Comparative evaluation of two different doses of oral paracetamol in alleviation of pain on Propofol injection in patients undergoing elective surgery under general anaesthesia.

Propofol is one of the most widely used intravenous anaesthetic agent for induction and maintenance of anaesthesia owing to its rapid onset and short duration. Propofol is an alkylphenol (2,6 diisopropylphenyl) oil at room temperature and insoluble in aqueous solution but is highly lipid soluble. Current formulation of 1% (weight/volume) propofol is available in 10% soybean oil, 2.25% glycerol, 1.2% purified egg phosphatide and disodium edetate 0.005% is added as a bacterial growth retardant.

The pain on propofol injection is undesirable, the incidence of which varies between 28% to 90%. Pain on propofol injection can be immediate or can also be delayed after 10-20s. The immediate pain is due to irritation of skin, mucous membranes and venous intima which stimulates the nociceptors and free nerve endings. Some patients recall the induction of anaesthesia with propofol as the most painful part of the perioperative period. As a result, several interventions have been investigated to alleviate the pain associated with propofol injection. Many pharmacological agents like inj. lignocaine, inj. ondansetron or opioids such as fentanyl, NSAIDS and inj. ketamine have been tried. Some non-pharmacological approaches like selecting an antecubital vein instead of hand vein or adjusting the speed of intravenous carrier fluid have also been evaluated. These approaches have varying success rate. Paracetamol (acetaminophen) is a para-aminophenol that poses analgesic and antipyretic activity similar to aspirin. Paracetamol is thought to have a strong central action and there are speculations of peripheral effects as well. Paracetamol is one of the most commonly used drugs. Its availability is good, cost is low, and its uses include primary care prescribed therapy, secondary care application and emergency treatment. Stated benefits of paracetamol include: the drug’s analgesic effects, preference to aspirin in avoidance of Reye’s syndrome, good patient tolerance, and iatrogenic complications are infrequent and minor. Paracetamol is one of the most popular and frequently used pain killer throughout the world. The mechanisms of action are sophisticated and cover both peripheral and central antinociceptive manners. The pain relief effect provided by paracetamol is via inhibition of the cyclooxygenase pathway centrally and peripherally, reducing the production of prostaglandins. Paracetamol has been postulated to be classified to the group of the so-called atypical NSAIDs, determined as peroxide sensitive analgesic and antipyretic drugs (PSAAD). "Pain relieving effect of paracetamol might also be a result of inhibition of nitric oxide (NO) formation. The synthesis of NO is through activation of L-arginine/NO pathway by substance. P (SP) and N-methyl-D-aspartate (NMDA) receptors. NO is an important neurotransmitter involved in nociceptive process of the spinal cord. Previous study suggest that paracetamol metabolite N-acylphenolamine induces analgesic effect directly via transient receptor potential vanilloid 1 (TRPV1) receptor expressed on central terminals of C-fibers in the spinal dorsal horn and leads to conduction block, shunt currents, and desensitization of these fibers. A recent study observed that the addition of 2% lidocaine (20mg) to 1% propofol (10ml) caused macroscopic precipitation at 90 min due to the instability of the emulsion when the case was delayed for 90 min after its preparation. Another study postulated that oral paracetamol has been shown to increase the incidence of no pain as well as to reduce the incidence of severe pain upon propofol injection, the results of this study are clinically useful and applicable to daily practice because oral paracetamol is readily and widely available, practically simple and convenient to use as well as economical.