In the present study, we evaluated the antinociceptive effects of intravenous magnesium sulphate by reducing perioperative analgesics requirements during hysteroscopy in patients under monitored anesthesia care. We demonstrate, in hysteroscopy, that adding intravenous magnesium sulphate to propofol-fentanyl anesthesia results in a reduction in intraoperative fentanyl needs. Patients receiving magnesium displayed slower heart rate and less postoperative pain.
Propofol is an intravenous sedative drug and exerts its effects through potentiation of the inhibitory neurotransmitter, γ-aminobutyric acid (GABA). It has gained widespread use due to its favorable drug effect profile such as rapid and smooth induction with nearly no excitation phenomena and fast terminal half-life time . Fentanyl is an agonist of the μ-opioid receptor which is known to be 100 times more potent than morphine. Analgesic effect occurs as soon as 1 to 2 min and lasts 2 to 4 hours . Propofol and fentanyl is metabolized mainly via the liver and excreted in the urine.
Nowadays, hysteroscopic surgeries are frequently performed in ambulatory surgery settings, which benefit the patients for shorter hospital stays and reduction of costs . This procedure has been considered a less invasive treatment, combine short operative time with early discharge, postoperative analgesia is always underestimated and ignored. However, severe pain is caused by uterine cervical dilatation and intrauterine tissue extraction, thus effective pain management is the key point for patients’ comfort and satisfaction. While opioids are the most effective antinociceptive agents, they have undesirable side effects, including respiratory depression, nausea, vomiting, urinary retention, constipation, ileus, and pruritus. Another problem is opioid addiction, a 4.8%-6.5% incidence of persistent opioid use after surgery in older children and adults in the United States . With this in mind, opioid-free anesthesia (OFA) was introduced to avoid current crisis. This can be achieved with alpha-2-agonists, ketamine, lidocaine, nonsteroidal anti-inflammatory drugs (NSAIDs) and magnesium, each working on a different target and therefore described as multitarget anesthesia . In hysteroscopy, non-opioid analgesics such as NSAIDs and dexmedetomidine had been evaluated. Although both of these drugs could reduce the pain after hysteroscopy, NSAIDs fail to eliminate the discomfort occurring during the procedure  and dexmedetomidine may cause prolonged hypotension and bradycardia .
A case report indicated that there is a close connection between hypomagnesaemia and pain. Séamus et al.  reported two patients with hypomagnesaemia suffer from severe cancer pain. Their pain was well controlled after treating with intravenous magnesium. During hysteroscopy, distending media is essential to allow for optimal uterine visualization. Nevertheless, excess absorption of large volumes of electrolyte-free, low-viscosity fluid can result in volume overload with hyponatremia and water intoxication . In our study, patients’ postoperative serum magnesium level was consistent with recent research  which significantly decreased. The use of diuretics is advocated to treat volume overload in hysteroscopy , but diuretics can reduce renal magnesium reabsorption. In the meantime, perioperative inadequate dietary intake of magnesium makes patients undergoing hysteroscopy more susceptible to hypomagnesaemia.
Magnesium has antinociceptive effect in animal and human models of pain . As a matter of fact, noxious stimuli activate the release of glutamate in the dorsal horn, which then activates the NMDA receptors, causing intracellular calcium influx, neuronal excitation, and central sensitization and hyperalgesia . Therefore, NMDA receptor antagonists play an important role in perioperative pain control. Furthermore, compared with acute cutaneous pain sensation, NMDA receptor antagonists provide better pain control for acute visceral pain .
Less opioid consumption and better analgesia were observed when patients’ magnesium deficiency was corrected. These observations support both the opioid-sparing effect and co-analgesic properties of magnesium. There are two major mechanisms by which hypomagnesemia can be induced: gastrointestinal or renal losses . As diet is the only source of magnesium, the most common cause of hypomagnesemia in surgical patients is prolonged NPO. Other risk factors include diarrhea, alcoholism, acute pancreatitis, uncontrolled diabetes mellitus, and medication such as a proton pump inhibitor and diuretics . Our results indicate that if patients have these risk factors with complex pain, assessing and correcting magnesium level will be necessary. There is a declining trend for the risk of oxygen desaturation and PONV in the magnesium group, although it did not reach statistically significant. This probably due to short operating time and propofol’s antiemetic effect. Moreover, the recovery of consciousness was not delayed in Group M, while Altan et al.  reported that magnesium sulphate caused a delay in recovery for patients undergoing spinal surgery. Magnesium sulphate is known to prolong and potentiate neuromuscular block by non-depolarizing neuromuscular blocking agents . Patients in our study did not receive muscle relaxant and they keep breathe spontaneously. Different surgical model may explain the diverse results on the time of recovery of consciousness between the present study and the result of Altan et al.
Intravenous administration of magnesium generally is associated with minor side effects. Common magnesium-related side effects include flushing, dizziness, and cardiovascular events. Nevertheless, a meta-analysis indicated that magnesium did not have a statistically significant effect on the incidence of dizziness, hypotension, or bradycardia . On the contrary, it was beneficial to reduce postoperative shivering. Hypomagnesaemia can produce numerous symptoms such as pain, weakness, tetany, hallucinations, and arrhythmias [8, 20]. A stable serum magnesium concentration might be helpful for patients’ comfort and postoperative recovery. Jee et al.  found that magnesium administration can reduce the release of catecholamine and vasopressin during laparoscopic cholecystectomy. Its antinociceptive effect and direct vasodilatory effect through a calcium channel blockade might explain the lower HR and MBP in Group M. Although there was no significant difference of hypotension between the two groups in our study, relatively lower MBP might be helpful to reduce intraoperative bleeding and stress response. Even though we did not record the specific reasons for adding bolus doses of fentanyl in our study, less fentanyl consumption can reflect fewer times of body movement. These advantages of magnesium sulphate may create good conditions for operation, shorten the duration of procedure, and eventually improve the satisfaction of gynecologists.
Some limitations of the present study should be noted. First, it was a single-center study, and the relatively small number of patients limited the ability to detect statistically significant differences in adverse events of fentanyl between two groups. Second, we only applied magnesium to propofol-fentanyl anesthesia in hysteroscopy. The combination of magnesium with some other medicine in different targets such as lidocaine, ketamine, and dexmedetomidine may be more effective to reduce opioids consumption, even achieve opioid-free anesthesia. Last, we didn’t record magnesium level when we assess postoperative pain scores, so it’s difficult to draw an accurate conclusion on the relationship between magnesium and pain. In further research, magnesium level and pain scores should be assessed dynamically and simultaneously.