Keywords Anesthesia - bupivacaine - laminectomy - local - magnesium sulfate - postoperative
pain
INTRODUCTION
Laminectomy is associated with considerable postoperative pain.[1 ]
[2 ]
[3 ] Good and optimal pain relief is important for postoperative laminectomy, and it
may influence the overall outcome.[4 ]
[5 ] Different modalities and drugs for pain management following lumbar laminectomy
have evolved over time. This includes intravenous, intramuscular, epidural, spinal,
instillation and infiltration routes of analgesia.[6 ] Addition of adjuvants like clonidine, magnesium and dexemedetomidine has shown promising
results.[7 ]
[8 ]
[9 ] Providing infiltration analgesia locally in the area of surgical trauma, with minimal
systemic side effects, is an attractive option.[8 ]
[10 ]
There are very few recent studies reporting the usage of infiltration anaesthesia
with local anaesthetics for relief of postoperative pain following lumbar laminectomy
procedures.[11 ]
[12 ]
[13 ] Magnesium is widely used in perioperative settings and has shown to decrease the
anaesthesia and analgesia requirements effectively.[9 ]
[14 ]
[15 ] And there are no studies revealing the use of magnesium as an adjuvant to infiltration
anaesthesia following lumbar laminectomy.
The objective of this study was to assess and compare the effectiveness and safety
of local infiltration of bupivacaine and bupivacaine plus magnesium sulphate for postoperative
analgesia in patients undergoing lumbar laminectomy.
MATERIAL AND METHODS
Following institutional ethics committee approval, informed and written consent was
obtained from 60 patients of American Society of Anaesthesiologists (ASA) class 1
and 2, scheduled to undergo lumbar laminectomy of ages 18-65 years and body mass index
<30. The exclusion criteria included patients with severe systemic disease, ASA class
3 and 4, allergy or intolerance to study drugs, psychiatric illness, seizure disorder,
regular narcotic use and refusal by the patient. All patients were familiarised with
a 10 cm visual analogue scale (VAS) preoperatively with 0: No pain, 1-3: Mild pain,
4-6: Moderate pain, 7-9: Severe pain and 10: The worst imaginable pain.
Preoperative VAS scores were obtained from all patients by asking the average intensity
of pain at the preanaesthetic checkup. Premedication consisted of tab Ranitidine 150
mg and tab Alprazolam 0.25 mg 2 hours prior to surgery. Patients were assigned into
two groups by computer randomisation. As per the randomisation number allocated, the
drug was prepared by an anaesthesia technician. The contents of the study drug were
blinded to the surgeon and the anaesthesiologist. The study drugs for both the groups
were prepared accordingly. Group BM: 50 mg of bupivacaine (10 ml), 500 mg of magnesium
sulphate (1 ml) made up to 20 ml solution with normal saline (NS), 10 ml given on
either side.
Group B
50 mg of bupivacaine (10 ml) made up to 20 ml solution with NS, 10 ml given on either
side.
In both groups, general anaesthesia technique was used. All the patients were induced
with standard dose of thiopentone sodium 4-7 mg/kg, fentanyl 2 μg/kg and injection
glycopyrrolate 0.2 mg intravenously. Muscle relaxation for tracheal intubation was
facilitated with loading dose of vecuronium 0.08 mg/kg. Intraoperative anaesthesia
and muscle relaxation was maintained with isoflurane 0.6-1% and atracurium infusion
dose of 0.3 to 0.6 mg/kg/hour. Intraoperative analgesia was maintained with continuous
infusion of fentanyl at a dosage of 1-5 μg/kg/hour. Standard monitoring techniques
like electrocardiography (ECG), blood pressure, pulse oximetry, capnography and heart
rate were used. Both atracurium and fentanyl infusions were stopped 15 minutes before
expected time for completion of the procedure. After the completion of the surgical
procedure, local infiltration with the study drug was given into the paravertebral
muscles on either side by the operating surgeon. After application of the plasters,
the patient was made supine and neuromuscular blockade was reversed with neostigmine
and glycopyrrolate. All the patients were extubated on the table. Once completely
awake, all the patients were assessed for pain. Patients who remained drowsy after
1 hour were excluded from the study.
After the operation, patients were transferred to postoperative ward where VAS pain
scores was obtained from all patients at 1, 2, 4, 6, 8, 12 and 24 hours. Rescue analgesia
was carried out with tramadol 100 mg (intramuscular, IM) to a maximum dose of 150
mg once the VAS recorded was > 5. The repeat second dose was given atleast after 30
minutes of the initial dose. The time to first analgesic consumption was recorded.
Analgesic duration was defined as the time from completion of surgery till the time
for first request for tramadol.
Patients were asked to indicate the degree of overall satisfaction with postoperative
pain management on a 5-point satisfaction scale after 24 hours of surgery: 0 = unsatisfactory/poor,
1 = somewhat satisfactory/adequate, 2 = satisfactory/adequate, 3 = very good and 4
= excellent.
Blood pressure, heart rate, respiratory rate and oxygen saturation and the presence
of side effects such as nausea, vomiting, sedation, hypotension, dizziness, headache,
dry mouth, allergic reaction, respiratory depression and urinary retention were recorded
postoperatively for each patient at the same time as pain assessment over 24 hours.
Statistical analysis
Data were expressed as mean and 95% confidence interval of mean for continuous variables
(height, weight, duration, age). Data was analysed using Statistical Package for the
Social Sciences (SPSS) version 15 (SPSS Inc, Chicago, IL). Normality and variance
of the data was assessed by Anderson Darling test and Modified Leven’s test, respectively.
Comparison of continuous data between groups was done using independent T-test (ANOVA
of means). Comparison of nominal data was done using Chi-square analysis and ordinal
data using Mann-Whitney test. P value less than 0.05 was considered statistically significant between groups.
Sample size for the study was estimated by taking into consideration the results of
two studies reported by Tauzin-Fin et al . (Acta Anaesthesiol Scand, 2009)[16 ] and Milligan et al . (J Bone Joint Surg (Br), 1993).[17 ] The study results by Tauzin et al . was as follows: Tramadol consumption in Group intravenous magnesium was 221 ± 64.1
mg and was 134 ± 74.9 mg in Group local magnesium. In another study by Milligan et al . morphine consumption was 37 ± 17.19 mg in Group bupivacaine and was 50.9 ± 19.14
mg in Group control. The effect size calculated from the results of these two studies
was found to be 1. In the power analysis by G power, the sample size required was
found to be 50 with α =0.05, power of (1–β) =0.95 and effect size = 1.0. As dropout
cases would be expected due to extended duration of surgery, a sample size of 60 was
selected for the study.
RESULTS
All the groups were comparable with respect to demographic variables (age, gender,
weight) [Table 1 ]. The data were found to be normally distributed and homoscedasticity of the data
was maintained with respect to the demographic data and baseline VAS score. The changes
in the VAS score at 1, 2, 4, 6, 8, 12 and 24 hour after completion of surgery were
depicted in [Table 2 ]. VAS scores were significantly less in B group when compared to BM group in the
first 4 hours and was considered significant (P value < 0.05). At 2 hours, number of patients with mild VAS was less in group BM
and number of patients with moderate VAS was less in group B compared with the other
group. At 4 hours, patients with moderate VAS was significantly less in group BM;
but again at 6, 8 and 12 hours postoperatively, patients with moderate VAS scores
were on a rise in group BM. VAS scores were statistically insignificant at 1 hour
and at 12 and 24 hour postoperatively [Figure 1 ].
Figure 1: Mean VAS scores at 1, 2, 4, 6, 8, 12 and 24 hour for two groups. Abbreviations: VAS
= Visual Analogue Scale; B = Bupivacaine; BM = Bupivacaine with magnesium; mod = moderate
Table 1
Demographic data
Parameters
Gr B
Gr BM
P value
B = Bupivacaine, BM = Bupivacaine with Magnesium, yrs = years, kgs = kilograms; Gr
= Group
Age (yrs)
41.33±3.96 (1.2)
40.4±4.2 (1.8)
0.35
Weight (kgs)
61.4±8.15 (1.82)
62.15±8.44 (1.88)
0.73
Gender
20/10
19/11
0.5
Table 2
VAS score at 1, 2, 4, 6, 8, 12 and 24 hour after completion of surgery
Groups
Preoperationpain (%)
Pain (hr) (%)
1
2
3
6
8
12
24
VAS = Visual analogue scale, B = Bupivacaine, BM = Bupivacaine with magnesium, hr=hour
B mild
15 (50)
21 (70)
23 (76.7)
2 (6.7)
12 (40)
9 (30)
13 (43.3)
7 (23.3)
Moderate
15 (50)
9 (30)
7 (23.3)
28 (93.3)
16 (53.3)
21 (70)
17 (56.7)
22 (73.3)
Severe
0
2 (6.7)
1 (3.3)
BM mild
8 (26.7)
14 (46.7)
16 (53.3)
13 (43.3)
7 (23.3)
1 (3.3)
9 (30)
13 (43.3)
Moderate
21 (70)
16 (53.3)
14 (46.7)
17 (56.7)
23 (76.7)
29 (96.7)
21 (70)
7 (56.7)
Severe
1 (3.3)
P value
0.13
0.058
0.052
0.001
0.1
0.006
0.21
0.18
The time to first analgesic consumption, tramadol consumption and the degree of overall
satisfaction with postoperative pain management on a 5-point satisfaction scale was
highly significant in group BM compared to group B (P < 0.001) [Figure 2 ].
Figure 2: Comparison of duration of analgesia, tramadol consumption and degree of satisfaction
in both the groups
There were no side effects like nausea, vomiting, allergic reaction, dry mouth, respiratory
depression and urinary retention in both the groups.
DISCUSSION
The results of our study showed that local infiltration of magnesium sulphate added
to bupivacaine provided better pain control without any added side effects compared
to bupivacaine alone. This was evident by reduction in the total analgesic consumption
and decrease in the number of patients requiring supplementary analgesics. The origin
of back pain sensation is mediated by nociceptors and mechanoreceptors from the vertebrae,
intervertebral disc, dura and nerve root sleeves, facet joint capsules, muscles, ligaments
and fascia. Innervation is by the posterior rami of the spinal nerve roots, which
are linked to the sympathetic and parasympathetic nerves. Inflammation of these structures
or mechanical compression of the nerves in this area results in pain.[18 ]
[19 ]
All surgical procedures initially stir up an array of nociceptive signals followed
by a secondary inflammatory response contributing considerably to postoperative pain.
This is called peripheral sensitisation. These signals further cause sustained alterations
in both the peripheral and the central nervous system called central sensitisation
that eventually leads to exaggeration and protraction of postoperative pain.[19 ]
After laminectomy, poorly managed pain may inhibit the early ability to mobilise the
patient. Good pain relief is important for patients undergoing laminectomy, and it
may considerably influence the overall outcome.[20 ]
[21 ]
In an attempt to improve fast rehabilitation after laminectomy, research has been
directed towards new techniques for postoperative analgesia. Different modalities
of pain therapy like intramuscular, intravenous, infiltration, epidural, spinal and
instillation are in use. Recent literature has focused on multimodal approach for
postoperative pain relief following lumbar decompression procedures. This included
both the use of opioids and non-opioid drugs parenterally. But parenteral use of such
drugs has limitations like respiratory depression, gastrointestinal irritation, renal
dysfunction, bleeding problems and bowel and bladder disturbances. Regional analgesia
in the form of spinal and epidural instillation of medications has shown to have delayed
neurological recovery.[22 ]
Infiltration analgesia nowadays has shown a significant steep rising curve for immediate
postoperative pain management. Infiltration with local anaesthetics acts directly
on the pain-producing mechanisms with lesser incidence of side effects. Therefore,
infiltration mode of analgesia was considered for this study. Literature has shown
effective use of bupivacaine, levo-bupivacaine and ropivacaine for infiltration analgesia.[12 ] Bupivacaine was regularly used for the same in our institute but not reported. Addition
of magnesium to local anaesthetic has shown to have beneficial effect in prolonging
the duration of analgesia.[23 ]
[24 ] Addition of adjuvants to local anaesthetics for postoperative analgesia in patients
undergoing lumbar laminectomy was rarely reported.
N -methyl-D-aspartate (NMDA) receptors play an important role in central nociceptive
transmission, modulation and sensitisation of acute pain states.[4 ]
[3 ]
[25 ] In addition to their central location, recent studies identified NMDA receptors
peripherally in the skin and muscles, and found that they play a role in sensory transmission
of noxious signals.[25 ] In its inactive state, the NMDA receptor is blocked by the presence of a centrally
positioned magnesium ion. Afferent activity in nociceptor fibres dislodges the central
magnesium ion from the NMDA receptor, therefore allowing calcium influx into the cell.
Magnesium can be considered as a physiological blocker of NMDA receptors.
Use of magnesium in the perioperative setting was reported widely in the literature.[14 ] Both intrathecal and systemic administration of magnesium has shown to enhance postoperative
analgesia through its voltage-dependent blockade of NMDA receptors.[9 ] This current study was done to determine whether magnesium might provide analgesia
when administered at surgical site, especially with the evidence of NMDA receptor
existence in the peripheral nerve fibres and immune cells in which their activation
was found to play a potential role in nociception.[19 ]
In the literature, it was reported that total analgesic consumption was a better parameter
than time to first analgesic request.[26 ] Magnesium has been demonstrated to reduce postoperative analgesic requirements significantly.
At the same time, the infiltration of magnesium with local anaesthetics has shown
effective pain relief following other procedures like radical prostatectomy and tonsillectomy.[16 ]
[25 ]
In this current study, patients receiving bupivacaine and magnesium had a significantly
longer time to first analgesic request with reduced overall analgesic consumption
and an overall higher degree of satisfaction. The proposed mechanism of magnesium
infiltration may be due to the reduction of NMDA-induced current thus promoting analgesia.
This was strongly evident by a significant reduction in the total analgesic requirements
in the first 24 hours after surgery.
In conclusion, magnesium sulphate seems justified to its use as a safe adjuvant to
local anaesthetics like bupivacaine in amplifying their effect for infiltration analgesia
in patients undergoing laminectomy surgeries.
