Clinical observation on the efficacy and safety of different doses of alfentanil for painless gastroscopy

ZHANG Jiao, CHEN Rui, LI Yuan, XIE Hai, WANG Shan

Department of Anesthesiology, the First Affiliated Hospital of Hainan Medical University, Haikou 570102, China

Keywords:Afentanil Painless gastroscopy Effectiveness Security Vital signs Adverse reaction

ABSTRACT

1.Introduction

Esophagogastroduodenoscopy (EGD) is one of the commonly used diagnostic and therapeutic methods in clinical practice.It enables the early detection of lesions and provides reliable evidence for clinical diagnosis and treatment[1].Pain-free EGD improves patients’ tolerance, reduces stress reactions, eliminates patients’ fear and discomfort, and facilitates smooth endoscopic examinations and treatments.It has several advantages, including fewer complications,faster recovery, and higher patient satisfaction[2,3].Studies have shown that the use of different analgesic medications combined with propofol in the pain-free EGD procedure is efficient and feasible[4,5].Currently used analgesic drugs in clinical practice include short- to intermediate-acting opioid analgesics such as fentanyl, alfentanil,sufentanil, remifentanil, and nalbuphine, as well as non-opioid analgesics such as tramadol[6,7].Alfentanil, an opioid receptor agonist, is an ultra-short-acting potent analgesic that rapidly takes effect and allows for fast recovery.It is suitable for short procedures and analgesia during examinations.Additionally, alfentanil has a low incidence of respiratory depression, is less likely to induce coughing,and maintains hemodynamic stability during anesthesia.Therefore,it is considered one of the ideal drugs for pain-free outpatient gastrointestinal endoscopy[8].Although alfentanil has been safely used in clinical practice in Europe and the United States for over 30 years, it is still a relatively new drug in China, and there are limited reports on its application in pain-free EGD.In this study, we focused on pain-free EGD patients and observed the effectiveness and safety of different doses of alfentanil in combination with propofol for pain-free EGD, as reported below.

2.Methods

2.1 Ethics and Grouping

This study obtained approval from the Ethics Committee of the First Affiliated Hospital of Hainan Medical College (Approval No.2020 [Scientific Research] No.142) and informed consent was obtained from the patients.

A total of 240 patients who underwent painless gastroscopy at the First Affiliated Hospital of Hainan Medical College from January 2021 to December 2021 were selected as the observational subjects.The inclusion criteria were ASA classification grade I-II and no gender restriction.The study subjects were randomly divided into six groups using a random number table method: control group and different doses of alfentanil (N1, N2, N3, N4, and N5 groups) with alfentanil injection doses of 5, 6, 7, 8, and 10 μg/kg, respectively,with 40 cases in each group.

2.2 Inclusion and Exclusion Criteria

Inclusion criteria: Patients scheduled for painless gastroscopy in our hospital[9], aged 18-60 years, with cardiac function grade I and ASA class I-II.Exclusion criteria: (1) Patients with hematological disorders, a history of highly reactive airway diseases, or a history of high-risk aspiration; (2) Patients with abnormal coagulation function, severe liver or kidney dysfunction, or a history of blood diseases; (3) Patients with electrolyte disorders or in the pregnancy or lactation period; (4) Patients with a history of mental illness or sedative-hypnotic drug use; (5) Patients with drug allergies or deemed unsuitable for this study by the researchers; (6) Patients with a history of hypertension; (7) Patients with sleep apnea syndrome;(8) Patients with a history of epilepsy or asthma.

2.3 Methods

Patients were instructed to fast for at least 8 h and refrain from drinking water for 4 h before the surgery.An explanation of anesthesia and examination methods was provided to enhance patient cooperation[10].After entering the examination room, an upper limb intravenous access was established, and the patient was positioned on the left side.Oxygen was administered through a nasal cannula at a flow rate of 3 L/min.Simultaneously, the patient’s blood pressure(BP), heart rate (HR), electrocardiogram (ECG), oxygen saturation(SpO2), and bispectral index (BIS) were continuously monitored,and the patient underwent routine pre-oxygenation for 5 min.The different dose groups received intravenous injections of alfentanil at doses of 5, 6, 7, 8, and 10 μg/kg (produced by China National Pharmaceutical Group Industrial Co., Ltd., National Medical Product Administration Approval No.H20123422), followed by intravenous injection of propofol (produced by Xi’an Libang Pharmaceutical Co., Ltd., National Medical Product Administration Approval No.H20010368) until the BIS value was maintained between 50～65.Once the BIS value reached the predetermined target, the gastroscopy procedure commenced.The control group received only intravenous injection of propofol (produced by Xi’an Libang Pharmaceutical Co., Ltd., National Medical Product Administration Approval No.H20010368) at an induction dose of 1.0～2.0 mg/kg, administered within 1～2 min.In cases where patients exhibited intolerance reactions during the examination(cough reflex, swallowing reflex, retching reflex, or limb response),additional doses of propofol were administered as needed until the patient had no intolerance reactions and the examination was completed.During the examination, the BIS value was maintained between 50 and 65.For patients with bradycardia (HR ＜ 50 beats/min) during the examination, intravenous injection of atropine 0.5 mg was administered as a routine treatment.For patients with a decrease in mean arterial pressure (MAP) exceeding 20% of the baseline or below 60 mmHg, intravenous injection of ephedrine 6 mg was administered.Jaw support or assistance with respiration was provided if SpO2＜ 90%, and positive pressure ventilation was performed if necessary.After the examination, the patients’electrocardiogram, blood pressure, and SpO2were continuously monitored until the patient regained consciousness safely.

2.4 Observational Parameters

(1) Demographic characteristics of the patients: Age, gender,body mass index (BMI), and ASA classification were recorded.(2)HR, systolic blood pressure (SBP), and apnea time (time from the cessation of chest movement to the resumption of movement) were recorded at various time points: before medication administration,before gastroscopy insertion, and 1 min after gastroscopy insertion[11].The occurrence rate of apnea time (time from the cessation of chest movement to the resumption of movement) during the examination was calculated for each group.(2) The incidence of gastroscopy intolerance reactions in the control group and the different doses of alfentanil group was recorded, including cough reflex, retching reflex, swallowing reflex, and limb response[12].(3)Adverse reactions: The incidence of postoperative pruritus, nausea and vomiting, anxiety and restlessness, dizziness and drowsiness,and diarrhea and constipation were recorded for each group.

2.5 Statistical Analysis

Statistical analysis was performed using SPSS 24.0 statistical software.Continuous variables were expressed as mean ± standard deviation (SD), and categorical variables were expressed as percentages (%).The chi-square test or Fisher’s exact test was used for categorical data.Repeated measures analysis of variance was used for comparisons at different time points, one-way analysis of variance was used for intergroup comparisons, and the LSD method was used for pairwise comparisons.A p-value ＜ 0.05 was considered statistically significant.

3.Result

3.1 Comparison of demographic characteristics

There were no statistically significant differences in gender ratio,age, BMI and ASA classification among the six groups (P＞0.05), as shown in Table 1

Tab1 Comparison of six groups of demographic characteristics(n=40,)

Tab1 Comparison of six groups of demographic characteristics(n=40,)

Group Cases Gender(female/male)Age(year)BMI(kg/m2 )ASA classification I/II control 40 22/18 36.98±5.72 24.34±4.13 21/19 N1 40 20/20 35.77±6.72 25.14±3.73 24/16 N2 40 19/21 37.28±5.04 26.08±3.03 24/16 N3 40 17/23 38.66±4.73 25.44±4.03 26/14 N4 40 19/21 36.18±6.72 27.36±3.10 23/17 N5 40 18/22 39.08±4.72 24.84±4.33 25/15

3.2 Comparison of HR, SBP, and Apnea Time among Six Groups

The SBP and HR between groups were compared before medication administration, before gastroscopy insertion, and 1 minute after gastroscopy insertion, with no significant differences observed (P＞0.05).Compared to before medication administration,SBP and HR in all groups decreased before gastroscopy insertion(P＜0.01).At 1 minute after gastroscopy insertion, the SBP and HR in the control group increased (P＜0.01), while there were no significant changes in SBP and HR in the N1 and N2 groups (P＞0.05).The N3 and N4 groups showed a decrease in SBP (P＜0.01), while HR remained unchanged (P＞0.05).The N5 group exhibited a decrease in both SBP and HR (P＜0.01).When compared to before gastroscopy insertion, the SBP and HR increased in the control, N1, N2, and N3 groups at 1 min after gastroscopy insertion (P＜0.01), while there were no significant changes in SBP and HR in the N4 and N5 groups(P＞0.05).The apnea time in the N1, N2, N3, N4, and N5 groups was lower than that in the control group (P＜0.01).There were no statistically significant differences in apnea time among the N1, N2,N3, and N4 groups (P＞0.05), while the N5 group exhibited a higher apnea time compared to the N1, N2, N3, and N4 groups (P＜0.01).Refer to Table 2 for details.

3.3 Comparison of Incidence Rates of Intolerance Reactions during Gastroscope Insertion

There were no statistically significant differences (P＞0.05) in the incidence rates of intolerance reactions during gastroscope insertion among the control group and the different doses of alfentanil groups.This includes the incidence rates of coughing, retching reflex,swallowing reflex, and limb movement.Please refer to Table 3.

Tab2 Comparison of HR, SBP and apnea time in six groups(n=40, )

Tab2 Comparison of HR, SBP and apnea time in six groups(n=40, )

Compared to pre-administration, ΔP＜0.05; compared to before endoscopy insertion, #P＜0.05; compared to the control group, ◆P＜0.05; compared to groups N1, N2, N3, and N4, *P＜0.05.

Group HR(times/min) SBP(mmHg) Respiratory Pause Time (min)1 minute After Gastroscope Insertion N1 80.23±6.78 75.34±6.71△ 81.67±5.63# 121.59±8.53 117.57±8.03△ 121.29±6.76# 3.79±0.71◆N2 81.31±6.82 76.51±6.75△ 81.41±6.12# 122.15±8.56 118.02±8.34△ 122.32±6.46# 3.67±0.66◆N3 80.19±6.75 75.98±6.74△ 80.39±6.43# 119.34±8.41 115.71±7.93△ 117.32±6.56△# 3.51±0.61◆N4 81.87±6.87 76.45±6.74△ 79.60±5.48 123.46±8.72 115.43±8.12△ 117.21±7.12△ 3.42±0.50◆N5 82.15±6.94 75.86±6.67△ 76.12±6.55△ 125.39±8.81 117.59±8.34△ 118.57±7.62△ 4.21±0.43*◆control 79.82±6.35 76.25±5.46△ 82.32±5.12△# 124.31±8.45 118.49±7.73△ 128.46±5.73△# 7.49±0.83 Before Administration Before Gastroscope Insertion 1 minute After Gastroscope Insertion Before Administration Before Gastroscope Insertion

Tab3 Comparison of the Incidence Rates of Intolerance Reactions during Gastroscope Insertion in Six Patient Groups [(n)%; n=40]

3.4 Comparison of Adverse Reactions in Six Groups

There were no statistically significant differences in the occurrence rates of itching, nausea and vomiting, anxiety and restlessness,dizziness and drowsiness, as well as diarrhea and constipation after painless gastroscopy among the six groups (P＞0.05), as shown in Table 4.

Tab4 presents the comparison of adverse reactions among the six groups [(n)%; n=40]

4.Discussion

Gastroscopy is commonly used in the clinical diagnosis and treatment of digestive system diseases, as it allows for clear visualization of lesion sites and provides guidance for clinical management[13].However, gastroscopic examination is an invasive procedure that often induces anxiety and fear in most patients,leading to adverse reactions such as vomiting, nausea, and restlessness.These reactions not only increase the risks during the examination but also affect the cooperation and accuracy of the procedure[14].Therefore, providing satisfactory sedation and analgesia is crucial in achieving a painless gastroscopic diagnostic and therapeutic process.Currently, it has been clinically demonstrated and supported by literature that the use of propofol alone fails to achieve the desired anesthetic and sedative effects[15].Fentanyl, an analgesic drug initially used for clinical anesthesia in the United States, has had limited domestic application.Studies have shown several pharmacokinetic and pharmacodynamic advantages of fentanyl[16]: (1) rapid onset of action and metabolism, (2) analgesic and anti-anxiety effects, and (3) relatively fast recovery and high safety.Foreign researchers have found that the optimal analgesic and sedative effects, with a low incidence of adverse reactions, are achieved when fentanyl is administered at a dosage of 5-10 μg/kg for painless gastrointestinal endoscopy[17].Therefore, this study chose fentanyl at doses of 5, 6, 7, 8, and 10 μg/kg combined with propofol for anesthesia.The study results revealed no statistically significant difference in the occurrence of intolerable reactions during gastroscopic insertion (coughing reflex, dry retching, swallowing reflex, and limb movements) among the groups receiving fentanyl at doses of 5, 6, 7, 8, and 10 μg/kg.The data demonstrated a decreasing trend in the incidence of intolerable reactions as the dosage of fentanyl increased, indicating an improvement in the effectiveness of anesthesia with increasing fentanyl dosage.The study conducted by Wang et al.[18] indicated that fentanyl is an ultra-short-acting analgesic that exhibits rapid onset and fast recovery, making it suitable for short procedures.When used in clinical practice, it has a low incidence of respiratory depression, is less likely to induce coughing, and maintains stable hemodynamics during the perioperative period, making it an ideal drug for painless gastrointestinal endoscopy in outpatient settings[19].In this study,although there was no statistically significant difference in the occurrence of coughing reflex, dry retching, swallowing reflex, and limb movements between the control group and different dosage groups of fentanyl, the group receiving fentanyl at a dose of 10 μg/kg showed significantly prolonged apnea time, second only to the control group.This result may be attributed to the adverse respiratory depression caused by excessive dosage of opioid drugs.Among the six groups, the occurrence rates of adverse reactions such as itching, nausea and vomiting, anxiety and restlessness, dizziness and drowsiness, and diarrhea and constipation did not differ significantly.However, when fentanyl at a dose of 8 μg/kg was used for painless gastroscopy, patients exhibited more stable heart rates and blood pressure, shorter apnea time, and the highest level of safety.

In summary, the combination of 8 μg/kg fentanyl with propofol for anesthesia in painless gastroscopy demonstrated a higher effectiveness of anesthesia, with stable respiratory and circulatory function in patients.Therefore, it represents a more reasonable drug combination scheme for anesthesia.