Rivastigmine patch (Exelon patch) compared to melatonin patch in prevention of postoperative delirium in the elderly

Abstract

Background Postoperative delirium (PD) is an acute, transient disorder of consciousness, attention, perception, and cognition. Many theories, such as decreased cholinergic neurotransmission and surgery-induced disturbances in melatonin secretion, were proposed as a potential cause for developing PD especially in the elderly. Previous studies concluded that perioperative rivastigmine significantly reduced the prevalence and severity of PD. Other studies concluded that oral perioperative melatonin was associated with a lower risk of PD. However, the effect of melatonin in patch form was not studied and the effect of perioperative rivastigmine and melatonin patch was not compared. Our aim was to compare rivastigmine patch to melatonin patch regarding the incidence and severity of PD in elderly patients undergoing major orthopaedic surgery. Methods In this double blinded randomized study, 180 elderly patients, ASA I–III, aged 60–85 years undergoing major orthopaedic surgery were divided into two equal groups; group R patients received a rivastigmine patch (4.6 mg) and group M patients received a melatonin patch (7 mg). Both patches were administered 24 h preoperative, on the day of operation and for the following 3 postoperative days. All patients received regional anaesthesia and basic monitoring in the form of NIBP, SPO2, and ECG. Patients were examined for PD using the Confusion Assessment Method (CAM) and level of sedation using the Ramsay Sedation Score (RSS) on the first, second, third, and 7th postoperative day, and for those who develop PD, a CAM-S score was done to assess the severity of PD. Drug-related side effects were recorded. Statistical analyses were performed using a standard SPSS software. Results CAM score was positive in a total of 39 patients. Rivastigmine patch significantly decreased the incidence of PD when compared to melatonin patch (P value 0.047). However, CAM-S indicated that the severity of PD was comparable. Patients were more sedated in the melatonin group. There were no melatonin- nor rivastigmine-related perioperative complications. Intraoperative SBP, DBP, and HR were slightly less in melatonin group, although statistically non-significant. Conclusions Rivastigmine patch is superior to melatonin patch in decreasing the incidence of PD in elderly patients undergoing major orthopaedic surgery; however, both drugs were comparable in decreasing its severity. Trial registration Clinical trails.gov, NCT04189666. December 6, 2019, prospectively registered

Melatonin Receptor Agonists for the Prevention of Delirium: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…Six hundred and eighty-three citations were collected from electronic searches of the following databases: SCOPUS=393, PubMed=37, CINAHL=21, Cochrane Controlled Trials Register=191. An additional 41 citations were derived from other sources (ClinicalTrials.gov identifiers=38, reference list of a relevant study=1, [ 15 ] hand search=2 [ 38 , 39 ] (Fig. 1 ).…”

“…Based on two studies with elderly patients, one study compared the efficacy of melatonin and clonidine [ 15 ], and another compared the efficacy of melatonin sleep patches (7 mg) and rivastigmine patches (4.6 mg) [ 38 ]. One study suggested that the melatonin-treated group had a significantly lower incidence of delirium than the clonidine-treated group [ 15 ].…”

“…One study suggested that the melatonin-treated group had a significantly lower incidence of delirium than the clonidine-treated group [ 15 ]. However, another study displayed a significantly greater incidence of delirium in the melatonin sleep patch group than in the rivastigmine patch group [ 38 ].…”