The Takeaway

Intraperitoneal dexamethasone, dexmedetomidine, and their combination reduce postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy

Study Design

• Prospective randomized triple-blind study
• 240 patients aged 20–50 years, ASA Class I or II
• Exclusion criteria were a history of psychotic illnesses, Parkinson’s disease, motion disorder, and a history of chemotherapy
• Patients were randomized equally into 4 groups.
  • Group I (control group) received 20 mL normal saline
  • Group II (dexamethasone group) received 8 mg dexamethasone, Group III (dexmedetomidine group) received dexmedetomidine 1mic/kg
  • Group IV (combination group) received the combination of both dexamethasone (8 mg) + dexmedetomidine (1mic/kg).
  • The medications were diluted in 20 mL normal saline.
• Main Outcome: incidence of PONV during the first 24 h following surgery

Physiology Background:

Why Does PONV Occur?

• Laparoscopic surgery increases PONV risk due to peritoneal insufflation, opioid use, and anesthetic agents.
• PONV is mediated by multiple pathways:
  • Chemoreceptor trigger zone (CTZ) in the medulla detects circulating emetogenic substances (opioids, anesthetics).
  • Vagus nerve activation from peritoneal irritation increases nausea signals.

How Does Dexamethasone Reduce PONV?

• Dexamethasone is a corticosteroid that acts on multiple levels:
  • Reduces inflammation in the peritoneal cavity, decreasing vagal activation.
  • Inhibits prostaglandins and cytokines, which are linked to nausea.
  • Modulates serotonin (5-HT) pathways, reducing stimulation of the CTZ.
• Its effects are delayed onset but long-lasting, making it useful for prolonged PONV prevention.

How Does Dexmedetomidine Reduce PONV?

• Dexmedetomidine is an α₂-adrenergic agonist that works by:
  • Decreasing sympathetic outflow, reducing stress-related nausea.
  • Enhancing parasympathetic tone, stabilizing the gastrointestinal tract.
  • Providing opioid-sparing analgesia, lowering nausea triggered by opioid use.
• Unlike dexamethasone, dexmedetomidine has a sedative effect, which can also contribute to a smoother recovery.

Why Does Combination Therapy Work Best?

• Dexamethasone and dexmedetomidine target different pathways in PONV development.
• By reducing both inflammatory and neurological triggers, their combination provides a synergistic effect.
• Patients in the combination group had lower nausea scores, reduced vomiting, and fewer rescue antiemetic requirements compared to either drug alone.

Excerpts

PONV, which is experienced by 20%–30% of surgical patients within 24 h postoperation, is attributed to anesthetic effects on the center for vomiting regulation in the medulla oblongata, or intraoperative hypoxia-induced nausea and vomiting

PONV can be treated with various medications, such as blockers of dopamine and serotonin receptors, antihistamines, corticosteroids, anticholinergics, and sedatives

While the intravenous (IV) route of administering medication being effective and rapid, it comes with several disadvantages. There is a higher risk of immediate systemic side effects and dosing errors. Thus, searching for other routes is crucial.

Intraperitoneal drug administration is gaining attention due to its potential benefits in managing postoperative pain and complications with fewer side effects when compared with other routes. Moreover, intraperitoneal administration has been compared to IV routes for its impact on PONV and provided a lower incidence of nausea, comparable incidence of vomiting, and severity of PONV with significantly lower side effects

We found that intraperitoneal instillation of dexamethasone, dexmedetomidine, and a combination of both can significantly reduce the incidence of nausea and vomiting and rescue antiemetics compared to the control group in laparoscopic procedures. The effect of dexamethasone and dexmedetomidine could be mediated by their action on glucocorticoid receptors, prostaglandin, catecholamines, serotonin, and substance P. This reduces nociceptive stimulus during the acute phase of postoperative pain, decreasing the incidence of PONV

In addition, the follow-up of BP and HR measurements showed insignificant differences among the four groups, which is considered one of the intraperitoneal route’s beneficial effects due to lower bioavailability

Laparoscopic surgeries can increase the incidence of PONV through different mechanisms. Different types and doses of anesthetic agents can influence the likelihood of PONV. The stress of surgery and the manipulation of the abdominal organs during laparoscopic procedures can stimulate the body’s “vomiting reflex,” causing nausea and vomiting. Carbon dioxide gas is always utilized during laparoscopic surgery to expand the abdominal cavity and create a workspace for the surgeon. The gas can irritate the diaphragm and peritoneum, potentially leading to postoperative discomfort and nausea. Pneumoperitoneum pressure created by the insufflated gas in the abdominal cavity can affect the diaphragm and stimulate the vagus nerve, which can result in nausea and vomiting. Increased surgical duration and patient factors such as age, gender, a history of motion sickness, a history of PONV, and certain medical conditions can increase the risk of nausea and vomiting after surgery

Ismail et al. compared the effect of intraperitoneal versus IV dexamethasone for reducing PONV after gynecological laparoscopic surgeries. Eighty patients were randomized equally to receive 8 mg dexamethasone intravenously (IV) or IP. Eleven women (27.5%) in the IV group versus only three (7.5%) women in the IP group experienced nausea during the first 24 h postlaparoscopy (p = 0.037). However, five patients (12.5%) in the IV group versus only two patients (5.0%) in the IP group experienced vomiting (p = 0.424). They reported that intraperitoneal dexamethasone at a dose of 8 mg at the end of gynecological laparoscopy reduces the incidence of postoperative nausea, which agreed with our findings but with a lower incidence of nausea and vomiting compared to our study that may be attributed to different surgeries.

Citation

Bauiomy,Hany, Kohaf,Neveen A., Saad,Mohammed, Rashed,Zaky Ftouh, Abosakaya,Ahmed M., Study the Effect of Intraperitoneal Dexamethasone, Dexmedetomidine, and Their Combination on PONV After Laparoscopic Cholecystectomy: A Randomized Triple-Blind Trial, Anesthesiology Research and Practice, 2025, 4976637, 8 pages, 2025. https://doi.org/10.1155/anrp/4976637

Article Link