Moderate sedation with midazolam and propofol is as safe as propofol monotherapy for colonoscopy, but more cost-effective

Abstract

BACKGROUND

Moderate sedation can significantly increase the acceptance of preventive colonoscopy, with different sedation regimens being used.

AIM

To compare sedation with low-dose midazolam in combination with propofol combination therapy (PCT) with sedation with propofol monotherapy (PMT) during preventive colonoscopy.

METHODS

Retrospective analysis of a total of 120 patients who were sedated with either PCT or PMT. The propofol dose administered, complications such as hypotension or hypoxia, examination time and time to discharge were evaluated. In addition, the costs of the respective sedations were calculated.

RESULTS

The propofol dose administered was significantly higher in the PMT group than in the PCT group (217 mg vs 65 mg, P < 0.01), the examination time was significantly shorter in the PMT group (18.6 minutes vs 21.4 minutes, P = 0.02) and the time to discharge was significantly shorter in the PCT group (49.4 minutes vs 57.7 minutes, P = 0.04). No patient experienced a sedation-related complication requiring treatment. The costs of sedation in the PCT group were significantly lower than those in the PMT group.

CONCLUSION

Sedation with midazolam in combination with propofol is as safe for performing outpatient preventive colonoscopy as monotherapy with propofol. Combination therapy may potentially reduce costs.

Key Words: Midazolam; Propofol; Preventive colonoscopy; Safety; Costs

Core Tip: Various guideline recommendations for sedation in gastroenterological endoscopy exist, but there is little data available on the use of combination therapy with low-dose midazolam in combination with propofol vs propofol monotherapy (PMT) for short-term outpatient procedures in patients with a low examination risk. This cohort study analysed the safety and costs of a combination therapy with low-dose midazolam in combination with propofol vs PMT in 120 patients undergoing preventive colonoscopy. Combination therapy was as safe as PMT, but was less expensive.

INTRODUCTION

Preventive colonoscopy is a suitable method for avoiding colorectal cancer. In Germany, preventive colonoscopy has been offered to all people with statutory health insurance above a certain age since October 2002. In 2024, 637537 people in Germany took advantage of the offer of preventive colonoscopy[1].

To improve acceptance of the examination, patients are usually offered sedation during the examination to ensure a comfortable and painless procedure.

There are various guideline recommendations for sedation in gastroenterological endoscopy, although these vary depending on local conditions and regulations[2]. Whereas in previous years benzodiazepines and/or opioids were mostly administered for sedation, the increasing use of propofol in recent years has led to a change in the analgesic sedation performed[3]. A recently published study on sedation practices in Europe confirmed this trend[4].

The German national guideline recommends sedation with propofol monotherapy (PMT), but there is little data available on the use of combination therapy with low-dose midazolam in combination with propofol vs PMT for short-term outpatient procedures in patients with a low examination risk. The aim of this study is therefore to evaluate low-dose midazolam administered as a fixed dose in combination with titrated propofol vs PMT in outpatient preventive colonoscopies.

MATERIALS AND METHODS

A retrospective study was conducted on 60 patients who received a fixed dose of 2.5 mg midazolam plus propofol administered as needed during preventive colonoscopy between 2023 and 2025 [examiner 1, propofol combination therapy (PCT)] compared to 60 patients who were sedated with on-demand administration of propofol as monotherapy (examiner 2, PMT).

The patients were examined in an outpatient practice where > 7000 diagnostic and therapeutic colonoscopies are performed each year. In 2024, examiner 1 performed a total of 1628 colonoscopies and examiner 2 performed 1816 colonoscopies. Both examiners have been specialists in gastroenterology for at least 8 years. Only patients who had no significant pre-existing conditions and were not taking any long-term medication, and who could therefore be classified as American Society of Anesthesiology (ASA) I to ASA II at most, were included in this comparison. All patients were consecutively enrolled in the study retrospectively beginning from 2024.

The target parameters examined included the necessary sedation dose for both regimens, examination time, necessary monitoring times, and respiratory or cardiological complications. In addition, the sedation costs for both procedures were determined.

Patients who took medication regularly or were allergic to one of the sedatives and patients with significant pre-existing cardiac or pulmonary conditions were excluded.

Patients were continuously monitored during the examination by measuring oxygen saturation, heart rate and blood pressure. Emergency equipment was available on site.

The examination time was defined as the time in minutes from insertion of the colonoscope to removal of the colonoscope from the rectum, whereby polyps that were accessible for outpatient removal were removed during the examination using forceps or a snare.

The monitoring time was defined as the time in minutes from the removal of the colonoscope to the discharge of the patient from the practice.

Complications such as hypoxia requiring treatment with O₂ administration, insertion of a Wendel/Güdelt tube or mask ventilation were documented, as were cases of hypotension requiring intervention with the administration of 0.9% NaCl.

To calculate the costs per sedation performed, the flat rate was used of 0.37 Euro per millilitre of propofol 1% and 0.96 Euro per millilitre of midazolam (1 mg) applicable in November 2025 at time of writing the manuscript.

The statistical analysis included mean values and medians with standard deviations. Differences between the groups were tested for significance using a two-tailed Student’s t-test, with a P value ≤ 0.05 considered statistically significant. For the retrospective data analysis, a vote was obtained and approved by the Regensburg Ethics Committee under No. 25-4430-104.

RESULTS

A total of 120 patients were evaluated, 60 in the PCT group and 60 in the PMT group. The two groups were comparable in terms of gender, age and body mass index (Table 1). In the PCT group, a mean dose of 65 mg propofol was required, while in the PMT group, a mean dose of 217 mg propofol was administered (P < 0.001). The mean examination time was significantly shorter in the PMT group with 18.6 minutes vs 21.4 minutes in the PCT group (P = 0.02). The mean monitoring time until discharge was significantly shorter in the PCT group with 49.4 minutes than in the PMT group with 57.7 minutes (P = 0.04) (Table 2).

Table 1 Patient characteristics, mean ± SD/median (interquartile range).

	Propofol combination therapy	Propofol monotherapy	P value
Intervention	2.5 mg midazolame + propofol	Propofol monotherapy
Number of patients	60 (female 30, male 30)	60 (female 29, male 31)
Age (years)	55.5 (50-69)	57 (50-69)	0.96
BMI (kg/m2)	25.4 ± 3.37	26 ± 3.03	0.33

BMI: Body mass index.

Table 2 Relevant results, mean ± SD.

	Propofol combination therapy	Propofol monotherapy	P value
Dose of propofol (mg)	65 ± 21	217 ± 61	< 0.01
Duration of examination (minute)	21.4 ± 6	18.6 ± 6	0.02
Duration until discharge (minute)	49.4 ± 17	57.7 ± 26	0.04

In neither group there was a drop in O₂ saturation that could not be controlled by addressing the patient or applying tactile stimulation. The insertion of a Wendel/Güdelt tube or mask ventilation was not necessary in any case. Likewise, there was no significant drop in blood pressure in either group that required the administration of 0.9% NaCl. The average costs of sedation per patient are shown in Table 3. These vary depending on the size of the syringe used, but there is a constant significant reduction of costs in the PCT group (Table 3).

Table 3 Costs per patient (Euro).

	Propofol combination therapy	Propofol monotherapy	P value
Mean cost per mililiter	2.87	8.01	< 0.01
Mean costs per 5 mL syringe propofol	3.69	8.55	< 0.01
Mean costs per 10 mL syringe propofol	4.31	9.20	< 0.01

DISCUSSION

Sedation makes endoscopic examinations much more comfortable for patients. Accordingly, several guidelines recommend to offer sedation to patients whenever possible[5,6]. Various medications are available for sedation, with different application regimens. Sedation practices vary depending on the preferences of the examiner and patient, local conditions, medical resources and national guidelines[4]. In some countries sedation for gastroenterological examinations is usually performed with benzodiazepines alone or in combination with an opiate, other guidelines recommend performing the procedure with PMT[6]. Many studies comparing different sedation regimens are available and provide partly contradictory results, which is certainly due to the heterogeneity of the procedures performed and the different dosages used.

Due to its short half-life, several studies have described a shorter recovery time with PMT sedation compared to midazolam sedation[7-9], although one study reported that the acceptance of the examination under PMT was lower due to increased pain[7]. However, propofol has the disadvantage of a narrow therapeutic range with a risk of hypotension and hypoxia without the possibility of antagonisation. This explains the requirement in some countries that propofol may only be administered by an anaesthetist[4]. The important aspect of the safety of the various regimens is addressed in a meta-analysis from 2019, in which a comparison of PMT vs traditional sedatives (benzodiazepines and/or opiates) showed no significant differences between the various types of sedation in terms of hypotension, oxygen drop, bradycardia or recovery time[10]. Most of the included studies compared a combination of midazolam with opiate vs PMT; only three included studies compared PMT vs therapy with midazolam and propofol.

In line with this meta-analysis, our data also show no differences in terms of cardiac or pulmonary complications requiring intervention in both regimens used. Although the examination time in the PMT group was mathematically significantly shorter in our patients, the difference in the mean examination time was only 3 minutes. Despite the slightly longer examination time in the PCT group, the propofol dose administered was significantly lower than in the PMT group. This observation has already been demonstrated in earlier studies[8,11]. The reason for the significantly lower propofol dose could be the additional anxiolytic effect of midazolam, which cannot be achieved with propofol. This has already been demonstrated in an earlier study in which patients premedicated with oral midazolam experienced significantly less anxiety during ERCP than patients who received propofol alone[12].

In contrast to other studies, combination therapy actually resulted in a shorter time to discharge in our patients, although the duration of the intervention was significantly longer than in the PMT group, which once again could possibly be due to the significantly lower propofol dose.

As already mentioned, there are very few studies comparing PMT vs PCT. The procedures examined in two studies were endoscopic submucosal dissections of the stomach and endoscopic ultrasound (EUS)[13,14] respectively, with fewer complications occurring under combination therapy in endoscopic submucosal dissections, while no differences were seen in EUS. Another study compared the two sedation regimens during endoscopic retrograde cholangiopancreatography (ERCP), and another compared them during 150 different endoscopic interventions[8,9].

Only two studies are available in which PCT was compared with PMT in the context of colonoscopy. VanNatta and Rex[15] described lower propofol doses and a shorter recovery time in the combination group in outpatients who underwent colonoscopy for various reasons, with no differences in complications. In this study, a dose of 1 mg midazolam was administered. A Spanish study also investigated the two sedation regimens in outpatient colonoscopies, although this study did not provide any information on the reason for the examination. Patients in the combination group received 2 mg of midazolam. Also in this study, patients in the PMT group required significantly higher doses of propofol compared to the combination group. Although the early recovery time was slightly longer in the combination group, the time until patient discharge was not. In the PCT group, the painfulness of the examination was rated lower and patient satisfaction was higher[11]. The reduction in propofol use can lead to cost savings, as already mentioned in a few studies[9,16]. Sedation represents a significant cost factor, particularly in countries where propofol may only be administered by anaesthetists[17].

Based on the costs used in the preparation of the manuscript, our patients in the PCT group had significantly lower sedation costs due to the reduction in propofol use. Based on the number of annual colonoscopies performed by the two examiners, this results in a purely mathematical saving of almost €10000 using the usual procedure with 10 mL syringes.

In 2024, there were 2357 registered gastroenterologists in private practice in Germany who participate in the statutory health insurance system[18]. Assuming that each gastroenterologist performs 1000 colonoscopies per year, the potential savings of PCT would be over €11 million. Of course, these calculations are purely hypothetical, as local conditions can vary significantly. An internet search regarding the costs of propofol in different countries revealed a considerable price range in countries like the United States or the United Kingdom, depending on package size. In addition, differences in pricing between hospitals and outpatient practices are likely.

Nevertheless, it appears that PCT could reduce costs without compromising the quality of sedation or increasing complication rates. The most important limitation of our study is certainly the lack of patient satisfaction assessment, which was not possible due to the retrospective nature of the evaluation. Nevertheless, patient complaints are usually carefully documented in the medical records, and no complaints were received for any of the patients evaluated. Another limitation is that it cannot be ruled out that the patients in the PCT group had a longer early recovery time or longer-lasting amnesia after the examination; however, none of the patients in either group required an extended sick note for the day after the examination. In addition, it has to be mentioned that, to improve comparability between the two groups, only patients with ASA class I and II were included. Therefore, no conclusions can be drawn from our results regarding patients with higher ASA classifications or more complex procedures.

CONCLUSION

In summary, our data show that combination therapy with midazolam is just as safe for performing outpatient preventive colonoscopy as monotherapy with propofol, but that the combination may reduce costs.