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propofol is a commonly used drug for induction of anesthesia because of its rapid onset and short duration of action , easy titration , and favorable profile for side effects .
however , despite these positive attributes , about 28 - 92% patients experience pain on injection of propofol , with one of three patients reporting severe or excruciating pain .
the mechanism of propofol injection pain is still unclear ; it has been postulated to be due to either a direct irritant effect giving rise to an immediate sensation of pain or an indirect effect via the release of mediators such as bradykinin leading to a delayed onset . as a result ,
several interventions have been investigated to alleviate the pain associated with propofol injection with varying results .
numerous physiological and pharmacological methods have been described in literature so as to decrease the incidence of this pain such as selection of a larger vein , decreasing the speed of injection , or diluting the propofol solution , or pretreatment with lignocaine , ondansetron , metoclopramide , opioids , and thiopentone . tramadol a centrally acting analgesic
we also hypothesized that intravenous ( iv ) administration of butorphanol , a synthetic opioid agonist  antagonist can also reduce pain during induction with iv propofol .
it is a kappa receptor agonist , as well as a mu - receptor antagonist , resulting in analgesic and sedative properties without profound respiratory depression or euphoria .
hence , we conducted this randomized , double - blind , placebo - controlled study to compare the efficacy of pretreatment with butorphanol and tramadol for alleviation of pain associated with propofol injection .
after obtaining approval from the institutional ethical committee and written informed consent of the study subjects , this prospective study was conducted on 90 adult patients belonging to the american society of anesthesiologists ( asa ) grade i and ii in the age group of 18 - 60 years scheduled for elective surgery under general anesthesia with propofol as an induction agent .
consecutive sampling technique with random assignment was used to allocate to one of the three groups of 30 patients each and respective drugs were given intravenously in the volume of 3 ml prior to injection of propofol .
patients with a history of chronic pain syndromes , thrombophlebitis , neurological disease , and allergy to the study drugs were excluded from the study .
the patients were informed of the possibility of a  burning sensation  in the forearm during induction of anesthesia .
the drugs were prepared in identical syringes and in equal volume by the anesthesia technician who was unaware of the study design and were marked with different codes ( i , ii , iii ) so that even the anesthesiologists who were recording the observations remained blinded to the drug .
a detailed preanesthesia checkup was conducted wherein the patients were educated on the use of visual analog scale ( vas ) for assessment of pain during the perioperative period .
all patients were advised to be kept nil per oral for 8 h prior to surgery and received uniform premedication in the form of tablet ranitidine 150 mg and tablet alprazolam 0.25 mg night before surgery . in the operating room
, an iv line was secured in a peripheral vein on the dorsum of the hand with an 18-gauge iv cannula .
the following monitoring was instituted : electrocardiogram for heart rate and rhythm , systolic blood pressure , diastolic blood pressure and mean arterial pressure , respiratory rate , and oxygen saturation .
recording of these parameters was done before induction , during induction , intraoperatively every 2 min up to first 10 min and thereafter every 5 min until the end of the surgical procedure .
group i patients received injection normal saline 3 ml iv ( placebo ) , while group ii and group iii patients received injection tramadol 50 mg and injection butorphanol 1 mg iv , respectively , made up to 3 ml by adding normal saline in a blinded manner .
a tourniquet was applied and inflated to 70 mm hg in which the iv line was secured .
then the study drugs ( tramadol , butorphanol , and placebo ) were administered through iv cannula at the rate of 0.5 ml / s .
after 2 min of injecting the study drug , tourniquet was deflated and immediately injection propofol 2.5 mg / kg at the rate of 0.5 ml / s was administered for induction of anesthesia .
patients were asked about the intensity of pain on propofol injection by using pain vas on a range of scores from 0 to 100 before the loss of consciousness .
side effects such as erythema , pruritus , sensation of heat , and allergic reaction were noted postoperatively immediately after the surgery and then 24 h after surgery . based on the distribution of pain vas scores in postsurgical patients who described their postoperative pain intensity as none , mild , moderate , or
severe the following cut points on the pain vas have been recommended for this study : no pain ( 0 - 4 mm ) ; mild pain ( 5 - 44 mm ) ; moderate pain ( 45 - 74 mm ) ; and severe pain ( 75 - 100 mm ) . based on the results of the previous study and assuming type - i error (  ) at 0.05 , type ii error (  ) at 0.1 , and power of the study at 80% so as to detect a difference of 20% in the incidence of pain between the study and control groups the sample size was calculated as 26 patients in each group . however , we chose 30 patients in each group considering possible dropouts and for better validation of results .
the decoding of drugs was done at the end of the study , and the entire data were compiled and analyzed by using analysis of variance and chi - square test .
analysis was performed using statistical software statistical product for social sciences ( spss version 11.0 for windows , chicago , spss inc . ) .
all the values were expressed as a mean  standard deviation ( sd ) ; range ; or percentage .
based on the results of the previous study and assuming type - i error (  ) at 0.05 , type ii error (  ) at 0.1 , and power of the study at 80% so as to detect a difference of 20% in the incidence of pain between the study and control groups the sample size was calculated as 26 patients in each group . however , we chose 30 patients in each group considering possible dropouts and for better validation of results .
the decoding of drugs was done at the end of the study , and the entire data were compiled and analyzed by using analysis of variance and chi - square test .
analysis was performed using statistical software statistical product for social sciences ( spss version 11.0 for windows , chicago , spss inc . ) .
all the values were expressed as a mean  standard deviation ( sd ) ; range ; or percentage .
the incidence of pain in group i was observed in 80% of the patients [ table 2 ] . in group
ii , 7 patients out of 30 felt pain accounting for an incidence of 23.33% , while in group iii , 6 patients out of 30 felt pain with an incidence of 20% . in group
i , the mean score of pain was ( vas  sd ) 2.27  1.51 while it was 1.14  1.74 and 1.03  1.72 in group ii and group iii patients , respectively [ table 3 ] . on statistical analysis ,
vas in group i was statistically significant as compared to group ii and iii ( p < 0.001 ) .
the other side effects observed besides pain included pruritus and erythema . in group ii and group iii , pruritus was seen in three ( 10% ) and two ( 6.7% ) patients , respectively , while erythema was observed in four ( 13.2% ) and two ( 6.7% ) patients , respectively , in group ii and iii .
the overall incidence of pruritus and erythema was 23.2% and 13.4% in group ii and iii , respectively , which were statistically insignificant [ table 4 ] .
incidence of pain on propofol injection mean score of pain with intergroup comparison side effects of pretreatment drugs in all groups
the results of our study imply a significant reduction in pain on propofol administration after pretreatment with tramadol or butorphanol in comparison to the control placebo group .
intergroup comparison revealed that the incidence and severity of pain with propofol injection was less in the study groups ( ii and iii ) when compared to the control group ( i ) , but comparable efficacy was observed among both the study drugs .
we chose a control group in this study by administering a placebo so as to gauge the efficacy of tramadol and butorphanol for the amelioration of propofol injection pain , rather than opting for traditionally established gold standard lignocaine pretreatment .
moreover , with the focus shifting to newer drugs in a quest to find a better alternative to alleviate the pain on propofol injection , it seems reasonable to use opioids as a part of standard induction regime .
opiates were shown to exert peripheral analgesic action in addition to their well - known central effects though a clear - cut discrimination between peripheral and central analgesics is debatable .
the analgesia produced by both peripheral and central mechanisms may be additive or even synergistic . moreover , peripheral opioid receptors have been described and shown to mediate analgesic effect when activated by opioid agonists . the analgesic effect observed in our study with both tramadol and
can be attributed to the peripheral analgesic effect secondary to their venous retention for 2 min .
the higher incidence of patients ( 80% ) experiencing higher mean vas scores ( 2.27  1.48 ) in group i ( placebo ) are comparable with the 74 - 83% incidence reported by various other studies .
tramadol has also been found to be as effective as lignocaine in reducing the incidence and severity of propofol - induced pain .
tramadol is a centrally acting weak -receptor agonist which inhibits noradrenaline re - uptake as well as promotes serotonin release , potentiates the monoaminergic system and can be used to treat moderate and severe pain .
in addition to its systemic effect , the local anesthetic effect of tramadol on peripheral nerves has been shown in both clinically and laboratory studies .
desmeules et al . confirmed that the analgesic effect of tramadol is apportioned between the opioid and monoaminergic components .
suggested that tramadol affects sensory and motor nerve conduction by a similar mechanism to that of lidocaine which acts on the voltage - dependent sodium channel leading to axonal blockage .
after the iv administration , the onset of analgesia occurs within 1 min with a peak effect in about 4 - 5 min .
the site of action of butorphanol in reducing the pain of propofol injection is not clear , but it could be either through opioid receptors ( central and or peripheral ) , local anesthetic action , or both .
the incidence of pain on propofol injection in this study after pretreatment with butorphanol was observed to be approximately 20% .
this incidence is almost similar to the findings of earlier study by aggarwal et al . who reported an incidence of merely 20% on propofol injection while using butorphanol as pretreatment .
the incidence of pain observed in the tramadol group ( 23.33% ) in the our study was comparable to the results of wong and cheong who compared lignocaine with placebo and observed an incidence of 27% and 83% , respectively ( p < 0.001 ) .
thus , it can be inferred that tramadol is as effective as lignocaine in alleviating propofol injection pain thereby granting the patient a smoother comfortable experience of propofol induction .
fewer side effects , like pruritus and erythema , were observed with tramadol pretreatment ( 10% and 13.2% , respectively ) while this incidence decreased further with butorphanol pretreatment ( 6.7% ) .
the findings of our study are nearly similar to the results of martin et al . who reported a similar incidence of pruritus and erythema with tramadol pretreatment .
thus , we conclude that pretreatment with perioperatively used opioids tramadol 50 mg or butorphanol 1 mg effectively reduced the pain of propofol injection with fewer self - limiting mild side effects such as pruritus and erythema . though statistical significance
could not be achieved among both study drugs , we propose future studies exploring use of both tramadol and butorphanol as a pretreatment in relieving pain on propofol injection in large samples of surgical population .
background and aims : pain of propofol injection has been recalled by many patients as the most painful part of the induction of anesthesia . 
 tramadol and butorphanol are commonly used analgesics for perioperative analgesia in anesthesia practice . however 
 , their potential to relieve propofol injection pain still needs to be explored.material and methods : a randomized , double - blind , placebo - controlled study was conducted on 90 american society of anesthesiologists i and ii adult patients undergoing elective surgery under general anesthesia with propofol as an induction agent . 
 consecutive sampling technique with random assignment was used to allocate three groups of 30 patients each . 
 group i patients received an injection of normal saline 3 ml intravenously ( placebo ) while group ii and group iii patients received injection of tramadol 50 mg and butorphanol 1 mg intravenously , respectively . before induction of anesthesia patients 
 were asked about the intensity of pain on propofol injection by using visual analog scale ( vas ) before the loss of consciousness . 
 descriptive statistics and analysis of variance with chi - square test were used to analyze the data . the value of p < 0.05 was considered as a significant and p < 0.0001 as highly significant.results:the incidence of pain in group i was observed in 80% of the patients , while it was observed in 23.33% and 20% of patients in group ii and iii , respectively . 
 mean vas scores were 2.27  1.51 , 1.14  1.74 , and 1.03  1.72 in group i , ii , and group iii patients , respectively . 
 the incidence of pruritus was 10% and 6.7% and erythema in 13.2% and 6.7% in group ii and iii , respectively.conclusion:pretreatment with both butorphanol and tramadol significantly reduced pain on propofol injection ; however , they exhibited comparable efficacy among each other . 
 thus , either of these two drugs can be considered for pretreatment to reduce propofol injection pain .