Research Article Special Issue: Anesthesia & Postoperative Effects
Comparative Assessment of Fentanyl and Butorphanol as a Post Operative Analgesic in Patients after Spinal Anaesthesia
Nishan Mathias1, Princy Louis Palatty2*, Preeti Jain3 and Sana Aboobaker4
1PG Pharmacology, Father Muller Medical College, Kankanady, Mangalore, Karnataka, India
2Professor in Pharmacology, Father Muller Medical College, Kankanady, Mangalore, Karnataka, India
3Associate Professor in Anaesthesiology, Father Muller Medical College, Kankanady, Mangalore, Karnataka, India
4MBBS Student, Father Muller Medical College, Kankanady, Mangalore, Karnataka, India
*Corresponding author: Princy Louis Palatty, Father Muller Medical College, Mangalore, Karnataka, India, Tel: 0824-2238331; Fax: 0824-2437402; E-mail: @
Received: March 31, 2015; Accepted: March 31, 2015; Published: March 31, 2015;
Citation: Mathias N, Palatty PL, Jain P, Aboobaker S (2015) Comparative Assessment of Fentanyl and Butorphanol as a Post Operative Analgesic in Patients after Spinal Anaesthesia. SOJ Anesthesiol Pain Manag, 2(3): 1-5.
Abstract Top
Introduction: Postoperative pain is the pain felt by the patient following a surgery which could be elective or emergency. This study investigates the efficacy and tolerability of butorphanol and fentanyl with a view to identify the safe and effective postoperative analgesic among them.
Methods: 60 patients undergoing spinal anaesthesia were randomly allocated to two groups receiving butorphanol or fentanyl. Patients falling into the category of ASA I/II were chosen and the VAS score of each of them were taken at various time points.
Results: Comparison of the mean of the various parameters shows that the mean age of the patients enrolled in the study was 45.17±12.12 with 63.3% being males and 36.7% being females. The mean time taken for Butorphanolto reduce the pain was 10±4.91 min while that of fentanyl was 19±7min. The mean duration of action for butorphanol was 107±35.6 min and of fentanyl was 116±19.9 min. Patients on both the drugs also experienced various adverse effects like chest heaviness, drowsiness, pruritus, nausea and vomiting.
Keywords: Postoperative pain; Butorphanol; Fentanyl; Visual Analogue Scale (VAS)
Introduction
"Greatest happiness, mankind can gain, Is not from pleasure, but relief of pain"- John Milton. Pain relief is one of the main aims of postoperative care. Despite the horde of analgesics available, optimal therapy for affording post operative pain relief is still elusive. The healthcare systems afford relief of pain. Postoperative care includes effective relief from suffering, anxiety, restlessness and helplessness as well. Relief of pain would reduce the incidence and development of late complications of surgery including chest infections, cardiovascular, gastrointestinal and metabolic symptoms [1]. There are wide ranging analgesics available, presently are listed (Table 1). This classification of analgesics is comprehensive and encloses all presently available
Table 1: Classification of analgesics.

OPIOID ANALGESICS

NSAIDS

NON OPIOID NON NSAID

Endogenous opioids: Endorphins,         Enkephalins, Dynorphins, Endomorphins

 

Natural opium alkaloids:

Phenanthrene derivatives: Morphine,

Benzylisoquinoline  derivative: Papaverine

 

Synthetic opium derivative:

Morphine derivatives: Hydromorphine

Codeine derivatives: Buprenorphine

Benzomorphans: Pentazocine

Phenylpiperidines: Meperidine

Miscellaneous: Dextromoramide tartrate

Miscellaneous:

Lefetamine

Meptazinol

Tilidine

Tramadol

Tapentadol

Acetaminophen

 

Salicylates: Acetylated aspirin

 

Salicylate salts:

Choline Magnesium

 

Propionic acid: Ibuprofen

 

Indolacetic acid: Indomethacin

 

Pyrrole acetic acid: Tolmetin

 

Anthranilic acid: Mefenamic acid

 

Phenylacetic acids: Diclofenac potassium

 

Enolic acid: Piroxicam

 

Naphthalenone: Nabumetone

 

COX-2 selective: Celecoxib

 

Miscellaneous: Dipyrocetyl

 

COX and LOX inhibitors: Licofelone

 

Flupirtine

Nefopam

Ziconotide

STEROIDAL ANALGESICS:

Flumedroxone

 

MISCELLANEOUS

Antidepressants: AmitryptIline, Fluoxetine

 

Anticonvulsants: Carbamazepine, Gabapentin

 

Alpha adrenergic agents: Clonidine

 

NMDA receptor antagonist: Ketamine, Memantine

 

Putative agents: Botulinum toxins, Thalidomide

 

5HT- agonist: Naratriptan, Eletriptan

 

Local anaesthetics: Lignocaine, Lopivacaine

 

Cholinergics:

Neostigmine, Magnesium,

Cannabinoids, Nabilone

 

Muscle relaxants: Carisoprodol, Methocarbamol

analgesics in proper order. The understanding of pain pathway would be helpful in manipulation, for pain relief. Postoperative pain is distressing and requires comprehensive care to achieve pain relief.

Opioids have been and continue to be, the choice for pain relief. Various methods used to tackle postoperative pain are intravenous infusions, brachial plexus injections, combined spinal epidural infusions and intravenous patient controlled analgesia [2].

Fentanyl is a synthetic opioid acting on the μ (mu) receptors and is almost 100 times more potent than morphine [3]. Butorphanol has agonistic action on K (Kappa) receptors and mixed agonist antagonist on μ (mu) receptors. The analgesic effect of Butorphanol is three times more potent than morphine.

Opioids have a wide spectrum of actions and effects. This study investigates the efficacy and tolerability of the two drugs, with a view to identify the safe and effective postoperative analgesic.

The aim of the study was to compare post operative pain relief with the two drugs Butorphanol and Fentanyl. The objectives revolved around noting the efficacy and adverse reactions of the two agents under constitution, despite using their equianalgesic doses.
Patients and Methods
The study was conducted at the post operative ward of Father Muller Medical College Hospital, Mangalore and the study period was from August 2009-July 2011.
Design
Randomized, prospective double blind study
Inclusion criteria
Adult patients of either sex of ASA I OR II, falling between the age groups of 20-65 years presenting for surgery under spinal anaesthesia were included after obtaining a written informed consent.
Exclusion criteria
• Patients with history of asthma
• H/o cardiac or hepatic disorders
• Taking centrally acting drugs like antidepressants
• Diminished mental competence, deafness, visual
disturbances which would prevent them to comprehend the Visual analogue scale (VAS)
• Pregnant or lactating mothers
Details of the study
Visual analogue scores was regularly evaluated and a score >3 was considered significant enough to warrant treatment with one or the other randomised blinded drug, by intravenous route. All patients were given 0.02 mg/kg midazolam, on arrival to the operation theatre. In the operation theatre base line heart rate, blood pressure, SpO2 were recorded before anaesthesia and repeated at intervals of 5 minutes for the remainder of the study.
At the end of the surgery, the vital signs and events noted and sent to in the postoperative ward. The VAS was used to document the severity of the pain.

The time at which the patient's complaints of pain with a significant VAS score of more than 3 was recorded as time 1, and the blinded drug was administered. The time 1 was recorded as time which the patient experienced relief of pain and the VAS score was again noted. The time when the patient again complained of pain was recorded time as 2 and the next dose of the blinded drug was administered.

The study drug was given when the score of 3 or more was recorded, the patient was randomly allocated to the study groups and relevant analgesics were administered intravenously. The equianalgesic doses of intravenous butorphanol (20mcg/kg) and intravenous fentanyl (1.0 mcg/kg) given to the respective groups are mentioned in Table 2. The volume of the study drug and the capacity of the loading syringe were identical in both the groups. After intravenous administration, the onset and duration of the analgesia were noted. The observer, patient and the staff nurse were unaware of the drug being given. The VAS, Sedation score (Ramsay sedation scale), SpO2, respiratory rate, heart rate SBP and DBP were monitored at intervals of 1, 5, 15, 30, 60, 120 minutes and so on till the patient had a VAS score equal to or more than 3.
Table 2: The equianalgesic doses of intravenous butorphanol (20mcg/ kg) and intravenous fentanyl (1.0 mcg/kg) given to the respective groups.
Before analysis the blending was removed to interpret results from both groups.
Results
Age distribution The mean age of the patients enrolled was 45.17± 12.12 with a mean of 44.20±11.53 and 46.13±12.80 in the butorphanol and fentanyl groups respectively
Sex distribution Out of total 60 patients, 63.3% of them were males and 36.7% of them were females
Time of onset and duration of action A mean time of around 10 minutes ± 4.91 was taken for butorphanol to help reduce the pain (onset of action Time 1- Time 2 ) while compared to fentanyl which took a mean time of 19 minutes ± 7. On the other hand the mean duration of action (Time 1 – Time 3) in butorphanol was 107 minutes ± 35.6 while that of fentanyl was 116 minutes ±19.9
Adverse effects Of the total 60 patients, 55% of them didn't experience any adverse effects. 21.7% complained of insufficient pain control, with a high significance in butorphanol when compared to fentanyl. The adverse effects included chest heaviness (1.7%), drowsiness (8.3%), Pruritus (13.3%), Nausea and vomiting (8.3%) and shivering (8.3%).
Accessory use of drugs Various accessory drugs were used to treat the adverse effects caused by fentanyl and butorphanol. Out of 60 patients, 21.7% were given other analgesics to bring down the pain, 6.7% were given antiemetics for nausea and vomiting and 13.3 % were given antihistamines.
Discussion
A pleasant postoperative period plays a vital role in the surgical outcome [4]. Our study tried to determine the comparative efficacy of both these drugs to produce postoperative analgesia. The study recruited 60 patients and divided them randomly into 2 separate groups to receive fentanyl and butorphanol respectively.

Our study showed a sex ratio of 63.3 % males and 36.7% females with a mean age of 44.2±11.53 in the case of butorphanol and 46.13±12.80 in the case of fentanyl. A study conducted by Frederic et al. showed that women experienced more pain and hence required a higher dose of morphine when compared to men in postoperative period [5] (Figure 1 and 2).

Butorphanol showed a rapid onset of analgesic effect (mean=10.00 min) when compared to that of fentanyl (mean=19.00 min) which was highly significant at a degree of freedom of 2.58. However the duration of analgesic effect with butorphanol (mean=107.50 min) and fentanyl (mean=116.00 min) was comparable but the difference doesn't hold any
Figure 1: Demographic details: sex ratio of sample.
Figure 2: Demographic details: sex ratio of sample.
Determinants of long acting and permanent contraceptive methods utilization among married women in Hossana town, Southern Ethiopia. A case - control study

The VAS score for butorphanol was lower at time 2 as opposed to fentanyl at the same time point. It was also noted that butorphanol had a relatively lower VAS score at time 3 as opposed to fentanyl . This indicates that butorphanol is capable of reducing the pain better than fentanyl as similar results were seen by Thakore et al. [4] Furthermore in our study we also observed that there were around 36.7% of the patients in the butorphanol group needed a rescue analgesic when compared to fentanyl which was 6.7% in contrast to the results obtained by Thakore et al. [5] (Figure 5 and Table 3(a,b,c)).

Adverse effects were observed in both the groups. Pruritus (16.7%) was the main complaint in fentanyl group whereas excessive shivering (16.7%) was the major adverse effect seen in butorphanol group in contrast to fentanyl group in which none experienced shivering. Apart from pruritus patients who received fentanyl also complained of chest heaviness (3.3%), drowsiness (13.3%), nausea and vomiting (10.0%). Other adverse effects among the butorphanol group included drowsiness (3.3%), itching (10.0%), nausea and vomiting (6.7%) (Table 3).

A study done by Scott et al. showed that patients on epidural fentanyl with bupivacaine showed that the most common side
Figure 3: Onset and duration of analgesic action.
Figure 4: Accessory drugs used.
Figure 5: Occurrence of adverse effects among study groups.
effect was pruritus occurring in 10.3% of the cases followed by sedation (7.4%), hypotension (6.6%), nausea (4.8%), inflammation at the site (3.8%) and paralysis (3.0%) [7].

Claxton et al. conducted further study on postoperative pain relief over the fentanyl and found that the incidence of nausea and vomiting after discharge was higher in morphine than in fentanyl group [8]. A similar study done by Wajima et al. which compared the effect of I.V butorphanol against brachial plexus administration showed the same adverse effects like nausea, vomiting and slight drowsiness and they too, were not significant [9].

In our study the equi-analgesic activity of both butorphanol and fentanyl, although similar, butorphanol has an edge over fentanyl due to its favourable safety profile. Conclusions from other studies also indicate that butorphanol and fentanyl have similar efficacy profile for postoperative analgesia. Infact, Butorphanol has remarkable analgesic affect and other effects like antistressor, sedative and anti shivering effect [10]. Postoperative pain gives rise to varied physiological and biological phenomena. Minimizing postoperative pain leads to, earlier mobilization and discharge from hospital, thus aiding recovery. Most of the opioid receptor agonists could bring about required postoperative. A rapid and effective analgesic is sought for postoperative pain. Opioids are the choice for severe pain but limited by the plentiful adverse effects.

The comparison of effect of fentanyl and butorphanol would bring out the better analgesics for postoperative care.

Butorphanol is a synthetic lipid soluble opioid agonist with minimal adverse effects. The duration and quality of analgesia was matched with that of fentanyl.

Respiratory depression was not seen with either of the comparator drugs. Some studies had noted with epidural Butorphanol a reduced carbon dioxide response curve. Various neuroaxial regional techniques e.g. epidural route is commonly employed for postoperative analgesia [11].

Fentanyl is highly lipophilic and rapidly diffuses with least tendency for respiratory depression with adverse effects due to systemic rather than spinal receptor binding [12].

The concomitant adverse effects of nausea, pruritus, shivering, vomiting and respiratory complications were recorded postoperatively upon questioning the patient but their frequency was reduced.

The limitations of our study included small sample size and inclusion of only spinal anaesthesia cases. It would be interesting to note gender variations. The type of surgery could have a bearing on the postoperative pain which has not been considered in our study.
Recommendations
Butorphanol and fentanyl could be advocated for regular postoperative analgesia due to its equianalgesic and minimal adverse effects. A study that incorporates more patients with various types of anaesthesia, considering various surgeries would be more conclusive. A pharmacogenomic evaluation could be undertaken.
Conclusion
The assessment of butorphanol and fentanyl as a postoperative analgesic in abdominal surgeries under spinal anaesthesia, was investigated. The interesting chemical and receptor activity dissimilarities brought these drugs under the scanner.
Table 3a: ANOVA Test.

Drug

Time

n

Min

Max

Mean

Std. deviation

Median

ANOVA

F

Value

d. f

p value

b

Time

1

30

0

0

.00

.000

.00

250.751

2.58

.000 HS

Time

2

30

5

30

10.00

4.913

10.00

Time 3

30

30

180

107.50

35.641

120.00

f

Time 1

30

0

0

.00

.000

.00

873.989

2.58

.000  HS

Time 2

30

5

35

19.00

6.998

20.00

Time 3

30

50

165

116.00

19.888

110.00

Table 3b: Pair wise comparison: Bonferroni.

Drug

(I)

Factor 1

(J)

Factor 2

Mean

Difference

(I-J)

Std. Error

p value

Level of significance

b

Time 1

Time 2

-10.000

.897

.000

HS

Time 3

-107.500

6.507

.000

HS

Time 2

Time 3

-97.500

6.423

.000

HS

f

Time 1

Time 2

-19.000

1.278

.000

HS

Time 3

-116.000

3.631

.000

HS

Time 2

Time 3

-97.000

3.429

.000

HS

Table 3c: Time of onset and duration of action.

Time

Drug

n

Min

Max

Mean

St. Deviation

Median

Mann Whitney Test Z value

p value

Change

1-2nd

b

30

-30

-5

-10.00

4.913

-10.00

4.88

.000 HS

f

30

-35

-5

-19.00

6.998

-20.00

Change 1-3rd

b

30

-180

-30

-107.50

35.641

-120.00

1.15

.249 NS

f

30

-165

-50

-116.00

19.888

-110.00

Change 2 – 3rd

b

30

-170

-20

-97.50

35.178

-110.00

1.08

.279 NS

f

30

-135

-30

-97.00

18.782

-90.00

It was a randomized double blinded prospective, study. The observations noted were for the equianalgesic loses for butorphanol and fentanyl. Belying the lesser frequency of adverse effects with butorphanol, tops with fentanyl following closely.

Documentary evidence along with the outcomes of our study shows minor adverse effects and good analgesic activity with butorphanol and fentanyl. Overall, on comparison of the equianalgesic doses for butorphanol and fentanyl it show similar post operative analgesic effect and propensity for ADR.
ReferencesTop
  1. Merskey H., Bugduk N. Classification of chronic pain. Description of chronic pain syndromes and definition of pain terms. 2nd ed. Seattle W A: IASP Press; 1994, Updated 2011.
  2. White PF, Kehlet H. Improving postoperative pain management: What are the unresolved issues. Anaesthesiology. 2010; 112 (1): 220-5. doi: 10.1097/ALN.0b013e3181c6316e.
  3. Auburn F, Salvi N, Coriat P, Riou B. Sex and age related differences in morphine requirements for postoperative pain relief. Anaesthesiology. 2005; 103(1): 156-60.
  4. Auburn F, Salvi N, Coriat P, Riou B. Sex and age related differences in morphine requirements for postoperative pain relief. Anaesthesiology. 2005; 103(1): 156-60.
  5. Scott DA, Beilby DS, McClymont C. Postoperative analgesia using epidural infusions of fentanyl and bupivacaine: A prospective analysis of 1,014 patients. Anaesthesiology. 1995; 83(4): 727-737.
  6. Claxton AR, McGuire G, Chung F, Cruise C. Evaluation of morphine vs fentanyl for postoperative analgesia after ambulatory surgery procedures. Anesth Analg. 1997; 84(3): 509-14.
  7. Wajima Z, Nakajima Y, Kim C, Kobayashi N, Kadotani H, Adachi H, et al. IV compared with brachial plexus infusion of postoperative analgesia. Br J Anaesth. 1995;74(4): 392-5.
  8. Katzung BG, Master SB, Trevor AJ. Basic & Clinical Pharmacology. 8th ed. New York: McGraw-Hill; 2001.
  9. DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 6th ed. New York: McGraw-Hill; 2005.
  10. Abboud TK, Zhu J, Gangolly J, Longhitano M, Swart F, Makar A, et al. Transnasal butorphanol: a new method for pain relief in postcesarean section pain. Acta Anaesthesiol Scand. 1991; 35(1): 14-8.
  11. Abboud TK, Afrasiabi A, Zhu J, Mantilla M, Reyes A, D'Onofrio L, et al. Epidural morphine or butorphanol augments bupivacaine analgesia during labor. Reg Anesth. 1989; 14(3): 115–20.
  12. Ckerman WE, Juneja MM, Kaczorowski DM, Colclough GW. A comparison of the incidence of pruritus following epidural opioid administration in the parturient. Can J Anaesth. 1989; 36(4): 388–91.
 
Listing : ICMJE   

Creative Commons License Open Access by Symbiosis is licensed under a Creative Commons Attribution 3.0 Unported License