Effects of Entonox in Comparison with Lidocaine on Pain Severity during Episiotomy Incision in Nulliparous Women: A Randomized Control Trial

Introduction

Episiotomy is usually performed with scissors before fetal head crowning, when the perineum is sufficiently distended and stretched, to prevent severe spontaneous perineal tears, facilitate delivery and reduce the time of baby’s exit from the womb (1). Despite the decreased rate of episiotomy in developed countries during the past years, total rate of trauma and injury to the genital tract after vaginal delivery is still high (2). This rate has been reported to be 8% in the Netherlands, 20% in England, 50% in the United States, 28% in Argentina, 40.6% in Australia and 54% in North America.

While there is no comprehensive statistics about episiotomy in Iran, its prevalence might be on the rise due to the high fertility rate in our country (3). In this regard, Khajavi et al. (2009) reported the prevalence of episiotomy in Iran to be 97.3% in nulliparous women (4). Although the routine use of episiotomy has declined in developed countries, episiotomy is still practiced in Asian countries due to the high susceptibility of Asian women with short perineum and strong tissue to extensive perineal tears (5).

Pain is a common phenomenon, regarded as an inevitable part of delivery and postpartum process (6). Injection of lidocaine is one of the usual pain relief methods in small operations (e.g., episiotomy) (7). Despite the benefits of this technique, exceeding the maximum dose of lidocaine could be associated with considerable side effects. However, these important complications are not common and often occur due to the accidental intravascular injection of local anesthetics during nerve block.

Neurotoxicity could lead to fidgeting, dizziness, tinnitus, slurred speech, and tonic and colonic seizures. Seizure is associated with the weakening of the central nervous system (CNS), apnea, vascular hypoxia and metabolic acidosis, which occur quickly and cause death in some cases. Despite the fact that cardiovascular system is resistant to the toxic effects of local analgesics, high plasma concentrations of analgesics can cause arteriolar smooth muscle relaxation, direct weakening of myocardia and severe hypotension (8).

Labor pain management encompasses the use of analgesics and anesthetics with minimum side effects. Lidocaine is currently used as a pain-relieving agent during episiotomy; however, it is associated with various side effects that cannot be controlled by the therapist. In addition, accidental intravascular injection of lidocaine could lead to the mentioned complications (9). Today, non-injection methods for analgesia have opened a new horizon in medicine, among which Entonox is considered the most important compound. Entonox is a weak inorganic gas consisting of 50% nitrous oxide and 50% oxygen. It is odorless and colorless, which serves as an effective inhaled analgesic (10).

Studies have shown that Entonox gas can be used as an analgesic in surgeries, such as colonoscopy and liver biopsy (11, 12). Furthermore, it has been declared that this gas can reduce the pain of joint dislocation along with other analgesics; this effect could be exerted independently or in combination with other analgesics in childbirth and sigmoidoscopy (13-15). Entonox can also be applied along with other analgesics to decrease the pain and discomfort caused by intra-articular injection of drugs, ophthalmologic surgeries, cancer treatment, peripheral vein cannulation and biopsy (16-20). However, independent use of this compound might be insufficient in some cases, such as the alleviation of the pain caused by shoulder dislocation (21).

On this theme, Becker (2008) has reported the analgesic effects of morphine at the dosage of 15 mg (22). In addition, Rosen (2003) evaluated labor pain and reported that the analgesic effects of nitrous oxide are more significant compared to opioids. Moreover, he compared this drug with paracervical block, revealing the short-term pain relief by Entonox, which was associated with lower anxiety and pain (23).

Entonox rapidly diffuses through the walls of the alveoli and is transported in the plasma as a solution without binding to hemoglobin (10). Due to its very low solubility in blood, it is transferred to the brain and spinal cord about 15 seconds after inhalation with appropriate concentration and effective pressure (24). As an anesthetic gas, Entonox weakens the CNS non-specifically.

According to the results obtained by Gilman, Entonox particularly acts through interactions with endogenous opioids system. In addition, its functionality is mostly observed in the areas of the brain and spinal cord with many morphine-sensitized cells (25). Side effects of Entonox start within 30 seconds after administration and maximize within two minutes (10). Oxygen in Entonox prevents the risk of hypoxia in patients (26).

Entonox could be easily administered and used as a simple and safe method with fast analgesic effects and quick returns (27). Moreover, Entonox has a short half-life without the need for sophisticated devices (10). This gas has glancing effects due to the rapid excretion from the lungs, while it has no significant impact on maternal cardiovascular, respiratory and nervous systems (28).

According to the American Gynecological and Obstetrical Society (AGOS), progress of pain management programs in different countries could improve the quality of obstetric care and promote normal vaginal delivery by proposing new pain-reliving methods, which ultimately reduces the rate of elective caesarean section. While it is recommended that episiotomy be applied in emergency cases only, application of this technique for many pregnant women, especially nulliparous women, is still inevitable. Moreover, pain relief is considered as one of the pillars of care during childbirth and thereafter.

Several studies have been performed in Iran, focusing on the effect of Entonox on labor pain (9, 29-31); nevertheless, no studies are found on the effect of Entonox on pain intensity during episiotomy. With this background in mind, this study aimed to compare the effects of Entonox and lidocaine on pain intensity during episiotomy incision in nulliparous women.

Materials and Methods

This clinical trial was conducted on 120 nulliparous women referring to Alhadi Hospital of Shushtar, Iran in 2015. Inclusion criteria were pregnant women with gestational age of 39-42 weeks (based on first-trimester ultrasound or first day of last menstruation), age range of 18-35 years, singleton pregnancy, nulliparous women, cephalic presentation and body mass index (BMI) of 19.8-30 kg/m² during the first trimester of pregnancy.

Exclusion criteria were the presence of respiratory, hepatic, renal, cardiovascular, and gastrointestinal tract diseases, hypertension, autoimmune diseases, diabetes, placental abruption, placenta previa, multiple pregnancy, pelvic stenosis, allergy to local analgesia or Entonox gas, prolonged delivery, and stopping the active phase and the second stage of labor. After obtaining the necessary approval from hospital authorities, study objectives were explained to the subjects and they were assured of confidentiality terms regarding their personal information. In addition, written informed consent was obtained prior to the study.

Sample size was estimated at 60 cases per group, and the participants were randomly assigned to two groups of intervention (Entonox) and control (lidocaine). The first and second subjects in each group were selected by coin flip and the following participants entered as just one amongjthat one subject was allocated to the intervention group and the next subject was assigned to the control group.

At the beginning of the study, the researcher explained about the research procedures, labor stages and visual analogue scale (VAS). VAS is a standard method to measure pain intensity, the reliability of which has been confirmed in numerous studies (32). Feting et al. (1992) used the test-retest method at intervals of 10-15 minutes to determine the validity of VAS. According to the results, coefficient of this scale was r=0.85, and VAS was introduced as a standard procedure to determine pain intensity (33). According to VAS, pain intensity is classified as none (score zero), mild (scores 1-3), moderate (scores 4-6), severe (scores 7-9) and very severe (score 10) (30).

Demographic questionnaires were completed by the researcher, and content validity was used to determine the scientific validity of this questionnaire and prepared checklists. To do so, the researcher used books, articles, scientific resources and numerous publications to codify the check-lists. The validity of the questionnaire was confirmed by 10 faculty members. Simultaneously, to determine the scientific reliability of data collection checklists, they were completed for 10 participants by a co-researcher midwife and another midwife, who were at the same level. Afterwards, the results were compared using Pearson’s correlation coefficient (0.8) and scientific reliability of tools was measured.

In order to synchronize the confounding variables (e.g., length and type of incision), vaginal examinations, which could interfere with the process of the study, were conducted by the researcher, who acted as a delivery agent and performed all incision and internal examinations. However, data collection and analysis was performed by a midwife, who was a co-researcher and blinded to the method of pain relief in the delivery room. After admission, mothers were transferred to the labor unit and monitored until the time of fetal head crowning and transfer to the delivery room.

In the control group, 5 ml of 2% lidocaine was injected to the perineum or entry of vagina by the researcher at seven, eight and nine h before the episiotomy incision. In the intervention group, Entonox gas was administered two minutes before the episiotomy procedure. Entonox cylinders should be stored at above 10°C for 24 hours prior to use. After the admission of mothers, they were trained how to inhale Entonox through deep and calm breaths. During episiotomy, Entonox was inhaled through face masks by the participants, and they were encouraged to take deep and slow breaths. Before the intervention, breathing techniques "deep breath, pause at the end of each breath, exhale slowly, rest" were taught to mothers and they were allowed to use Entonox gas at any time.

Changes in heart rate, blood pressure and oxyhemoglobin saturation were recorded through a pulse oximetry test from the beginning of Entonox inhalation to the end of the incision. In addition, side effects of Entonox were recorded by midwife on duty during the inhalation period. To avoid bias, mother's satisfaction with both analgesic methods was recorded using the “completely satisfied, satisfied, dissatisfied, completely dissatisfied” options after completing the repair of episiotomy and leaving the delivery room by the researcher. Moreover, pain intensity was measured in both groups using VAS (10 cm) in the delivery room by a midwife and score of five was considered as moderate pain.

This study was approved by the Ethics Committee of Ahvaz University of Medical Sciences, Ahvaz, Iran with the ethical code of IR.AJUMS.REC.1394.151, funded by the university.

Data analysis was performed in SPSS version 22 using Mann-Whitney U and Chi-square tests. In addition, P-value of less than 0.05 was considered statistically significant.

Results

In this study, the intervention and control groups were homogenous regarding demo-graphic characteristics (e.g., age, educational level, place of residence, income status, occupational status, BMI and maternal factors, including gestational age, severity and duration of contractions at the second phase, duration of the second phase, need for and rate of induction, participation in labor preparation classes, prenatal exercises and perineal exercises during the last month of pregnancy) (P<0.05) (Tables 1-3).

None of the patients in the intervention group required lidocaine administration along with Entonox for pain relief during episiotomy. Furthermore, all these subjects recommended Entonox gas as an analgesic method during episiotomy incision.

Evaluation of the transient side effects observed in the intervention group revealed that 20 patients (33.3%) had no specific side effects, 26 (43.3%) cases had dizziness, seven (11.7%) individuals had dry mouth and seven (11.7%) participants had increased drowsiness. In this study, the most common observed side effect was dizziness. All the side effects were transient and were eliminated after the inhalation period.

Pain intensity during the episiotomy incision was estimated by the VAS ruler and no significant difference was observed between the two groups (P=0.52). Moreover, there were no cases of very severe pain in the groups. After the comparison of maternal satisfaction, no statistically significant difference was observed between the intervention and control groups (P=0.70). It is noteworthy that no cases of completely dissatisfied were observed in the study groups (Table 4).

Discussion

According to the results of the currentresearch, no significant difference was observed between the intervention and control groups regarding pain intensity during episiotomy (P=0.52). Therefore, Entonox, which is a non-injection method, can be used as an alternative to lidocaine, which is the standardmethod of pain