Propofol and the risk of delirium: Exploring the anticholinergic properties of propofol

Brown, Kristine E.; Mirrakhimov, Aibek E.; Yeddula, Kalpana; Kwatra, Madan M.

doi:10.1016/j.mehy.2013.06.027

Cited by 22 publications

(15 citation statements)

References 39 publications

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“…Known risk factors for delirium, including ISS and propofol dose, were negatively associated with delirium-comafree days in this analysis. [27][28][29][30] Similarly, as expected, ventilator-free days were positively associated with delirium-coma-free days. 30 Benzodiazepines are a known risk factor for ICU delirium.…”

Section: Discussionsupporting

confidence: 73%

“…A multiple linear regression analysis was performed to determine factors associated with days free from delirium or coma. Known risk factors for delirium, including ISS and propofol dose, were negatively associated with delirium‐coma‐free days in this analysis . Similarly, as expected, ventilator‐free days were positively associated with delirium‐coma‐free days .…”

Section: Discussionsupporting

confidence: 73%

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Effect of Neuromuscular Blocking Agents on Sedation Requirements in Trauma Patients with an Open Abdomen

2019

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The appropriate level of sedation in patients with an open abdomen following damage control laparotomy (DCL) is debated. Chemical paralysis with neuromuscular blocking agents (NMBAs) has been used to decrease time to abdominal closure. We sought to evaluate the effect of NMBA use on sedation requirements in patients with an open abdomen and to determine the effect of sedation on patient outcomes. A retrospective cohort study was conducted at an American College of Surgeons’ verified level 1 trauma center. Adult trauma patients who underwent DCL between 2009 and 2015 were included. Patients with an intensive care unit length of stay of less than 48 hours and those who died before abdominal closure were excluded. The NMBA+ group received continuous NMBA within 24 hours of DCL; the NMBA− group did not. The primary outcome was cumulative sedation dose during the 7 days following DCL. Secondary outcomes included Richmond Agitation‐Sedation Scale (RASS) score, mechanical ventilation‐free days, and delirium‐coma‐free days. Delirium‐coma‐free days were analyzed with linear regression. A total of 222 patients were included (NMBA+ 125; NMBA− 97). Demographics were similar between groups including age, Injury Severity Score, and mechanism of injury. The median time to closure in the overall cohort was 2 days (interquartile range [IQR] 1–2 days). Propofol and fentanyl were the primary sedatives used. The NMBA+ group received higher cumulative doses of propofol (NMBA+ 5405 mg, IQR 3103–10,573 mg; NMBA− 3601 mg, IQR 1605–6887 mg; p=0.007), but not of fentanyl. Time to abdominal closure, but not NMBA use, was associated with a higher cumulative propofol dose on multivariate analysis. The NMBA+ group had significantly lower RASS scores on the first 3 days following DCL. Mechanical ventilation‐free days (NMBA+ 20 days vs NMBA− 18 days, p=0.960) and delirium‐coma‐free days (NMBA+ 18 days vs NMBA− 18 days, p=0.610) were similar between the groups. On linear regression, cumulative propofol dose was associated with fewer delirium‐coma‐free days (β‐coefficient −0.007, 95% confidence interval −0.015 to −0.003). In trauma patients managed with DCL, higher cumulative sedative doses were administered in patients who received adjunctive NMBA, although NMBA therapy was not associated with a higher cumulative propofol dose on multivariate analysis. Consideration must be given to the potential effect of sedation on delirium and awakening following DCL.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionsupporting

confidence: 73%

Effect of Neuromuscular Blocking Agents on Sedation Requirements in Trauma Patients with an Open Abdomen

2019

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“…These properties make propofol an appealing agent for procedural sedation either alone or in combination with an opioid [ 9 – 13 ]; however, the disadvantage is potential respiratory depression or hypotension without a reversal agent [ 14 ], requiring constant monitoring by an anesthesia provider. Furthermore, propofol use has been associated with delirium in some, but not all, clinical studies [ 15 ]. This delirium may be the result of the fact that propofol has been shown to interact with muscarinic acetylcholine receptors.…”

Section: Introductionmentioning

confidence: 99%

Effect of remimazolam besylate compared with propofol on the incidence of delirium after cardiac surgery: study protocol for a randomized trial

Yang

et al. 2021

Trials

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Background Delirium is an acute cognitive disorder that presents with fluctuation in cognition, apathy, and non-organized thinking, resulting in increased morbidity, mortality, intensive care unit (ICU) stay, and total healthcare costs. In patients undergoing cardiac surgery, delirium also increases the risk of postoperative complications, such as respiratory insufficiency, sternum instability, and need for re-operation of the sternum. This study aims to understand the incidence of delirium in patients after cardiac surgery in patients sedated with remimazolam besylate versus propofol. Methods In this prospective, double-blind, randomized controlled clinical trial, we aim to recruit 200 patients undergoing cardiac surgery between January 1, 2021, and December 31, 2021, who will be randomized to receive either remimazolam besylate or propofol infusions postoperatively, until they are extubated. The primary outcome is the incidence of delirium within 5 days after surgery. Secondary outcomes include the time of delirium onset, duration of delirium, ICU length of stay, hospital length of stay, and mechanical ventilation time. Discussion The key objective of this study is to assess whether remimazolam besylate reduces the incidence of delirium in patients after cardiac surgery compared to propofol sedation. In this preliminary randomized controlled clinical trial, we will test the hypothesis that the use of remimazolam besylate lowers the incidence of delirium when compared to propofol in patients undergoing cardiac surgery. Trial registration chictr.org.cn ChiCTR2000038976. Registered on October 11, 2020

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“…These cases raise concern for the inappropriate use of CIWA-Ar in patients at high risk of delirium that is unrelated to alcohol or sedative-hypnotics. During the patients' hospital courses, they presented with head trauma, intubation, advanced age, depression, malnutrition, and infections -all of which are known risk factors for delirium [1,24,25]. While initiating CIWA-Ar protocol in these patients was warranted given the unreliable histories provided by them regarding alcohol and benzodiazepine usage, the continuation of the protocol may have been inappropriate given the known risk factors of delirium and the clinical limitations of CIWA-Ar.…”

Section: Discussionmentioning

confidence: 99%

Iatrogenic Delirium in Patients on Symptom-Triggered Alcohol Withdrawal Protocol: A Case Series

Wang¹,

Park²,

Albert³

et al. 2021

Cureus

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In this report, we present a case series involving four patients placed on the Clinical Institute Withdrawal Assessment for Alcohol, Revised (CIWA-Ar) protocol for alcohol or sedative-hypnotic withdrawal syndromes, who developed delirium on sustained or increasing symptom-triggered benzodiazepine dosages. In each of the four cases, delirium was not present on admission and resolved in the hospital itself with fixed benzodiazepine tapers. Cases were selected from an electronic medical record database of patients admitted to a United States-based university hospital and placed on CIWA-Ar between 2017 and 2018. This case series illustrates the major limitations of CIWA-Ar including its subjective nature, its susceptibility to inappropriate patient selection, and its requirement for providers to consider alternative etiologies to alcohol and benzodiazepine withdrawal syndromes. These cases demonstrate the necessity of considering other assessment and treatment options such as objective alcohol withdrawal scales, fixed benzodiazepine tapers, and even antiepileptics. An effective systems-based approach to overcoming these challenges may include setting time limits on CIWA-Ar orders within the electronic health record (EHR) system.

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Propofol and the risk of delirium: Exploring the anticholinergic properties of propofol

Cited by 22 publications

References 39 publications

Effect of Neuromuscular Blocking Agents on Sedation Requirements in Trauma Patients with an Open Abdomen

Effect of Neuromuscular Blocking Agents on Sedation Requirements in Trauma Patients with an Open Abdomen

Effect of remimazolam besylate compared with propofol on the incidence of delirium after cardiac surgery: study protocol for a randomized trial

Iatrogenic Delirium in Patients on Symptom-Triggered Alcohol Withdrawal Protocol: A Case Series

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