Pretreatment with Magnesium Sulfate to Alleviate Pain on Propofol Injection: A Prospective Randomized Double Blind Study

Background and aim of study: Propofol is one of the most frequently used medications for inducing and maintaining anesthesia. However, propofol injection causes pain and discomfort in more than 70% of patients. This study was performed to determine the effect of magnesium sulfate on reducing pain at the onset of anesthesia induced by propofol injection. 
Materials and methods: A total of 80 healthy adult patients were selected in this study with either sex, scheduled for routine elective surgical procedure under general anesthesia. The patients enrolled were divided randomly into two groups of 40 patients each. Group I received 30 mg/kg of intravenous magnesium sulfate in 5 ml. Group II (placebo group) received 5ml of 0.9% intravenous normal saline 1 minute before propofol injection. The patients were asked to report their pain during injection of propofol. For all statistical tests, p<0.05 was taken to indicate a significant difference. 
Results: The incidence of pain experienced in magnesium sulfate group was 30% patients and in saline group was 60% patients, which is statistically significant p<0.05. The severity of POPI was also lower in magnesium sulfate group than the saline group (p<0.05). The incidence of mild and moderate pain in groups I versus group II was 22.5% versus 37.5% and 7.5% versus 22.5% respectively p<0.05. There was no severe pain recorded in any groups. 
Conclusion: Magnesium sulfate can be used before induction of anesthesia to reduce pain on propofol injection. 
Mediscope Vol. 6, No. 2: Jul 2019, Page 73-77

propofol causes pain on injection is not fully understood. However, the activation of pain mediators, such as the kinin cascade system, has been suggested as a possible cause. 3 A number of different interventions have been used to alleviate pain incidence and intensity during propofol injection, including administrating lignocaine, heating or cooling, diluting propofol, injecting it into a large vein, and using ondansetron, metoclopramide, clonidine, ketamine, narcotics, thiopentone and magnesium sulfate. It is not clear, which is the most effective. [4][5][6][7][8] Magnesium sulfate is used to reduce propofol-induced pain. 9 It is a natural calcium antagonist, which can be used as an adjuvant agent to reduce postoperative pain. [10][11][12] Various studies have shown that magnesium sulfate can reduce the need for opiates, such as propofol, remifentanil, and vecuronium. 13.14 This study was undertaken to evaluate the efficacy of 30 mg/kg of intravenous magnesium sulfate in comparison with placebo (normal saline) on incidence and severity of pain on propofol injection (POPI).

Materials and methods
This randomized double blinded controlled trial was performed in National Institute of ENT Dhaka, during July to September of 2018.Eighty patients with ASA class (American Society of Anesthesiologists) I-II aged 20-50 years, who were scheduled for elective ENT surgery under general anesthesia, were included and written informed consent was obtained separately before surgery. Patients with history of allergy to magnesium sulfate, neurological disorders, use of analgesic or sedative drugs in the 24 hours prior to surgery were excluded. All routine investigations were done for GA fitness.
The patients enrolled were divided randomly into two groups of 40 patients each. Group I was allocated to receive 30 mg/kg of intravenous magnesium sulfate. Group II (placebo group) was allocated to receive 5ml of 0.9% intravenous normal saline. Study drugs were prepared in the same shape of 5ml syringe, by an anesthesiologist who was not involved in the study.
On arrival to the operation room, standard monitoring was applied to all patients including pulse oximeter, electrocardiogram and noninvasive arterial blood pressure.A 20-gauge intravenous cannula was placed on the dorsum of non-dominant hand of the patient and Ringer's solution was started. Patients received no premedication. While the venous drainage was occluded by placing an air-filled tourniquet (pressure inflated to 70 mm Hg) on the upper arm by an assistant; a blinded anesthesiologist injected prepared study drug or saline according to the allocation. The occlusion was released after one minute. First one-fourth of induction dose (2 mg/kg) of propofol was injected slowly over 10 seconds. The pain intensity was measured based on McCririck and Hunter scale. 15 After the assessment of pain, induction of anesthesia was completed with the remaining dose of propofol then tracheal intubation was facilitated with the injection of succinylcholine. Anesthesia was maintained with injection of fentanyl, vecuronium, oxygen, nitrous oxide (66%) and halothane. When surgery was completed general anesthesia was reversed as usual. 2= Moderate pain (pain reported in response to questioning and accompanied by a behavioral sign or pain reported spontaneously without questioning).
3= Severe pain (strong vocal response or response accompanied by facial grimacing, arm withdrawal or tears).
Statistical analysis: For comparison of quantitative variables between the two groups, the unpaired t-test and for qualitative variables the Chi-squared test was used. The statistically significant level was P<0.05.

Results
There was no significant demographic difference between the groups (Table 1).
Basal MAP and HR were comparable in both groups. There was no significant difference of MAP and HR between magnesium sulfate and saline groups during pre-intubation or three minutes post-intubation period (p>0.05) ( Table II).
The incidence of pain experienced in magnesium sulfate group (group I) was 30% patients and in group II (saline group) was 60% patients, which is statistically significant p<0.05 (Table III). The severity of POPI was also lower in magnesium sulfate group than the saline group (p<0.05) ( Table III). The incidence of mild and moderate pain in groups I versus group II was 22.5% versus 37.5% and 7.5% versus 22.5% respectively p<0.05. There was no severe pain recorded in any groups.

Discussion
Propofol, an excellent IV anesthetic agent belonging to the phenol group, can irritate the skin, the mucous membrane and the venous intima. The mechanism of pain is attributed to the activation of the kinin-kallikrein system that releases bradykinin, causing vasodilatation and hyper-permeability, thereby increasing contact between the aqueous phase propofol and the free nerve endings. Several authors have studied the mechanisms and methods of reducing propofol injection pain.
The results obtained from the present study showed, the overall incidence and severity of pain were significantly less in magnesium group compared to placebo group. The incidence of pain experienced in magnesium sulfate groups 30% patients and insaline group is in 60% patients. The severity of POPI is also lower in magnesium sulfate group than the saline group. Khoshfefrat

Conclusion
Pretreatment with a dose of 30 mg/kg magnesium sulfate intravenously administered one minute before propofol injection can reduce the incidence and severity of pain on propofol injection without significant adverse effects.