|Year : 2020 | Volume
| Issue : 1 | Page : 13-17
“A comparative evaluation of intraarticular bupivacaine and neostigmine with bupivacaine and fentanyl for post operative analgesia in arthroscopic knee surgeries: A prospective randomized study”
Raj Bahadur Singh1, Mohd Asim Rasheed2, Sanjay Choubey3, Saurav Shekhar1, Ritu Singh1
1 Assistant Professor, Dept. of Trauma and Emergency (Anesthesiology), IGIMS, Patna, India
2 Associate Professor, Dept. of Anesthesiology, Super Specialty Cancer Institute & Hospital, Lucknow, India
3 Professor, Dept. of Anesthesiology, ELMC& H, Lucknow, India
|Date of Submission||06-Jan-2020|
|Date of Acceptance||11-Jan-2020|
|Date of Web Publication||16-Nov-2020|
Mohd Asim Rasheed
Associate Professor, Super Specialty Cancer Institute & Hospital, Lucknow
Source of Support: None, Conflict of Interest: None
Context : Now a days arthroscopic surgeries are very commonly performed and are associated with post-op pain. Various method of relieving pain is present like NSAIDS, Opiods, peripheral nerve blocks and local anaesthetics. In this study we are trying to search a novel method to control post operative pain . The present study aims to compare the effects of intraarticularly instilled Bupivacaine and Neostigmine with Bupivacaine and Fentanyl for pain relief following knee arthroscopic surgery.
Aims and objective : To compare the efficacy of bupivacaine and Fentanyl with bupivacaine and Neostigmine administered intraarticularly for postoperative pain relief in patients undergoing knee arthroscopic surgeries and comparing duration of analgesia, hemodynamic parameter and side effects if any.
Material and Method- It is a prospective randomized study. Sample size was 75 divided in three groups.
◼ GROUP P - Intraarticular injection 19ml of 0.25% bupivacaine as control group + 1 ml NS
◼ GROUP N- Intraarticular injection of 19 ml of 0.25% bupivacaine + 1 ml (500 mcg ) of neostigmine.
◼ GROUP F- Intraarticular injection of 20ml of 0.25% bupivacaine + 1 ml (50 mcg )of fentanyl.
Result : Demographic variable amongst all three groups were matched. In this study mean duration of analgesia time in group P is significantly lower than group N and Group F (p value < .05)however duration of analgesia time in Group N and Group F are comparable but Group N showed slightly higher duration of Analgesia.
Conclusion : Thus, we found that addition of neostigmine or fentanyl to bupivacaine increases the duration of analgesia in the post-operative period.
Keywords: Intraarticular, Bupivacaine, Neostigmine, fentanyl, Analgesia.
|How to cite this article:|
Singh RB, Rasheed MA, Choubey S, Shekhar S, Singh R. “A comparative evaluation of intraarticular bupivacaine and neostigmine with bupivacaine and fentanyl for post operative analgesia in arthroscopic knee surgeries: A prospective randomized study”. J Indira Gandhi Inst Med Sci 2020;6:13-7
|How to cite this URL:|
Singh RB, Rasheed MA, Choubey S, Shekhar S, Singh R. “A comparative evaluation of intraarticular bupivacaine and neostigmine with bupivacaine and fentanyl for post operative analgesia in arthroscopic knee surgeries: A prospective randomized study”. J Indira Gandhi Inst Med Sci [serial online] 2020 [cited 2021 Mar 2];6:13-7. Available from: http://www.jigims.co.in/text.asp?2020/6/1/13/300731
| Introduction|| |
Arthroscopic knee surgeries are commonly performed for various diagnostic and therapeutic purposes. They are associated with variable postoperative pain. After a knee arthroscopic surgery, different drugs are used through intraarticular administration to induce analgesia., Adequate pain relief is a prerequisite for early mobilization, rehabilitation and discharge of these patients. Acute postoperative pain management remains a challenge despite multimodal analgesic techniques. Several analgesic strategies such as systemic medication (narcotic, NSAID), central or peripheral nerve block, and intraarticular drug administration of ketorolac, 5 β 2 - agonists,,,, opioids, local anesthetics, have been used to interrupt the pain pathway, which is called a multimodal approach. However, none is free from limitations such as needs for special equipments, monitoring, and risks of complications. Utilizing the peripheral receptors for postoperative pain management is an important mode of such an approach. The intraarticular route of drug administration is an example for management of pain after joint surgery utilizing the peripheral receptors. It provides analgesia locally with minimal systemic side effects. A number of adjuvants either alone or in combination with bupivacaine have been tried to improve the quality and duration of analgesia and have shown good results. However, the analgesic efficacy of these intraarticularly instilled different agents is yet to be established. Although different studies were conducted in the past, there is consensus of opinion regarding the need to have more comparative studies on the efficacy, side effects, and complications of the different types of analgesia,.
Yet the search for a novel alternative is continuing. New interest has focused on the cholinergic system that modulates pain perception and transmission. The acetylcholine esterase inhibitor Neostigmine has demonstrated dose dependent analgesia following spinal or epidural administration The analgesic effects of neostigmine is by muscarinic presynaptic inhibition of neostriatal glutamatergic afferents, Fentanyl is a highly lipid soluble, strong μ-receptor agonist and phenyl piperidine derivative has rapid onset and short duration of action.
The present study aims to compare the effects of intraarticularly instilled Bupivacaine and Neostigmine with Bupivacaine and Fentanyl for pain relief following knee arthroscopic surgery.
| Aims|| |
- To compare the efficacy of bupivacaine and Fentanyl with bupivacaine and Neostigmine administered intraarticularly for postoperative pain relief in patients undergoing knee arthroscopic surgeries.
| Objectives|| |
To compare :-
- Duration of analgesia in the study groups.
- Hemodynamic parameter changes in the study groups.
- side effects, if any.
| Material and Methods|| |
This study is a prospective randomized study and carried out in Department of Anaesthesiology of a tertiary care hospital, which is a medical college. After obtaining clearance from institutional ethical committee study was carried out for the period of approximately one year. Sample size calculation was done with the help of statistician Sample size has been calculated by the formula given bellow-
Type I error δ = 5%
Type II error
Power of study= 90%
Data loss =10%
The sample size comes out to be n = 25 in each group and statistical analysis of the data were carried out with the help of SPSS/PSAW (Statistical package for social science / Predictive Analytics Software) and by using ANOVA and Chi Square test.
75 ASA I & II patients undergoing rthroscopic Knee Surgery was included in the study. Inclusion criteria was Patients scheduled for elective arthroscopic knee surgery, ASA GRADE I & II and Age group of 20-50 years whereas exclusion criteria was patient refusal to participate in study, patient with comorbid illness like cardiovascular diseases, renal disease ,chronic pulmonary disease, hepatic disease or of coagulation disorder and also those patient who had history of allergy to any of study drugs. We have also excluded those patients who had history of analgesic intake within 24 hours before surgery.
Patient was allocated randomly by computer generated random allocation in three groups and study drug was given by operating surgeon who was unaware about the drug.
- GROUP P - Intraarticular injection 19ml of 0.25% bupivacaine as control group + 1 ml NS
- GROUP N- Intraarticular injection of 19 ml of 0.25% bupivacaine + 1 ml (500 mcg ) of neostigmine.
- GROUP F- Intraarticular injection of 20ml of 0.25% bupivacaine + 1 ml (50 mcg )of fentanyl.
All patient were undergone for Pre Anesthetic Checkup and assessed in night before surgery and also kept fasting one night before surgery. Each patient were given Tab Alprazolam 0.25 mg and Tab Pantoprazole 40 mg in night before surgery as a premedication. After taking written informed consent for surgery and anesthesia as well as for participation in study patient were wheeled to operation theatre. All non-invasive monitors were connected like ECG, NIBP, SpO2 and pulse oximeter. A 18 G cannula was secured in left hand and 500 ml of Ringer’s lactate was given as a preloading fluid. Surgery was carried out in Sub- Arachnoid Block. Inj Ephedrine 6mg/ml given in aliquots Once systolic blood Pressure drops bellow 90mmHg Hy(fall in MAP below 20% of baseline ). Bradycardia (HR<50bpm) was treated by Atropine 0.6mg IV. Respiratory depression (RR<8 breath per min or SpO2<95%) was treated by oxygen supplementation and respiratory support if required. Nausea and Vomiting was treated with Injection Ondansetron 0.1mg/kg IV.
All patients undergone arthroscopic knee surgery after inflation of a thigh tourniquet to a pressure of 100 mmHg above the systolic B.P. Intra operative Hemodynamic monitoring like systolic ,diastolic, mean ,heart rate and SpO2 was carried out initially for every 5 minutes in the first hour then 10 minutes for the next hour and half hourly till the end of surgery.
After completion of surgery, the study drug combination was administered with all aseptic care through a syringe into the knee joint space with the help of 18G needle. Patients were shifted to Post-Operative ward thereafter. Hemodynamic parameters were recorded every two hours and VAS scoring will be carried out at 0, 1, 2, 4, 8, 12, and 24 hours post surgery. The duration of adequate analgesia was measured from the time ‘0’ until the first use of rescue analgesic. Total number of rescue analgesics given in 24 hours were recorded. 10-point visual analog scale (VAS) (where 0 denotes no pain and 10 denotes worst imaginable pain)15.Time to First complain of pain and when VAS score >4 was recorded in the post-operative Period. Injection Paracetamol 1gm i.v. was given as a rescue analgesiati Adverse effects like nausea, vomiting, pruritus, hypotension and urinary retention were documented and managed accordingly.
| Result:|| |
Patient demographic profile were matched in all three groups in terms of number, sex, weight, age and surgical duration.[Table 1]
In this study mean duration of analgesia time in group P is significantly lower than group N and Group F (p value <.05)however duration of analgesia time in Group N and Group F are comparable but Group N showed slightly higher duration of Analgesia.
Number of time rescue analgesia required in Group P was 2.3 whereas group N was 0.60 and by group F was 0.56. All patient of Group P required rescue analgesia in first 24 hrs where as only 18 patient required rescue analgesia in Group N and by 20 patients of Group F. Amount of rescue analgesia drug which was Paracetamol in this study was more in Group P, whereas Group N and Group F had low requirement which was statistically significant ( p value <.05). [Table 2]
In this study in terms of complication only 5 patient had hypotension in Group P where as in group N 4 patient showed hypotension and Group F 6 had episode of hypotension. None of patient had Bradycardia in any group. This complication is mainly due to sub arachnoid block.
In all three groups none of patient had respiratory depression, only 5 patient had drowsiness in Group F. Nausea, vomiting and itching mainly occurred in Group F patients. Due to sub arachnoid block urinary retention occurred in 2 patient of group P,2 patient of Group N and 3 patients of Group F. [Table 3]
| Discussion:|| |
Pain control in day care arthroscopy is required for patient comfort and for early hospital discharge. Intraarticular administration of single-dose local anesthetics solutions is used to provide better analgesia after knee arthroscopy and reduce the requirement of post-operative analgesia. Intraarticular route of drug administration utilizes the peripheral receptors for postoperative pain management. It provides analgesia locally along with minimal systemic side effects., A variety of analgesic techniques have been used to manage postoperative pain after arthroscopic knee surgery. Single-dose of Lidocaine, prilocaine, bupivacaine and Clonidine have all been administered intraarticularly (IA) to provide intraoperative local anesthesia and postoperative analgesia. Intraarticular administration of drugs provided local analgesia with minimal systemic adverse effects. These drugs mainly included local anesthetics (e.g., lidocaine and bupivacaine), opioids (e.g., morphine and fentanyl), and β2-agonists (e.g., clonidine) etc, and they were found to achieve variable durations of analgesia.,,,,
Various studies have evaluated cholinesterase inhibitors for producing dose-dependent analgesia by modulating pain perception and transmission in human tissues. Duarte et al showed that the intra-plantar administration of acetylcholine in animals resulted in anti-nociceptive effects. The presence of choline acetyl transferase in the primary afferents and of cholinergic receptors at the central nerve endings of small afferent fibres has opened a new area for further research It is postulated that acetylcholine acts as an analgesic agonist at muscarinic receptor type I or II, similar to the spinal subtypes. The likely mechanism of action includes hyperpolarization of neurons, decrease in pro-nociceptive neurotransmitters and activation of the nitric oxide-cyclic guanosine monophosphate pathway. Administration of the cholinesterase enzyme inhibitor, neostigmine will increase the endogenous acetylcholine levels at the peripheral nociceptors and may cause analgesia.
It has already been seen that intra-thecal or epidural administration of cholinesterase inhibitors such as edrophonium or neostigmine produces a dose-dependent analgesia and displays a synergistic or additive analgesia when administered simultaneously with alpha-adrenergic agonists and opioids,,. However, adverse effects like vomiting, nausea, headache, bradycardia, hypotension and pruritus limited the subarachnoid administration of neostigmine.
It was found during various studies that intraarticular drug administration produces prolonged postoperative analgesia and decreased requirement of rescue analgesia as compared to intravascular administration. It may be due to a slower rate of absorption through poorly vascular intraarticular surface.
We evaluated the three groups in terms of Sex (M/F), Weight, Age and Surgical Time(Hrs) and found the difference between them to be statistically insignificant. We found in our study that the duration of analgesia was only 360±72 min. with bupivacaine alone whereas it was longer (statistically significant) with neostigmine and fentanyl, though the difference in duration between neostigmine and fentanyl was statistically insignificant (1200±120 min. and 1080±100 min.)
We evaluated the frequency of rescue analgesia in our study and found it to be significantly lower in plain bupivacaine group as compared to neostigmine and fentanyl. Difference between Group N and group F was found to be statistically insignificant. The above observation is reflected in the amount of Paracetamol required as a rescue analgesic and the need of postoperative analgesia in first 24hrs which also produced identical result amongst the three groups. This finding is clinically very relevant as addition of either neostigmine or fentanyl produces a prolonged pain free period and decreased frequency of intermittent pain which helps in early discharge and a greater patient comfort specially in day care surgeries.
We analyzed the complications in our study and found hypotension to be the most common complication among the three groups, though the difference in occurrence amongst the three group was statistically insignificant.
Group F patients suffered episodes of drowsiness and itching which was not seen in group P and group N. Drowsiness is a matter of concern specially in day care surgeries as it can prolong the hospital stay. Itching can also lead to patient discomfort and hence these complications should be kept in mind when we are using fentanyl as an adjuvant. Incidence of nausea and vomiting was present in all three groups though it was higher in group F which can again prolong the duration of hospital stay. Thus in our study we found a higher incidence of complication in group F which suggests that fentanyl should be used cautiously in day care surgeries.
| Conclusion:|| |
Thus, we found that addition of neostigmine or fentanyl to bupivacaine increases the duration of analgesia in the postoperative period. It also decreases the incidence of break through pain and hence reduces the analgesic requirement leading to a greater degree of patient comfort. We also observed that fentanyl produces a greater no. of similar complications as compared to neostigmine and some complications which are unique to fentanyl itself like drowsiness and itching. Hence, we suggest to use fentanyl cautiously in pediatrics and old age patients, patients posted for day care surgeries and patients prone to nausea and vomiting.
| References|| |
Devi MM, Gupta S, Amaravathi R, Udupa S, Hegde A, Ghosh S. Comparison of efficacy of intra-artìcular plain bupivacaine and bupivacaine with adjuvants (dexmedetomidine and magnesium sulfate) for postoperatìve analgesia in arthroscopic knee surgeries: A prospectìve, randomized controlled trial. Anesth Essays Res 2018;12:848-54.
] [Full text]
Nahravani M, Tekye SM, Alipour M, Makhmalbaf H, Aghaee MA. Analgesia Following Arthroscopy - a Comparison of Intra-articular Bupivacaine and/or Midazolam and or Fentanyl. Arch Bone Jt Surg. 2017;5(1):28-31.
El-Hamamsy M, Dorgham M. Intra-artìcular adjuvant analgesics following knee arthroscopy: comparison between dexmedetomidine and fentanyl. Res J Med Med Sci. 2009;4(2):355- 60.
Gurkan Y, Kilickan L, Buluc L, Muezzinoglu S, Toker K. Effect of diclofenac and intra-artìcular morphine/bupivacaine on postarthroscopic pain control. Minerva Anestesiol 1999;65:741-55.
Gupta A, Axelsson K, Allvin R, Liszka-Hackzell J, Rawal N, Althoff B, et al. Postoperative pain following knee arthroscopy: The effect of intra-articular keterolac and/or morphine . Reg Anesth Pain Med 1999;24:225-30.
Gentili M, Houssel P, Osman M, Henel D, Juhel A, Bonnet F. Intra- artìcular morphine and clonidine produce comparable analgesia but the combinatìon is not more effectìve. Br J Anaesth 1997;79:660-1.
Buerkle H, Huge V, Wolfgart M, Steinbeck J, Mertes N, Van Aken H, et al. Intra-artìcular clonidine analgesia after knee arthroscopy. Eur J Anaesthesiol 2000;17:295-9.
Reuben SS, Connelly NR. Postoperatìve analgesia for outpatìent arthroscopic knee surgery with intraartìcular clonidine. Anesth Analg 1999;88:729-33
Tan PH, Buerkle H, Cheng JT, Shih HC, Chou WY, Yang LC. Double-blind parallel comparison of multìple doses of apraclonidine, clonidine, and placebo administered intraartìcularly to patìents undergoing arthroscopic knee surgery. Clin J Pain 2004;20:256-60
Likar R, Kapral S, Steinkellner H, Stein C, Schafer M. Dosedependency of intra-artìcular morphine analgesia. Britìsh J Anaesth 1999;83:241- 4.
Varkel V, Volpin G, Ben-David B, Said R, Grimberg B, Simon K, et al. Intra-artìcular fentanyl compared with morphine for pain relief following arthroscopic knee surgery. Can J Anaesth 1999; 46:867-71.
Manuar MB, Majumdar S, Das A, Hajra BK, Dutta S, Mukherjee D, et al. Pain relief after Arthroscopic Knee Surgery: A comparison of intra- artìcular ropivacaine, fentanyl, and dexmedetomidine: A prospectìve, double-blinded, randomized controlled study. Saudi J Anaesth 2014;8:233-7.
Gupta V,Rajesh MC,Jos S,Ramdas EK . Pain relief following arthroscopy: A comparative study of intra-artricular bupivacaine ,neostìgmine and clonidine. Indian J Pain. 2019;33:147-50
Drosos GI, Stavropoulos NI, Katsis A, Kesidis K, Kazakos K, Verettas DA, et al. Post-operatìve pain after knee arthroscopy and related factors. Open Orthop J 2008;2:110-4.
Singh RB, Chopra N, Choubey S, Tripathi RK, Prabhakar, Mishra A. Role of Clonidine as adjuvant to intrathecal bupivacaine in patìents undergoing lower abdominal surgery: A randomized control study. Anesth Essays Res. 2014;8(3):307-312. doi:10.4103/0259- 1162.143119
Chirwa S, Macleod B, Day B. Intraartìcular bupivacaine after arthroscopic meniscectomy: A randomized double-blind study. Arthroscopy 1989; 5:33-5.
Katz J, Kaedine C, Hill J. The pharmacokinetics of bupivacaine when injected intra-articularly after knee arthroscopy. Anaesth Analg 1988; 67:872-5.
Raja SN, Ross ED, Johnson CA. Comparison of post operatìve analgesics effects of intra-artìcular bupivacaine and morphine following arthroscopic knee surgery. Anaesthesiology 1992; 77:1143-7.
Cook TM, Tuckey JP, Nolan JP. Analgesia after day-case knee arthroscopy: double-blind study of intra-articular tenoxicam, intraartìcular bupivacaine and placebo. BJA 1997; 78: 163-168.
Li C, Qi J Efficacy of dexmedetomidine for pain management in knee arthroscopy A systematìc review and meta-analysis. Medicine (2017) 96:43(e7938)
Tamosi?nas R, Brazdzionyte E, Tarnauskaite-Augutìene A, Tranauskaite-Keraitìene G. Postoperatìve analgesia with intraartìcular local anesthetìc bupivacaine and alpha2-agonist clonidine after arthroscopic knee surgery. Medicina (Kaunas). 2005;41(7):547-52.
Paul S, Bhattacharjee DP, Ghosh S, Dawn S, Chatterjee N. Efficacy of intra-artìcular dexmedetomidine for postoperatìve analgesia in arthroscopic knee surgery. Ceylon Med J. 2010 Dec;55(4):111-5.
Mohammed Babrak Manuar, Saikat Majumdar, Anjan Das, Bimal Kumar Hajra, Soumyadip Dutta, Dipankar Mukherjee, Tapobrata Mitra, and Ratul Kundu. Pain relief after Arthroscopic Knee Surgery: A comparison of intra-artìcular ropivacaine, fentanyl and dexmedetomidine: Saudi J Anaesth. 2014 Apr-Jun; 8(2): 23337.
Datta R, Madhusudanan TP. Pain relief following Arthroscopy - a comparatìve study of Intra-artìcular Bupivacaine, Morphine and Neostìgmine. Med J Armed Forces India. 2004;60(2):123-127. doi:10.1016/S0377-1237(04)80100-X
Imani F, Entezary S, Razi M, Jafarian AA, Yousefshahi F, Etemadi, H Safari S. Anesth Pain Med. The effect of intra-artìcular meperidine and bupivacaine 0.5% on postoperatìve pain of arthroscopic knee surgery; a randomized double blind clinical trial. 2015 Feb 19; 5(1):e27470. doi: 10. 5812/ aapm. 27470.eCollectìon 2015.
Senapatì S, Basu A, Bhattacharya D, Hazra S, Sarkar D, Dandapat P. Comparison of analgesic effect of intra-artìcular administratìon of levobupivacaine and clonidine versus ropivacaine and clonidine in day care knee arthroscopic surgery under spinal anesthesia. Indian J Pain 2016;30:38-42.
[Table 1], [Table 2], [Table 3]