Preventing Pain on Injection of Propofol: A Comparison between Peripheral Ketamine Pre-Treatment and Ketamine Added to Propofol

Abstract

The purpose of this study was to examine possible peripheral mechanisms for the reduction of propofol injection pain by the addition of ketamine. We hypothesised that pH changes associated with the addition of ketamine to propofol decrease propofol-induced pain on injection. We compared the efficacy of intravenous ketamine pretreatment under tourniquet with ketamine added to the propofol. In the pre-treatment group, patients received ketamine 10 mg in a total volume of 1.0 ml with 0.9% saline (n=94; Group P) under tourniquet for 30 seconds before administration of propofol after release of the tourniquet. In the mixture group, propofol 9 ml was mixed with ketamine 10 mg in 0.9% NaCl 1.0 ml (n=94, Group M). Pain was assessed with a four-point scale: 0=no pain, 1=mild pain, 2=moderate pain, 3=severe pain at the time of propofol injection. The pH of propofol, ketamine and a range of propofol-ketamine mixtures were also measured. Forty-eight patients (51%) in Group P complained of pain on injection compared with 28 patients (30%) in Group M (P=0.005). The pH of the 1% propofol-ketamine mixture was 5.84 while 1% propofol had a pH of 7.86. Our results support pH changes as a more important cause for the decrease in propofol injection pain with the addition of ketamine to propofol than a peripheral effect of ketamine.

Prevention of pain on injection of propofol: systematic review and meta-analysis

“…The primary outcome was the number of patients reporting any pain Studies excluded (n=106): Reviews (n=7) 1 3 4 14-17 Animal studies (n=2) 18 19 Not randomised controlled trials (n=15) [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] Improper assessment of pain (n=7) [35][36][37][38][39][40][41] Duplicate publication (n=2) 42 43 Methodological concerns (n=15) [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59] Did not measure pain from propofol injection (n=20) [60][61][62][63][64][65][66][67][68]…”

Comparison of propofol versus propofol–ketamine combination in pediatric oncologic procedures performed by non‐anesthesiologists

“…The use of propofol alone compared with the combination propofol–ketamine was associated with a higher incidence of major desaturations, mostly in children younger than 5 years. The combination of ketamine and propofol for procedural sedation may theoretically be beneficial because using lower doses of each agent may result in a reduction of the undesirable adverse effects 17–21.…”

“…The combination of propofol with low‐dose ketamine could offer some theoretical advantages over propofol alone: More analgesia, less hypotension, the use of a lower dose of propofol, and consequently, a lower risk of respiratory depression, and less infusion pain 16, 17. When ketamine is utilized in combination with propofol, a rise in propofol pH has been identified as a possible further local analgesic mechanism 18. The adjunctive use of ketamine during propofol sedation provides significant analgesia and minimizes the need for supplemental opioids 19, thus preserving hemodynamic stability 20.…”

Experience with a propofol-ketamine mixture for sedation during pediatric orthopedic surgery

“…Pretreatment with ketamine has previously been demonstrated to decrease injection pain with subsequent bolus use of propofol (19,20). Further to this, the combination of the two in solution has been shown to be more effective than pretreatment with ketamine prior to propofol injection (21).…”