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

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.

Inclusion Criteria:

• Aged 20 to 50 years of either gender
• ASA ( American Society of Anesthesia) class 1 and 2
• Scheduled for elective surgical procedure under general anesthesia

Exclusion Criteria:

• Patients with known history of allergy to lidocaine or Propofol
• Obese patients
• Anticipated difficult intubation
• ASA 3 and 4
• Already on any analgesics and pregnant patients

The whole arm with the intravenous catheter was covered with a green sheet, from where the mixture of propofol-lidocaine was given.