A Prospective Observational Cohort Pilot Study of the Association Between Midazolam Use and Delirium in Elderly Endoscopy Patients

Dickson Lee; Fiona Petersen; Maurice Wu; Gwenda Chapman; Melanie Hayman; Kerrilyn Tomkins; Jeremy Fernando


BMC Anesthesiol. 2021;21(53) 

In This Article


The aim of the study was to look at the feasbilty of this study protocol and the relationship between midazolam use and the development of delirium in elderly patients ≥65 years of age undergoing low-risk endoscopy procedures. There is currently a paucity of evidence around the use of midazolam in this patient demographic and existing evidence regarding midazolam is likely to inaccurately portray its impact on the development of delirium by studying the benzodiazepine class collectively; including longer acting agents such as diazepam and temazepam. Much of the existing data involves critically ill intensive care patients, or patients undergoing major surgery, which act as further confounders. This study aims to highlight the relationship between midazolam use and delirium as a primary outcome in elderly low risk day surgery patients. Our study, acknowledging its small sample size, found zero cases of delirium. This is in keeping with the hypothesis that the available evidence regarding midazolam exposure and delirium are not reflective of this low risk patient population.

Our study showed a high rate of midazolam administration in elderly patients undergoing low risk endoscopy at the study site.[2] Forty of forty-three (93.0%) elderly patients meeting inclusion criteria received midazolam; this is contrary to guideline recommendations. Agostini and Inouye (2003), showed that in those greater than 65 years of age, the incidence of delirium in postoperative patients of all procedure types is 15 to 53%.[17]

A study by Aya et al (2019) studied the incidence of delirium in elderly patients undergoing ambulatory surgery. This study found an incidence of delirium to be 1.4% (2 of 141 patients) three to 5 days after surgery using the FAM-CAM tool. While a larger sample size is needed to validate these results, it is important data that shows a low rate of post-operative delirium after ambulatory surgery; this suggests that patients undergoing ambulatory procedures form a demographic that is significantly different to previously studied groups. The findings of this paper compliment the goals of our study by emphasizing the impact of major surgery on the development of delirium and how ambulatory surgery differs.[18]

In this low risk population, there was an absence of postoperative delirium in all patients who received midazolam. This finding is discordant to the results of the study by Marcantonio et al. (1994), which showed a significantly increased incidence of delirium following the administration of benzodiazepines and additionally, the study population demonstrated an absence of delirium despite the presence of the previously identified confounding factors making delirium more likely.[2] While the results from this study are promising, there are several factors that limit the conclusions of our study. The authors acknowledge that a significant limitation of the study is a result of the small sample size. The initially hypothesized incidence of delirium in the post-operative elderly population based on currently available research had likely underestimated the required numbers to impart adequate study power. While a larger sample size would significantly improve the power of the study, this was not possible due to (1); a high proportion of patient-carer pairs not providing consent, and (2); factors which did not allow for the FAM-CAM interview to be administered 24–48 h pre and post procedure (i.e. procedures being brought forward). Additionally, the authors acknowledge that the study dropout rate secondary to inability to follow up patient-carer pairs introduces additional bias in the study. Despite these limitations, based upon the Hanley and Lippman-Hand's rule of threes, it could be suggested that the 95% confidence interval for the incidence of post-operative delirium in midazolam exposed elderly patients undergoing endoscopy is between 0 and 7.5%.[19]

A future area of research includes a larger or multi-centre study to validate our findings through the expansion of catchment and sample size. If a larger study with a similar methodology was conducted this may produce equipoise to perform a definitive randomised control trial on this topic.