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fractures have a high incidence rate in traffic accidents and are one of the three most important complications during accidents ( 1 ) .
each year millions of people all over the world suffer from bone fractures , the complications of which threaten the patients health for several years ( 2 , 3 ) .
one of the most important measures in the management of such patients in the emergency unit is fixation and pain control .
opioids are one of the main and most effective medications to relieve pain ( 4 , 5 ) by suppression of pain center in the cns through stimulation of  and  receptors .
however , complications such as dependence , tolerance , suppression of respiratory center and activation of vomiting center are some of their problems ( 6 ) .
nonetheless , this group of medications has gastrointestinal complications and even some of them exhibit renal and hepatic toxicity ( 7 ) .
paracetamol , aminophylline , tramadol , nefopam etc are some other drugs that have been evaluated in different studies for pain relief .
it is one of the medications , which is used for general anesthesia and sedation .
ketamine is an antagonist of n - methyl - d - aspartate ( nmda ) ( 8 , 9 ) and is used in iv , intramuscular , enteric , subcutaneous , intra - nasal , rectal and epidural forms .
however , at higher doses it can have complications such as hallucination , dysphoria , nightmares , an increase in intracranial pressure , hypertension , tachycardia , tremors and clonic - tonic seizures ( 10 , 11 ) .
several studies have shown that ketamine is effective in pain relief ; however , in the majority of studies available , ketamine has been used in conjunction with other analgesics and no study is available in which use of this medication alone has been comprehensively evaluated for pain relief . on the other hand , studies available have not evaluated the use of this medication in trauma patients in emergency units .
therefore , the present study was designed to evaluate the effect of ketamine alone on pain relief in trauma patients referring to an emergency unit of a third - level hospital .

 study design and setting 
  the present double - blind clinical trial was carried out in 2012 - 2013 in al - zahra and ayatollah kashani educa - tional centers in isfahan , iran .
the subjects consisted of patients with fractures of long bones , referring to the emergency unit .
the protocol of the study was ap - proved by the ethics committee of isfahan university of medical sciences .
the study was registered in iranian registry of clinical trial ( irct number : irct2015042812072n3 ) .  
the inclusion criteria consisted of an age range of 18 - 55 years , fractures of long bones and consent to participate in the study .
exclusion criteria consisted of drug abuse , trauma to the head , symptoms and signs of increased intracranial pressure , a decrease in consciousness level , respiratory problems , a history of asthma , contraindications for ketamine ( i.e. a history of cardiac problems , especially congestive heart failure , ischemic cardiac conditions , hypertension and patients with cerebrovascular attack ) and morphine ( i.e. asthma , respiratory problems , hemodynamic instability ) .
in addition , in case of any allergic reaction to any of the medications used , the patient was excluded from the study .
the sample size was estimated at 63 subjects in each group based on numeric rating scale ( nrs ) at 95% confidence interval , a study power of 80% , a standard deviation of 1.6 for pain severity and a minimum difference significance of 2 between the two groups ( 12 ) .  
first the patients demographic and clinical data were recorded , which consisted of background diseases , drugs taken , drug abuse , drug allergies , the last meal eaten , location of fracture and severity of pain .
then the eligible patients were randomly divided into two groups : the group receiving iv morphine at a dose of 0.1 mg / kg and the group receiving iv ketamine at a dose of 0.5 mg / kg . to make sure of the double - blind protocol of the study ,
preparation of the solutions , injections and registration of the results were carried out by three different physicians who had no contact or relationship with each other .
the data on the injection of medications were available only to the chief researcher and the medical care personnel were granted access to such data only when drug complications arose . in such a case ,
the severity of pain was registered before injection and 10 minutes after injection based on nrs ( 13 ) . in cases
in which pain did not subside after 10 minutes ( a decrease in pain severity equal to or less than 3 ) , the patient received half the initial dose again .
demographic variables ( % ) of patients 
 statistical analysis 
  data were entered into spss 11.5 and were analyzed after being transferred to stata 11.0 software .
the severity of pain before administration of medications and 10 minutes after initiation of treatment , was reported as means  standard deviations and analyzed using independent t - test .
then kaplan - meier curves and log rank analysis were used to evaluate the success of treatment , which was defined as a decrease of 3 scores in pain severity .
126 patients were included in the study and randomly divided into two equal groups of morphine and ketamine .
the mean ages of the patients in the morphine and ketamine groups were 53.614.3 and 35.113.5 years , respectively ( p=0.54 ) .
forty - five ( 71.4% ) and 51 ( 80.95% ) patients were male in the ketamine and morphine groups , respectively ( p=0.21 ) .
the mean pain severity scores at admission in the ketamine and morphine groups were 8.80.8 and 8.950.8 , respectively ( p=0.32 ) . after therapeutic intervention , the severity of pain decreed significantly in the ketamine ( 2.71.8 ; p<0.001 ) and morphine groups ( 2.41.5 ; p<0.001 ) , with no significant differences between the two groups ( p=0.28 ) , indicating that both medications are equally effective in alleviating pain ( figure 1 ) .
kaplan - meier curve showed that five minutes after initiation of injection , ketamine and morphine resulted in a successful decrease in pain severity in 33 ( 52.4% ) and 38 ( 60.3% ) patients , respectively .
this rate increased to 59 ( 93.65% ) and 61 ( 96.8% ) patients , respectively , after 10 minutes .
log rank test did not show any significant difference in success rates between the two groups ( p=0.62 ) ( figure 2 ) .
none of the patients receiving morphine exhibited any complications ; however , during the intervention , six patients ( 9.5% ) receiving ketamine developed emergence phenomenon ( p=0.28 ) . and
four patients ( 6.3% ) in this group required a rescue dose due to the short period of the drug effect ( p=0.12 ) .
the results of the present study showed that administration of a low dose of ketamine ( 0.5 mg / kg ) results in a significant decrease in pain severity of long bone fractures .
the incidence of drug complications was higher in the ketamine group compared to the morphine group ( p=0.028 ) , with emergence phenomenon in four subjects .
although the incidence of this complication was higher in the ketamine group , other studies have emphasized that since ketamine is one of the safest and most appropriate medications for sedation in emergency wards , such a complication should not preclude its use because this complication is resolved spontaneously without any therapeutic intervention ( 14 ) .  
the majority of studies available have evaluated the efficacy of combination treatment with morphine/ ketamine in decreasing pain due to fractures .
galinski et al showed that use of low doses of ketamine decreases the need for morphine up to 26% and its efficacy when administered alone is similar to that of morphine in alleviating pain ( 5 ) .
weinbroum et al evaluated the simultaneous administration of morphine / ketamine compared with morphine alone in decreasing pain severity after surgery and showed that simultaneous administration of morphine and ketamine results in a significant decrease in pain severity perception by patients ( 15 ) .
a systematic review , too , showed that use of ketamine as a supplementary medication results in a decrease in the need for morphine , preventing unfavorable complications ( 16 ) .
means ( sd ) of pain severity in patients receiving ketamine and morphine before and after intervention . *
nrs : numeric rating scale .   the treatment success rate in the morphine and ketamine groups at different time intervals .
mccarty et al , too , reported that ketamine is an appropriate , rapid and safe sedative agent , which facilitates reduction of fractures in children in the emergency unit .
however , they claim that ketamine should only be administered in locations , such as emergency units , where precise monitoring of patients is possible and an experienced physician is available in the center for the management of airways ( 17 ) .
snijdelaar et al reported that the combination of ketamine / morphine significantly decreases the need for morphine and has better analgesic effects ( 18 ) .
jennings et al reported similar findings but emphasized that more minor complications are seen with a combination of morphine / ketamine ( 12 ) .  
one of the most important limitations of the present study was a short follow - up period of patients . in the present study ,
all the patients were evaluated for only 10 minutes , which precluded evaluation of the effect of ketamine at longer periods .
therefore , it is suggested that in future studies the efficacy of the medication be evaluated at longer follow - up periods .
due to ethical considerations , it was not possible to follow the patients without any medicinal intervention and use only placebo .
it was shown in the present study that iv administration of ketamine results in pain relief in bone fracture patients . however , the effect of this medication on the recurrence of pain is still unknown .
therefore , it is possible that further administration of the medication will prevent recurrence of pain .
in addition , the efficacy of other routes for administration of the medication , such as intramuscular , intra - nasal and local use , should be evaluated in future studies .
in addition , use of different administration regimens , such the continuous use or infusion , should be evaluated in future studies .
the results of the present study showed that administration of a low dose of ketamine ( 0.5 mg / kg ) results in a significant decrease in the severity of acute pain in patients with fractures of long bones .
all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors .
introduction : the selective medication for pain control in many clinical situations is morphine but its complications prevent its widespread use . 
 ketamine has been introduced as an alternative for morphine in some studies . 
 however , the efficacy of its solitary use has not yet been evaluated . 
 therefore , the present study was undertaken to evaluate the effect of ketamine alone in relieving pain in trauma patients referring to an emergency unit . 
 methods : in this double - blind clinical trial , patients with long bone fractures were randomly divided into two groups of treatment with intravenous ( iv ) morphine at a dose of 0.1 mg / kg and treatment with iv ketamine at a dose of 0.5 mg / kg . pain severity of the patients was recorded before and 10 minutes after injection based on numeric rating scale . 
 the means in the two groups were compared using independent t - test . then the kaplan - meier curve and log rank analysis were used to evaluate the success of treatment . 
 results : 126 patients were included in this study . 
 the mean ages of the patients in the morphine and ketamine groups were 33.614.3 and 35.113.5 years , respectively ( p=0.54 ) . 
 after therapeutic intervention , the pain severity significantly decreased in ketamine ( 2.71.8 ; p<0.0001 ) and morphine ( 2.41.5 ; p<0.0001 ) groups , with a similar effect of both medications on alleviating pain ( p=0.28 ) . 
 the success rate of the treatment at 10-minute interval in groups receiving ketamine and morphine were 59 ( 93.65% ) and 61 ( 96.8% ) patients , respectively ( p=0.62 ) . 
 conclusion : the results of the present study showed that administration of ketamine at a low dose ( 0.5 mg / kg ) results in a significant decrease in the severity of acute pain in patients with fractures of long bones . 
 this palliative effect is very similar to that of morphine .