The International Association for Study of Pain (IASP)1 defines pain as an unpleasant, sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage2. Immediately following bone fracture, mechanosensitive nerve fibres that innervate bone are mechanically distorted resulting in these nerve fibres rapidly discharging and signaling the initial injury to the spinal cord and brain3,4,5. Many of these mechanosensitive nerve fibres that detect and signal the initial fracture pain are located in the periosteum which is tightly opposed to the outer cortical wall of mineralized bone5. Previous studies have shown that many of the sensory nerve fibres that innervate the periosteum are mechanosensitive C and A-delta nociceptors3,6,7,8 that rapidly respond to mechanical distortion of the adjacent bone or increased intraosseous pressure6,9,10. Following bone fracture, any movement or loading of the fractured bone would be expected to result in mechanical stimulation of mechanosensitive sensory nerve fibres that innervate the periosteum, mineralized bone, and marrow 11,12,10,13,14.

Following bone fracture, mechanical injury to sensory or sympathetic nerve fibres that innervate the bone may occur generating a neuropathic pain state11,12. Various methods, such as using opioids and non-steroid anti-inflammatory drugs,  topical  anaesthetics  and  regional  nerve  block  are  applied  for  pain management.32,33,34,35,36 Intravenous (IV) infusion of lidocaine is one of the methods used for analgesia.37,38,39,40,41

Lidocaine is a relatively safe drug in the amide group, which acts as an analgesic, anti-hyperalgesia and anti-inflammatory agent in low doses and is affective in relieving neuralgia, burn and procedural pains42. This drug induces its analgesic effects via stimulating secretion of anti-inflammatory cytokines (interleukin- 1) receptor antagonist and blocking central and peripheral voltage-dependent sodium channels43. In cases that opioids lack efficient effectiveness, IV injection of lidocaine has been used as a proper replacement42,44,45.

Although many studies have indicated the role of IV lidocaine in pain relief after trauma or surgery and decrease in the need for other opioids, there are also studies that do not agree37. For example, in one study continuous infusion of low doses of lidocaine, had not reduced use of other analgesics46. In addition, for induction of analgesia after tonsillectomy surgery, infusion of IV lidocaine did not play an effective role in reducing pain after surgery47.  Nalbuphine is a newer opioid drug with antagonism at µ receptors and agonism at κ receptors, with no significant effects on delta receptors. Nalbuphine elicits analgesia through a complex interaction of supraspinal κ3 and spinal κ1 mechanisms48.

Aim- the aim of study is- study the efficacy and analgesic benefit with intravenous lidocaine and intravenous nalbuphine upper extremity fractures patients.

This is a prospective, observational study done in department of anaesthesiology in Shri Rawatpura Sarkar Institute of Medical Sciences and Research, Raipur in Patients coming to emergency with upper extremity fractures-Distal end of radius fractures hospital was selected from April 2024 to April 2025 in total 80 patients. Group A – Patients receiving i.v. lidocaine. Group B- Patients receiving i.v. nalbuphine. Randomization of the sample was done by the computer-generated block using random number generator to create list of random numbers. To ensure an equal number of patients in each group, block randomization was done.

Inclusion Criteria of the patients:

Patients with the following criteria were included in the study:

1. Patients in the age group 20years-65years (both gender).
2. Patients belonging to ASA Grade I, II.
3. Patients with upper extremity fractures-Distal end of radius fractures.
4. Patients who had given their free consent for participation in the study.

Exclusion criteria of the patients:

Patients with the following criteria were not included in the study:

1. Patients who had not given their free consent for participation in the study
2. Patients belonging to ASA Grade III and IV
3. Patients of age <20 years or >65 years
4. Patients with central nervous system disorders, patients on anticonvulsant therapy.
5. Patients having cardiac diseases, respiratory diseases.
6. Patients with h/o of chronic pain using regular analgesics, sedatives and anticonvulsants
7. Patients with hypersensitivity to this drug
8. Patients with impaired renal function

Methodology:

Patients who suffered upper extremity fractures- Distal end of radius fractures, and those who fulfil the inclusion criteria were selected. They were informed about the procedure and were told that one of the two analgesic drugs were be administered intravenously which would improve the quality of pain relief and were shifted to the perioperative area where all monitors and all emergency resources were available. They were explained and shown the VAS (visual analog scale) before start of the study.

They were divided into 2 groups receiving either IV lidocaine (1.5 mg/kg during 2 minutes followed by infusion at the rate of 0.5mg-2mg/kh/hr) or IV Nalbuphine (0.15mg/kg) over 2minutes. The study was designed as a triple blind manner as the patient, person injecting the drug and examiner was blind to the type of drug consumed. Both drugs were colourless and odourless and to make them look alike, both drugs were injected in a 10cc volume with syringes with the same shape and colour. Injection was performed by a senior resident of anaesthesiologist. Before the injection of drug, vital signs of the patient and their pain score using visual analog scores (VAS) were assessed. A checklist consisting of demographic data (age, gender), vital signs (number of breaths per minute, systolic and diastolic blood.

Pressures, heart beats per minute, and oxygen saturation percentage) and pain severity on presentation and 5, 10, 15, 20, 25, and 30 minutes after injection was filled for all the patients. The senior resident in charge of the patient was responsible for gathering the data, but evaluation of vital signs of the patient was performed by someone other than the one injecting the drugs, who was blind to the type of drug used.

To measure pain severity, VAS scale was used. Pain score of 3 to 6 was considered as moderate pain and score ≥6 is considered as severe pain. At least 3 points drop in pain score was considered as success in pain management. If pain was still present after 30 minutes, Parenteral diclofenac 75mg dose was prescribed as a bolus. At least 3 scores drop in pain severity was considered success and less than 3 scores as failure in treatment on 15th and 30th minutes. In addition, patients were assessed regarding manifestation of any side effects such as confusion; tremor; stupor; seizure; restlessness; anxiety; lethargy; sleepiness; hallucination; strabismus; syncope; hypotension; bradycardia; cardiac failure; new arrhythmia; cardiac failure; anaphylaxis; status asthmaticus; respiratory depression; edema; nausea; vomiting; rash and tinnitus. It was determined that in case of any drug side effects, the patient should be excluded from the study and be rapidly treated for relieving the side effect. Patient was handed over to orthopaedician for reduction of fracture.

We had accepted a p<0.05 as significant. We mean that we are ready to accept that the probability that the result is observed due to chance is 5%

Confidence level = 95% Confidence interval = 5.22 Sample size = 40

Find the smallest sample sizes required to achieve a fixed margin of error, using simple random sampling.

Therefore,

n = {(r+1) (Zα/2 + Z1-β) δ2} /rd2

n = (1+1) (1.96+0.84) (10.366)2 /1* (19.29 - 12.8 )2 = 1684.878 / 42.12 = 40.112≈40

The total sample size required for the study 80, each group contain 40 patients (Total population = 80)

Study Design:

1. The study was a randomized, prospective, triple-blinded study.
2. The study was duly approved by the ethics committee of the hospital.
3. Patients were enrolled for the study after taking their informed consent.

Statistical Analysis

The collected data were organized, tabulated and statistically analysis using “MedCalc”. The data were analyzed by appropriate statistical tools. Data were presented as mean with standard deviation or proportions as appropriate. Mean, median, standard deviation and variance were calculated and following statistical significance tests were applied.

1. T-test were used to compare two independent groups of continuous data.
2. Chi-square tests were used to compare categorical data.
3. Student t-test was employed to compare for difference between two means.
4. Test of Significance for Difference of Proportions.
5. “2 x 2” diagnostic table was used for sensitivity, specificity, positive predictive value, negative predictive value, odds ratio, etc.
6. “ANOVA” also used for different calculation.

Finally, the calculated values were compared with the tabulated value at particular degree of freedom and finds the level of significance. A “p-value” was considered to be non-significant if p> 0.05 and significant if p<0.05.

The patients who were accepted for the study were in age group 20-65 years. Both the groups were compared for significance in difference of age distribution. Both the groups were comparable and the difference found between the groups was non- significant with p > 0.155. Both the groups were compared for ASA Grade. The apparent difference was not found to be significant in both groups. In Group A, 45% patients were ASA Grade 1 and 55% were ASA Grade 2. In Group B, 55% were ASA Grade 1 and 45% ASA Grade 2, suggesting ASA Grade in both groups were comparable (p value= 1.000).

Table- 1 ASA grade

On an average, 71.05 people in the lignocaine group required rescue analgesia compared to 107.15 people in the nalbuphine group. However, the difference observed was non-significant (p=0.575). The effect in patients after 5 min. in both the groups was comparable and statistically non-significant. The effect in patients after 10 min. in both the groups was comparable and statistically non-significant.

The effect in patients after 20 min. in both the groups was comparable and statistically non-significant.

The effect in patients after 25 min. in both the groups are compared and are found that all hemodynamic parameters in group A are well maintained and are superior to group B but statistically non-significant between two groups, drop in VAS score in group A is superior to group B which was also statistically significant.

The side effect of nalbuphine in patients can be seen after 25 minutes. 40% patients have no side effect after 25 min, 40% patients have mild sedation, 20% patients have nausea. The effect in patients after 30 min. in both the groups are compared and all hemodynamic parameters in group A are well maintained than in group B but found to be statistically non-significant; drop in VAS scores in group A is found to be more significant which is also statistically significant.

Table 2: Time wise progression of VAS score

The side effect of nalbuphine in patients can be seen after 30 minutes. 37.5% patients have no side effect after 30 min and 42.5% patients have mild sedation and 20% patients have nausea.

This is a prospective, observational study done in department of anaesthesiology in Shri Rawatpura Sarkar Institute of Medical Sciences and Research, Raipur in Patients coming to emergency with upper extremity fractures-Distal end of radius fractures hospital was selected from April 2024 to April 2025. This is Randomized prospective triple blinded study in which 80 patients of age group between 20-65 yrs., patients belonging to both ASA 1 and ASA 2 were taken up.

Our study was done to find out a good analgesic agent for management of acute pain in upper extremity fractures (Distal end of radius fracture), which is a very severe kind of acute pain. Keeping in mind the various side effects associated with opioid agents against the unparalleled efficacy of pain relief, we sought to compare an opioid agonist – antagonist Nalbuphine with an amide local anaesthetic, Lidocaine.

Objectives of the study are:

• To record and analyse the onset of action, duration of analgesia and level of analgesia in both the groups.
• To record and analyse the hemodynamic changes.
• To record and analyse the side effects of both the drugs (if any).

The patients who were accepted for the study were in age group 20-65 years. With reference to Table no 1, there was no significant difference (p = 0.257) in age in Group A and Group B. Both the groups were compared for distribution of BMI. The apparent difference was not found to be significant (p = 0.155) in both groups with Group A and Group B. Both groups were compared in terms of gender distribution. The apparent difference between the two groups was not significant (p>0.05).

Group A has 45% of ASA 1 patients whereas Group B has 55%; Group A has 55% of ASA 2 patients and Group B has 45%. The apparent difference between two groups was not significant (p=1.000). Hence, both the groups were comparable in all respects except the analgesic used for acute pain management. Therefore, it is reasonable to presume that any difference in the two groups with regards to the incidence of pain, haemodynamic variation from baseline and complications was basically a result of the choice of analgesic drug adopted for each group.

Both the individual drugs were effective at progressively reducing the VAS scores for pain beginning 5 minutes after drug administration, which was statistically highly significant Also, according to the findings of our study, all the patients were respondents, both the drugs provided good pain relief with VAS score < 5beginning at 25 min after drug administration. However, the VAS score in Lidocaine group was significantly lesser at both 25 and 30min when compared to Nalbuphine

The findings of my study are in accordance with study of Clattenberg et al (2019)⁷⁹; Arash Foroucan et al(2017)⁸³; Soleimanpour et al (2012)⁸⁹; Anca Grigoraetalin (2012)⁸⁸; Vigneault et al(2010)⁹⁰. Akhgar et al (2021)⁷⁷ showed that IV lidocaine can be a good choice in pain management in biliary colic and can reduce pain in less time than morphine sulfate (in 10 min) without adding significant side effects; however, primary outcome was the comparison of these two drugs after 60 min of drug administration in pain reduction which showed no significant difference between two groups. The findings of this study are in concurrence with our study and we have used a synthetic opioid instead of morphine here. Lesser patients in Group A required rescue analgesia compared to patients in Group B, which was found statistically non- significant. Numerous studies have shown the efficacy of intravenous lidocaine for effective pain management and its role in reducing the demand for opioids or need for rescue analgesia. Clatternberg et al (2019)⁷⁹; Arash Foroucan et al (2017)⁸³, which are in concurrence with our findings.

There was no statistically significant difference in systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate and oxygen saturation in both the group throughout the course of observation shows that both the drugs have good hemodynamic stability.

El-Tahan et al 2009's⁹⁴ clinical study found that giving IV lidocaine before caesarean section surgery reduces the rise in heart rate, average arterial pressure, and plasma cortisol levels. Their results showed that intravenous lidocaine may be regarded a safe and effective option for decreasing the mother's stress reaction to surgery during caesarean birt Side effects in both the groups were compared and found that no side effects were observed in Group A and mild sedation, nausea were observed at 20min, 25min, 30min in Group B.

Our study was the first of its kind to evaluate the role of intravenous nalbuphine administration in managing fracture pain. Due to the lack of studies on nalbuphine for acute pain management in fracture pain, we have reviewed the literature for other routes of its administration. Intrathecal nalbuphine, as an adjuvant to bupivacaine, has been found to pro duration of analgesia without increasing the incidence of side effects (Mukherjee et al, 2011)⁹⁵. However, Etches et al,(1991) ⁹⁶found that epidural nalbuphine failed to provide a analgesia in patients undergoing thoracotomy. The lack of effectiveness of nalbuphine may be attributed to the difference in the type of surgery and routes to the administration. Nalbuphine has as potent an analgesic effect as morphine, but with a better safety and fewer side effects such as pruritus, respiratory depression, and PONV (Zeng et al 2015)⁹⁷. Indeed, our study that the side effects in the nalbuphine group were without significant differences compared lidocaine group. Furthermore, epidural nalbuphine in 10 mg dose with lidocaine revealed none of the following side effects: PONV, sedation, pruritus, or respiratory depression (Camann et al, 1991)⁹⁸. Fewer side effects of nalbuphine may be attributed to its central antagonist activity mu receptors. The exact mechanism of the peripheral action of nalbuphine is not well known. Different theories were postulated to explain the analgesic action of the opioids in IVRA; opioids might exert their peripheral action through peripheral opioid receptors. Also, opioids may have their own local anesthetic effect by blocking sodium channels at the peripheral nerve endings (Armstrong et al, 1993)⁹⁹.

According to the results of this study, IV lidocaine seems to be helpful in pain management in upper extremity fractures. It seems that since the majority of the participants in the current research were either young or in their forties, the likelihood of experiencing cardiac adverse effects was inherently reduced. It appears more reasonable to make a decision on the negative effects of injecting the medication after doing research on different age groups and taking into account their varied underlying diseases.

In the present study the findings suggested that, both the drugs provided good pain relief which was significant from 10min of administration of the drugs with VAS score <5 at 25 and 30 min. However the VAS score in Lidocaine group was significantly lesser at both 25 and 30 min when compared to Nalbuphine. There were no medication side effects seen in patients receiving IV Lidocaine but mild sedation and nausea were observed in patients receiving IV Nalbuphine. And the important thing was that the chance of not managing pain in the lidocaine group vs the nalbuphine group was less than one, confirming its superior efficacy, although it is statistically non-significant.

We compared the analgesic efficacy, total requirement of rescue analgesia and side effects of Lidocaine (IV) with Nalbuphine (IV) in acute fracture pain management in patients of upper extremity fractures-Distal end of radius fracture. Based on the results of the present study, both the drugs provided good pain relief which was significant from 10min of administration of the drugs with VAS score <5 at 25 and 30 min. However, the VAS score in Lidocaine group was significantly lesser at both 25 and 30 min when compared to Nalbuphine. There were no medication side effects seen in patients receiving IV Lidocaine but mild sedation and nausea were observed in patients receiving IV Nalbuphine. Our study confirmed that both the drugs are hemodynamically stable and safe. And the important thing was that the chance of not managing pain in the lidocaine group vs the nalbuphine group was less than one, confirming its superior efficacy, although it is statistically non- significant. Inj. Lidocaine IV at a dose of 1.5mg/kg (bolus) followed by infusion at a dose of 0.5-2mg/kg could be considered as a reasonable alternative choice for acute pain management in upper extremity fractures-Distal end of radius fractures.

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