|Year : 2022 | Volume
| Issue : 4 | Page : 225-230
Comparison of intraperitoneal dexamethasone, dexmedetomidine, and dexamethasone–dexmedetomidine combination on postoperative nausea, vomiting, and analgesics requirement after gynecological laparoscopy: A randomized clinical trial
Vinit Kumar Srivastava1, Pooja Shree1, Sanjay Agrawal2, Ambikesh Pandey1, Kavita Babbar3, Kumari Manju3
1 Department of Anesthesiology, Apollo Hospitals, Bilaspur, Chhattisgarh, India
2 Department of Anesthesiology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
3 Department of Obstetrician & Gynaecology, Apollo Hospitals, Bilaspur, Chhattisgarh, India
|Date of Submission||07-Aug-2022|
|Date of Decision||19-Sep-2022|
|Date of Acceptance||27-Sep-2022|
|Date of Web Publication||31-Oct-2022|
Vinit Kumar Srivastava
Department of Anesthesia, Apollo Hospitals, Bilaspur, Chhattisgarh 495006
Source of Support: None, Conflict of Interest: None
Background: Female patients who undergo gynecological laparoscopic surgery are more likely to suffer from postoperative nausea and vomiting (PONV). The study aimed to probe and investigate the effectiveness of intraperitoneal administration of dexamethasone, dexmedetomidine, and combination in reducing the incidence of PONV and postoperative analgesic requirements in laparoscopic hysterectomies. Materials and Methods: One hundred ninety-two female patients undergoing laparoscopic hysterectomies were randomly assigned to four groups. Anesthesia was identical in each group. Patients in the group D1 received dexamethasone 8 mg, group D2 received dexmedetomidine 1 μg/kg, group D3 received dexamethasone 8 mg + dexmedetomidine 1 μg/kg combination, and group D4 received 20 mL normal saline intraperitoneally at the end of the surgery, before trocar removal. The primary outcome was the incidence of PONV experienced by the patients within 24-h postoperative period. Results: In the first 24 h postoperatively, the incidence of PONV was significantly reduced in D1, D2, and D3 groups compared with D4 (P = 0.001); however, there were no significant differences among the three groups. The requirement for rescue antiemetic and rescue analgesic was similar among the groups but significantly decreased compared with the control group (group D4) (P = 0.002 and P = 0.0003, respectively). Conclusion: Intraperitoneal administration of dexamethasone, dexmedetomidine, and a combination of dexamethasone–dexmedetomidine in laparoscopic hysterectomies significantly reduces both PONV and postoperative analgesics requirements compared with the control group.
Keywords: Dexamethasone, dexmedetomidine, intraperitoneal, laparoscopic hysterectomy, postoperative nausea and vomiting
|How to cite this article:|
Srivastava VK, Shree P, Agrawal S, Pandey A, Babbar K, Manju K. Comparison of intraperitoneal dexamethasone, dexmedetomidine, and dexamethasone–dexmedetomidine combination on postoperative nausea, vomiting, and analgesics requirement after gynecological laparoscopy: A randomized clinical trial. Bali J Anaesthesiol 2022;6:225-30
|How to cite this URL:|
Srivastava VK, Shree P, Agrawal S, Pandey A, Babbar K, Manju K. Comparison of intraperitoneal dexamethasone, dexmedetomidine, and dexamethasone–dexmedetomidine combination on postoperative nausea, vomiting, and analgesics requirement after gynecological laparoscopy: A randomized clinical trial. Bali J Anaesthesiol [serial online] 2022 [cited 2023 Mar 22];6:225-30. Available from: https://www.bjoaonline.com/text.asp?2022/6/4/225/359933
| Introduction|| |
Laparoscopic hysterectomy is a standard gynecological surgical treatment used to treat a variety of gynecological conditions. It has distinct advantages over open surgical procedures such as decreased tissue damage, less blood loss, early ambulation, reduced analgesic requirements, avoiding big surgical incision thereby allowing quicker recovery, and shorter hospital stay with reduced healthcare expenditures. In contrast, laparoscopic surgery may be associated with a higher incidence of postoperative nausea and vomiting (PONV). The incidence of PONV in gynecologic surgery occurs at a rate of 40%–75%, even as high as 90%., PONV is associated with female gender, previous PONV, motion sickness, smoke-free status, and opioid use. The laparoscopic surgical patient also experiences mild-to-moderate pain, especially on the first postoperative day. The main reasons for the appearance of pain are intraabdominal tissue dissection/trauma, peritoneal stretching due to pneumoperitoneum, diaphragmatic irritation, and gas retention following surgery.
There have been several studies showing that dexamethasone and dexmedetomidine both prevent PONV when administered intravenously in different doses.,, Ismail et al. concluded that administering intraperitoneal dexamethasone at the end of a gynecological laparoscopy decreases postoperative nausea. Asgari et al. found that a single dosage of dexamethasone given into the peritoneal cavity relieved pain following gynecological laparoscopic surgery.
The use of intraperitoneal dexamethasone, dexmedetomidine, and a combination for the prevention of PONV and analgesic requirement in gynecological laparoscopic surgeries has not been explored, according to a review of the literature. Therefore, the present study aimed to probe and investigate the effectiveness of intraperitoneal administration of dexamethasone, dexmedetomidine, and a combination in reducing the incidence of PONV and postoperative analgesic requirements in laparoscopic hysterectomies.
| Materials and Methods|| |
The Institutional Ethics Committee approved this prospective, randomized, double-blind trial, and the patients who took part in it gave written informed permission. The study protocol was registered and approved by Clinical Trials Registry India (registry number CTRI/2019/08/020888 on August 26, 2019).
This study comprised 204 female patients between the ages of 30 and 65 who were scheduled for elective laparoscopic hysterectomy under general anesthesia and had an ASA (American Society of Anesthesiologists) physical status I-II. Patients with known sensitivity to the study treatment, body mass index of more than 40 kg/m2, a history of chronic analgesic, opioid, or other antiemetic drug usage, motion sickness, central nervous system problems, cardiovascular disease, or a history of psychiatric illness were excluded from the trial.
With the use of a computer-generated table of random numbers, the 192 patients who met the qualifying criteria were randomly assigned to four groups of 48 patients each. Group D1 received dexamethasone 8 mg diluted in 20 mL normal saline intraperitoneally at the end of the surgery, before the removal of trocar. Group D2 received dexmedetomidine 1 μg/kg diluted in 20 mL normal saline intraperitoneally at the end of the surgery, before the removal of trocar. Group D3 received dexamethasone 8 mg + dexmedetomidine 1 μg/kg combination diluted in 20 mL normal saline intraperitoneally at the end of the surgery, before the removal of trocar. Group D4 received 20 mL of normal saline intraperitoneally at the end of the surgery, before the removal of trocar.
All of the patients had the same anesthetic procedure. On the night before surgery, all patients were given oral alprazolam 0.5 mg as a preanesthetic drug. All patients were monitored with a 5-lead electrocardiogram, pulse oximeter, and noninvasive automated blood pressure as they arrived in the operation room. Injection midazolam 0.03 mg/kg, injection fentanyl 1.5 μg/kg, and injection propofol 1.5–2 mg/kg were used to induce patients, followed by vecuronium 0.1 mg/kg body weight. An adequate size cuffed endotracheal tube was used to complete orotracheal intubation using a Macintosh laryngoscope. After intubation, a nasogastric tube was placed to empty the stomach of air and gastric contents. Anesthesia was maintained by 1:1 ratio of oxygen and nitrous oxide mixture, intermittent fentanyl, vecuronium, and continuous propofol infusion. End-tidal carbon dioxide (EtCO2) levels were kept between 35 and 40 mmHg by maintaining ventilation. Pneumoperitoneum was used to keep intraabdominal pressure at 14 mmHg throughout the laparoscopic procedure. All of the groups used the same surgical procedure. A bolus dose of fentanyl 0.5 μg/kg was given to patients who had hypertension (mean arterial pressure, >20% higher than baseline) or tachycardia. After accomplishment of surgery, all study drugs were administered intraperitoneally by the surgeon as per group allocation before laparoscopic trocar withdrawal. The drugs were prepared by in a sterile manner by personnel not involved in the patient management and handed over to scrub nurse for instillation at the end of the surgery before trocar withdrawal. All infusion drugs were terminated after skin closure, and neostigmine (40 μg/kg) and glycopyrrolate (10 μg/kg) were infused before tracheal extubation to reverse the neuromuscular blockade.
The primary outcome was the incidence of PONV developed by the patients during the postoperative period. The use of analgesics in the first 24 h following surgery, the need for rescue antiemetic medicines, and the need for rescue analgesics were all secondary outcomes.
All patients were explained a visual analogue score (VAS) of 0–100 mm for PONV during their preoperative appointment. A score of 0 indicated no nausea, whereas a score of 100 indicated the greatest possible sickness. The frequency of vomiting was given a score of 100. Ondansetron 4 mg intravenously (IV) was given slowly as a rescue antiemetic when moderate or severe nausea (VAS score >40) or vomiting was present.
The patients in all four groups were given paracetamol (10 mg/mL) as a postoperative analgesic via a patient-controlled analgesia (PCA) pump (Smith Medical ASD, Inc., USA). The loading dose of paracetamol was 4.5 mg/kg, followed by a continuous infusion of 0.5 mg/kg/h, a demand dose of 1 mg/kg/hr, and a lock-out interval of 30 min for 24 h (total paracetamol dose was limited to 10 mg/kg/4 h). In the 24-h postoperative period, the total paracetamol requirement was recorded. As a rescue analgesic, patients with VAS > 4 received a bolus dose of diclofenac aqueous (75 mg IV infusion). The total amount of rescue analgesic consumed in the first 24 h after surgery was also documented. During the first 24 h after surgery, the patients were asked to describe any dizziness, headache, neck/shoulder pain, or fainting, as well as any delayed consequences such as wound infection or a delayed wound healing.
A two-sided P level was used to calculate the sample size. In laparoscopic surgery, the reported incidence of PONV is 50%. According to a pilot study, the incidence of PONV is reduced by 20% in study groups after medication treatment. For the results to be significant (with α = 0.05 and β = 0.80), each group would need to comprise 39 patients. To account for any dropouts or protocol breaches, we enrolled 48 patients in each group.
The Graph Pad Prism 7.0 statistics software (USA, Biomatters, Ltd) was used for the statistical analysis. One-way analysis of variance (ANOVA) was used to analyze the demographic data. The Chi-square test was used to compare the incidence of PONV between groups. ANOVA was used to investigate the 24-h paracetamol requirement. Statistical significance is defined as a P value of <0.05.
| Results|| |
The study enrolled a total of 204 female patients, with 192 of them being randomly allocated into four groups of 48 each [Figure 1]. Twelve patients were excluded because they refused to participate (n = 6), were taking chronic analgesics (n = 4), or had their surgery cancelled (n = 2). Ten patients were not included in this study on the account of abdominal hysterectomy (n = 3), abdominal drain placement (n = 5), extubation after 4 h of surgery (n = 1), and PCA pump failure (n = 1). Their information was included in the demographic profile comparison, but they were not submitted to any further statistical analysis.
The patients were demographically similar in all four study groups [Table 1]. Overall, the incidence of nausea (0–24 h postoperatively) was significantly decreased in D1, D2, and D3 groups than in the D4 group (P = 0.006), and the incidence of vomiting was similarly significantly decreased in D1, D2, and D3 groups (P = 0.001) [Table 2]. In the first 24 h after surgery, the number of patients with PONV was substantially higher in the D4 group than in the other groups (P = 0.001).
The difference of analgesics requirement among the four groups was statistically highly significant (P < 0.001). The requirement for rescue antiemetic and rescue analgesic medication was similar among experimental groups, but compared with the control group (group D4), significantly decreased (P = 0.002 and P = 0.0003, respectively). Only 17% of patients require rescue antiemetics in the group D3 [Table 3]. In terms of the occurrence of adverse effects, no significant differences exist between the groups.
| Discussion|| |
PONV is common in laparoscopic surgery patients who do not get antiemetic prophylaxis, necessitating prophylaxis in patients with a high-risk factor, such as female sex, laparoscopic surgery, patients taking postoperative opioids, and those who have a history of PONV and motion sickness. Female sex and laparoscopic surgery were found to be risk factors for a high incidence of PONV in our study. The incidence of PONV in the first 24 h postoperatively (primary outcome) was 46.7% in the control group (D4 group) in the present study (nausea 40% and vomiting 42%). Watcha and White also reported that the average incidence of PONV is 40%–60% in their study.
In this modern era, intraperitoneal instillation of drugs is a new method of drug administration for the prevention of postoperative nausea, vomiting, and pain. Dexamethasone at a dose of 8 mg intraperitoneally was administered by Ismail et al. in their study to reduce postoperative nausea after gynecological laparoscopy. Similar to intravenous dexamethasone, Bakri et al. reported that intravenous dexmedetomidine at a dose of 1 µg/kg reduces the incidence and severity of PONV. Various authors have investigated the use of intraperitoneal dexamethasone and dexmedetomidine to relieve postoperative pain following laparoscopic surgery.,,, We also employed intraperitoneally dexamethasone 8 mg, dexmedetomidine 1 µg/kg, and a combination of these drugs to reduce PONV, as well as postoperative pain.
In our study, we found that the incidence of nausea and vomiting in the dexamethasone group (D1 group) was 15% during the first 24 h postoperatively, whereas the incidence of nausea and vomiting during the same time interval was 7.5% and 5%, respectively, in a study done by Ismail et al. in gynecological laparoscopy by using the same dose of dexamethasone intraperitoneally; high incidence of nausea and vomiting in our study, because of long duration of anesthesia and surgery. According to Bakri et al., the incidence of PONV is 21% by using dexmedetomidine at a dose of 1 µg/kg intravenously, whereas in our study, the incidence of PONV was 20% with the intraperitoneal route of administration. This confirms that the intraperitoneal dexmedetomidine is also effective. A combination of dexamethasone and dexmedetomidine is more effective than each drug alone, because of the incidence of PONV was only 11% in this group during 24 h postoperatively. Because of the multiple etiology of PONV (the sex of patient, previous PONV, motion sickness, smoke-free status, duration and type of surgery, type of anesthesia, level of preoperative anxiety, and the use of perioperative anesthetic drugs), the present study suggests that multimodal antiemetic therapies are more effective than single antiemetic therapy in preventing PONV.
There is no specific mechanism of dexamethasone’s role in preventing PONV, but it affects glucocorticoid receptors that play a role in the vomiting pathway; prostaglandin secretion inhibition by central mechanism and decrease in the central serotonin activity are a few of the plausible causes of beneficial effects., Dexmedetomidine on the other hand by its effect on central alpha-2 adreno-receptors with a consequent decrease in catecholamine secretion may play a role in decreasing PONV.,
The three types of postoperative pain in laparoscopic surgery are visceral, parietal, and referred shoulder pain, which can be characterized by intensity, latency, and duration. As initially proposed by Bisgaard et al. and Ure et al., parietal pain is the most common cause of pain following laparoscopic surgery. Newer studies, however, have suggested that in the early convalescent period, visceral pain may be a main contributory factor. Surgical manipulation and tissue destruction in visceral organs during the surgical process cause this visceral pain., The inflammation of the peritoneum due to carbon dioxide pneumoperitoneum is also a contributory factor for pain.
In a study by Fares et al., dexmedetomidine 1 μg/kg administered intraperitoneally with bupivacaine enhances postoperative analgesia duration and quality. Additionally, Shukla et al. confirmed that intraperitoneal administration of 1 µg/kg dexmedetomidine plus bupivacaine is superior to bupivacaine with tramadol or bupivacaine alone. Asgari et al. reported that intraperitoneal dexamethasone 16 mg (single dose) may significantly reduce the severity of postoperative pain and also decrease the need for postoperative narcotics usage in laparoscopic surgery. In our study also, paracetamol requirement is minimum in dexamethasone–dexmedetomidine combination followed by the dexmedetomidine and dexamethasone group, because both drugs have different mechanism to reduce postoperative analgesics requirement. Anti-inflammatory effect of dexamethasone may have a beneficial role in providing postoperative analgesia. It suppresses both inflammation and immune responses. This reduction in the dexmedetomidine group is due to the effect on the spinal cord, especially α2a and α2c adrenoceptors as well as modulating the descending noradrenergic pathways leading to 30%–50% reduction in the requirements of analgesics. For postoperative pain management, we have avoided the use of opioids as their use is associated with increased PONV. We have observed better analgesia in patients receiving dexmedetomidine compared with dexamethasone. Similar findings were also demonstrated by Bakri et al.
Dexmedetomidine blocks the release of substance P from nociceptive pathways by inhibiting the activation of α2-adrenoreceptors, which are located within the dorsal root neurons. The decrease in substance P is associated with reduced nociceptive stimulus during the acute phase of postoperative pain. In laparoscopic surgery, the release of inflammatory mediators due to tissue damage directly stimulates the peripheral nociceptors. Dexamethasone inhibits the release of inflammatory mediators such as bradykinin, prostaglandin, and leukotriene, thereby reducing inflammation. Therefore, a combination of dexamethasone and dexmedetomidine intraperitoneally is expected to consistently reduce pain in laparoscopic hysterectomies.
There are some limitations of the study. As the patients in our study were followed up to 24 h after surgery, the presence of any nausea and vomiting after the period of observation was not studied. We were unable to quantify postoperative discomfort due to the fact that it is a subjective sensation. Furthermore, because patients were lost to follow-up after 5 days, we were unable to assess the occurrence of long-term dexamethasone adverse effects. Because there are so few studies on the use of intraperitoneal dexamethasone and dexmedetomidine for the reduction of PONV in the literature, more research with different doses of these drugs and a combination of other postoperative antiemetic is needed to provide the best results in terms of PONV relief and postoperative pain relief after laparoscopic surgeries.
| Conclusion|| |
Intraperitoneal administration of dexamethasone, dexmedetomidine, and a combination of dexamethasone–dexmedetomidine in elective laparoscopic hysterectomies significantly reduce the incidence of PONV and the need for postoperative analgesics as compared to the control group. Dexamethasone–dexmedetomidine combination is better than dexamethasone and dexmedetomidine alone.
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Conflicts of interest
There are no conflicts of interest.
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