Keywords
fentanyl consumption - postoperative pain - pregabalin - preoperative anxiety
Introduction
Despite better understanding of acute pain physiology over the past decade, approximately
80% of patients undergoing surgical procedures experience postoperative pain.[
1
] Acute postoperative pain is a predictor of chronic pain syndromes as a result of
surgery.[
2
] Although opioids are important component of postoperative pain management, they
are associated with side effects,[
3
] and so, the multimodal analgesic approach has been recommended for the management
of acute postoperative pain.[
4
]
,
[
5
] Experimental models of neuropathic pain and inflammatory hyperalgesia have shown
that γ-amino butyric acid analogues, such as gabapentin and pregabalin, have antinociceptive
and antihyperalgesic properties. It has been suggested that central neuronal sensitisation
may result in amplification of postoperative pain,[
6
] and that preoperative administration of gabapentin, before inflammatory trauma or
surgical stimulation, may reduce the degree of central sensitisation.[
7
] Compared with gabapentin, pregabalin has better pharmacokinetic properties and fewer
drug interactions, due to an absence of hepatic metabolism.[
8
] Apart from its analgesic potency, pregabalin possesses anxiolytic properties.[
9
]
The primary objectives of this study were to investigate the effect of pregabalin
premedication on preoperative anxiety and to evaluate the effect of pregabalin premedication
on postoperative pain scores (both stationary and movement related) and opioid (fentanyl)
consumption in patients operated for lumbar laminectomy and discectomy. The prevailing
hypothesis was, with the decrease in preoperative anxiety, the management of postoperative
pain would be better if these patients were given oral pre-gabalin at a dose of 150
or 300 mg as compared to placebo. The secondary objectives were to investigate the
side effects of pregabalin administration in these patients and to study the efficacy
of pregabalin premedication in attenuating/modifying the hemodynamic and bispectral
index (BIS) responses during induction of anesthesia and orotracheal intubation.
Materials and Methods
This was a prospective, randomized, double-blind, placebo-controlled study. After
obtaining approval from the institute’s Ethics Committee, written informed consent
was obtained from sixty adults of either sex between the age group of 18 and 65 years,
belonging to the American Society of Anesthesiologists physical status I and II, with
symptoms of nerve root compression, posted for elective lumbar laminectomy and discectomy,
were included in the study. Patients who were unable to understand the operation of
patient-controlled analgesia (PCA) device, with known allergy to pregabalin/gabapentin
and/or fentanyl, any history of drug and/or alcohol abuse, intake of non-steroidal
anti-inflammatory drugs (NSAIDs) within 24 h prior to operation, impaired kidney function,
taking sedatives or anticonvulsants and pregnant females were excluded from this study.
The patients were randomized with computer-generated block randomisation, into three
groups of 20 each, either to receive placebo (B-complex), pregabalin 150 mg or pre-gabalin
300 mg, 2 h before anesthetic induction. All patients received 0.2 mg glycopyrrolate
intramuscularly, 1 h before surgery. Patients’ anxiety level was assessed by 100 mm
visual analogue scale (VAS) in the ward before administration of the study drug. Assessment
of the score was repeated in the preinduction room and in the operating room (OR).
In the OR, patients’ baseline pain intensity at rest and during movement (from supine
to lateral position) was assessed using VAS for pain. Simultaneously, baseline values
of heart rate (HR), mean arterial blood pressure (MABP), BIS, respiratory rate (RR)
and oxygen saturation (SpO2) were noted.
Anesthesia was induced with fentanyl 2 µg/kg, propofol 1.5-2 mg/kg and tracheal intubation
facilitated with rocuronium 1 mg/kg. Anesthesia was maintained with nitrous oxide
and oxygen in 2:1 ratio with isoflurane (end tidal 0.8%–1.2%) and intermittent doses
of rocuronium. Fentanyl was repeated as per requirement, at the discretion of the
attending anesthesiologist. Mechanical ventilation was adjusted to keep the end-tidal
CO2 concentration between 36 and 38 mmHg. Lactated Ringer’s solution was used for maintenance
requirements of fluids throughout the surgery. Monitoring during anesthesia consisted
of continuous electrocardiogram, HR, SpO2, NIBP, BIS, airway pressure, temperature and endtidal anesthetic concentrations.
BIS sensors were attached as per instructions of the manufacturer and connected to
Aspect-2000 BIS monitor (Aspect medical system, Natick, MA, USA). All parameters were
recorded at 15 min interval. After intubation, the eyes and face were covered with
cotton pads. Patients were positioned prone on a Wilson’s frame, with head in neutral
position over a horseshoe headrest. Under proper aseptic precaution, the surgical
site was infiltrated with lignocaine 1% with adrenaline (1:200,000). At the end of
the surgery, patients were turned supine. Neostigmine 50 µg/kg and glycopyrrolate
10 µg/kg were given to reverse the residual neuromuscular blockade. Trachea was extubated
when the patient was fully awake.
On arrival to the intensive care unit, patient’s pain intensity at rest and during
movement was assessed using pain VAS. Simultaneously, values of HR, MABP, RR and SpO2 were noted and taken as the values at 0 h. Then, the measurements were repeated at
hourly intervals until 8 h. Pain medications were converted to oral NSAIDs after the
study period.
Patients were given a bolus dose of fentanyl 1 µg/kg through PCA pump. The incremental
dose was set at 0.25–0.5 µg/kg with a lock-out interval of 10 min and 4 h limit of
0.4 mg. No background infusion was given. All patients received oxygen through face
mask with a flow of 3 L/min throughout the study period. A single observer, who was
blinded to the groups, recorded all the measurements. Total dose of fentanyl consumed
intra- and postoperatively over the 8 h period was noted. Sedation was assessed using
Ramsay 5 point sedation score at every 2 h up to 8 h. Adverse effects such as postoperative
nausea and vomiting (PONV), dizziness, headache and visual blurring were noted.
Statistical Analysis
Sample size was computed to assess a mean difference of 15 mm in VAS score for pain
between pregabalin groups and placebo group. With an assumption of standard deviation
of 15 mm in each group, the required sample size for α-error of 0.05 and power of
80% was estimated to be 16 individuals per group. We included twenty patients per
group to cover for dropouts from the study. Outcomes were analyzed using one-way ANOVA
for continuous variables and Kruskal-Wallis test for categorical variables. Postoperative
fentanyl consumption was analyzed using one-way ANOVA and Fisher’s exact test. The
VAS for pain was compared by repeated-measures analysis followed by multiple comparisons
with least square deviation method. The incidence of side effects was analyzed using
Fisher’s exact test. Statistical significance between the groups was analyzed using
post hoc comparison (multiple comparisons) by Bonferroni’s method. A p-value < 0.05 was considered statistically significant. The statistical analysis was
performed using the Statistical Package for Social Science software (SPSS for Windows,
Version 15.0. Chicago, SPSS Inc.).
Results
A total of sixty patients enrolled and completed the study. The demographic characteristics
such as mean age, weight, duration of anesthesia and hemodynamic parameters were comparable
in all the three groups ([
Table 1
]). The intergroup comparison revealed comparable (p = 0.159) VAS scores for anxiety in Groups P1 and P2; however, the VAS anxiety score
was significandy lower in Group P1 and Group P2 as compared to Group C ([
Table 2
]).
Table 1
Baseline characteristics
|
Variable
|
Group C (n = 20)
|
Group P1 (n = 20)
|
Group P2 (n = 20)
|
p-Value
|
|
Abbreviations: BIS, bispectral index; HR, heart rate; MABP, mean arterial blood pressure;
SD, standard deviation; VAS, visual analog scale.
Note: All values expressed as mean ± SD, p < 0.05 significant.
|
|
Age (y)
|
41.6 ± 11.5
|
43.8 ± 11.5
|
40.8 ± 11.0
|
0.69
|
|
Weight (kg)
|
68.4 ± 9.2
|
66.5 ± 10.3
|
68.3 ± 12.8
|
0.83
|
|
Duration of anesthesia (min)
|
171.3 ± 50.0
|
174 ± 43.1
|
173 ± 41.2
|
0.98
|
|
VAS score
|
46.5 ± 15.7
|
17.5 ± 6.4
|
14.0 ± 6.0
|
0.001
|
|
MABP (mm Hg)
|
107.4 ± 9.5
|
102.6 ± 11.2
|
100.3 ± 8.2
|
0.70
|
|
HR (beats/min)
|
82.8 ± 14.8
|
81.6 ± 11.6
|
76.0 ± 11.8
|
0.21
|
|
BIS
|
97.7 ± 0.5
|
97.7 ± 0.5
|
97.1 ± 1.0
|
0.008
|
Table 2
Intergroup comparison of visual analogue scale scores for anxiety
|
Group (n = 20)
|
VAS score
|
p-Value
|
|
Abbreviations: SD, standard deviation; VAS, visual analog scale.
Note: All values expressed as mean ± SD, p < 0.05 significant.
|
|
Group C
|
46.5 ± 15.7
|
0.001
|
|
Group P1
|
17.5 ± 6.4
|
|
|
Group C
|
46.5 ± 15.7
|
0.001
|
|
Group P2
|
14.0 ± 6.0
|
|
|
Group P1
|
17.5 ± 6.4
|
0.16
|
|
Group P2
|
14.0 ± 6.0
|
|
Intraoperative Hemodynamics
Baseline and postinduction MABP and HR were comparable in the three groups ([
Table 1
]). During the first 4 min after intubation, the increase in MBP and HR was significantly
less in the P2 group ([
Table 3
]).
Table 3
Mean arterial blood pressure and heart rate after induction
|
Variable
|
Group C (n = 20)
|
Group P1 (n = 20)
|
Group P2 (n = 20)
|
p-Value
|
|
Abbreviations: HR, heart rate; MABP, mean arterial blood pressure; SD, standard deviation.
Note: All values expressed as mean ± SD, p < 0.05 significant.
|
|
MABP 0
|
116.5 ± 15.1
|
105.4 ± 17.1
|
96.3 ± 16.4
|
0.001
|
|
MABP 1
|
113.0 ± 14.7
|
105.8 ± 17.6
|
93.1 ± 15.5
|
0.001
|
|
MABP 2
|
103.8 ± 10.2
|
97.1 ± 15.8
|
89.6 ± 14.0
|
0.006
|
|
MABP 3
|
98.1 ± 11.1
|
90.9 ± 12.3
|
88.0 ± 14.5
|
0.04
|
|
MABP 4
|
94.9 ± 9.9
|
86.4 ± 14.5
|
85.1 ± 14.1
|
0.04
|
|
MABP 5
|
88.9 ± 9.6
|
83.6 ± 13.6
|
83.9 ± 12.9
|
0.30
|
|
MABP 10
|
85.0 ± 6.6
|
78.4 ± 9.0
|
78.2 ± 9.9
|
0.02
|
|
HR 0
|
109.1 ± 18.8
|
98.7 ± 15.4
|
89.8 ± 18.4
|
0.004
|
|
HR 1
|
110.2 ± 16.1
|
97.8 ± 12.6
|
89.7 ± 16.7
|
0.001
|
|
HR 2
|
102.7 ± 13.5
|
92.4 ± 11.7
|
87.3 ± 17.9
|
0.005
|
|
HR 3
|
100.3 ± 14.6
|
89.1 ± 13.1
|
85.9 ± 19.0
|
0.01
|
|
HR 4
|
95.5 ± 13.5
|
85.9 ± 13.0
|
83.6 ± 19.7
|
0.05
|
|
HR 5
|
91.1 ± 13.8
|
83.6 ± 12.1
|
81.5 ± 18.9
|
0.12
|
|
HR 10
|
82.0 ± 12.7
|
76.5 ± 10.4
|
75.0 ± 13.9
|
0.18
|
Effect on Bispectral Index
Baseline BIS was significantly less in Group P2, compared to Group C and Group P1
([
Table 1
]). Postinduction, it decreased in all the three groups, with the most significant
decrease in Group P2 ([
Table 4
]). Postintubation, an increase in BIS value was noticed in Group C ([
Table 5
]) only during the first 2 min (p = 0.001).
Table 4
Hemodynamic and bispectral index parameters after induction
|
Variable
|
Group C (n = 20)
|
Group P1 (n = 29)
|
Group P2 (n = 20)
|
p-Value
|
|
Abbreviations: BIS, bispectral index; HR, heart rate; MABP, mean arterial blood pressure;
SD, standard deviation.
Note: All values expressed as mean ± SD, p < 0.05 significant.
|
|
MABP (mmHg)
|
87.4 ± 8.7
|
86.3 ± 8.8
|
81.4 ± 8.2
|
0.068
|
|
HR (beats/min)
|
87.0 ± 13.7
|
81.9 ± 12.1
|
76.2 ± 14.03
|
0.05
|
|
BIS
|
59.9 ± 5.9
|
56.6 ± 5.5
|
55.4 ± 4.9
|
0.03
|
Table 5
Bispectral index response after induction
|
Variable
|
Group C (n = 20)
|
Group P1 (n = 29)
|
Group P2 (n = 20)
|
p-Value
|
|
Abbreviations: BIS, bispectral index; HR, heart rate; SD, standard deviation.
Note: All values expressed as mean ± SD, p < 0.05 significant.
|
|
BIS 0
|
69.4 ± 5.3
|
63.2 ± 5.9
|
56.6 ± 6.3
|
0.001
|
|
BIS 1
|
71.2 ± 5.2
|
65.0 ± 5.6
|
57.5 ± 6.2
|
0.001
|
|
BIS 2
|
67.0 ± 4.7
|
63.1 ± 4.2
|
56.6 ± 6.4
|
0.001
|
|
BIS 3
|
63.2 ± 5.1
|
60.4 ± 4.5
|
55.6 ± 6.3
|
0.001
|
|
BIS 4
|
60.9 ± 4.8
|
58.5 ± 4.3
|
53.4 ± 6.2
|
0.001
|
|
BIS 5
|
59.2 ± 4.7
|
56.1 ± 5.4
|
53.2 ± 5.8
|
0.001
|
|
BIS 10
|
57.0 ± 2.82
|
53.2 ± 5.2
|
57.4 ± 4.3
|
0.001
|
Intraoperative Fentanyl Consumption
Total intraoperative fentanyl consumption was significantly higher in Group C as compared
to Group P1 and Group P2 whereas it was comparable in the P1 and P2 groups ([
Table 6
]).
Table 6
Intergroup comparison of total fentanyl consumption in intra- and postoperative period
|
Group (n = 20)
|
Fentanyl (µg)
|
p-Value
|
|
Abbreviation: SD, standard deviation.
Note: All values expressed as mean ± SD, p < 0.05 significant.
|
|
Intraoperative fentanyl consumption
|
|
Group C
|
201.5 ± 46.4
|
0.002
|
|
Group P1
|
151.8 ± 39.2
|
|
|
Group C
|
201.5 ± 46.4
|
0.04
|
|
Group P2
|
167.5 ± 44.1
|
|
|
Group P1
|
151.8 ± 39.2
|
0.77
|
|
Group P2
|
167.5 ± 44.1
|
|
|
Postoperative fentanyl consumption
|
|
Group C
|
339.1 ± 88.0
|
0.001
|
|
Group P1
|
213.0 ± 112.9
|
|
|
Group C
|
339.1 ± 88.0
|
0.001
|
|
Group P2
|
190.8 ± 45.3
|
|
|
Group P1
|
213.0 ± 112.9
|
1.00
|
|
Group P2
|
190.8 ± 45.3
|
|
Mean Visual Analog Scale Scores for Pain at Rest and Pain on Movement
Both the mean VAS scores for pain at rest and pain on movement in the first 8 h were
significantly less in the pregabalin groups (P1 and P2) as compared to placebo (p = 0.001). However, they were comparable in P1 and P2 groups ([
Figs. 1
] and [
2
]).
Total Postoperative Fentanyl Consumption
Fentanyl consumption in the postoperative period was significantly reduced in P1 and
P2 groups versus control group. However, it was comparable between P1 and P2 groups
([
Table 6
]).
Side Effects
The level of sedation was higher in P2 group in the first 4 h. The incidence of PONV
was significantly more in control group compared to P1 and P2 groups (p = 0.018). Dizziness and blurring of vision were seen significantly in more number
of patients in Group P2.
Discussion
The current concept of multimodal postoperative analgesia is mainly based on the combination
of opioids, NSAIDs or paracetamol and perioperative administration of local anesthetics.
The use of opioids may be limited by adverse effects, such as nausea, vomiting, excessive
sedation, pruritus and urinary retention which can prolong the postoperative recovery
period. NSAIDs are associated with damage to gastrointestinal mucosa, bleeding, renal
toxicity, allergic reactions and heart failure.[
10
] Cyclooxygenase-2 selective NSAIDs may have prothrombotic properties, increasing
the risk of stroke and myocardial ischemia.[
11
] Anxiety is an unpleasant emotion and most patients awaiting elective surgery experience
preoperative anxiety. It may also adversely influence anesthetic induction and patient
recovery, as well as decrease patient satisfaction with the perioperative experience.
Pregabalin has analgesic properties,[
12
]
,
[
13
]
,
[
14
]
,
[
15
] opioid-sparing effects[
12
]
,
[
13
] and relieves anxiety.[
14
] Pregabalin probably reduces or modulates the release of excitatory neurotransmitters,[
2
]
,
[
16
] leading to reduction in the level of anxiety and pain. Although pre-gabalin has
been studied previously, a dose-ranging study has not been conducted in patients undergoing
lumbar laminectomy and discectomy. In light of the previously published studies, we
chose to evaluate the efficacy of pregabalin in doses of 150 and 300 mg in patients
undergoing lumbar laminectomy and discectomy, respectively. The minimum recommended
dose of pregabalin has been advocated to be 150 mg, but not all the previous studies
with 150 mg pregabalin have shown a benefit. Therefore, we compared the dose response
of 150 with 300 mg. In previous studies, pregabalin has been administered 1 h prior
to induction of anesthesia.[
12
]
,
[
13
]
,
[
14
]
,
[
15
] It has been observed that pregabalin displays a linear pharmacokinetics, and the
time to peak plasma concentration is within 1 to 2 h. The decision to administer pregabalin
2 h prior to induction of anesthesia was primarily to ensure that the peak plasma
effect of pregabalin has been achieved at the time of assessing anxiety prior to induction
of anesthesia. The inclusion of a placebo group in our study was to evaluate the influence
of anesthetic technique on postoperative pain relief. In this study, the anesthetic
regimen was standardised. Hence, the true protective effect of pregabalin could be
revealed by comparing the analgesic outcome in the treatment and placebo groups.
Fig. 1 Visual analog scale scores for pain at rest.
Fig. 2 Visual analog scale scores for pain on movement.
In this study, it has been observed that preoperative administration of pregabalin
in single dose of 150 and 300 mg was effective in significantly reducing preoperative
anxiety as compared to placebo. At the same time, all our patients were arousable
and responding to commands (respiratory assessment score ≤3). Earlier, it has been
observed that the decrease in anxiety after premedication with pregabalin 150 and
300 mg was similar to that of diazepam 5 mg in day-care gynecological surgeries.[
14
] On the contrary, White et al[
17
] did not find any decrease in preoperative anxiety after administration of pre-gabalin
at doses from 75 mg to 300 mg. This could probably be due to the short time interval
from administration of the study medication to induction of anesthesia in their study
groups.
The mechanism by which pregabalin attenuates the pressor and BIS responses to laryngoscopy
and intubation is unknown. Our results suggested that a single oral dose of pregabalin
300 mg could significantly attenuate hemodynamic response to tracheal intubation compared
to placebo and pregabalin 150 mg. Baseline BIS was significantly lower in the pregabalin
300 mg group suggestive of increase in sedation/hypnosis level in this group even
before induction. Induction of anesthesia expectedly decreased BIS in all the three
groups, but the impact on BIS was greater in the pre-gabalin 300 mg group. To our
knowledge, no randomized controlled trial (RCT) has observed the effect of pregabalin
premedication on hemodynamic and BIS response to laryngoscopy and tracheal intubation,
till date.
It was also observed that pregabalin at doses of 150 and 300 mg might cause a reduction
in intraoperative opioid consumption. The total intraoperative fentanyl consumption
in pregabalin group was significantly less as compared to placebo. On the contrary,
all the previous studies have demonstrated no effect on total intraoperative analgesic
use.[
15
]
,
[
17
]
In the present study, the mean VAS pain scores at rest and on movement were decreased
by pregabalin premedication of 150 and 300 mg as compared to placebo, suggesting that
pregabalin effectively alleviates pain. The significant finding here is that pregabalin
causes reduction in movement-evoked pain. These results are similar to the findings
of Jokela et al in which they found that the area under curve for VAS scores for pain
at rest, 1 to 8 h after surgery, and on movement were lower in the pregabalin 150
mg group than that of placebo.[
14
] Similarly, another RCT in patients undergoing laparoscopic cholecystectomy concluded
that postoperative pain (at rest and on movement) scores were reduced in the pregabalin
group in the first 24 h postoperatively.[
15
] On the contrary, Mathiesen et al in abdominal hysterectomy patients, observed that
pain scores remained similar for both pregabalin as well as placebo groups.[
18
]
In our study, premedication with both 150 and 300 mg doses of pregabalin resulted
in significantly less consumption of fentanyl in the first 8 h, postoperatively. Many
studies sought to determine whether perioperative pregabalin was effective in reducing
postoperative pain and whether it had opioid-sparing effects. However, differences
in the pregabalin dosages and types of surgery have yielded contrasting results. Reuben
et al observed that, in patients undergoing decompressive lumbar laminectomy with
posterior spinal fusion, pregabalin 150 mg before and after surgery was as effective
as celecoxib in reducing post-operative pain and patient-controlled morphine consumption,
and the combination of both drugs was most effective.[
12
] Mathiesen et al observed that pregabalin at the dose of 300 mg causes 50% reduction
in 24 h postoperative morphine requirement.[
13
] Jokela et al observed that analgesia was better during the first 8 h post-operatively,
after premedication with pregabalin 150 mg in patients undergoing day-care gynaecological
laparoscopic surgeries.[
14
] Agarwal et al in their study patients found that pregabalin premedication of 150
mg is an effective method of reducing postoperative pain and fentanyl consumption.[
15
] In patients undergoing laparoscopic cholecystectomy, administration of pregabalin
600 mg significantly reduced postoperative pain and morphine consumption, at the cost
of increased incidence of dizziness.[
16
] On the contrary, White et al found that pregabalin at the doses of 75, 150, and 300 mg did not cause any postoperative pain relief.[
17
] This could probably be due to the nature of superficial surgical procedures with
relatively low levels of pain in the postoperative period. Furthermore, patients were
observed for only 2 h postoperatively whereas pregabalin has a biological half-life
of 5.5 to 6.7 h, and boluses of fentanyl were given to patients on complaining of
moderate-to-severe pain instead of PCA. Peng et al observed that pregabalin 75 mg provided limited analgesic benefit in the postoperative period.[
19
]
In our study, the incidence of PONV was significantly less in pregabalin groups as
compared to placebo. Explanation for this could be due to decreased amount of fentanyl
consumption in both intra- and postoperative period. In a study by Jokela et al, the
authors observed that incidence of PONV was same in pregabalin 75, 300 mg groups and placebo group.[
14
] Mathiesen et al found no difference in PONV in placebo and pregabalin 300 mg groups.[
13
]
,
[
18
] Agarwal et al also did not observe any difference in PONV between pregabalin 150
mg and placebo groups in patients undergoing laparoscopic cholecystectomy.[
15
]
Dizziness and somnolence have been demonstrated to be the most common adverse effects
of pregabalin in controlled studies of chronic pain.[
20
] In our study, the incidence of pregabalin-related side effects such as dizziness
and visual blurring was significantly more in pregabalin 300 mg group compared to
control and pregabalin 150 mg groups. The level of sedation was also significantly
higher in pre-gabalin 300 mg group during the first 4 h postoperatively. Mathiesen
et al observed increased sedation in patients receiving pregabalin 300 mg.[
13
] Agarwal et al found that 150 mg pregabalin was not associated with increased incidence
of sedation and side effects.[
15
]
There are some limitations in our current study design. First, only a single dose
of pregabalin was administered before surgery, and the maximum dose in our study was
300 mg. However, since the half-life of pregabalin is 5.5 to 6.7 h, the effect of
repeat doses of pregabalin remains to be studied. Second, we used a simple but well-validated
measure of acute-state anxiety, namely the VAS score, because of the limited time
available to perform the pre-operative assessments. Clearly, more sophisticated psychological
testing procedures might have been able to ascertain subtle and more specific effects
of the drug on the patients’ level of acute anxiety.
Conclusion
From this study, we conclude that pregabalin in both the doses given 2 h prior to
the surgery can significantly reduce preoperative anxiety and intraoperative requirement
of fentanyl compared to placebo. Both the doses of pregabalin significantly decreased
postoperative pain VAS scores at rest and on movement during the first 8 h after surgery.
Increased incidence of sedation, dizziness and visual blurring was observed more with
pregabalin 300 mg group, while reduced incidence of PONV was seen with either of the
doses. Therefore, the single use of pregabalin in doses between 150 and 300 mg is
both safe and effective for reducing preoperative anxiety with a favourable postoperative
analgesic profile.
