Comparison of propofol and dexmedetomidine infused overnight to treat hyperactive and mixed ICU delirium: a protocol for the Basel ProDex clinical trial

Abstract

Background/objectivesDelirium is a neurobehavioural disturbance that frequently develops particularly in the intensive care unit (ICU) population. It was first described more than half a century ago, where it was already discovered as a state that might come along with serious complications such as prolonged ICU and hospital stay, reduced quality of life and increased mortality. However, in most cases, there is still lack of proof for causal relationship. Its presence frequently remains unrecognised due to suggested predominance of the hypoactive form. Furthermore, in the general ICU population, it has been shown that the duration of delirium is associated with worse long-term cognitive function. Due to the multifactorial origin of delirium, we have several but no incontestable treatment options. Nonetheless, delirium bears a high burden for patient, family members and the medical care team.The Basel ProDex Study targets improvement of hyperactive and mixed delirium therapy in critically ill patients. We will focus on reducing the duration and severity of delirium by implementing dexmedetomidine into the treatment plan. Dexmedetomidine compared with other sedatives shows fewer side effects representing a better risk profile for delirium treatment in general. This could further contribute to higher patient safety.The aim of the BaProDex Trial is to assess the superiority of dexmedetomidine to propofol for treatment of hyperactive and mixed delirium in the ICU. We hypothesise that dexmedetomidine, compared with propofol administered at night, shortens both the duration and severity of delirium.Methods/designThe Basel ProDex Study is an investigator-initiated, one-institutional, two-centre randomised controlled clinical trial for the treatment of delirium with dexmedetomidine versus propofol in 316 critically ill patients suffering from hyperactive and mixed delirium. The primary outcome measure is delirium duration in hours. Secondary outcomes include delirium-free days at day 28, death at day 28, delirium severity, amount of ventilator days, amount of rescue sedation with haloperidol, length of ICU and hospital stay, and pharmaceutical economic analysis of the treatments. Sample size was estimated to be able to show the superiority of dexmedetomidine compared with propofol regarding the duration of delirium in hours. The trial will be externally monitored according to good clinical practice (GCP) requirements. There are no interim analyses planned for this trial.Ethics and disseminationThis study will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the International Conference on Harmonization- Good Clinical Practice (ICH-GCP) or Europäische Norm International Organization for Standardization (ISO EN 14155; as far as applicable) as well as all national legal and regulatory requirements. Only the study team will have access to trial specific data. Anonymisation will be achieved by a unique patient identification code. Trial data will be archived for a minimum of 10 ...

Comparison between Dexmedetomidine and Midazolam for Sedation in Patients with Intubation after Oral and Maxillofacial Surgery

“…The Ramsay scores of patients reach 2-4, and there was no statistically significant difference in sedation depth for the two drugs. In respect of the analgesic effect, studies have shown that dexmedetomidine can be safely used more than 72 h, significantly reducing the analgesic demand with 50%~70% compared with propofol [15,16]. Our results also show that the dexmedetomidine group required less analgesic than the midazolam group, so dexmedetomidine may have a certain degree of analgesic effect.…”

“…The results suggested that after admission to ICU, the BPS score in dexmedetomidine group was slightly decreased, then kept at a low level, and was lower than that in the midazolam 60 participants assessed for eligibility 16 3 BioMed Research International group at T3-T5. There was no statistically significant difference between the two groups in other time points as indicated in Figure 3 3.5.…”

Dexmedetomidine in prevention and treatment of postoperative and intensive care unit delirium: a systematic review and meta-analysis

“…The results of our meta-analysis suggest that dexmedetomidine may be more efficient in reducing ICU delirium incidence than placebo standard sedatives and opioids. The evidence on treatment of ICU delirium with dexmedetomidine is limited, as only three trials with different comparators each were suitable for our investigation, and needs to be further investigated [ 66 ]. Additionally, it is necessary to standardize clinical outcomes in general, and especially in the treatment section to facilitate meta-analyses, thereby ensuring robust evidence.…”

Study protocol for a prospective randomised double-blind placebo-controlled clinical trial investigating a Better Outcome with Melatonin compared to Placebo Administered to normalize sleep–wake cycle and treat hypoactive ICU Delirium: the Basel BOMP-AID study

“…The administration of dexmedetomidine compared with propofol to treat disturbed circadian rhythm in the other two types of delirium-hyperactive and mixed-is being investigated in our counterpart study: The Basel ProDex clinical study-Comparison of propofol and dexmedetomidine infused overnight to treat hyperactive and mixed ICU delirium (Study Protocol, BMJ Open, July 2017). 16…”