Anesthesiology, Article

Pain management of acute limb trauma patients with intravenous lidocaine in emergency department

a b s t r a c t

Introduction: This study was designed to assess the possible superiority of intravenous lidocaine to morphine for pain management.

Methods: This was a randomized double blind controlled superiority trial, carried on in the emergency depart- ment (ED). traumatic patients older than 18-year-old with the complaint of acute pain greater than 4 on a nu- meric rating scale (NRS) from 0 to 10 on their extremities were eligible. One group received IV lidocaine (1.5 mg/kg), and the other received IV morphine (0.1 mg/kg). Pain scores and adverse effects were assessed at 15, 30, 45 and 60 minutes and patients’ satisfaction was evaluated two hours later. A minimum pain score reduction of 1.3 from baseline was considered clinically significant.

Results: Fifty patients with the mean age of 31.28 +- 8.7 were enrolled (78% male). The demographic character- istics and pain scores of the two groups was similar. The on-arrival mean pain scores in two groups were, lido- caine: 7.9 +- 1.4 and morphine: 8.0 +- 1.4 (p = 0.57) and after 1 hour were, lidocaine: 2.28 +- 1.2 and morphine: 3.2 +- 1.7. Although the pain score decreased significantly in both group (p = 0.027), there were not any clinically and statistically significant difference between the two groups (p = 0.77). Patients’ satisfaction with pain management in both groups were almost similar (p = 0.49).

Conclusion: The reduction in pain score using IV lidocaine is not superior to IV morphine in adult ED patients with traumatic limb pain.

(C) 2017

  1. Introduction

Pain is one of the most common complaints of traumatic patients visiting the emergency departments (ED). Although sufficient pain management is crucial, up to half of patients believe more could be done to alleviate their pain [1]. Many studies have been done in this era as well as ongoing ones to evaluate the efficacy of pain management in traumatic patients using different medications along with various techniques. However, it seems that, there is significant mismanagement in this regard [2]. For instance, Karmakar et al. reported that fear of re- spiratory depression, confronting drug (opioid) seeking behavior and fear of hemodynamic instability have led to insufficient pain

? Source of support: None.

?? Conflict of interest: None.

* Corresponding author.

E-mail address: [email protected] (S. Bagheri-Hariri).

management in patients with multiple rib fractures [3,4]. On the other hand, lack of sufficient pain management might result in unexpected re- sponses like releasing inflammatory cytokines, cortisol, and catechol- amines that could lead to higher morbidity and mortality [5]. From the perspective of emergency medicine (EM), the main goal in pain man- agement is finding a rapid, safe and efficient analgesic. There are a vari- ety of medications for pain management in the ED including acetaminophen, Non-steroidal anti-inflammatory drugs (NSAIDS), and opioids. Each one has its own onset of action and side effects.

Lidocaine is well-known as a local Anesthetic agent that is being used to control pain due to its anti-inflammatory, antihyperalgesic and anal- gesic properties [6]. But intravenous (IV) lidocaine administration has recently been taken into consideration in this regard. For example, IV li- docaine has been used to reduce pain in patients with renal colic andafterlaparoscopy and laparotomy. These studies have supported that IV lidocaine can reduce the intensity of post-operative pain, de- crease the need for opioids and other analgesics, and result in shorter

0735-6757/(C) 2017

hospital length of stay and lower morbidity [7-10]. Lidocaine has not been reported as a potential drug of abuse. The major reported side ef- fects are headache and shivering although cardiovascular, gastrointesti- nal and Respiratory effects have been rarely reported and should still be taken into account.

Considering the above, the current study was designed to test the hypothesis that IV lidocaine was superior to IV morphine for pain reduc- tion in patients with acute traumatic limb pain visiting the ED.

  1. Material and methods
    1. Study design

This study was a randomized double blind superiority clinical trial conducted during June 2014 in the ED of a referral hospital and trauma center, in Tehran, Iran. The study protocol was approved by the ethical committee of Tehran University of Medical Sciences. The patients were included after obtaining informed consent. The study was regis- tered and approved by the Iranian clinical trial registry (IRCT2014080518698N1 at


Trauma patients older than 18-year-old, came to the ED in person or were transferred by the emergency medical service (EMS), with acute extremity injury and a pain score N 4 ona 0-10 numerical rating scale (NRS) were considered eligible for enrollment.

Patients with any alteration in the level of consciousness (Glasgow coma scale (GCS) b 15), hemodynamic instability, history of opioid use, alcohol or any sedative-hypnotic drug use in the past 48 h, history of chronic disease including cardiac, renal or hepatic diseases, history of asthma, epilepsy, and history of allergic reaction to lidocaine or mor- phine were excluded.

Sample size calculation

Based on a similar previous study, we estimated a study sample size of 25 patients in each group [11].

This sample size would give 80% power to detect a minimally impor- tant difference of 1.3 points on the NRS at the level of 5% significance. [12].


block randomization was used in this study. Block sizes were 2 by 2 (13 blocks). The acceptable sequences for packages within each block were: AABB (1), ABAB (2), BBAA (3), BABA (4), BAAB (5), and ABBA

(6). Each acceptable possibility of the blocks had been marked from 1 to 6 as above. Then a dice was used to generate the sequence of the blocks from 1 to 13. In the end, blocks were set by means of the gener- ated sequence from 1 to 13, then packages within blocks were sequen- tially numbered from 1 to 50. Concealment was completed by wiping off the letter A and B on the syringes and then each package was sealed with tape. Participants were consecutively numbered from 1 to 50 con- sidering the time of triage. Allocation was performed by blindly matching the patient’s number and package. Randomization sequence and concealment were performed by the study supervisor (EM attend- ing). Allocation and matching of the number of participants to the pack- age number in order to receive the intervention was performed by the study investigators (EM residents). Participants, research investigators (EM residents) and nurses were blinded to the content and the se- quence of treatment within blocks.


Eligible patients were first triaged and admitted in the ED. Parallel to standard and routine ED management, such as limb immobilization in a temporary splint, the study investigators (designated and trained emer- gency medicine residents) explained the purpose and method of study of the patients, evaluated the patients for the exclusion criteria and obtaining informed consent.

Two sets of 25 sterile, colourless and ready-to-inject 10cm3 syringes were prepared and named syringe A (lidocaine) and syringe B (mor- phine sulphate) before concealment. Syringes A contained 150 mg lido- caine (15 mg/ml lidocaine) with a Therapeutic dose of 1.5 mg/kg IV with the posted label “inject 1 ml/10 kg IV slowly over 2-3 minutes”. Syringe B contained 10 mg morphine (1 mg/ml MS) with the therapeutic dose of 0.1 mg/kg with the posted instruction label as “inject 1 ml/10 kg IV slowly over 2-3 min”. The contents of both sets of syringes looked iden- tical (clear). Then, each of them were put in identical and sterile packages.

Outcome assessment

The primary hypothesis was that compared with IV morphine, IV li- docaine would reduce the pain at 60 min by N 1.3 points. Based on the existing literature, an absolute reduction of 1.3 point on the NRS, or a 30% relative reduction in pain score from baseline, are considered clini- cally significant. [13].

The secondary outcome was any subjective reports of possible ad-

verse effects and the patients’ overall satisfaction with their pain management.

Pain scores were assessed using the NRS in the current study (with a minimum of 0, no pain, to a maximum of 10, the worst pain ever). All participants’ pain scores were assessed before and after intervention at 15, 30, 45 and 60-min by the investigator. If the NRS scores remained N 5 or the relative risk reduction in pain score was b 30% from baseline after the first 15 min or at any other time-point and the patients re- quested additional analgesia, a fixed dose of 50 ug fentanyl was given in- travenously as the rescue dose in both groups.

During the observation period, the vital signs (blood pressure, pulse oximetry, respiratory rate and heart rate) were monitored and recorded by emergency medicine residents and nursing staff. Participants were constantly monitored for adverse effects, such as nausea, vomiting, ver- tigo, pruritus and decreased level of consciousness. After 60 min, pa- tients were asked how satisfied they were with their pain management during the past one hour. All participants expressed their satisfaction for pain management based on the 6-item Likert scale from very satisfied to very dissatisfied.

Statistical analysis

All data were gathered on individual data sheets for each subject (appendix 1) and were analyzed by SPSS version 16, Chicago, SPSS Inc., using the Kruskal Wallis, Wilcoxon, paired t-test and repeated mea- sures ANOVA.

  1. Results

From 143 subjects with acute limb trauma who visited the ED in Jun 2016, 93 subjects were eligible to participate in this study. Based on the exclusion criteria, 43 subjects were excluded, and 50 subjects signed the written informed consent and enrolled in the study. In the next step, 25 patients were randomly assigned to the lidocaine group and 25 patients were assigned to the morphine group. Fig. 1 shows the CONSORT flow- chart of study patients.

Fifty patients with the mean age of 31.28 +- 8.7 years were enrolled (78% male). Baseline characteristics of studied patients are reported in Table 1. Considering gender, age, weight and height, there was not a


Lost to follow-up (n = 0) Discontinued intervention (n = 0)

Lost to follow-up (n = 0) Discontinued intervention (n = 0)


Analysed (n = 25)

Excluded from analysis (n = 0)

Analysed (n = 25 )

Excluded from analysis (n = 0 )

Fig. 1. CONSORT diagram.


Allocated to lidocaine group (n = 25) Received IV lidocaine (n = 25)

Did not receive IV lidocaine (n = 0)

Allocated to morphine group (n = 25) Received IV morphine (n = 25)

Did not receive IV morphine (n = 0)

Randomized (n = 50)

Excluded (n = 93 )

Not meeting inclusion criteria (n = 50) Declined to participate (n = 10)

Other reasons (n = 33)

Assessed for eligibility (n = 143)


significant difference between the two groups. It should also be noted that all subjects were Caucasians. The main cause of pain in both groups was long bone fracture, followed by laceration. There was not a signifi- cant difference between both groups regarding cause of pain (p = 0.8). The initial pain scores in the lidocaine and morphine group were similar (7.92 +- 1.38, 8 +- 1.44, respectively). All subjects in this study had initial pain scores above 5 as this was an inclusion criterion. In both groups, 10 subjects (20%) reported having a pain score equal to

10. The median in both groups was an NRS of 8, which is considered se- vere pain (Table 2).

Table 2 and Fig. 2 show the mean NRS score in both groups at 15, 30, 45 and 60 min. In order to evaluate pain reduction in each group, re- peated measurements of the analysis of variance (rANOVA) were ap- plied. Within each group, during the one-hour observation, all patients expressed statistically significant pain score reduction in 60 min (in the lidocaine arm NRS decreased from 7.92 +- 1.38 to 2.28

+- 1.2 and in the morphine arm from 8 +- 1.44 to 3.2 +- 1.78). However, when comparing the two groups, there was not a significant statistical difference in pain score reduction (after 60-min; lidocaine arm mean pain score: 2.28 +- 1.2 versus morphine arm mean pain score: 3.2 +-

1.78 p = 0.77). As presented in Table 2, at 30 min, there is a clinically important difference between pain scores in the two groups (lidocaine NRS 3.8 +- 1.8 versus morphine NRS 5.4 +- 2.6).

Table 1

Baseline characteristics in the lidocaine and morphine groups

In any given time during the study, there was not a significant change in SPO2, systolic and diastolic blood pressure and pulse rate. However, the respiratory rate and heart rate showed statistically signif- icant reduction in the morphine group compared to the lidocaine group (p = 0.001) (Table 3). The only adverse effect reported in both groups was nausea and vomiting (1 subject in each group). 11 patients in each group requested the rescue dose after 20 min. Hence, a fixed dose of 50 ug fentanyl was administered similarly in both groups (p

= 1). In the lidocaine group, 10 subjects received a single rescue dose and 1 subject received two rescue doses of fentanyl. On the other hand, in the morphine group, 6 subjects received one dose and the re- maining 5 patients received two rescue doses.

Finally, based on the 5-item Likert scale, there was not a significant difference between both groups in terms of satisfaction with pain man- agement (Table 4).

  1. Discussion

It was observed that the reduction in pain score was similar and ac- ceptable for both morphine and lidocaine arms, thus IV lidocaine is not superior to IV morphine. This study was powered to test the validity of

Table 2

NRS pain scores in the lidocaine and morphine groups at 15, 30, 45, 60 min after intervention

Interval Lidocaine group Morphine group p-value


Lidocaine group

Morphine group






Median Mean

8 8




8 0.57

Male, n(%)

19 (76%)

20 (80%)









Age (year), mean +- SD

31.4 +- 8.73

31.16 +- 8.7









Weight (Kg), mean +- SD

71.23 +- 7.2

73.2 +- 6.8









Height (cm), mean +- SD

168.4 +- 6.5

168.9 +- 7.2









Fig. 2. Pain scores changes in both groups.

our hypothesis that lidocaine would produce a clinically superior pain score reduction (NRS ? 1.3) compared to morphine; however, we were unable to demonstrate lidocaine superiority in acute limb trauma pain management.

Although there was a statistically significant difference in respirato- ry rate depression and heart rate reduction in the morphine group, those subjects were clinically stable and without major complications during follow-up. There was not a difference between both groups with regard to other adverse effects, the need for fentanyl rescue dose and patients’ satisfaction with pain management.

Studies have been done to show the pharmacokinetics of lidocaine and morphine in humans. Berkenstadt et al. have evaluated morphine and lidocaine clearance and distribution in critically ill ICU patients. Compared to healthy individuals, morphine clearance and distribution was statistically reduced in ill patients. However, these parameters indi- cate no difference for lidocaine between healthy and ill individuals [12]. This might reveal that lidocaine could be used as a safe substitute for morphine with less likelihood of toxicity.

When considering the use of lidocaine for pain management, most studies were done in surgical settings. A meta-analysis done in 2010 showed that in patients undergoing abdominal surgery, preoperative li- docaine could result in lower pain scores, reduced intraoperative and

postoperative analgesic requirements, more rapid return of bowel func- tion and finally decreased length of hospital stay [11]. Another study has shown improvements in postoperative recovery in patients who re- ceived lidocaine before abdominal laparoscopy. These patients required less opioid use for pain management compared to the control group [14]. Lidocaine has also successfully reduced pain scores in patients with fibromyalgia during and after infusion [15]. It is also capable of controlling allodynia and hyperalgesia due to nerve injuries such as post-herpetic neuralgia or nerve trauma [16]. It can also reduce ische- mic limb pain [17]. A study done on 240 patients with renal colic also showed greater pain reduction in the IV lidocaine group compared to the IV morphine group [18]. None of the mentioned studies have report- ed a significant adverse effect after lidocaine administration.

A lidocaine patch has been used to control pain in patients with rib

trauma and has resulted in significant pain reduction. However, there was no change in opioid use [19]. Intravenous lidocaine for acute pain management in patients with acute trauma has not been studied before. This small study supports the use of IV lidocaine in cases of acute limb trauma with similar safety and efficacy as morphine but the small sam- ple size was not powered to detect rare adverse events. Patients were satisfied in general with the administration of lidocaine. Despite the concern that the administration of intravenous lidocaine might cause

Table 3

Changes in vital sign in the lidocaine and morphine groups


15 min

30 min

45 min

60 min


Systolic blood pressure


123.2 +- 9.6

123 +- 8.2

121.9 +- 8.8

121.8 +- 9.8

121.7 +- 9.1



126 +- 9.61

124.6 +- 9

125.9 +- 9.2

126.3 +- 7.7

122.4 +- 10.2

Diastolic blood pressure


69.8 +- 7

70.3 +- 6.6

71.3 +- 6.1

70 +- 7.1

70.5 +- 7.5



73 +- 8.3

72.5 +- 8.3

72.2 +- 7.1

70.6 +- 7.7

69.7 +- 8.7

Respiratory rate


12.5 +- 0.9

13.6 +- 1.7

12.3 +- 1.3

12.1 +- 1.1

12.2 +- 0.6



14.4 +- 2

12.3 +- 0.7

13 +- 1.7

13.4 +- 1.2

13.4 +- 1.5

Heart rate


81.32 +- 5.64

80.48 +- 4.91

81.12 +- 6.26

79.68 +- 4.75

80.4 +- 5



83.92 +- 8.12

83.48 +- 8.39

81.8 +- 8.14

80.48 +- 6.49

80.4 +- 5.8

O2 saturation


96.08 +- 0.81

96.12 +- 0.52

96.2 +- 0.76

96.16 +- 0.76

96.32 +- 0.94



96.4 +- 1.24

96.72 +- 1.24

96.64 +- 1.07

96.5 +- 1.01

96.72 +- 1.24

Table 4

Pain management satisfaction based on the 6-item likert scale


Extremely satisfied

Very satisfied

Somewhat satisfied

Somewhat dissatisfied

Very dissatisfied

Extremely dissatisfied


1 (4%)

7 (28%)

7 (28%)

8 (32%)

2 (8%)

0 (0%)


1 (4%)

9 (36%)

7 (28%)

4 (16%)

4 (16%)

0 (0%)

systemic complications such as seizures, our findings suggest that intra- venous lidocaine could be considered safe.


In order to minimize confounding parameters, the study population included healthy individuals over 18 years old. Further studies could be done on Pediatric populations as well as patients with other comorbid- ities. In this study, fentanyl was used as a rescue analgesic. This could be a potential confounding factor although it was used in both groups equally. The small size of both groups might be a limitation, as the pain may have decreased over time alone as well as with other interven- tions such as using splints. Since this was a single center and small-sized study with an observation period of one hour, the identification of ad- verse effects was limited. Finally, despite the above limitations, the clin- ical observation that there was a clinically significant decrease in pain scores with the use of intravenous lidocaine in trauma might be signif- icant. However, an increased sample size might be able to show wheth- er IV lidocaine is more effective than morphine or not.

  1. Conclusion

In conclusion, this study shows that pain reduction with IV lidocaine is not superior to IV morphine for adult ED patients with extremity trauma.


Authors would like to show their deepest gratitude for those pa- tients who willingly participated in this trial.


This research did not receive any specific grant from funding agen- cies in the public, commercial, or not-for-profit sectors.


  1. Smith J, Rockett M, S SC, Squire R, Hayward C, Ewings P, et al. PAin SoluTions In the Emergency Setting (PASTIES)-patient controllED analgesia versus routine care in

emergency department patients with pain from traumatic injuries: randomised trial. BMJ (Clin Res Ed) 2015;350:h2988-h.

  1. Dijkstra B, Berben S, van Dongen R, Schoonhoven L. Review on pharmacological pain management in trauma patients in (pre-hospital) emergency medicine in the Netherlands. Eur J Pain (London, England) 2014;18(1):3-19.
  2. Karmakar M, Ho A. Acute pain management of patients with multiple fractured ribs. J Trauma 2003;54(3):615-25.
  3. Alimohammadi H, Baratloo A, Abdalvand A, Rouhipour A, Safari S. Effects of pain re- lief on arterial blood o2 saturation. Trauma Mon 2014;19(1):e14034.
  4. Desborough J. The stress response to trauma and surgery. Br J Anaesth 2000;85(1): 109-17.
  5. Kandil E, Melikman E, Adinoff B. Lidocaine infusion: a promising therapeutic ap- proach for chronic pain. J Anesth Clin Res 2017;8(1).
  6. Ventham N, Kennedy E, Brady R, Paterson H, Speake D, Foo I, et al. Efficacy of Intra- venous Lidocaine for Postoperative Analgesia Following Laparoscopic Surgery: A Meta-Analysis; 2015.
  7. Marret E, Roli M, Beaussier M, Bonnet F. Meta-analysis of intravenous lidocaine and postoperative recovery after abdominal surgery. Br J Surg 2008;95(11):1331-8.
  8. Couceiro TCdM, Lima LC, Couceiro LM, Valenca MM. Intravenous lidocaine to treat postoperative pain. Revista Dor 2014;15(1):55-60.
  9. Omote K. Intravenous lidocaine to treat postoperative pain management novel strat- egy with a long-established drug. Anesth J Am Soc Anesth 2007;106(1):5-6.
  10. McCarthy GC, Megalla SA, Habib AS. Impact of intravenous lidocaine infusion on postoperative analgesia and recovery from surgery. Drugs 2010;70(9):1149-63.
  11. Berkenstadt H, Mayan H, Segal E, Rotenberg M, Almog S, Perel A, et al. The pharma- cokinetics of morphine and lidocaine in nine Severe trauma patients. J Clin Anesth 1999;11(8):630-4.
  12. Farrar JT, Young JP, LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001;94(2):149-58.
  13. De Oliveira Jr GS, Fitzgerald P, Streicher LF, Marcus R-J, McCarthy RJ. Systemic lido- caine to improve postoperative quality of recovery after ambulatory laparoscopic surgery. Anesth Analg 2012;115(2):262-7.
  14. Sorensen J, Bengtsso A, Backman E, Henriksson K, Bengtsson M. Pain analysis in pa- tients with fibromyalgia: effects of Intravenous morphine, lidocaine, and ketamine. Scand J Rheumatol 1995;24(6):360-5.
  15. Attal N, Rouaud J, Brasseur L, Chauvin M, Bouhassira D. Systemic lidocaine in pain due to Peripheral nerve injury and predictors of response. Neurology 2004;62(2): 218-25.
  16. Vahidi E, Shakoor D, Meybodi MA, Saeedi M. Comparison of intravenous lidocaine versus morphine in alleviating pain in patients with critical limb ischaemia. Emerg Med J 2015;32(7):516-9.
  17. Soleimanpour H, Hassanzadeh K, Vaezi H, Golzari SE, Esfanjani RM, Soleimanpour M. Effectiveness of intravenous lidocaine versus intravenous morphine for patients with renal colic in the emergency department. BMC Urol 2012;12(1):13.
  18. Zink KA, Mayberry JC, Peck EG, Schreiber MA. Lidocaine patches reduce pain in trau- ma patients with rib fractures. Am Surg 2011;77(4):438-42.

Leave a Reply

Your email address will not be published. Required fields are marked *