A randomized trial comparing intravenous paracetamol,topical lidocaine,and ice application for treatment of pain associated with scorpion stings

Abstract

Objective:

Appropriate treatment for scorpion-associated pain was not previously studied in detail in the literature. The aim of this study was to compare the efficacy of three treatment modalities in patients with painful scorpion stings using visual analog scale (VAS) scores.

Materials and Methods:

A randomized study was carried out during a 1-year period in patients with scorpion stings who did not have any systemic signs or symptoms. Patients were treated with intravenous paracetamol, topical lidocaine, or ice application. Pain intensity was evaluated using VAS score at the time of presentation to emergency department and at 30th, 60th, 120th, and 240th minutes. Changes in VAS scores from baseline were recorded.

Results:

A total of 130 patients were included in the statistical analysis. Significant reduction in pain intensity was observed with topical lidocaine group when compared with the ice application group (p < 0.001) and paracetamol group (p < 0.001) in all selected time intervals. The median reduction in scores at 30 min after therapeutic intervention was 25.0 mm for topical lidocaine, 14.5 mm for ice application, and 10.0 mm for intravenous paracetamol. No adverse events were reported.

Discussion:

Our results revealed that topical lidocaine is superior to both intravenous paracetamol and local ice application and its effect lasts several hours after envenomation.

conclusion:

Topical lidocaine is an effective and safe treatment in scorpion sting associated with pain in patients with nonsystemic signs and symptoms.

Introduction

Scorpion envenomation is common in tropical and subtropical regions, especially in North Africa, Latin America, India, and the Middle East, where it is seen as a public health problem. ¹ The epidemiology of scorpion envenomation in the world is poorly known. There are considerable geographical variations at the level of both the incidence and severity. ² Scorpion sting cases are particularly common in the southeastern region of Turkey due to geographical location, climate, and socioeconomic structure. The most important health-threatening scorpions found in Turkey are Androctonus crassicauda, Leiurus quinquestriatus, Mesobuthus gibbosus, and Mesobuthus eupeus species, all of which belong to the Buthidae family. ^3,4

The main clinical features of scorpion envenomation are localized reactions (e.g. local pain at the sting site radiating along with corresponding dermatomes, mild local edema around the sting site, localized paresthesia, and pruritis) that occur in up to 97% of affected people; systemic manifestations (e.g. fever, sweating, hypertension, and vomiting) are uncommon (3%). ⁵ Cardiorespiratory manifestations, mainly cardiogenic shock and pulmonary edema, are the leading causes of death after scorpion envenomation. ⁶

The clinical picture depends on the anatomical location of the sting, victim’s age, weight, and health status. Most human victims of scorpionism experience local pain or a burning sensation at the site of the sting, but they do not develop general envenomation. ^7,8 Pain is the most common symptom of localized reactions. Almost all patients have localized pain at presentation, which is the only symptom in most patients. ^1,9–11 It was reported that local pain was seen in 95.1% of patients in a recent study held in the same region with our study. ¹² Pain is usually immediate, intense, persistent, with feelings of partial recoveries and relapses. ² Paracetamol has been recommended for pain management for mild envenomation. ¹³ Application of ice and local anesthetic to the area of the sting has also been recommended to reduce pain. ¹⁴ However, accurate treatment for pain resulting from the scorpion stings was not previously studied in detail in the literature. In this study, we aimed to compare three pain management modalities for scorpion stings in patients without systemic signs and symptoms.

Methods

Study design

This prospective and randomized study was carried out between October 2011 and November 2012 in a rural hospital in Mardin, a city in the southeast Turkey. The emergency department (ED) of this hospital admits approximately 110,000 patients per year, and admissions with scorpion stings are commonly encountered due to regional features. This study aimed to compare three treatment groups in patients with painful scorpion stings such as intravenous paracetamol, topical lidocaine gel, and ice application. All of the study drugs or applications are currently used for scorpion stings in this ED. The research was conducted in accordance with the tenets of the Declaration of Helsinki, and patients were asked to sign an informed consent before they enrolled in the study.

Selection of participants

The study was carried out in patients with scorpion stings who did not have any systemic signs or symptoms. Inclusion criteria were presentation to the ED due to pain associated with scorpion sting with only localized reactions (e.g. local pain at the sting site radiating along with corresponding dermatomes, mild local edema around the sting site, localized paresthesia, and pruritis), age over 18, and approval to participate in the study by signing the informed consent form. Exclusion criteria included questionable stings, late presentations (over 6 h), age under 18, known allergy to paracetamol, nonsteroidal anti-inflammatory drugs or lidocaine, use of any oral/intravenous analgesic drug within 24 h of ED presentation, refusal to participate in the study, and simultaneous abnormal skin conditions including local infections, ulcerations, and scars. Patients were also excluded if they had systemic signs and symptoms including hemodynamic instability, electrocardiographic abnormality, rapidly progressing local edema, abnormal neurological examination findings, autonomic symptoms (sweating, pallor, salivation, nausea, and vomiting), chest pain, pulmonary edema, or altered mental status.

Study protocol

Individuals included in the statistical analysis were allocated randomly in one of the three groups using sealed envelopes such as intravenous paracetamol (Perfalgan^® 10 mg/mL, 100 mL, Bristol Myers Squibb, New York City, New York, USA), topical lidocaine (Anestol^® pomade %5, İlsan, Turkey), and ice application. One gram of intravenous paracetamol was given to the paracetamol group and topical 5% lidocaine was applied directly to the sting site over a particular surface area in the lidocaine group. Ice packs were applied to the sting site intermittently for 10 min in ice application group. Ice application was performed 3 times with 10-min intervals. Intravenous paracetamol and topical lidocain were given only once. If pain persisted 30 min after presentation, narcotics were used as rescue medication.

Random selection of envelopes and drug administrations were done by two different ED nurses in each shift, who were blinded to the study. Pain intensity was evaluated using visual analog scale (VAS) score (0 to 100 mm; 0 = no pain, 100 = worst possible pain) before receiving the chosen treatment modality at baseline and at predetermined time intervals. Patients who were specified to have inadequate pain relief received 50 mg pethidine hydrochloride (Aldolan^® 50 mg/mL, 2 mL, Liba, Turkey) for pain control. Historical and demographic features were recorded on a standardized data collection form. The primary outcome measure was change in pain intensity at 30th, 60th, 120th, and 240th minutes. All adverse events were recorded on the study form.

Data analysis

SPSS 11.0 (SPSS Inc., Chicago, Illinois, USA) was used for statistical analyses. The Kolmogorov–Smirnov test was used for statistical analysis to verify data normality. Continuous variables were expressed as mean ± standard deviation for normally distributed data and median (with minimum−maximum values) for non-normally distributed data. The parametric comparisons for the three groups were performed by analysis of variance, and for nonparametric comparisons, the Kruskal–Wallis test was performed. Homogeneity of variances was tested with Levene’s test. Subgroup analyses were carried out with the Mann–Whitney U test with Bonferroni correction. Categorical variables were evaluated via Pearson’s χ ² test and shown with the number of cases and percentages. Statistical significance was assumed for p < 0.05.

Results

A total of 181 patients were evaluated in the initial step for eligibility, and 130 patients were included in the statistical analyses (Figure 1). Patients were randomly allocated to paracetamol group (n = 45, 34.6%), topical lidocaine group (n = 43, 33.1%), and ice application group (n = 42, 32.3%). Main demographic characteristics and initial vital signs are shown in Table 1.

Figure 1.

Patient flow chart.

Table 1.

Main demographic characteristics and vital signs of patients.

	Paracetamola	Topical lidocainea	Ice applicationa	p Value
Age	34.00 (19–81)	31.00 (18–70)	40.50 (18–80)	0.055
Male gender	22 (34.9%)	22 (34.9%)	19 (30.2%)	0.859
Systolic BP (mmHg)	125 (100–170)	120 (100–150)	120 (100–165)	0.132
Diastolic BP (mmHg)	80 (60–90)	70 (60–95)	75 (60–90)	0.083
Pulse (beat/min)	83.56 ± 10.07	82.28 ± 10.03	84.69 ± 10.21	0.547
Respiratory rate (breath/min)	13 (11–18)	13 (11–17)	13 (11–16)	0.740
Body temperature (°C)	36.6 (36.0–37.2)	36.7 (36.0–37.5)	36.7 (36.1–37.3)	0.347
Oxygen saturation (%)	98.0 (95.0–99.0)	98.0 (95.0–99.0)	98.0 (95.0–99.0)	0.914

BP: blood pressure.

^a n (%) or median (minimum−maximum) or mean ± SD.

All the patients were discharged from ED after at least a 4-h observation period, and no complications or adverse events were observed in the follow up. Scorpion sting sites were upper extremity (60.0%), lower extremity (35.4%), and torso (4.6%). While 90 patients (69.2%) presented to ED within the first 30 min after scorpion sting, 25 patients presented at the 30th–60th minutes period, and 15 patients after 1 h. There was no statistically significant relationship between the presentation time to ED and the treatment modality (p = 0.092). According to local symptoms, 98 patients (75.4%) reported local paresthesia, 42 patients (32.3%) local swelling, and 10 patients (7.7%) pruritus at the sting site.

VAS scores were evaluated at presentation (baseline), 30th, 60th, 120th, and 240th minutes. The baseline VAS score of the paracetamol group was 80 mm (60–90), while it was 70 mm in the topical lidocaine group (60–85) and 62.5 mm in the ice application group (50.0–76.3). There was no statistically significant difference between any of the three groups at baseline VAS scores (p = 0.060). Changes in VAS scores are shown in Table 2. A significant reduction in pain intensity was observed in the topical lidocaine group compared with the ice application group (p < 0.001) and the paracetamol group (p < 0.001) at the 30th minute (Figure 2). No statistically significant difference was observed between ice application and paracetamol groups at the 30th (p = 0.624), 60th (p = 0.505), 120th (p = 0.348), and 240th (p = 1.000) minutes. Topical lidocaine was also found superior to other two treatment modalities in specified time intervals for evaluating pain intensity (p < 0.001).

Figure 2.

Change in 30-min VAS. VAS: visual analog scale.

Table 2.

Comparison of differences in VAS scores between treatment groups regarding time intervals.

	Paracetamola	Topical lidocainea	Ice applicationa	p Value
Change in 30th minute VAS (mm)	10.00 (0–40)	25.00 (0–52)	14.50 (0–40)	<0.001
Change in 60th minute VAS (mm)	20.00 (0–60)	40.00 (10–70)	23.00 (0–50)	<0.001
Change in 120th minute VAS (mm)	35.00 (0–90)	52.00 (10–100)	30.00 (0–70)	<0.001
Change in 240th minute VAS (mm)	45 (28–62.5)	60 (50–75)	45 (33.75–55.25)	0.004

VAS: visual analog scale.

^aMedian (minimum−maximum) or mean ± SD.

Discussion

To our knowledge, this is the first study comparing different treatment modalities in the management of pain resulting from scorpion stings. Findings after scorpion envenomation are categorized into four clinical grades. Grade I corresponds to benign envenomations and manifests with localized reactions including pain and/or paresthesia at the scorpion sting site. Grade II signs and symptoms include fever, chills, excessive sweating, nausea–vomiting, diarrhea, hypertension, and priapism. Systemic symptoms like cranial nerve abnormalities, somatic skeletal neuromuscular dysfunction, nausea, vomiting, and pulmonary edema are associated with Grade III and IV signs and symptoms. ^15,16 Our study population consisted of only Grade I envenomations.

Pain is a major concern in the management of scorpion stings. Pain resulting from scorpion stings may last as long as 10–15 h, sometimes even longer (up to 24 h). In the majority of cases, pain is the only clinical sign and persists during the first 2 h following the sting. ²

Paracetamol, application of ice, and local anesthetics have been recommended for pain management for mild envenomation. ^13,14,16,17 When the stings occur at a finger, a ring of local anesthesia can provide good relief. In 95% of the cases, this treatment will be sufficient for an adult. ² However, it is uncertain which modality is superior to the others and there is insufficient data about pain management in scorpion envenomation in the literature.

In this study, significant reduction in pain intensity was observed in all three modalities. Yet topical lidocaine was found to be superior to the other two treatment modalities in specified time intervals. No statistically significant difference was observed between ice application and paracetamol groups at any of the time interval VAS scores. As the pain accounts for a major problem for an emergency physician to deal with in Grade I scorpion envenomations, topical lidocaine seems to be the best choice for pain management. No side effects were reported due to these treatment methods.

Previous literature reports that systemic symptoms vary from 2% to 22% in scorpion envenomation. ^4,11 In a study, which was conducted on 511 cases, patients were grouped by age, where the 0–10-year-old group compared with those 11 years and older group presented higher proportion of cases with systemic signs (7% vs. 2%). ⁸ In this study, Grade I patients were the target group. Only 6 (3.3%) of 181 patients (number of patients before exclusion criteria was performed) had systemic symptoms, and they were excluded from the study. In this study, the percentage of patients with systemic symptoms was relatively less when compared to previous studies. All the patients with systemic symptoms were treated with antivenom and admitted to intensive care unit.

Epidemiological studies have shown that the affected body parts are mostly the extremities. ^10,18–20 In this study, 95.4% of the patients had scorpion stings in their extremities such as hand, arm, leg, thigh, or foot. Similarly in a recent study that was conducted in the same region of Turkey, most of the stings were seen in the exposed extremities (92.9%). ¹⁰ Ulug et al., in their study, reported lower limbs as the most affected part of the body (58.6%); controversially, in this study (60%) and other studies from our country, upper extremities are found to be the most affected parts of the body. ^12,19,21,22

Our study has three major limitations. First, this was a single center study with a relatively small sample size. On the other hand, scorpion envenomation is a rare condition, and the majority of patients with mild stings do not seek medical care. Second, people living in different geographical regions have different pain thresholds. The pain perception of the study population might have affected our results. Absence of a placebo group was the third major limitation of the study.

Conclusions

Pain management is the main concern to be addressed in mild scorpion envenomation. Topical lidocaine is associated with reduction in pain resulting from scorpion stings in patients with no systemic signs and symptoms. Our results also revealed that topical lidocaine is superior to intravenous paracetamol and local ice application and its effect lasts several hours after envenomation.