Arch Gynecol Obstet DOI 10.1007/s00404-014-3462-7

GENERAL GYNECOLOGY

Topical anaesthetic patches for postoperative wound pain in laparoscopic gynaecological surgery: a prospective, blinded and randomised trial Sebastian Berlit • Benjamin Tuschy • Joachim Brade • Franz Hu¨ttner • Amadeus Hornemann • Marc Su¨tterlin

Received: 25 May 2014 / Accepted: 8 September 2014 Ó Springer-Verlag Berlin Heidelberg 2014

Abstract Purpose Aim of this prospective study was to investigate the effectiveness of eutectic mixture of local anaesthetic (EMLAÒ) patches on every abdominal incision for pain relief after gynaecologic laparoscopic surgery. Methods A total of 121 women were prospectively randomised to receive either placebo (control group) or EMLAÒ (study group) patches on all abdominal incisions. Postoperative pain was assessed 24 and 48 h after surgery using the short form of the McGill Pain Questionnaire (SFMPQ). The amount of analgesic pain medication on demand was assessed in both groups. Results Sixty women were allocated to the study group and 61 patients to the control group before laparoscopic surgery. There were no statistically significant differences regarding age, body mass index (BMI), duration of surgery and blood loss comparing both groups. There were no statistically significant differences between both groups with regard to postoperative total pain scores 24 h (McGill total score: 31.77 ± 27.95 vs. 36.80 ± 31.39, p = 0.3535)

S. Berlit and B. Tuschy contributed equally to this work. S. Berlit (&)
B. Tuschy
A. Hornemann
M. Su¨tterlin Department of Obstetrics and Gynaecology, University Medical Centre Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany e-mail: [email protected] J. Brade Department of Medical Statistics and Biomathematics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany F. Hu¨ttner Department of Obstetrics and Gynaecology, Stadtklinik Frankenthal, Frankenthal, Germany

and 48 h (McGill total score: 19.18 ± 20.09 vs. 26.61 ± 27.70, p = 0.0942) after surgery. Time to mobilisation after surgery (hours) was significantly shorter in the study group (5.01 ± 3.72 vs. 5.78 ± 3.04, p = 0.0423). Conclusion Despite of a significant reduction of time for mobilisation transdermal anaesthetic patches after gynaecologic laparoscopic surgery did not lead to decreased postoperative pain scores. Keywords EMLA patch
Gynaecologic laparoscopy
Postoperative pain
Transdermal anaesthetics
Postoperative mobilisation

Introduction It is obvious that an inadequate pain management can lead to a delayed discharge and may negatively impact surgical outcome due to psychological and physiological complications. It is known that postoperative pain leads to an increase in sympathetic tone, which impairs neuroendocrine and metabolic catabolism as well as muscle functioning [1]. Furthermore Apfelbaum et al. [2] found out that severe postoperative complications, such as coronary ischemia, deep venous thrombosis and pulmonary embolism are related to ineffective pain management after surgery. Authors also describe, that patient’s demoralisation and dissatisfaction with hospital care are associated with uncontrolled pain [2]. In general, the experience of pain up to seven days after surgery is not uncommon, and uncontrolled pain is one of the main causes for a delayed discharge or unanticipated readmission after surgical intervention [3]. Lovatsis et al. [3] stated that only 40–60 % of women, who underwent gynaecologic laparoscopic surgery in an

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outpatient setting, were satisfied with postoperative pain control. Estimations of postoperative wound pain state that 50–75 % of patients suffer inadequate pain relief [4]. One might argue that due to the introduction of minimal invasive surgery in nearly every surgical specialty wound pain is considerably reduced. However, authors still report a high incidence of postoperative pain, even after minor laparoscopic surgeries [5, 6]. Some investigations show that 80 % of patients require opioid analgesia after laparoscopic surgery [7]. It has been proven that an effective pain management leads to a decrease of complications after surgery, a faster hospital discharge, less resource utilisation and hence lowered direct and indirect costs [8]. To improve patients’ care it is inevitable to provide an adequate pain management. Therefore, postoperative pain management was increasingly investigated and is a matter of ongoing debate. In a recent systematic review of the literature Shaun et al. found out that preemptive administration of local infiltrative anaesthetics at the incision site reduces postoperative pain compared to placebo but achieves an analgesic effect similar to a local infiltrative anaesthesia at the end of the surgery [9]. The authors state that local analgesia should be administered, but that timing of application (before vs. after surgery) is not significantly different in case of infiltrative anaesthetics [9]. A disadvantage of infiltrative analgesia is the additional trauma to the abdominal wall, which might lead to complications such as infection, haematoma and possibly intravasal application with potential circulatory complications. This is why we designed this prospective investigation with a non-invasive form of non-opioid analgesic local therapy after laparoscopy. Aim of the study was to investigate if topical application of local anaesthesia patches after laparoscopy reduces postoperative pain.

Methods and materials Between May 2012 and March 2013, 121 women were included in this study. All of these patients underwent gynaecologic laparoscopic surgery due to benign reasons at the University Medical Centre Mannheim, Heidelberg University, Germany. The study was approved by the Ethics Committee II of the Medical Faculty Mannheim, Heidelberg University (2012-351 N-MA), and was registered in the German Clinical Trial Register (DRKS-Nr00003869). Written informed consent was obtained from all participating women. Exclusion criteria were malign gynaecologic diseases, conversion to laparotomy or previous adverse reaction to local anaesthesia. Also an age below 18 years and patients consuming regular analgesic medication were excluded. Written information about the

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investigation was provided and women were assigned to either group randomly using pairs of sealed envelopes including a note stating either ‘‘study group’’ or ‘‘control group’’. All laparoscopic surgeries were performed under general anaesthesia as a standardised procedure. A 10-mm optic trocar was inserted beneath the umbilicus and two 5-mm trocars were placed laterally in the lower abdomen. Intraoperative pressure was 15 mmHg maximum. In case of laparoscopic supracervical hysterectomy (LASH) or fibroid resection the left incision in the lower abdomen was extended to 12–15 mm to introduce a morcellator. The study group consisted of 60 patients in whom eutectic mixture of local anaesthetic (EMLAÒ) patches (Astra Zeneca, Wilmington, DE, USA) were applied on every incision directly after finishing surgery. EMLAÒ patches consist of lidocaine 2.5 % and prilocaine 2.5 % on a cellulose and cotton disc. A standard patch was allocated on top of the EMLAÒ patch to ensure blinding to patients and nurses. Sixty-one women were in the control group and received standard patches only. Due to the identical look of the patches in both groups neither patients nor nurses were aware if anaesthetic or placebo patches was applied. All patches were removed the next morning after surgery in women of both groups. All patients received analgesics on demand according to a standardised escalating pain management, starting with non-steroidal anti-inflammatory drugs and ending with opioids. Pain medication on demand was given as follows: paracetamol 4 g per day, diclofenac resinate twice a day, ibuprofen 400 mg three times a day as possible maximum dosages per day. In case of insufficient analgesia with these measures pethidine hydrochloride 50 mg and/or piritramide 7.5 mg were applied. The principle outcome parameter was postoperative pain 24 and 48 h after surgery. Secondary endpoints were length of hospital stay, need of additional medication for pain relief and time to mobilisation after surgery (end of surgery until first mobilisation). The questionnaire used was the short form of the McGill Pain Questionnaire (MPQ-SF), which contains three sections: a list of 15 pain describing terms recording the intensity of types of pain experienced, an analogue scale, and a six-point present pain intensity index (PPI) [10]. The pain describing section (McGill 1) is divided in 11 sensory pain descriptors and 4 affective pain descriptors with a 0–3 scale (marked ‘none’, ‘mild’, ‘moderate’, and ‘severe’), so that potential score ranges were 0–33 and 0–12. The second section (McGill 2) of the questionnaire is an analogue scale ranging from 0 to 100, indicating no pain to worst possible pain. The third component (McGill 3) is a six-point PPI with the following scores: 0 = no pain, 1 = mild, 2 = discomforting, 3 = distressing, 4 = horrible, 5 = excruciating. The scores of these three sections are added to obtain a total score (McGill total).

Arch Gynecol Obstet

All data were recorded in an Excel datasheet. Arithmetic means and standard deviations were calculated for normal distributed metric variables. Metric non-normally distributed variables were expressed as median ± range. Nonparametric Mann–Whitney U test and student t test were applied as appropriate. Chi-square test and Fisher’s exact test were used to compare descriptive variables. Data were recorded and assessed using SPSS statistics software (SPSSÒ version 17.0, SPSS Inc. Chicago, USA). A p value below 0.05 was considered statistically significant.

Results There were no statistically significant differences regarding age, BMI, duration of surgery, time to discharge and blood loss comparing both groups as shown in Table 1. The most

Table 1 Demographic and surgical parameters of the study (n = 60) and control group (n = 61)

frequently performed surgeries in the study and the control group were laparoscopic supracervical hysterectomy (LASH) (15/60, 25 vs. 18/61, 30 %), uterine fibroid resection (7/60, 12 vs. 13/61, 21 %) and total laparoscopic hysterectomy (TLH) (6/60, 10 vs. 7/61, 11 %). The distribution of different surgeries in both groups was comparable without a significant difference. A detailed description of the surgical procedures accomplished is shown in Table 2. Furthermore, there were no significant differences regarding the uterine weight in case of hysterectomy (222.25 ± 309.38 vs. 194.56 ± 192.07; p = 0.7146), neither concerning the weight of uterine fibroids in case of fibroidectomy comparing both groups (38.71 ± 34.96 vs. 89.67 ± 103.07; p = 0.2270). In the study group, time to first mobilisation (hours) after surgery was significantly shorter compared to the control group (5.01 ± 3.72 vs. 5.78 ± 3.04; p = 0.0423). Postoperative pain experienced after surgery was determined by the McGill (short form) pain questionnaire as explained above. Analysis of the pain describing section (McGill 1) showed significantly less pain in the study

Variable

Study group mean ± SD

Control group mean ± SD

p value

Age (years)

43.07 ± 12.55

40.11 ± 10.06

0.1556

Table 3 Pain scores using the short form of the McGill questionnaire of the study (n = 60) and the control group (n = 61)

BMI (kg/m2)

25.96 ± 4.69

26.96 ± 6.29

0.3285

Variable

Duration of surgery (min)

71.68 ± 31.15

82.52 ± 36.93

0.0837

Time to discharge (h) Blood loss (ml)

61.97 ± 16.67 27.83 ± 38.67

60.49 ± 11.56 60.16 ± 123.43

0.5723 0.0551

SD standard deviation, BMI body mass index

Table 2 Performed surgeries in the study (n = 60) and control group (n = 61) Variable TLH (13)

Study group n (%)

Control group n (%)

6 (10)

7 (11)

15 (25)

18 (30)

7 (12)

13 (21)

Salpingooophorectomy (18)

12 (20)

6 (10)

Ovarian cyst extirpation (28)

16 (27)

12 (20)

Adhesiolysis (4)

0 (0)

4 (7)

Resection of endometriosis (2)

1 (2)

1 (2)

EUG (2) TOA (1)

2 (3) 1 (2)

0 (0) 0 (0)

LASH (33) Uterine fibroid resection (20)

Overall p value 0.1644

TLH total laparoscopic hysterectomy, LASH laparoscopic supracervical hysterectomy, EUG ectopic pregnancy, TOA tubo-ovarian abscess

Study group mean ± SD

Control group mean ± SD

p value

McGill 1 (24 h)

5.59 ± 5.46

8.42 ± 8.50

0.0318*

McGill 2 (24 h)

24.68 ± 23.44

26.74 ± 23.95

0.6331

McGill 3 (24 h)

1.50 ± 0.93

1.65 ± 0.96

0.3942

McGill total (24 h)

31.77 ± 27.95

36.80 ± 31.39

0.3535

McGill 1 (48 h)

4.12 ± 5.82

5.70 ± 7.95

0.2153

McGill 2 (48 h)

13.98 ± 16.09

19.79 ± 21.20

0.0923

McGill 3 (48 h)

1.08 ± 0.95

1.12 ± 0.78

0.8020

McGill total (48 h)

19.18 ± 20.09

26.61 ± 27.70

0.0942

Time to mobilisation (h)

n = 57 5.01 ± 3.72

n = 58 5.78 ± 3.04

0.0423*

SD standard deviation, h hours * Significant difference

Table 4 Pain medication of study (n = 60) and control group (n = 61) Non-opioid medication

Study group n (%)

Control group n (%)

p value

Within 24 h after surgery

43 (72)

43 (71)

0.3600

24–48 h after surgery

28 (47)

35 (57)

0.0538

After 48 after surgery

10 (17)

11 (18)

0.8738

Patients received either paracetamol 4 g per day, diclofenac resinate twice a day or ibuprofen 400 mg three times a day

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group 24 (5.6 vs. 8.42; p = 0.0318), but not 48 h after surgery (4.12 vs. 5.7; p = 0.2153). All other obtained pain scores were not significantly different comparing the two groups. A detailed description of the different McGill scores is depicted in Table 3. Also the amount of analgesic medication on demand throughout the hospital stay showed no significant differences, as shown in Table 4. Opioid analgesics were necessary as a single dose application (piritramide 7.5 mg) in only one patient of either group. There were no severe intra- or postoperative complications in the investigated patients and no skin irritation occurred while using EMLAÒ patches.

Discussion Nowadays minimal invasive surgery is increasingly used and it is the standard treatment for various malignant as well as benign gynaecologic diseases. Whereas patients do not perceive the number of incisions or the duration of hospital stay as a problem, the postoperative pain seems to be an underestimated concern, hence only 40–60 % of women who underwent gynaecologic laparoscopy are satisfied with postoperative pain control [3, 11]. Previous studies showed that pain after laparoscopic surgeries can be subdivided into three categories, which are parietal, visceral and shoulder tip pain (due to overstretching the diaphragm or ligaments of the liver) [12, 13]. Of these three categories parietal pain, hence pain due to incision of the abdominal wall, is known to dominate over the other possible pain components [14, 15]. Due to this reason our aim was to diminish the clinically most important pain type in a non-invasive way. There are several studies dealing with different ways, e.g. extended assisted ventilation with an open umbilical trocar valve to reduce residual carbon dioxide, intraperitoneal lidocaine, infiltrative lidocaine or intravenous lidocaine, to treat postoperative pain after minimal invasive surgery: Radosa et al. [16] showed that an extended assisted ventilation with an open trocar valve results in less abdominal and postoperative shoulder tip pain. In a recent published study Kim et al. [17] stated that intravenous lidocaine injection in patients undergoing laparoscopic gastrectomy reduces postoperative opioid consumption and results in better pain scores after surgery. Another way for local pain relief is intraperitoneal instillation of lidocaine, which is known to be a safe and effective treatment during laparoscopic tubal ligation performed under conscious sedation [17, 18]. Also transdermal analgesics have been applied in few earlier studies successfully [19–21]. Liang et al. [22] showed that the application of EMLAÒ in patients who underwent stereotactic gamma knife radiosurgery reduced the postoperative wound pain significantly. In a small prospective

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randomised investigation Kwon et al. [23] evaluated the efficiency of topical lidocaine patches after gynaecological surgery in 40 women with a significant reduction of wound pain one and 6 h after surgery. Surprisingly, the number of prospective studies using this gentle form of anaesthesia is scarce and EMLAÒ patches after gynaecological laparoscopy have not been investigated before. Opioids are the most frequently used anaesthetic drugs to reduce postoperative wound pain [24]. Studies investigating transdermal analgesic methods mainly used topical fentanyl patches. Disadvantage of an opioid analgesia are possible adverse events (i.e. respiratory depression, nausea, vomiting, constipation, urinary retention) [20, 25]. Another restraint of fentanyl patches is the fact that the analgesic effect reaches its maximum after 17–28 h, so that acute postoperative pain is not treated [25]. Due to slow pharmacokinetics and hence an ineffective postoperative pain relief as well as a high incidence of respiratory depression, use of opioid patches for treatment of postoperative wound pain is now contraindicated [25]. Port site infiltrative anaesthesia using amide-type local anaesthetics has been shown to efficiently reduce postoperative pain and is performed as a standard procedure by many physicians of surgical specialties [9]. As already mentioned above, an advantage of transdermal analgesics is the fact that no further trauma to the abdominal wall is set, reducing the risk of possible side effects. Furthermore analgesic patches emit their agents continuously. Hence theoretically pain reduction should last longer and due to a more constant absorption also more reliably, avoiding plasmatic concentration spikes, which are typical for infiltrative anaesthetics [19]. Possible side effects have to be kept in mind when applying EMLAÒ patches. The clinically most important side effects are skin irritation and in rare occasions, after excessive use, methemoglobinemia [26]. According to Taddio et al. [27] single doses of EMLAÒ do not cause methemoglobinemia. Our results are in partial accordance with the results of Kwon et al. [23]. The topical application of lidocaine in our investigation led to a significant reduction of pain within the first 24 h after surgery (McGill 1), although the other pain evaluating sections of the McGill questionnaire showed no significant differences. Even so, there might be a non-significant trend for lower postoperative pain scores in favour of women of the study group. Differing from the above-mentioned study we evaluated postoperative pain 24 and 48 h after surgery and not within the first 12 postoperative hours. This way a potential bias due to analgesics applied during surgery was diminished. Also, in contrast to our investigation, Kwon et al. [23] re-applied lidocaine patches every 12 h. Despite a trend in pain reduction, this is the first investigation, which showed a significant reduction of time

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to postoperative mobilisation using topical anaesthetic patches. In general, it has to be emphasised that an early postoperative mobilisation is the most important therapeutic approach preventing thrombosis and pneumonia after surgery. We are aware of the fact, that the use of anaesthetic patches after gynaecologic laparoscopy is associated with additional costs, only partially resulting in statistically significant reduced postoperative pain. A reapplication of topical analgesics (EMLAÒ-patches) might lead to a further reduction of pain after laparoscopic surgery, as performed by Kwon et al. [23]. Minimally invasive surgical procedures are associated with a beneficial postoperative outcome due to reduced pain, fewer adverse events, lower intraoperative blood loss, a lower percentage of wound infections and quicker return to normal activity compared to women who underwent conventional abdominal approaches [28]. Nevertheless, one has to keep in mind that only 40–60 % of women who undergo gynaecological laparoscopic surgery in an outpatient setting are satisfied with postoperative pain control by systemic analgesics [3]. This emphasises the importance of an adequate postsurgical pain management, but the potential benefit of topical anaesthetic patches as an additional analgesic approach after gynaecological laparoscopy seems to be limited.

Conclusion Despite a significant reduction of time to postoperative mobilisation the application of topical anaesthetic patches did not reduce postoperative pain after gynaecologic laparoscopic surgery. In our opinion the effectiveness of this additional analgesic approach seems to be doubtful. Conflict of interest conflict of interest.

The authors declare that they do not have any

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