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Received : 03-01-2021

Accepted : 27-01-2021

Available online : 01-06-2021



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Divya, Raghu, Indira, and Roy: Comparision of dexmedetomidine and fentanyl as adjuvants to 0.5% hyperbaric bupivacaine in spinal anesthesia in elective lower abdominal surgeries


Introduction

Anaestheiology is practice of medicine dedicated to pain relief and total care of surgical patient perioperatively. Pain is defined as "an unpleasant sensory and emotional experience associated with, actual or potential tissue damage."1 Anaesthesiologists challenge is to devise a technique for postoperative analgesia with least side effects. August Bier (1861-1949), a German surgeon, is “Father of Intrathecal Anesthesia”  popularized spinal anesthesia2 and it is choice of anaesthesia in lower abdominal surgeries. Advantages are rapid onset of anaesthesia, optimal operating conditions, effectively attenuates neuroendocrine stress response, control of immediate post-operative pain and cost effective. Local anesthetics are limited by short duration of action and there is early demand for rescue analgesics. Adjuvants3 are added to improve quality and duration, provide better postoperative analgesia and patient comfort.4  Local anesthetic adjuvants (46) include classical opioids to a wide range group of drugs with varying mechanisms of action. Adjuvants decrease dose of local anaesthetic and their side effects. (myocardial depression, hypotension, bradycardia, heart block, and ventricular arrhythmias). A common problem during lower abdominal surgeries under spinal anesthesia is visceral pain, nausea, and vomiting.5 Fentanyl is µ receptor agonist 80 times more potent than morphine as an analgesic6, 7 added to spinal 0.5% heavy bupivacaine improves quality of spinal analgesia, reduces visceral and somatic pain.7 However their addition may have side effects like pruritus, respiratory depression, urinary retention, postoperative nausea and vomiting which limits their use.8 Dexmedetomidine is highly selective α2-agonist, S-enantiomer of veterinary sedative medetomidine.9, 10 Food and Drug Administration has approved its use for short-term ICU sedation, it is reported to provide sedation that parallels natural sleep, anxiolysis, analgesia, sympatholysis, and anaesthetic-sparing effect with minimal respiratory depression. α2-agonists produce clinical effects by binding to G-Protein-coupled α2-AR.11 It was under evaluation as neuraxial adjuvant as it provides prolonged analgesia, hemodynamic stability with minimal side effects. Based on earlier human studies, it was hypothesized, dexmedetomidine 5μg added to 0.5%heavy c bupivacaine produces profound postoperative analgesia with minimal side effects.12, 13, 14 In this study we compared 5 µg dexmedetomidine with fentanyl 25µg added to 3ml 0.5% hyperbaric bupivacaine as adjuvants in spinal anaesthesia.

Materials and Methods

A randomized comparative double blind study was carried out at Osmania General Hospital during 2016-2018. Institutional Ethics Committee has approved the study which included 100 ASA I, II patients scheduled for elective lower abdominal surgeries (Appendectomy, inguinal hernioraphy, ovarian cystectomy, TAH, vaginal hysterectomy, cystolithotomy, cystolithotripsy, ovarian cystectomy, internal urethrotomy etc.,) under spinal anaesthesia.

Inclusion criteria

  1. ASA physical status class I and II.

  2. Age between 18 – 60 years of either sex.

Exclusion criteria

  1. ASA grade III and IV

  2. Infection at the site of injection

  3. Coagulopathy or anticoagulation

  4. Congenital anomalies of lower spine

  5. Active disease of CNS

  6. History of allergy to local anesthetics

Patients were alloctaed into two groups by simple randomization technique, based on study drugs assigned to each group.

Group D (50 no’s) - 5μg Dexmedetomidine (5 μg added by taking 50 μg in a insulin syringe) + 3ml 0.5% heavy bupivacaine hcl.

Group F (50 no’s) - 25μg Fentanyl+ 3ml 0.5% heavy bupivacaine hcl.

At preanaesthetic assessment, all patients were evaluated and investigated for systemic diseases. Participants were explained about SAB procedure and educated about using ‘VAS”. A written and informed consent was obtained from all participants in the study. Pre-op preparation of patients included overnight NPO, premedication -Tab. Rantidine 150 mg, Tab. Alprazolam 0.5 mg.

Procedure

On day of surgery, anaesthesia work station and emergency cart were kept ready in OR. On arrival of patient on OR table, 18G iv access was secured on left forearm, patient was connected to multi parameter monitor and baseline vitals were recorded, preloading was done with 15ml /kg Ringer’s Lactate 15 mins prior to start of procedure. Subarachnoid block was performed under aseptic precautions with patient in right lateral position using 26G Quincke’s spinal needle, test drugs assigned to study groups were deposited intrathecally and patient turned supine immediately. Time of onset of T10 sensory block and peak sensory block was noted using pin prick method, Motor block was assessed with Modified Bromage scale and time of onset of bromage 3 motor block was noted. NIBP, ECG NIBP, ECG, HR and SpO2 was recorded every 2 minutes for first 10 minutes, every 10 minutes for next 50 min and every 15 minutes till end of surgery.

Bromage Scale:

Bromage 0 - patient is able to move the hip, knee and ankle.

Bromage 1 - patient is unable to move the hip but is able to move the knee and ankle.

Bromage 2 - patient is unable to move the hip and knee but able to move the ankle.

Bromage 3 –patient is unable to move the hip, knee and ankle.

Modified Ramsay Sedation Score for assessing intraoperative sedation

1 = agitated, restless.

2 = cooperative, tranquil.

3 = responds to verbal commands while sleeping.

4 = brisk response to glabellar tap or loud noise while sleeping.

5 = sluggish response to glabellar tap or loud noise while sleeping.

6 = no response to glabellar tap or loud noise while sleeping.

Intraoperatively all the patients were observed for

  1. Hypotension described as > 20% fall of baseline blood pressure, treated with 200 ml Ringer’s Lactate bolus and 6mg ephedrine i.v.,

  2. Bradycardia defined as HR < 50 bpm, treated with 0 5 mg atropine iv.

  3. Respiratory depression defined as respiratory rate < 9 breaths/min and SpO2< 90% on room air, incidence was recorded in data sheet for analysis.

  4. Side effects.

Regression time of sensory block and motor blockade to reach modified Bromage 0 was noted.

Visual analogue scale used for assessing postoperative pain. VAS > 6 rescue analgesic was given and time noted.

Statistical methods

Statistical analysis was done by Statistical package for social sciences (SPSS) version 17.0, (SPSS Inc, Chicago, IL) statistical analysis software. 

Results on continuous measurements are presented on Mean ±SD (Min-Max) and categorical measurements are presented in Number (%). Significance is assessed at 5% level. Student t test (two tailed, independent) was used to find significance of study parameters on continuous scale between two groups (Inter group analysis) on metric parameters.(43,44) p value was determined.

P > 0.05 is not significant.

P < 0.05 is significant.

P < 0.001 is highly significant

Observations and Results

Table 1

Age, gender, height and weight distribution of patients in the study

Age distribution

Gender distribution

Group F

Group D

Group F

Grooup D

No

%

No

%

M(%) / F(%)

M(%) / F(%)

18-20yrs

02

4

0

0

25 (50%) / 25(50%)

25(50%)/ 25(50%)

21-30yrs

03

6

04

8

31-40yrs

13

26

26

52

41-50yrs

22

44

14

28

Comparisio of Height(cms) & Weight(kgs)

51-60yrs

08

16

05

10

Group F

Group D

P value

>60yrs

02

4.

01

2

Height

155.66±5.16

156.10±5.83

0.690

Total

50

100

50

100

Weight

58.12±12.35

56.90±10.18

0.591

Mean±SD

43.76±10.33

40.86±9.27

Table 2

Comparison of variables in subarachnoid block    

Variables

Group F

Group D

‘p’ value

Time from injection to T10(min)

03.38±0.83

02.62±0.56

<0.001

Time from injection to highest Sensory (min)

11.47±1.23

11.72±1.23

0.314

Onset of Bromage 3 (min)

10.38±1.08

10.59±1.00

0.317

Regression to bromage 0 (min)

152.90±8.31

419.70±16.85

<0.001

The variables of subarachnoid block were compared in both groups it was found the time to attain T10 level significantly lower in group D(02.62±0.56 min, p <0.001). The difference in highest level of sensory block (T4 and T5), time to reach highest level, time to onset of bromage 3 was insignificant. Time to regression to bromage was significantly delayed in Group D (419.70±16.85min, p<0.001).

Table 3

Comparison of systolic blood pressure (mmHg) between two groups

SBP(mmHg)

Group F

Group D

‘p’ value

Pre op

128.60±11.70

126.20±9.54

0.264

2min

125.12±12.11

119.40±10.65

0.014

4min

119.10±11.34

114.84±10.85

0.058

6min

115.24±9.77

112.76±10.84

0.233

8min

112.42±9.04

110.92±10.86

0.455

10min

110.22±9.87

110.50±10.50

0.891

20min

109.46±9.70

109.38±10.77

0.969

30min

107.66±9.49

108.34±10.57

0.736

40min

106.64±9.98

107.32±10.20

0.737

50min

106.82±10.18

107.12±9.75

0.881

60min

108.98±9.74

107.82±9.20

0.542

75min

111.24±9.57

108.60±8.88

0.156

90min

114.58±8.32

110.56±8.55

0.019

Table 4

Comparison of diastolic blood pressure (mm Hg) between two groups

DBP (mmHg)

Group F

Group D

‘p’ value

Pre op

80.10±8.58

80.78±7.81

0.679

2minutes

77.38±9.68

74.18±9.22

0.094

4minutes

72.46±8.56

71.06±9.48

0.440

6minutes

69.04±8.65

69.44±9.56

0.827

8minutes

65.76±7.87

67.74±10.31

0.283

10minutes

62.30±8.39

66.68±10.31

0.022

20minutes

60.92±9.23

65.12±9.96

0.031

30minutes

61.36±7.40

64.80±9.66

0.048

40minutes

60.90±8.25

64.94±9.62

0.026

50minutes

61.28±8.50

64.76±9.28

0.053

60minutes

62.98±8.79

65.16±8.90

0.221

75minutes

65.75±7.53

65.62±8.30

0.933

90minutes

69.00±7.54

67.18±8.42

0.258

Table 5

Comparison of MAP (mmHg) between two groups

MAP (mmHg)

Group F

Group D

‘p’ value

Pre op

97.02±9.99

94.98±7.02

0.238

2minutes

93.29±10.02

89.25±8.97

0.036

4minutes

88.00±8.86

85.65±9.27

0.198

6minutes

84.44±8.48

83.88±9.50

0.757

8minutes

81.31±7.67

82.13±10.08

0.648

10minutes

78.27±8.37

81.28±9.98

0.105

20minutes

77.10±8.63

79.87±9.84

0.138

30minutes

76.79±7.38

79.31±9.50

0.142

40minutes

76.14±8.15

79.06±9.35

0.099

50minutes

76.46±8.49

78.88±8.95

0.169

60minutes

78.31±8.62

79.38±8.41

0.533

75minutes

80.91±7.65

79.94±7.98

0.541

90minutes

84.19±7.14

81.64±8.02

0.096

Table 6

Comparison of Heart Rate in study groups

HR(bpm)

Group F

Group D

‘p’ value

Pre op

82.68±12.42

84.36±13.71

0.522

2minutes

82.04±12.16

83.36±13.94

0.615

4minutes

81.02±11.16

83.82±14.32

0.278

6minutes

79.78±10.72

83.02±14.03

0.198

8minutes

78.58±9.67

80.34±12.51

0.433

10minutes

77.60±8.79

77.75±10.80

0.938

20minutes

76.42±8.14

76.26±11.38

0.936

30minutes

75.46±7.70

75.48±11.20

0.992

40minutes

74.68±7.67

74.92±10.87

0.899

50minutes

74.48±7.70

74.92±9.70

0.802

60minutes

74.18±7.57

74.98±8.64

0.624

75minutes

73.40±7.57

74.90±8.54

0.355

90minutes

72.78±7.11

73.84±8.22

0.492

Table 7

Comparision of RR and SpO2 between two groups

Variables

Group F

Group D

‘p’ value

Respiratory rate (RR)

16.10±1.61

16.10±1.61

1.000

SpO2

97.92±0.75

97.92±0.75

1.000

Hemodynamic stability in both study groups was comparable throughout study period, incidence of hypotension and bradycardia was seen in 14 patients and 7 patients respectively in group D, there were no other side effects noted.

Table 8

Side-effects noted in study groups

Side-effects

Group F (n-50)

Group D (n-50)

No.

%

No.

%

Nausea

3

6

0

0.0

Vomiting

1

2

0

0.0

Pruritis

3

6

0

0

Hypotension

8

16

14

28

Bradycardia

0

0.0

7

14

Urinary retention

0

0.0

0

0.0

Respiratory depression

0

0.0

0

0.0

Table 9

Comparison of modified Ramsay sedation score

MRSS

Group F

Group D

‘p’value

30mins

2.00±0.00

2.00±0.00

1.000

60mins

2.00±0.00

3.00±0.00

<0.001

90mins

2.16±0.37

3.40±0.49

<0.001

120mins

2.14±0.35

2.00±0.00

0.006

150mins

2.00±0.00

2.00±0.00

1.000

180mins

2.00±0.00

2.00±0.00

1.000

Sedation score in the perioperative period was significantly more at 60min(3.00±0.00, p value <0.001) and 90 mins (3.40±0.49, p value <0.001).

Table 10

Comparison of visual analogue scale

VAS

Group F

Group D

‘p’ value

6hours

3.50±0.51

0.00±0.00

<0.001

12hours

5.90±0.97

3.50±0.51

<0.001

18hours

7.28±0.95

5.52±0.51

<0.001

24hours

7.24±0.96

3.62±0.69

<0.001

Postoperative pain score was significantly lower (‘p’<0.001) in dexmedetomidine group and need for rescue first 24hrs was less.

Discussion

Post operative pain and suffering results in significant physiological, psychological, economic and social adverse effects.15 Spinal anaesthesia is a popular technique for lower abdominal surgeries and is effective in immediate post-operative pain relief. Various analgesic regimens have been used to ensure adequate postoperative pain relief as local anaesthetics have short duration of action and potential to produce deleterious effects like cardiac arrhythmias, central nervous system depression, seizures and allergic reactions.16, 17, 18 Co-administration of adjuvants prolong duration of sensory-motor block, limit cumulative dose requirement of local anaesthetics improve efficacy and contribute in their own special manner to potentiate analgesic effect of local anaestheticsm.19 Neuraxial administration of opioids as adjuvants is one method for postoperative pain management, which allows early ambulation, and decrease length of hospital stay however they are often associated with side-effects like nausea, vomiting, respiratory depression and hyperalgesia. Intrathecal Fentanyl as adjuvant to bupivacaine is an established method,20, 21 it has rapid onset,22, 23 enhances intra and postoperative analgesia without prolonging motor block.22 Fentanyl is more lipid soluble and rapidly eliminated from CSF making late respiratory depression less likely. The clinical experience gained in use of α2adrenoreceptor agonists intrathecally is described with clonidine, clinical studies are needed to prove efficacy, safety, suitable dose of dexmedetomidine as an adjuvant spinal local anesthetics. α2-agonists bind to presynaptic C-fibers, postsynaptic dorsal horn neurons, complementary action of local anesthetics and α2 agonists s at spinal level accounts for profound analgesic properties. Intrathecal α-2 receptor agonists have been found to significantly prolongs duration of spinal anaesthesia, have antinociceptive action for both somatic and visceral pain.24 Fentanyl and Dexmedetomidine were compared as adjuvant to heavy bupivacaine in our study, Group F received 3ml of 0.5% heavy bupivacaine and 25µg Fentanyl, Group D received 3ml of 0.5% heavy bupivacaine and 5μg Dexmedetomidine intrathecally in patients posted for elective infra umbilical surgeries.

The following parameters were observed during study

  1. Time of onset of action.

  2. Highest level of sensory and motor blockade.

  3. Time of onset of Bromage 0.

  4. Intraoperative heart rate, Blood pressure, SpO2.

  5. Intraoperative sedation.

  6. Regression to Bromage 3.

  7. Postoperative requirement of analgesia.

Study results demonstrate 25μg Fentanyl prolongs duration of bupivcaine induced sensory block, as reported in study by Wang et al.,25 in parturients undergoing caesarean delivery intrathecal Fentanyl didn’t enhance onset of Bupivacaine induced spinal block as reported by Hunt et al.,26 Opioids and local anaesthestics exert their antinociceptive effect in spinal cord by different mechanisms. Fentanyl, exerts its action by opening K+ channels and reducing Ca2+ influx, result in inhibition of transmitter release. It also has a direct postsynaptic effect, causing hyperpolarisation and a reduction in neuronal activity. Bupivacaine, acts mainly by blockade of voltage gated Na+ channels in axonal membrane, interfere with synaptic transmission by a presynaptic inhibition of Ca++ channels in addition to their effects on nerve conduction. A combination of these effects may explain observed synergism between Bupivacaine and Fentanyl in our study group. Intrathecal fentanyl as adjuvant reduces visceral and somatic pain.27 Talke et al.,28 observed antishivering property of α-2 adrenergic agonists, shivering was not observed in both the study groups. Intrathecal Fentanyl as an adjuvant to bupivacaine prolonged sensory block without prolonging motor block though fewer patients in this group demanded pain relief,29 Harbhejsingh et al., showed Fentanyl, 25μ (o.3μ/kg) intrathecally, reduced analgesic requirement without increasing incidence of side effects nausea or pruritus and desaturation in early postoperative period, 29 number of studies have shown 25μ Fentanyl provides maximum duration of post-operative analgesia with minimal side effects like respiratory depression and pruritus, in present study pruritus was observed in few patients which is insignificant. Varrassi et al, noted 25μg Fentanyl in spinal anaesthesia, in non premedicated elderly males did not alter respiratory rate, ETCO2, minute ventilation, respiratory drive or ventilatory response to CO2, concluded 50μg Fentanyl causes an early respiratory depression.30 Hala EA Eid et al., 15μg dexmedetomidine intrathecally showed significantly higher sedation scores which can be beneficial for patients undergoing lengthy complex surgeries as an alternative to epidural or prolonged general anesthetics.31 However, such high sedation scores may be harmful in elderly and high risk surgical patients owing to excessive sedation and respiratory depression.

Belzarena et al., Fentanyl 0.5μ/kg and 0.75μ/kg intrathecally, increased duration of postoperative analgesia in parturients following caesarean delivery (640 ± 141 min and 787±161 min, respectively); however, it was associated with a decrease in respiratory rate and increased incidence of sedation and pruritus.32 Fentanyl 50-100 μg in epidural provides postoperative analgesia 3-4 hrs duration, similar to duration of analgesia following 25μg dose of subarachnoid Fentanyl.

Rajni Gupta, Reetu Verma, Jaishri Bogra et al., compared 5μgDexmedetomidine with 25μg Fentanyl as adjuvants to spinal heavy bupivacaine, found dexmedetomidine is associated with prolonged motor and sensory block, hemodynamic stability, reduced demand for rescue analgesics in 24hrs as compared to Fentanyl33 which are similar to our study. Sedation score was more in group D patients (3.8 ±0.5) as compared to group F (2.2±0.53) which is statistically significant (P<0.05). The findings correlate with our study mean sedation score in group D (3.40 ± 0.49) was significant (p<0.001)compared with group F (2.16 ± 0.37), postoperative analgesic requirements in first 24hrs was significantly less in Group D (p <.001). Incidence of nausea vomiting and pruritis was known in our study but was insignificant. α-2adrenergic agonist also have antishivering property as observed by Talkeet al and Maroof M et al., there was no incidence of shivering in our study.34, 35 Epidural dexmedetomidine 2μg/kg for postoperative analgesia in humans did not result in any neurologic deficits36 Fukushima et al,. Dexmedetomidine 3μg or 30 μg clonidine added to13 mg spinal bupivacaine produced same duration of sensory and motor block with minimal side effects in urologic surgeries Kanazi et al., from this study, we assumed 3-5μg dexmedetomidine and 30-45μg clonidine are equipotent as adjuvants to spinal Bupivaciane.37 Both Fentanyl and Dexmedetomidine provided good quality intraoperative analgesia, clinically better in group D. Al-Ghanem et al., had compared 5μg Dexmedetomidine and 25μg Fentanyl as adjuvants10mg isobaric Bupivacaine in vaginal hysterectomy and concluded that 5μg Dexmedetomidine produces more prolonged motor and sensory block. These findings correlate with our study, sensory and motor block duration was significantly longer in Dexmedetomidine group (419.70±16.85mins, p value <0.001)and good patient satisfaction.38 Al-Mustafa et al., studied effect of Dexmedetomidine 5μg and 10 μg with Bupivacaine in urological procedures, Dexmedetomidine prolongs duration of spinal anaesthesia in a dose dependent manner and attenuates visceral pain in abdominal surgeries under spinal anaesthesia. In our study also no patient perceived visceral pain in both D and Fgroups.39

Rajni Gupta, Reetu Verma, Jaishri Bograetal, (2011) used Dexmedetomidine 5μg as an intrathecal adjuvant to ropivacaine produces prolonged duration of motor and sensory block.40 They also found that intraoperative ephedrine requirement was more in group D as compared to group R. In our study intraoperative incidence of hypotension was observed in 14 patients of group D.41

Limitations of the study

  1. Population involved includes young and otherwise healthy patients.

  2. The effect in older patients with cardiovascular comorbidities are yet to be investigated.

  3. This study also lacks an active control for systemic effects of Dexmedetomidine.

Recommendations

Further studies that compare effect of intrathecal and IV Dexmedetomidine on spinal Bupivacaine may also be warranted.

Conclusion

In conclusion, 5 μg dexmedetomidine is a good alternative to 25 μg fentanyl as an adjuvant to 0.5% heavy bupivacaine in spinal anesthesia. It provides a better quality of perioperative / intraoperative analgesia, hemodynamic stability, minimal side effects, and reduced demand for rescue analgesics in 24 hr as compared to Fentanyl. Hence, Dexmedetomidine seems to be a better choice as Intrathecal adjuvant with Bupivacaine.

Source of Funding

None.

Conflict of Interest

The authors declare that there is no conflict of interest.

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