Emir, S., Erturgut, P., & Vidinlisan, S. (2013). Comparison of granisetron plus dexamethasone versus an antiemetic cocktail containing midazolam and diphenhydramine for chemotherapy induced nausea and vomiting in children. Indian Journal of Medical and Paediatric Oncology, 34(4), 270–273. 

To determine if the addition of midazolam and diphenhydramine to granisetron plus dexamethasone reduces chemotherapy-induced nausea and vomiting (CINV) in children receiving highly emetogenic chemotherapy (HEC)

Children were randomly assigned to receive one of two regimens on alternating cycles of chemotherapy. The first regimen was granisetron 0.04 mg/kg plus dexamethasone 0.2 mg/kg, and the second regimen was midazolam 0.04 mg/kg, diphenhydramine 2.5 mg/kg, and granisetron 0.04 mg/kg plus dexamethasone 0.2 mg/kg. The intervention drugs were diluted in 100 ml of 5% dextrose and administered via infusion one hour prior to chemotherapy. Patients and nurses tracked CINV symptoms in a daily diary, and CINV symptoms were assessed on day 1 (acute phase) and days 2–5 (delayed phase) of the chemotherapy cycle.

• N = 23  
• MEDIAN AGE = 7 years (range = 1–16 years)
• MALES: 56.5%, FEMALES: 43.5%
• KEY DISEASE CHARACTERISTICS: Neuroblastoma, germ cell tumor, rhabdomyosarcoma, Ewing's sarcoma, hepatoblastoma, adrenocortical carcinoma 
• OTHER KEY SAMPLE CHARACTERISTICS: Pediatric; all patients received cisplatin 

• SITE: Single-site    
• SETTING TYPE: Not specified    
• LOCATION: India

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics

Randomized, controlled trial

• Complete response = no nausea and vomiting
• Partial response = one to two emetic episodes but no rescue therapy
• No response = more than three emetic episodes or rescue therapy.

In the acute phase, of the children who received the first regimen, 84.4% had a complete response rate compared to 90.3% who received the second regimen (95% CI: 0.78, 96, p = 0.37). Of the children who received regimen 1, 15.5% had a partial response, and 9.6% of those who received regimen 2 had a partial response. In the delayed phase, 64.4% of patients who received regimen 1 had a complete response compared to 51.6% who received regimen 2. Partial response rates were observed in 31.1% of patients in regimen 1 and 41.9% in regimen 2. Failure rates were 4.4% in regimen 1 and 6.45% in regimen 2. Children receiving regimen 2 had more adverse events including hypotension (two patients) and marked sedation (four patients).

The addition of midazolam and diphenhydramine does not improve CINV in children receiving HEC.

• Small sample (< 30)
• Risk of bias (no blinding) 
• Measurement/methods not well described

The addition of midazolam and diphenhydramine does not improve CINV associated with HEC in pediatric patients, and the addition increased the number of adverse side effects children experienced. Nurses should consider different interventions to help control CINV in pediatric patients who are receiving HEC.