Propofol belongs to the group of phenols that can directly irritate the skin, mucous membrane and venous intima and could immediately stimulate nociceptors and free nerve endings [ 12 ]. The concentration of aqueous free propofol is related to injection pain. By its indirect action on the endothelium, it was suggested that propofol activates the kallikrein-kinin system and releases bradykinin, thereby producing venous dilation and hyperpermeability, which increases the contact between aqueous phase of propofol and free nerve endings, results in delayed pain within half a minute [ 8 , 13 ].
Recently several studies have suggested that propofol had no effect on the concentration of bradykinin in plasma, compared with saline control group [ 14 , 15 ]. Strategies to reduce the pain on injection includes addition of lidocaine, cooling or diluting the propofol solution, and pretreatment with lidocaine, ephedrine, ondansetron, metoclopramide, nafamostat mesilate, opioids, thiopental, or ketamine [ 1 , 2 , 12 , 16 - 20 ].
The most frequently used analgesic method is IV lidocaine 0. The incidence and the severity of pain following propofol injection is directly related to site of injection and smaller size of the vessels [ 8 ]. In children, younger the age, higher is the incidence and severity of pain on propofol injection [ 21 ] attributable to the smaller size of vein in younger children.
The present study also pointed out that incidence of pain on propofol injection was different between the different IV sites, and the highest frequency was observed in dorsum of hand. This finding is consistent with the previously published studies [ 9 , 13 , 22 ]. The injection procedure itself affects the incidence and severity of pain on injection, the pain can be reduced by the injection of propofol into the vein of antecubital fossa [ 8 , 9 ].
However, it is not feasible to recommend all anesthetists to choose the antecubital fossa vein to avoid propofol injection pain as the IV site in antecubital fossa is relatively uncomfortable to patients and has a tendency to occlude. In a study conducted to examine the influence of aging on lidocaine requirements for propofol-induced pain, the elderly patients needed relatively small dose of lidocaine to reduce the pain compared with the young patients [ 23 ].
In our study, the significant differences and the downward tendency with age were observed in the pain incidence of female patients. The exact reason for this difference is not known, but it could be because of the aging influence on pain thresholds [ 3 , 24 ]. Till date, the relationship between gender and propofol injection pain needs to be established. It has been accepted that there is no gender difference in the incidence of pain on propofol injection without any specific references or targeted research work [ 3 , 23 ].
Therefore, this study evaluated the differences in pain incidence between male and female. Gender is the baseline data in any research for selecting or distributing the patients, and this gender related bias is an important demographic parameter that is observed during conduct of any clinical study. The present study showed that male patients had lower incidence of injection pain than female patients.
Propofol is distributed in two phases with an outer aqueous phase and an inner lipid phase in the propofol emulsion preparation. Only the outer aqueous phase comes into contact with intima of the vein, so the concentration of an irritating agent in the aqueous phase is considered to the main cause of pain due to propofol injection [ 6 , 25 ].
The proposed reason of gender difference in propofol-induced pain is firstly due to the mechanical effect that male has larger sized veins than female while another factor suggested is the difference of pain sensitivity observed between the gender and this emphasizes the necessity of specifying the patients' gender while investigating propofol-associated withdrawal.
Clinically, it is a fact that female experiences greater pain intensity, with or without related distress, and shows heightened sensitivity to experimentally induced pain compared to that of males [ 26 - 30 ].
Further analysis is needed to evaluate the relationship between gender and pain-related variables. Continued research at the genetic and receptor levels may support the need to develop gender-specific drug therapies [ 29 ].
Our finding must be considered within the context of the study limitation. First, the patients were not assigned to subgroups by randomization. Second, the sample size for subgroup was relatively small.
Third, the comparison for pain intensity with pretreatment was not evaluated. Further studies should consider these limitations and evaluate other possible factors that could affect the injection pain, and develop strategies for preventing or reducing the pain on injection of propofol, considering the factors such as drug property, kinds of pretreatment and procedure and associated clinical factors.
Propofol induced pain is a common problem during induction of general anesthesia. Our results showed that the younger age patients, the patients with a peripheral IV site and female patients are more sensitive to pain following IV injection of propofol. Therefore clinicians need to have strategies to reduce or prevent the pain for patients, who have factors affecting the pain on injection of propofol. National Center for Biotechnology Information , U. Journal List Korean J Anesthesiol v.
Korean J Anesthesiol. Published online Mar Find articles by Hye-Joo Kang. Dexmedetomidine pretreatment alleviates propofol injection pain. Ups J Med Sci. Impact of time interval between remifentanil and propofol on propofol injection pain. J Clin Anesth. Prevention of pain on injection of propofol: systematic review and meta-analysis.
The effect of temperature upon pain during injection of propofol. McCrirrick A, Hunter S. Pain on injection of propofol: the effect of injectate temperature.
Mechanism of injection pain with long and long-medium chain triglyceride emulsive propofol. Can J Anaesth. Pain on injection with microemulsion propofol.
Br J Clin Pharmacol. Effect of alkalinisation of lignocaine for propofol injection pain: a prospective, randomised, double-blind study. Anaesth Intensive Care. Picard P, Tramer MR. Prevention of pain on injection with propofol: a quantitative systematic review. Anesth Analg.
Preemptive dexmedetomidine to prevent propofol injection pain in children. Ir J Med Sci. Perioperative infusion of dexmedetomidine at a high dose reduces postoperative analgesic requirements: a randomized control trial. Anti-nociceptive, analgesic and pathohistological effects of intrathecal dexmedetomidine and bupivacaine in rats. Braz J Anesthesiol.
Dexmedetomidine: exploring its potential role and dosing guideline for its use in intractable pain in the palliative care setting. J Pain Palliat Care Pharmacother. Molecular mechanisms underlying the analgesic property of intrathecal dexmedetomidine and its neurotoxicity evaluation: an in vivo and in vitro experimental study. Does dexmedetomidine reduce postoperative pain after laparoscopic cholecystectomy with multimodal analgesia?
The effects of increasing plasma concentrations of dexmedetomidine in humans. Does dexmedetomidine reduce the injection pain due to propofol and rocuronium?
Eur J Anaesthesiol. Dexmedetomidine reduces the incidence of fentanyl-induced cough: a double-blind, randomized, and placebo-controlled study. Effect of prior administration of cold saline on pain during propofol injection. Temperature of propofol does not reduce the incidence of injection pain. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.
No use, distribution or reproduction is permitted which does not comply with these terms. Introduction Propofol, a common intravenous anesthetic, is extensively used in induction, sedation, and maintenance of general anesthesia because of its rapid onset and quick patient recovery 1 , 2.
Materials and Methods Study Design and Ethical Aspects This study was designed as a double-blinded, randomized, and placebo-controlled clinical trial and all patients underwent oral and maxillofacial surgery at the Affiliated Stomatological Hospital of Sun Yat-sen University.
Study Participants All patients were scheduled for elective surgery under general anesthesia between September and July Figure 1. Table 1. Table 2. Table 4. A quantitaive systematicreview. Clinical strategies for preventing the pain on injection. Anaesthesia ; Oxford University Press is a department of the University of Oxford.
It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In. Advanced Search. Search Menu. We do not know whether there is a difference between using propofol for sedation and using it for induction with respect to patient recall.
In our study, we found that most of patients undergoing elective open thyroidectomy viewed propofol injection pain as a relatively minor problem. The incidence of recall of propofol injection pain was low and the majority of those who recalled regarded it as temporary and acceptable pain, which was lighter than intravenous puncture pain. Voluntary reporting system in anaesthesia: is there a link between undesirable and critical events?
Qual Health Care. Which clinical anesthesia outcomes are both common and important to avoid? The perspective of a panel of expert anesthesiologists.
Anesth Analg. Which clinical anesthesia outcomes are important to avoid? The perspective of patients. Br J Anaesth. Assessing parents preferences for the avoidance of undesirable anesthesia side effects in their children undergoing surgical procedures.
Paediatr Anaesth. PubMed Google Scholar. Rashiq S, Bray P. Relative value to surgical patients and anesthesia providers of selected anesthesia related outcomes. Patient preferences for anesthesia outcomes associated with cesarean delivery.
Main concerns of patients regarding the most common complications in the post-anesthetic care unit. Rev Bras Anestesiol. Prevention of pain on injection of propofol: systematic review and meta-analysis. Article PubMed Google Scholar. Prevention of pain from propofol injection.
A neuroanatomical construct for the amnesic effects of propofol. Systemic or intra-amygdala infusion of an endocannabinoid cb1 receptor antagonist am blocked propofol-induced anterograde amnesia.
Neurosci Lett. Nyhus E, Curran T. Midazolam-induced amnesia reduces memory for details and affects the erp correlates of recollection and familiarity. J Cogn Neurosci. Amnesia for electric dental pulp stimulation and picture recall test under different levels of propofol or midazolam sedation. Acta Anaesthesiol Scand. Reducing the pain of microemulsion propofol injections: a double-blind, randomized study of three methods of tourniquet and lidocaine.
Clin Ther. Propofol in a modified cyclodextrin formulation: first human study of dose—response with emphasis on injection pain. Pain on injection from propofol may be avoided by changing its formulation. Reduced pain on injection with a 0. Eur J Anaesthesiol. Rapid injection of propofol reduces vascular pain and facilitates laryngeal mask airway insertion.
J Clin Anesth. Does lidocaine more effectively prevent pain upon induction with propofol or etomidate when given preemptively than when mixed with the drug? Prevention of pain on injection of propofol: a comparison of lidocaine with different doses of paracetamol. Honarmand A, Safavi M. Prevention of propofol-induced injection pain by sufentanil: a placebo-controlled comparison with remifentanil.
Clin Drug Investig. Reduction of pain on injection of propofol: a comparison of fentanyl with remifentanil. Tversky A, Kahneman D. Judgment under uncertainty: heuristics and biases.
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