This study, which is a prospective randomized controlled trial, was performed on 400 patients who underwent fentanyl injection in hospitals affiliated to Shiraz University of Medical Sciences in 2018. Patients with non-emergency surgery aged 14 to 69 years were included in the study, while patients with a history of asthma, chronic obstructive pulmonary disease, chronic cough, upper respiratory tract infection in the two weeks before surgery, a history of smoking, steroid or bronchodilator treatment, or people taking ACE inhibitors were excluded.
The study was approved by the ethics committee of Shiraz University of Medical Sciences (IR.SUMS.MED.REC.1394.61), the institutional review board, and Iranian Registry of Clinical Trials (IRCT.ir; date: 09/03/2018-No. IRCT20141009019470N74) and conducted in compliance with local regulatory requirements, Good Clinical Practice (GCP), and the Declaration of Helsinki . All stages of the research and the goals were explained by the researcher to all the patients and written informed consent was obtained from all patients or their legally authorized representatives. Also, it is ensured that the reluctance to participate in the study has no effect on their treatment process and they can leave our study whenever they wish. Assuming 95% confidence level (first type alpha error 5%) and 80% power and considering the observation of at least 0.30 and expecting differences in treatment results between the intervention (0.25) and control (0.55) groups, we calculated that a total of 82 patients (i.e. 41 cases in the intervention group and 41 in the control group) would be required for the analysis (Fleiss with CC).
The Patients were then divided into four groups of 100 which were equivalent in sex and age, based on block randomization.
Group 1 (Integrated Protocol Group): In this group, one minute before fentanyl injection, 2 mg/kg lidocaine was injected into the patient and after 55 seconds, Huffing maneuver was performed after a deep inspiration for less than 5 seconds, and subsequently the patient was injected with 2.5 µg /kg fentanyl.
Group 2 (lidocaine group): In this group, one minute before fentanyl injection, 2 mg/kg lidocaine was injected into the patient and then fentanyl was injected into the patient at 2.5 µg/kg.
Group 3 (Huffing group): In this group, one minute before fentanyl injection, the Huffing maneuver was performed after a deep inspiration for less than 5 seconds and then fentanyl was injected at a rate of 2.5 µg /kg.
Group 4 (control group): In this group, one minute before the injection of fentanyl, 2 cc/kg of normal saline was injected into the patient and then fentanyl was injected at the rate of 2. 5 µg /kg.
Then the patients were monitored by a neutral observer for two minutes, which was blinded from the patients grouping, and the presence or absence of reflex cough as well as the severity of cough (as 1–2 coughs assigned as first-degree cough, 3–4 as grade 2, while 5 coughs and more than 5 grade 3) was reported in each patient.
During these 2 minutes, all secondary changes related to fentanyl such as changes in heart rate or changes in blood pressure that required intervention were recorded. For the induction of anesthesia, propofol was injected for all patients if no coughs were recorded during the initial 2 minutes after fentanyl injection, while in cases where coughs persisted, propofol injection was delayed until the cessation of coughs. All data were collected and entered into SPSS statistical software for statistical analysis and analyzed using the chi-square test for qualitative variables and student test for quantitative variables. P-value < 0.05 was also considered significant.