervention . 
 vital signs were not significantly different among the subgroup of patients receiving one or two boluses of dexmedetomidine or additional medications . 
 procedure time was significantly shorter in the group receiving only one dexmedetomidine bolus and increased with second bolus or additional medications ( p < 0.0001 ) . 
 discharge time was longer for children experiencing bradycardia ( p = 0.0012 ) . 
 conclusion . 
 high dose dexmedetomidine was effective in 78.5% of cases ; 21.5% of patients required additional medications . 
 side effects occurred in approximately 25% of cases , resolving spontaneously . 
1. Introduction
2. Materials and Methods
3. Results
4. Discussion