Baden Prevention and Reduction of Incidence of Postoperative Delirium Trial (PRIDe): a phase IV multicenter, randomized, placebo-controlled, double-blind clinical trial of ketamine versus haloperidol for prevention of postoperative delirium

Abstract

BackgroundDelirium is a neurobehavioural syndrome that frequently develops in the postoperative setting. The incidence of elderly patients who develop delirium during hospital stay ranges from 10-80%. Delirium was first described more than half a century ago in the cardiac surgery population, where it was already discovered as a state that might be accompanied by serious complications such as prolonged ICU and hospital stay, reduced quality of life and increased mortality. Furthermore, the duration of delirium is associated with worse long-term cognitive function in the general ICU population. This long-term experience with delirium suggests a high socioeconomic burden and has been a focus of many studies. Due to the multifactorial origin of delirium, we have several but no incontestable options for prevention and symptomatic treatment. Overall, delirium represents a high burden not only for patient and family members, but also for the medical care team that aims to prevent postoperative delirium to avoid serious consequences associated with it.The purpose of this study is to determine whether postoperative delirium can be prevented by the combination of established preventive agents. In addition, measured levels of pre- and postoperative cortisol, neuron specific enolase (NSE) and S-100β will be used to investigate dynamics of these parameters in delirious and non-delirious patients after surgery.Methods/designThe Baden PRIDe Trial is an investigator-initiated, phase IV, two-centre, randomised, placebo-controlled, double-blind clinical trial for the prevention of delirium with haloperidol, ketamine, and the combination of both vs. placebo in 200 patients scheduled for surgery. We would like to investigate superiority of one of the three treatment arms (i.e., haloperidol, ketamine, combined treatment) to placebo.DiscussionThere is limited but promising evidence that haloperidol and ketamine can be used to prevent delirium. Clinical care for patients might improve as the results of this study may lead to better algorithms for the prevention of delirium.Trial registrationClinicalTrials.gov, NCT02433041. Registered on 7 April 2015.Swiss National Clinical Trial Portal, SNCTP000001628. Registered on 9 December 2015.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2498-6) contains supplementary material, which is available to authorized users.

Serum biomarkers of delirium in the elderly: a narrative review

“…Dopamine excess and inflammation are important assumptions competing with or contributing to the hypothesis of cholinergic deficiency [57], but the focus should lie on modifiable factors causing delirium [18]. This includes stress reduction due to minimization of light and noise disturbances at night and adequate pain management among other things, but also preventive drug therapy in high-risk cohorts [58, 59]. Most importantly, the pathophysiology of delirium remains poorly understood [60] despite being first described by Hippocrates more than 2500 years ago [61].…”

“…Second, we focused on patients aged 60 and older, which led to the exclusion of numerous publications reporting other potentially important biomarkers for the elderly population including key articles on delirium biomarkers [63–68]. Interestingly, putative delirium biomarkers such as NSE and S-100β were reported/found to be irrelevant [59]. Third, there is an imbalance between medical and surgical patients investigated.…”

Related Factors and Treatment of Postoperative Delirium in Old Adult Patients: An Integrative Review

“…The current reported incidence of postoperative delirium in reference to old adults is underestimated [20]. It varies significantly as a function of the age of the patient, their preoperative status (according to the ASA classification system), whether surgery is planned or emergency, the type and duration of surgery, the diagnostic methods used, and the criteria used [1,[21][22][23][24][25][26][27][28]. At least two of every three cases of delirium occur within the first postoperative day, with peak onset occurring on the second postoperative day.…”

Nursing Delirium Screening Scale, a Tool for Early Detection of Delirium: Integrative Review

“…Its administration takes about two minutes and is accessible for clinical practice. It has been validated in different languages such as Danish (4), Turkish (5), Czech (6), and Korean (7), and used in different clinical practice scenarios: palliative care patients (8,9), cardiac surgery (10,11), liver transplantation (12), orthopedic surgery (13), urological surgery (14,15), scheduled post-operative patients (16)(17)(18)(19), post-anesthesia with medications such as ketamine (20), hospitalization (21), geriatrics hospitalization (22), oncologic hospitalization (23), and ICUs (24)(25)(26). The results of these studies report an average sensitivity of 96 % and specificity of 81 % using this scale.…”