Intrathecal magnesium sulfate as a spinal adjuvant in two different doses, combined with 0.5% heavy bupivacaine for infraumbilical surgeries.

UNLABELLED: The spinal anesthesia has the definitive advantage that profound nerve block can be produced in a large part of the body by the relatively simple injection of a small amount of local anesthetic. BACKGROUND AND AIMS: The use of adjuvant drugs with local anesthetics for spinal is intended to improve the success of regional anesthesia. The present study evaluated magnesium sulfate in two different doses and fentanyl as an adjuvant to bupivacaine for spinal anesthesia.
MATERIALS AND METHODS: Following Institutional Ethical Committee approval and written informed consent, a prospective randomized double-blinded study was conducted in 81 cases. Patients included were of either gender belonging to American Society of Anesthesiology (ASA) I or ASA II status undergoing elective infraumbilical surgeries of <3 h. Patients were randomized into four groups and were administered an intrathecal solution of (1) Group NS: 3 cc of 0.5% bupivacaine + 0.5 cc of NS. (2) Group F: 3 cc of 0.5% bupivacaine + 25 mcg fentanyl (0.5 cc). (3) Group M 50: 3 cc of 0.5% bupivacaine + 50 mg magnesium sulfate diluted to 0.5 cc with NS. (4) Group M 100: 3 cc of 0.5% bupivacaine + 100 mg magnesium sulfate diluted to 0.5 cc with NS. The variables assessed were visual analog pain scale, pruritus, intensity of motor block and somnolence before and after intrathecal injection at 5, 10, 15, 30, 45, and 60 min in the 1(st) h, at every 30 min in next hour and then hourly thereafter.
RESULTS: The mean duration of analgesia in normal saline group, fentanyl group, M 50 and M 100 groups are 272.8 (standard error [S.E.] of mean 22.9), 360.0 (S.E. of mean 28.8), 252.5 (S.E. of mean 15.0), 276.6 (S.E. of mean 29.5) min, respectively.
CONCLUSION: The addition of magnesium sulfate in the two different doses (50, 100 mg) does not affect the quality of block or duration of analgesia. However, M 100 is as effective as fentanyl as far as the duration of analgesia is concerned.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Spinal anesthesia is widely used technique for performing different orthopedic, urological, obstetrical, and other infraumbilical surgical procedures. Recent developments have led to greater patient satisfaction and accelerated functional recovery, and shortened the duration of stay in the hospital significantly. It is a common practice to combined opioids and other adjuvant drugs along with local anesthetic agents. Many other drugs such as epinephrine, clonidine, ketamine, and neostigmine[1234] have also been tried alone and even in combination with opioids as an adjuvant to local anesthetic agents to prolong the duration of analgesia. Although opioids are associated with many side effects such as respiratory depression, nausea and vomiting, pruritus, urinary retention, and hemodynamic instability, but they do not delay motor recovery.

In recent past, other drugs such as magnesium sulfate, dexmedetomidine, dexamethasone, and midazolam[5678910111213141516] have been used as an adjunct in spinal anesthesia along with local anesthetic.

Magnesium sulfate acts by blocking N-methyl-D-aspartate (NMDA) channels in voltage dependent fashion and can prevent the induction of central sensitization by peripheral nociceptive stimulation. The study was conducted to test magnesium sulfate in two different doses as an adjuvant to local anesthetic in spinal anesthesia for surgeries below the level of the umbilicus.

MATERIALS AND METHODS

Following the approval of Institutional Ethics Committee and written informed consent a prospective randomized double-blinded study was conducted from February 2005 to July 2005 in 81 cases. Patients included in study were 18–60 years of age and of either gender [Figure 1] belonging to American Society of Anesthesiology (ASA) I or ASA II status undergoing elective surgeries of <3 h, below the level of umbilicus. All the patients were evaluated preoperatively and fully informed consent was obtained. Patients with hepatic and/or renal disease, diabetic, uncontrolled hypertension, allergic to opioids, receiving magnesium, with the use of another method of analgesia like nerve block or epidural anesthesia were excluded from the study. Premedication did not include any sedative or analgesic. H2 blocker was administered the night before and on the morning of surgery. Patients were kept fasting overnight. Totally, 81 Patients (sample size as calculated from the mean age of the study group planned that is, 18–60 [Table 1], standard deviation of the population 12.55, standard error [S.E.] 1.9149) were randomized into four groups and were administered intrathecal solution of:

Figure 1

Distribution of patients according to sex in groups

Table 1

Age comparison

Group NS: 3 cc of 0.5% bupivacaine + 0.5 cc of NS

Group F: 3 cc of 0.5% bupivacaine + 25 mcg fentanyl (0.5 cc)

Group M 50: 3 cc of 0.5% bupivacaine + 50 mg magnesium sulfate diluted to 0.5 cc with NS

Group M 100: 3 cc of 0.5% bupivacaine + 100 mg magnesium sulfate diluted to 0.5 cc with NS.

After shifting the patient in the operating room baseline values of heart rate, blood pressure (systolic blood pressure [SBP], diastolic blood pressure [DBP], and mean arterial pressure) [MAP], and SpO2 were recorded. After securing intravenous (i.v.) access all patients were preloaded with 10 ml/kg body weight of Ringer's lactate or 500 ml of Ringer's lactate whichever is high. Under strict aseptic precautions subarachnoid block was administered with the patient in sitting posture using the midline approach at L3/L4 or L4/L5 level with 25-gauge Quincke tip needle by the observer or the consultant anesthesiologist (blinded to the study drug) 3.5 cc of study drug was administered into the intrathecal space once the free flow of cerebral spinal fluid (CSF) is confirmed. The drugs used were Sensorcaine Heavy, manufactured by AstraZeneca Pharma India Limited; Magnesium Sulfate, manufactured in India by Hindustan Pharmaceuticals; Fendrop manufactured by Sun Pharmaceuticals. Patients in whom more than two attempts were taken to administer the block or in whom an approach other than midline was opted were deleted from the study. Patients were made supine once the drug was administered. No tilt of the table was allowed till 20 min after the administration of the drug at which time the level of the blockade was noted as the “highest level of block achieved (sensory level). The sensation was tested by pinprick method with 23-gauge i.v. needle.” The variables assessed were visual analog pain scale (VAS) which was explained to the patient preoperatively, pruritus, intensity of motor block, and somnolence before intrathecal injection and after intrathecal injection at 5, 10, 15, 30, 45, and 60 min in the 1st h, at every 30 min in next hour and then hourly afterward. VAS 0 was “no pain,” VAS “10” was “worst pain ever in life.”

Pruritus was assessed before the intrathecal injection and at 5, 10, 15, 30, and 45 min afterward. Pruritus was graded as,

No pruritus

Pruritus without scratching, and treatment not required

Pruritus with scratching, and treatment is desirable

Severe pruritus and scratching, and treatment is required

Intractable pruritus and scratching.

The intensity of motor block and somnolence were assessed simultaneously. The Bromage score of healthy limb only was recorded.

Motor block was assessed as [Bromage score Table 2]:

Table 2

Bromage score

None – Full flexion of knees and feet

Partial – Just able to move knees

Almost complete – Able to move feet only

Complete – Unable to move feet and knees.

Somnolence was categorized as:

Fully awake

Somnolent and responds to call

Somnolent and no response to verbal stimulation

Asleep and responds to only painful stimulation.

SBP and DBP 5 min before (i.e., baseline parameters) and every 3 min for the first 15 min after the administration of subarachnoid block and every 5 min afterwards.

Systolic blood pressure 20% below the baseline or <90 mm Hg was treated with i.v. bolus of lactated Ringer's solution and ephedrine 6 mg if required. Patients who complained of shivering were administered 1 mg of midazolam i.v. stat. The duration of analgesia was recorded as the time from injection or from time when the VAS is 0 (in those patients VAS more than or equal to 1 before intrathecal injection) until the patient's request for additional analgesia. Rescue analgesia was fentanyl 1 mcg/kg intravenously. Any other events intraoperatively, and in 24 h postoperative period pertaining to anesthesia was recorded.

STATISTICAL ANALYSIS

Data were subjected to statistical analysis. The software used for statistical analysis was SPSS for Windows, Release 10.0.5 (27 Nov 1999), Standard Version. Chicago, IL, USA. Continuous variables were analyzed with Student's t-test, analysis of variance, Fisher's F-test, Levene's test for equality of variance, Pearson correlation as appropriate. In Student's t-test, we have applied one sample t-test, independent sample t-test, and paired sample t-test. Other parameters were analyzed by descriptive statistics as appropriate.

DISCUSSION

Magnesium possesses a property of NMDA receptor antagonist. NMDA receptor antagonist plays an important role in the prevention of central sensitization of pain. Glutamate and aspartate neurotransmitters are released in response to noxious stimuli and bind to the NMDA receptors and various other excitatory amino acid receptors. NMDA receptors activation leads to calcium and sodium influx into the cell, efflux of potassium and initiation of central sensitization, and wind-up.[1718] NMDA channels are blocked in a voltage-dependent manner by magnesium, and it leads to a marked reduction in NMDA-induced currents.[19] Insufficient blood–brain barrier penetration to achieve effective CSF concentrations limits the parental application of magnesium for antinociceptive modulation as NMDA receptor antagonist. Intrathecal magnesium could potentiate opioid spinal analgesia and avoid the potential side effects of larger doses of i.v. magnesium that may be required to observe antinociceptive modulation in humans.

The study was conducted to test magnesium in two different doses and fentanyl as an adjuvant to local anesthetic in spinal anesthesia for surgeries below the level of the umbilicus.

In our study majority of patients, the level of block achieved is T10 in all the four groups. The conditions favorable for surgery like Bromage score 3 was achieved earliest in NS Group by 10 min, M 100 group by 15 min followed by Fentanyl, and M 50 by 20 min [Table 2] Changes in time for complete recovery [Tables 3 and 4] and duration of analgesia [Tables 5 and 6] are not statistically significant. The addition of magnesium was not shown to prolong the duration of analgesia.

Table 3

Time for complete motor recovery

Table 4

Relation between age and time for complete motor recovery

Table 5

Duration of analgesia

Table 6

Duration of analgesia

Of the 81 patients enrolled, 2 patients were deleted from the study because there was inadequate block even after 10 min of injection. Two patients were excluded from the study because the surgeons decided to resect the rib hence general anesthesia was administered. Two patients were deleted from the study because the duration of surgery exceeded 180 min. One patient was deleted from NS Group during statistical analysis because the duration of analgesia in this patient was 1156 min, which is interfering with the statistical tests applied.

In our study with the use of fentanyl, magnesium sulfate 50 mg and magnesium sulfate 100 mg as adjuvant to hyperbaric bupivacaine delay in onset of time to reach sensory block up to T10 level and motor blockade to Bromage score 3 is observed. A similar delay in onset of the spinal blockade was reported by Jabalameli and Pakzadmoghadam[8] and another recent study by Kathuria et al.[13] who also compared two different doses of magnesium sulfate as an adjunct to local anesthetic intrathecally. Our results are also comparable to the results of another recent study by Sunil et al.,[14] who compared Dexmedetomidine 10 µg, Fentanyl 25 µg, and magnesium sulfate 50 mg as adjuvant to hyperbaric bupivacaine for spinal anesthesia, and similar delay is noted in the onset of sensory and motor block in magnesium group. Malleeswaran et al. and Ozalevli et al.[1516] also reported similar delay in onset of sensory and motor block with the use of magnesium sulfate as an adjuvant to bupivacaine. Ozalevli et al.[16] used isobaric bupivacaine and suggested that the change in pH and baricity of bupivacaine due to the addition of magnesium sulfate contributed to the delayed onset.

CONCLUSION

In our study, the mean duration of analgesia in normal saline group, fentanyl group, M 50, and M 100 groups are 272.8 (S.E. of mean 22.9), 360.0 (S.E. of mean 28.8), 252.5 (S.E. of mean 15.0), 276.6 (S.E. of mean 29.5) min, respectively. The quality of block and duration of analgesia are not affected by the addition of magnesium sulfate in the two different doses as tested (50, 100 mg). However, M 100 is as effective as fentanyl. Fentanyl is an opioid and availability is license dependent. In terms of cost effectiveness and easy availability may be magnesium sulfate 100 is preferable to fentanyl as an adjuvant to local anesthetic for spinal anesthesia.