Assessment of Pain on Propofol Injection.
Condition: Injection Site Irritation
Study type: Interventional

Summary: 
      Title: Assessment of pain on lidocaine-Propofol admixture injection: Comparing large
      antecubital vein and small vein dorsum of hand.

        -  Objective: To evaluate the pain on Propofol - lidocaine admixture injection using
           different sizes of veins on upper limb.

        -  Design: Prospective randomized clinical trial Place and duration of study: Department of
           Anesthesia, King Saud University Riyadh May 1, 2013 - May 31, 2014).

        -  Patient and methods: Total 160 adult patients were divided in two groups. Age 20-50
           years of either gender, American Society of Anesthesiologist (ASA) class 1 and 2,
           scheduled for elective surgery under general anesthesia were included in the study.
           Patients with known history of allergy to lidocaine or Propofol, obese patients,
           anticipated difficult intubation, already on any analgesics and pregnant patients were
           excluded from the study. Both groups received an admixture of Propofol (1%) - lidocaine
           (2%) on induction of anesthesia through antecubital vein (Group- 1) or through a vein on
           dorsum of hand (Group- 2). Pain was assessed as none, mild, moderate or severe. Results:
           Moderate to severe pain on intravenous injection of Propofol-lidocaine admixture through
           antecubital vein and small vein on dorsum of hand was 20% vs 71%. Conclusion: There is
           marked reduction of pain when Propofol - lidocaine admixture was injected through
           antecubital vein as compared to small vein on dorsum of hand.

        -  Key words: Propofol, injection, pain
    

Detailed description: 
      Propofol is the most commonly used drug for induction of anesthesia because of its rapid
      onset, short duration of action, easy titration and with fewer hemodynamic Effects.
      Hypersensitivity reaction with Propofol is very rare and reported incidence of pain on
      injection is 26-70%. As Propofol is extensively used for the induction of anesthesia its pain
      on injection cannot be neglected. Propofol was launched for clinical practice in 1977 in
      Cremophor form and reformulation as aqueous solution was launched in 1986, an oil-in water
      emulsion containing soybean oil. Many interventions have been tried for the reduction of pain
      on Propofol aqueous solution injection. Unfortunately none of the intervention was found to
      be successful to abolish the pain completely. So far the mechanism of pain on Propofol
      injection is not clear.

      The everyday uses of Propofol in many settings of the hospitals mandate its painless use. The
      proposed mechanisms of pain are release of local mediators and / or direct irritant effect of
      Propofol on nerve endings.

      In this study the investigators combined two interventions, Propofol - lidocaine admixture
      and different size of veins, to evaluate the pain on Propofol injection. The admixture of
      Propofol-lidocaine was injected through two different sizes of veins which are commonly used
      for intravenous cannulations, large antecubital vein and small vein on dorsum of hand.

      Propofol is a commonly used drug for induction of anesthesia and sedation in intensive care,
      emergency room and for endoscopic procedures. Unfortunately, despite its popularity pain on
      its injection is still unresolved problem. The exact mechanism of this pain is not clear so
      far.

      Some investigators suggest that the lipid solvent for Propofol activates the plasma
      kallikrein-kinin system and produces bradykinin. This modifies the injected local vein causes
      vasodilation and hyper-permeability. This modification of the peripheral vein may increase
      the contact between the aqueous phase Propofol and free nerve endings of the vessel resulting
      in Pain.Others investigators believe that Propofol as a member of phenol group can have
      direct irritant effect on local vein by stimulating nociceptors and free nerve endings giving
      rise to an immediate sensation of pain. Based on these assumptions of Propofol induced pain
      pathway, different investigators postulated different interventions to alleviate this
      problem. Different pharmacological and non-pharmacological interventions have been tried for
      the reduction of pain on Propofol injection. The injection of Propofol through large
      antecubital vein was considered as a superior method than any other non pharmacology measures
      like changing the temperature of Propofol, large intravenous catheter and speed of
      injection.Pharmacological interventions with different drugs have been tried, pretreatment
      with lidocaine with venous occlusion. Propofol-lidocaine admixture, pretreatment with
      Ketamine, opioids,non-steroidal anti-inflammatory drugs ,magnesium sulfate, ondansetron,
      tramadol, acetaminophen, dexamethasone and Propofol emulsions containing medium and long
      chain triglycerides have been studied and reviewed extensively.

      Among the all above interventions, Propofol lidocaine admixture is well known to be the best
      simple method. Lidocaine is a local anesthetic. It reduces the pain by two possible
      mechanisms, direct effect of local anesthetic on vascular smooth muscle and modifying the
      power of Hydrogen (pH) of Propofol. As lidocaine is a weak base solution when it dissolves
      with lipid it decrease the pH of the mixture. Thus, more Propofol in lipid phase cause less
      pain on injection.Injection of Propofol through large vein is another effective way in
      reducing pain. The vein diameter, flow rate, and endothelial structure might account for the
      reduction in pain. The injection of Propofol through a large antecubital vein, minimize the
      extent to which a high concentration of Propofol comes into contact with the sensitive
      endothelial wall. Furthermore Propofol will move faster from the injection site when more
      blood will be available to dissipate the bolus. Additionally, the composition of nociceptors
      along the endothelial wall might differ between the smaller veins of the hand and the larger
      antecubital veins. A meta-analysis showed that among the non-pharmacological and
      pharmacological interventions for the most effective method was the use of large antecubital
      vein followed by pretreatment with lidocaine combined with venous occlusion.

      In this study the investigators have combined the two best and simple methods and compared
      the Propofol injection pain using two different sizes of veins on upper limb. The
      investigators have used small vein on dorsum of hand and large antecubital vein in the
      forearm. The investigators found that using large vein is superior to the small vein. Walker
      B.J. et al. reported that pretreatment with lidocaine using tourniquet is statistically
      superior to Propofol-lidocaine admixture. Whereas, Kim et al. investigated three doses of
      lidocaine mixed with Propofol 40 mg, 30 mg and 20 mg. The incidence of pain was 50%, 65% and
      80% respectively.

      In this study the investigators tested the efficacy of 20 milligram lidocaine in Propofol.
      When lidocaine -Propofol admixture was injected through small vein on dorsum of hand produces
      more pain as compared to large antecubital vein. This study results are comparable to the
      findings of Kim et al. However, combination of two strategies was unable to abolish Propofol
      injection pain completely. Based on these observations the investigators recommend whenever
      possible Propofol should be given in a mixture with lidocaine through large vein.
    

Intervention name(s): Propofol lidocaine through large vein; Propofol lidocaine through small vein
Intervention type(s): Drug; Drug
Intervention description(s): A mixture of 2% lidocaine 1 ml and 1% propofol 2mg/kg was given through a large antecubital vein to assess pain severity on propofol injection during general anesthesia induction; A mixture of 2% lidocaine 1 ml and 1% propofol 2mg/kg was given through a small vein on the dorsum of hand to assess pain severity on propofol injection during general anesthesia induction
Other intervention name(s): Group I; Group II
Intervention MeSH terms: Lidocaine; Propofol
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Patients were randomized into two groups, eighty each. In all patients 15 to 30 minutes before shifting to the operation room a 20 gauge intravenous catheter was inserted either in a large antecubital vein (Group-1) or in a vein on dorsum of hand (Group-2). Lactate Ringer infusion was initiated at the rate of 120 ml/h. The arm was covered with green sheet. Patients received admixture of 2% lidocaine (1ml) in 1% propofol (19ml) either through large antecubital vein (Group-1, n = 80) or (Group-2, n = 80) through a vein at dorsum of hand. In both groups initially, thirty percent of the calculated dose of propofol (2mg/kg) was injected through an intravenous catheter. All patients were informed to report the researcher about the intensity of pain they experienced in numbers. Then induction of anesthesia was continued as routine.
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Propofol; Injection pain; Veins