Transdermal Ketoprofen Patch in Comparison to Eutectic Mixture of Local Anesthetic Cream and Subcutaneous Lidocaine to Control Pain Due to Venous Cannulation.

BACKGROUND: This study was established to compare the analgesic and side effects between transdermal ketoprofen patch 30 mg and eutectic mixture of local anesthetic (EMLA) cream applied to the peripheral venous cannulation site and lidocaine injection before cannulation. PATIENTS AND METHODS: One hundred and five adult patients who had been scheduled for elective general surgery with patients' physical status American Society of Anesthesiologists classes I and II were randomly divided into three groups: Group I (EMLA group) received EMLA cream, Group II (lidocaine group) received subcutaneous infiltration of 1 ml of 2% lidocaine HCl 10 min before cannulation, and Group III (ketoprofen group) received a transdermal ketoprofen patch 30 mg. Groups I and III received their cream or patch 60 min before cannulation. The pain resulting from cannulation by an 18G cannula was assessed by a visual analog scale (VAS) at the time of cannulation and every 2 h for another 6 h for all groups. Signs of inflammation at the site of cannulation (erythema, induration, edema, and blanching) were observed at the site of cannulation for 24 h.
RESULTS: Ketoprofen patch, EMLA cream, and lidocaine injection were found to be equal in controlling pain caused by venous cannulation with no significant difference in VAS. Signs of inflammation at the site of cannulation (blanching, erythema, and induration) were very evident in Group I (EMLA) which showed significant difference than in other two groups.
CONCLUSIONS: EMLA cream, ketoprofen patch, and lidocaine injection have equal ability to alleviate pain due to cannulation when applied before the procedure, but ketoprofen patch is more superior as it had less local inflammatory effect in comparison to EMLA cream and without double puncture as with lidocaine injection.

INTRODUCTION

Although venous cannulation is considered by many practitioners as a minor procedure, but it is often painful and sometimes a difficult process to go through. Venous cannulation is a mandatory step in anesthesia and in many other critical situations like resuscitation. Rapid anesthesia of the skin has long been a problem associated with common procedures such as venipuncture, intravenous cannulation, and skin biopsy. It was reported that 10.3% from 10,000 surgical patients suffered from thrombophlebitis after intravenous cannulation.[1] Thrombophlebitis is clinically recognized by the presence of erythema, induration, and edema.[2] Local anesthetics in one form or another are used to overcome pain on cannulation.[3] Apart from the benefit of rapidity of onset and effective pain relief, the use of local anesthetic agents is associated with a number of disadvantages, such as pinprick pain on lidocaine subcutaneous (s.c.) infiltration[4] and blanching of the skin following the application of eutectic mixture of local anesthetic (EMLA) cream.[5]

In this study, we endeavored to compare the analgesic effect and the incidence of side effects between the transdermal ketoprofen patch, EMLA cream, and s.c. infiltration of lidocaine at the site of venous cannulation.

PATIENTS AND METHODS

After approval from the ethical and medical committee, written informed consent was obtained from 105 patients aged from 18 to 55 years and patients' physical status American Society of Anesthesiologists classes I and II undergoing elective general surgery to proceed for this prospective, randomized, double-blind study which was conducted in Ain Shams University Hospitals between March 2017 and February 2018.

Exclusion criteria involved the following types of patients: patients with skin lesion or infection at the site of venous line application, patients with bronchial asthma, renal impairment, non-steroidal anti-inflammatory drugs (NSAIDs) allergy, chronic NSAIDs intake, peptic ulcer, any psychiatric disease, alcohol or drug dependence, or noncooperative patients.

Patients were randomly divided into three groups. Group I (EMLA group) received a thick layer of EMLA cream 5 g per 5 cm2 (5% AstraZeneca) 60 min before venous cannulation, Group II (lidocaine group) received s.c. infiltration of 1 ml 2% lidocaine HCl at the site of cannulation, and Group III (ketoprofen group) received ketoprofen patch containing ketoprofen 30 mg (KefenTech Plaster, each sheet is 10 cm × 7 cm × 2.36 g, Jeil Pharmaceutical Co., Ltd) 60 min before cannulation. The EMLA cream and the ketoprofen patch were applied at the proposed site of venous cannulation. Patches and cream and s.c. infiltration were applied by an anesthetist who was not oriented by the idea of the study.

An 18G cannula (BD Venflon 18 GA 1.2 mm × 4.5 mm, Becton Dickinson Infusion Therapy AB SE-251 06 Helsingborg, Sweden) was used for cannulation on the dorsum of the nondominant hand for all patients by an experienced anesthetist who was not aware by the idea of the study. The cannula was secured in place with a transparent adhesive dressing (Tegaderm CHG, 8.5 cm × 11.5 cm 3M Health Care Business, Carl-Schurz-Str. 141453 Neuss, Germany). All patients whom venous cannulation was unsuccessful from first attempt were subsequently excluded from the study.

Pain was assessed by a visual analog scale (VAS) 0–10 (0 = no pain and 10 = worst pain) at the time of cannulation and every 2 h for another 6 h postoperatively. Signs of inflammation (erythema, induration, edema, and blanching) were observed at the site of cannulation during this time for 24 h postoperatively.

All values were presented as mean ± standard deviation. The results were analyzed statistically using ANOVA test and Chi-square test/Fisher's exact test. Demographic data were analyzed with ANOVA for continuous variables and Chi-square test for categorical variables. The VAS pain scores were analyzed with a Mann–Whitney U-test. The package SPSS 21 (IBM Corp., Released 2013, IBM SPSS Statistics for Windows, Version 21.0., Armonk, NY, USA) was used for statistical analysis. A P < 0.05 was considered statistically significant.

RESULTS

Each group included 35 patients from the beginning. All patients with failed cannulation from the first attempt were excluded from the study which included three patients in Group I, four patients in Group II, and four patients in Group III. Remaining 94 patients were included in the study and distributed as follows: Group I included 32 patients, Group II included 31 patients, and Group III included 31 patients [Table 1].

Table 1

Demographic data

Blanching only happened to patients in Group I which is statistically significant at 0 h, 4 h [Figure 1], 8 h, and 12 h [Table 2].

Figure 1

Inflammatory responses in all three groups at 4 h

Table 2

Incidence of blanching

Erythema occurred in all three groups, but it was with significant difference in Group I at 4 and 8 h [Table 3 and Figure 2].

Table 3

Incidence of erythema

Figure 2

Incidence of erythema in all three groups

Induration also developed in all three groups, but it was with significant difference in Group I at 4 and 8 h [Table 4 and Figure 3].

Table 4

Incidence of induration

Figure 3

Incidence of induration in Group I at 4 and 8 h

No significant difference was found in all three groups as regards edema formation [Table 5 and Figure 4].

Table 5

Incidence of edema

Figure 4

Incidence of edema in all three groups

VAS was nearly the same in all three groups with no significant difference [Tables 6 and 7].

Table 6

Incidence and severity of pain due to cannulation at 0 h

Table 7

Visual analog scale and interquartile range in all three groups

DISCUSSION

Pain due to venous cannulation continues to be a problem with respect to the smooth initiation of anesthesia and can impact a patient's comfort and ability to relax prior to induction of anesthesia. Patients may continue to have pain and discomfort at the cannulation site even after removal of the cannula. It constitutes an important complaint in outpatients after discharge.[6] In this study, we compared the analgesic effect and side effects of EMLA cream, lidocaine s.c. infiltration, and transdermal ketoprofen patch. It was found that the three methods are equally effective in reducing pain at and after venous cannulation. EMLA cream is associated with more inflammatory response, especially blanching than the transdermal ketoprofen patch and lidocaine s.c. infiltration.

ELMA cream is a eutectic mixture of the two amide local anesthetics (lidocaine 2.5% and prilocaine 2.5%). It is used on the normal intact skin to induce local anesthesia approximately 60 min after application. The most common local adverse effect of EMLA cream is transient blanching of the skin. Erythema is also observed, but it is usually noted 2 h after its application. This is may be due to the fact that it causes initial localized vasoconstriction which causes blanching; then, it causes vasodilation which results in erythema and induration.[7] This cutaneous side effect usually subsides in 6 h. Other side effects for EMLA cream include contact dermatitis, urticaria, methemoglobinemia, and petechial eruptions.

Lidocaine 2% s.c. infiltration is a common method in attenuating pain at venous cannulation rapidly, but it has the disadvantage of double pinprick to the patient.

NSAIDs which can be applied topically are recently used to decrease pain (acute and chronic).[8] They have the ability to reduce pain by decreasing the inflammatory response to cannulation. Their advantage is that they enhance local drug delivery to the site of cannulation with less systemic side effects.[910] Their anti-inflammatory effect leads to minimizing thrombophlebitis percentage.[10] Ketoprofen has several advantages over other NSAIDs such as diclofenac or indomethacin as a transdermal preparation with highest cutaneous permeability owing to its low molecular weight, low melting point, and high lipophilic nature. A low molecular weight is associated with elevated transdermal absorption.[1112]

Some studies evaluated the efficacy of transdermal anti-inflammatory patches compared to placebo effect only as Agarwal et al., who evaluated the efficacy of transdermal diclofenac patch in attenuating venous cannulation pain and reported a median VAS score of 3 (2-4). They concluded that diclofenac patch is effective in decreasing cannulation pain.[13] Furthermore, Agarwal et al. compared EMLA cream against diclofenac patch to control pain due to venous cannulation[14] and concluded that transdermal diclofenac patch and EMLA are equally effective in reducing venous cannulation pain, but signs of edema, induration and erythema are less commonly detected with the transdermal diclofenac patch.

Other studies evaluated the efficacy of these patches compared to EMLA cream as Dutta et al., who found that the topical application of piroxicam gel before intravenous cannulation is ineffective in reducing pain after cannulation, but it reduces the inflammatory changes at the site of cannulation.[6] Smith et al. studied the analgesic effect of topical ibuprofen for skin analgesia before venipuncture.[4] They reported that there was no significant difference in visual analogue scale pain scores for pinprick after 15 and 60 minutes of application of placebo, ibuprofen and EMLA cream. They did not favor ibuprofen cream to be clinically beneficial for venous cannulation.

On the other hand, Agarwal et al. studied the efficacy of transdermal diclofenac patch versus EMLA cream in decreasing intravenous cannulation pain and as regards their inflammatory response. They concluded that both methods are effective in reducing venous cannulation pain, but signs of inflammation are less frequently observed with the transdermal diclofenac patch.[13]

Furthermore, Kumar et al. support our results as regards the analgesic effect of transdermal ketoprofen in reducing pain and inflammation following venipuncture,[15] but they only compared diclofenac patch with placebo.

In our study, we compared three methods of attenuation of venous cannulation pain and signs of inflammation, EMLA cream, ketoprofen patch, and s.c. infiltration of lidocaine 2%. It was found that three methods are nearly equally effective in attenuation of venous cannulation pain. Signs of inflammation, especially blanching, are more frequently observed with the use of EMLA cream.

CONCLUSIONS

We concluded that the transdermal ketoprofen patch is an effective and safe method for attenuation of venous cannulation patch as it attenuates venous cannulation pain at and after cannulation with minimal inflammatory response at the site of cannulation and without the need of pricking the patient double pinprick as with lidocaine 2% s.c. infiltration.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.