***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: Propofol has the disadvantage of pain on injection .  A higher partition of propofol in the aqueous phase of the preparation causes a higher incidence of pain on injection while addition of 1 % lignocaine to propofol reduces pain . The low concentration of this local anaesthetic and the rapid pain relief observed indicates that mechanisms other than local anaesthesia are involved , that is change in pH. We performed a clinical study to investigate the influence of lignocaine and pH on pain during injection of 1 % Diprivan . Ten parts of 1 % Diprivan were mixed with one part of saline , 1 % lignocaine or hydrochloric acid to achieve the same pH as that after addition of lignocaine . Diprivan 1 % mixed with 1 % lignocaine and with hydrochloric acid gave mean pain ratings ( 1 - 10 ) of 0.32 ( SD 0.75 ) ( n = 25 ) and 0.88 ( 1.30 ) ( n = 24 ) , respectively . These ratings were significantly lower than ratings after injection of a saline-Diprivan mixture ( 2.18 ( 2.06 ) , n = 22 ) . The pH of the 1 % Diprivan formulation decreased after mixing with 1 % lignocaine . The concentration of propofol in the aqueous phase was lower when 1 % Diprivan was mixed with 1 % lignocaine ( 0.376 g litre-1 ) or HCl ( 0.392 g litre-1 ) compared with 1 % Diprivan and saline ( 0.476 g litre-1 ) mixed in the same proportion . Thus pH changes may modify propofol-induced  pain on injection by a mechanism different from the effect of the local anaesthetic on the vascular endothelium . Our findings may explain why lignocaine mixed with propofol causes less pain than injection of lignocaine followed by propofol A r and omised , double‐blind , controlled trial was undertaken to compare three different methods of reducing pain during the intravenous injection of propofol . In 101 patients undergoing daycase surgery , verbal rating scores , for pain during injection of  propofol  were compared immediately after intravenous pretreatment with ketorolac 10 mg , lignocaine 10 mg or saline .  Neither pain during injection ( p = 0.129 ) , nor venous sequelae at 7 days postoperatively were significantly different between the three treatments . Pain during propofol injection remains a confounding clinical problem We have investigated if alfentanil acts via peripheral opioid receptors to relieve the pain which occurs on injection of propofol . Thirty seconds before induction of anaesthesia and immediately after a tourniquet at 50 mm Hg greater than systolic pressure was inflated on the upper arm , patients were given either  placebo ( n = 22 ) , alfentanil 1 mg ( n = 22 ) or lignocaine 40 mg ( n = 22 ) via an i.v . cannula in the dorsum of the h and . Pain during injection of propofol was assessed using a three-point verbal rating scale , recorded at 8-s intervals . We found a significant reduction in pain after lignocaine compared with the two other groups ( P < 0.001 ) , but there was no difference between the placebo and alfentanil groups . We conclude that alfentanil does not relieve pain on injection with propofol via an action on peripheral opioid receptors when alfentanil is limited to the forearm for 30 s before induction of anaesthesia The purpose of this study was to define the optimum dose of lignocaine required to reduce pain on injection of propofol . We conducted a prospect i ve , r and omized , double-blind trial on 310 patients undergoing anaesthesia . Patients were allocated to four groups according to the lignocaine dosage : group A ( control ) , no lignocaine ; group B , lignocaine 0.1 mg kg-1 ; group C , lignocaine 0.2 mg kg-1 ; group D , lignocaine 0.4 mg kg-1 . Our results showed that a dose of lignocaine 0.1 mg kg-1 significantly reduced the incidence of pain and that there was no improvement when the dose was increased The effects of addition of 1 ml of lignocaine ( 10 mg ) or isotonic saline to 19 ml of the emulsified preparation of propofol ( Diprivan ® ) were studied in a r and omised , double – blind trial in 80 patients .  The incidence and severity of pain on injection of propofol were significantly reduced by the addition of lignocaine ( P < 0.01 ) Propofol has been shown to cause pain on injection . This study investigated the effect of warming propofol to 37 ° C on the pain of intravenous injection .  One hundred and one women on outpatient gynaecology lists were allocated to receive propofol either at room temperature or at 37 ° C . Warming propofol decreased the incidence of pain on injection by 37 % ( p < 0.001 ) , and also decreased the severity of pain reported by patients ( p < 0.001 ) . We conclude that warming propofol to 37 ° C provides a simple and safe method of reducing the incidence of pain on injection without the addition of other agents Background and Objectives . We observed clinical ly that tramadol and metoclopramide appear to have local anesthetic action . Tramadol is a central ‐acting analgesic . Metoclopramide is a commonly used antiemetic . The local anesthetic effect of tramadol in reducing propofol injection pain has never been mentioned , although it was speculated with metoclopramide . Methods . We conducted a double‐blind , placebocontrolled study by injecting tramadol or metoclopramide intradermally in 10 healthy volunteers ( 5 men , 5 women ; age 25‐56 years ) . Each subject received 0.5 mL of four solutions in r and om order on the volar side of the forearm . These solutions were 25 mg tramadol , 5 mg metoclopramide , 5 mg lidocaine , and 0.5 mL normal saline .  Pain on injections and the degree of local anesthesia ( tested by pinprick , light touch , and cold ) at each site was reported on a 0‐3 scale at design ed time intervals . Results . Like 1 % lidocaine , tramadol and metoclopramide  demonstrated loss of sensation for pinprick , light touch , and cold for 15 minutes after intradermal injection ( P < .01 ) . Conclusions . Intradermal tramadol or metoclopramide can produce local anesthetic effect Phase II and III studies are tightly controlled trials investigating adverse effects before government approval of a new drug . However , because postapproval Phase IV studies involve a much larger and more complex population , the true nature of adverse effects can be seen . We analyzed Phase IV data for the new drug propofol with regard to the incidence of adverse events , and evaluations of such events by anesthesiologists versus postanesthesia care unit ( PACU ) nurses . Data pertained to 25,981 patients , 1722 institutions , and 1819 anesthesiologists giving propofol in three anesthetic regimens . Inclusion criteria were liberal : age , 18 - 80 yr ; ASA physical status I-III ; no continuing pregnancy ; and no prior adverse anesthetic experience . Anesthesiologists and PACU nurses used data collection forms to record demographic , perioperative , and outcome variables ; to evaluate recovery ( excellent , good , or poor ) ; and to describe adverse events . Adverse events were reported for 2813 patients ( 10.8 % ) ; the most common events were pain on injection ( 5.2 % ) , hypotension ( 1.1 % ) , nausea/vomiting ( 1.9 % ) , and excitement ( 1.3 % ) . The incidences of pain on injection and nausea/vomiting were approximately one-half and one-fifth , respectively , the values reported in earlier studies . Six hundred thirty-three patients ( 2.4 % ) had a " poor " recovery according to one or both of the evaluators ( the anesthesiologist or PACU nurse ) . The PACU nurse was more influenced by nausea , vomiting , or postoperative pain ; and the anesthesiologist was more influenced by postoperative confusion or delayed emergence from anesthesia . For only 0.6 % of patients did both evaluators rate recovery as poor . Anesthesiologists gave more weight to intraoperative adverse events , and nurses to postoperative events . ( ABSTRACT TRUNCATED AT 250 WORDS Using venous retention with a tourniquet ( 70 mm Hg ) , we performed a r and omized , double-blind study to assess the efficacy of IV pretreatment with fentanyl , morphine , meperidine , or lidocaine in reducing propofol injection pain . Immediately after venous occlusion with a tourniquet , IV fentanyl 150 micro g ( Group A , n = 35 ) , morphine 4 mg ( Group B , n = 35 ) , meperidine 40 mg ( Group C , n = 35 ) , 2 % lidocaine 3 mL ( Group D , n = 35 ) , or normal saline 3 mL ( Group E , n = 35 ; as placebo control ) was given to adult patients . The venous retention of the drug was maintained for 1 min , followed by tourniquet release and IV administration of propofol 100 mg . Pain assessment was made immediately after the propofol injection . Lidocaine and meperidine significantly reduced propofol injection pain more than placebo ( P < 0.05 ) , but there were more side effects in the meperidine group . Fentanyl and morphine reduced the intensity of propofol injection pain ( P < 0.05 ) and had some effect in reducing the incidence of propofol injection pain , but the difference did not reach statistical significance . The order of efficacy was lidocaine [ nearly = ] meperidine > morphine [ nearly = ] fentanyl . We postulate that the peripheral analgesic effect of these opioid is due to their local anesthetic activity . Implication s : Propofol , a commonly used anesthetic , often causes pain on injection . Given as venous retention pretreatments 1 min before propofol , meperidine and lidocaine were found to significantly reduce the propofol injection pain , whereas fentanyl and morphine only slightly reduced the propofol injection pain . ( Anesth Analg 1998;86:382 - 6 & NA ; Propofol has a high incidence of pain with injection , particularly into small veins . We sought to determine whether concomitant administration of lidocaine could prevent this pain . In a r and omized doubleblind trial , 368 women were allocated to one of four groups to receive 19 mL of propofol mixed with either 1 mL of 0.9 % saline , 1 mL of 0.5 % ( 5 mg ) lidocaine , 1 mL of 1 % ( 10 mg ) lidocaine , or 1 mL of 2 % ( 20 mg ) lidocaine . The pain of injection was scored as none , mild , moderate , or severe . There was a significant reduction in the overall incidence of pain from 73 % with saline to 32 % with 20 mg of lidocaine . A highly significant negative dose‐response relationship between the dose of lidocaine and the severity of pain was demonstrable , both at induction of anesthesia and as recalled in the recovery room ( P < 0.001 for both ) . Lidocaine ( 20 mg IV ) will significantly reduce the incidence and severity of pain with propofol injection , but about 6 % of patients will still suffer unpleasant pain if the dorsum of the h and is used We undertook a r and omized , placebo-controlled , double-blind study to compare the use of alfentanil 1 mg and lidocaine 40 mg for the reduction of pain during injection of propofol . Eighty-nine patients were r and omly allocated to one of three groups : Group L , lidocaine 40 mg added to 180 mg propofol ; Group A , alfentanil 1 mg 30 s prior to propofol ; or Group P , placebo ( normal saline ) . The incidence of pain in the placebo group was 67 % . Both treatment groups had a significantly lower incidence of pain than the placebo group ( P < 0.002 ) . There was no significant difference in the incidence of pain between the groups receiving lidocaine or alfentanil ( 13 % and 24 % , respectively ) . There was no significant difference in the induction dose of propofol between the groups . Fifty-two percent of patients who experienced pain at induction had recall of that pain in the recovery room . Alfentanil 1 mg and lidocaine 40 mg are both effective in reducing pain during injection of propofol . ( Anesth Analg 1996;82:469 - 71 STUDY OBJECTIVE To investigate if the use of a new double lumen i.v . set ( DLIS ) decreases the incidence of propofol injection pain compared with single lumen i.v . set ( SLIS ) administration . DESIGN Prospect i ve , r and omized , double-blinded study . SETTING Operating rooms in a university hospital . PATIENTS 50 adult ASA physical status I and II patients of both genders undergoing general anesthesia for elective surgery . INTERVENTIONS Patients were injected with propofol either through a DLIS or a SLIS . MEASUREMENTS AND MAIN RESULTS Three different 
    Output:
    
IV lidocaine before the injection of propofol was less analgesic .
Temperature had no significant effect .
There was a lack of data for all other interventions to allow meaningful conclusions .
The diameter of venous catheters and speed of injection had no impact on pain .