Effect of Infusion of Lidocaine, Magnesium and Remifentanil Perioperatively in Patients Undergoing Mastectomy

Effect of Infusion of Lidocaine, Magnesium and Remifentanil Perioperatively in Patients Undergoing Mastectomy

Effect of Intravenous Infusion of Lidocaine, Magnesium Sulphate and Remifentanil Perioperatively in Patients Undergoing Mastectomy: a Prospective, Randomized and Double-blind Study

This study aims to compare the quality of perioperative analgesia of lidocaine, magnesium sulphate and remifentanil in patients undergoing mastectomy

The opioid analgesics are commonly used in clinical practice for pain management in the perioperative period. However, many side effects are associated with its use, such as respiratory depression, nausea, vomiting, drowsiness, itching, urinary retention, constipation, hyperalgesia and impaired immune function. Therefore, alternative techniques and drugs have been used to replace their use. One is the intravenous infusion of lidocaine, a local anesthetic widely used in anesthetic practice. Another is intravenous infusion of magnesium sulphate, a bivalent salt used as a central nervous system depressor, reducing intracranial hypertension, in the treatment of epilepsy; eclampsia; in chronic alcoholism; in hyaline membranes, such as hyperosmotic diuretic; in malnutrition; hypomagnesaemia; in thrombotic microangiopathy; in sickle cell anemia, uterine tetany and atypical ventricular tachycardia. Studies show that the use alone or combined of lidocaine and magnesium sulphate during surgery significantly decreased postoperative pain. The mechanisms of analgesia this local anesthetic in surgical trauma may be blocking neuronal transmission in the lesion site alleviating neurogenic response, and anti-inflammatory systemic intrinsic activity. Intraoperative lidocaine promotes, besides analgesia, decreased consumption of both inhalational anesthetic and opioids; faster return of bowel movements; decreasing the production of interleukins and reduction of airway reactivity. This anesthetic also has significant anti-inflammatory properties, reduces cytokine release both in vitro and in vivo by inhibiting neutrophil activation. N-methyl-D-aspartate (NMDA) receptors are critically involved in the induction and maintenance of neuronal hyperexcitability after traumatic events, therefore, the use of NMDA antagonists before the incision reduces the excitability of the central nervous system and its result is the reduction of clinical hyperalgesia. Magnesium sulphate is an antagonist of glutamate NMDA receptor, which gives analgesic, anticonvulsant and sedative. It acts as a natural physiological calcium antagonist regulating access to the intracellular space. Shows the effect of muscle relaxation by inhibiting the release of acetylcholine at the neuromuscular junction, thereby hypermagnesaemia decreases sensitivity to acetylcholine of the endplate and the potential amplitude endplate. Besides there are few studies with use of these adjuvants during the perioperative period, the intravenous injection of local anesthetic still arouses oddity among professionals; therefore, the investigators interest in the subject. The patients underwent a prospective, randomized, double blind study, in which the examiners responsible for intra and post-operative will not know which group they were randomly allocated: Lidocaine group (n = 30); Lidocaine and Magnesium group (n = 30); Magnesium group (n = 30) or Remifentanil group (n = 30). Rapid infusion of 0.9% saline 500 ml, in the M and LM group, is added to this solution the loading dose of magnesium sulfate with 50 mg/kg and in group L will only be infused saline 0.9% . Two infusion pumps containing the result of randomization: Lidocaine 3 mg/kg/h and 0.9% saline (L group); magnesium sulphate 15 mg/kg/h and 0.9% saline (M group); lidocaine 3 mg/kg/h and magnesium sulphate 15 mg/kg/hr (LM group); and Remifentanil group (R group). In the clinical record, the following information will be emphasized: Blood pressure and heart rate intraoperative, perioperative side effects, quantify pain by Visual Analogue Scale (VAS) (ranging from 0 to 10 cm, zero being found when the patient is no pain and ten, with maximum or unbearable pain), Verbal Rating Scale (VRS), consisting of a list of phrases (no pain, mild pain, moderate pain, intense pain, maximum pain) and qualification of pain assessed by the amount of analgesics required postoperatively and the time to request them. The results were analyzed statistically with the Statistical Package for Social Sciences (SPSS) version 22 (SPSS Inc., Chicago, IL, EUA) using parametric and nonparametric tests, depending on the nature of the variables studied. Data were tested for normality using the Shapiro-Wilk test. Measures of central tendency (means) and dispersion (standard deviation) were used. The level of significance was set at < 0.05. The following tests were used: Mann-Whitney test for age, duration of anesthesia and surgery, time to first analgesic supplementation, total amount of analgesics, pain intensity; Student t-test for weight and height.

Patients in remifentanil group received an intravenous bolus injection of 2 mg/kg lidocaine followed by a continuous remifentanil infusion of 0,1 mcg/kg/min.

Patients in lidocaine group received an intravenous bolus injection of 2 mg/kg lidocaine followed by a continuous lidocaine infusion of 3 mg/kg/hr.

Patients in lidocaine group received an intravenous bolus injection of 50 mg/kg magnesium sulphate followed by a continuous magnesium sulphate infusion of 15 mg/kg/hr.

Patients received an intravenous bolus injection of 2 mg/kg lidocaine plus 50 mg/kg magnesium sulphate followed by a continuous lidocaine infusion of 3 mg/kg/hr plus 15 mg/kg/hr magnesium sulphate

Patients in Remifentanil group received an intravenous bolus injection of 2 mg/kg lidocaine followed by a continuous remifentanil infusion of 0,1 mcg/kg/min.

Patients in Lidocaine group received an intravenous bolus injection of 2 mg/kg lidocaine followed by a continuous lidocaine infusion of 3 mg/kg/hr.

Patients in Magnesium group received an intravenous bolus injection of 50 mg/kg magnesium sulphate plus an intravenous bolus injection of 2 mg/kg lidocaine followed by a continuous magnesium sulphate infusion of 15 mg/kg/hr.

Patients in Magnesium and Lidocaine group received an intravenous bolus injection of 2 mg/kg lidocaine plus 50 mg/kg magnesium sulphate followed by a continuous lidocaine infusion of 3 mg/kg/hr plus 15 mg/kg/hr magnesium sulphate

Qualification of pain assessed by the amount of analgesics required postoperatively and the time to request them

Quantify pain by Visual Analogue Scale (VAS, ranging from 0 to 10 cm, zero being found when the patient is no pain and ten, with maximum or unbearable pain)

Verbal Rating Scale (VRS), consisting of a list of phrases (no pain, mild pain, moderate pain, intense pain, maximum pain)

Intraoperative hemodynamic stability analysis through the incidence of tachycardia, hypertension, bradycardia, hypotension and consumed vasopressors

Incidence of adverse effects such as time of awakening, nausea, vomiting, pruritus, urinary retention, drowsiness

Inclusion Criteria: Female patients scheduled for elective surgery performed mastectomy; Physical Status P1 and P2 of the American Society of Anesthesiology (ASA); Exclusion Criteria: Patients with less than 18 years and above 75 years of age; Patients who are allergic to morphine and / or lidocaine and / or remifentanil and / or magnesium sulphate; Patients with chronic pain; Patients with severe hepatic disease; Patients with severe renal disease; Patients with neurological disorders; Patients included in other clinical currently or within the past three months under general anesthesia studies; Patients who refuse to participate in the study; Any other condition that in the opinion of the investigator, may pose a risk to the patient or interfere with the study objectives;

De Oliveira GS Jr, Castro-Alves LJ, Khan JH, McCarthy RJ. Perioperative systemic magnesium to minimize postoperative pain: a meta-analysis of randomized controlled trials. Anesthesiology. 2013 Jul;119(1):178-90. doi: 10.1097/ALN.0b013e318297630d.

Vigneault L, Turgeon AF, Cote D, Lauzier F, Zarychanski R, Moore L, McIntyre LA, Nicole PC, Fergusson DA. Perioperative intravenous lidocaine infusion for postoperative pain control: a meta-analysis of randomized controlled trials. Can J Anaesth. 2011 Jan;58(1):22-37. doi: 10.1007/s12630-010-9407-0.

Mendonca FT, Pellizzaro D, Grossi BJ, Calvano LA, de Carvalho LSF, Sposito AC. Synergistic effect of the association between lidocaine and magnesium sulfate on peri-operative pain after mastectomy: A randomised, double-blind trial. Eur J Anaesthesiol. 2020 Mar;37(3):224-234. doi: 10.1097/EJA.0000000000001153.