acetaminophen and Delirium of Mixed Origin studies

Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.
paracetamol : A member of the class of phenols that is 4-aminophenol in which one of the hydrogens attached to the amino group has been replaced by an acetyl group.

Research Excerpts

Excerpt	Relevance	Reference
"To evaluate the effect of postoperative intravenous (IV) acetaminophen (paracetamol) vs placebo combined with IV propofol vs dexmedetomidine on postoperative delirium among older patients undergoing cardiac surgery."	9.30	Effect of Intravenous Acetaminophen vs Placebo Combined With Propofol or Dexmedetomidine on Postoperative Delirium Among Older Patients Following Cardiac Surgery: The DEXACET Randomized Clinical Trial. ( Banner-Goodspeed, V; Eikermann, M; Gallagher, J; Gasangwa, D; Marcantonio, ER; Mathur, P; Mueller, A; O'Gara, B; Packiasabapathy, S; Patxot, M; Shaefi, S; Shankar, P; Subramaniam, B; Talmor, D, 2019)
"The inclusion of IV acetaminophen as part of a multimodal pain regimen led to fewer episodes of delirium in this study."	7.96	Delirium Reduced With Intravenous Acetaminophen in Geriatric Hip Fracture Patients. ( Connolly, KP; Kleinman, RS; Mehta, SN; Neuman, MD; Stevenson, KL, 2020)
"Postoperative delirium is common among older cardiac surgery patients."	7.01	Scheduled Prophylactic 6-Hourly IV AcetaminopheN to Prevent Postoperative Delirium in Older CaRdiac SurgicAl Patients (PANDORA): protocol for a multicentre randomised controlled trial. ( Banner-Goodspeed, VM; Davis, R; Kelly, L; Khera, T; Marcantonio, ER; Mathur, PA; Mcgourty, M; Narayanan, S; Novack, L; Palihnich, K; Subramaniam, B; Talmor, D, 2021)
"Postoperative delirium is common in elderly cardiac surgery patients."	6.87	Dexmedetomidine and intravenous acetaminophen for the prevention of postoperative delirium following cardiac surgery (DEXACET trial): protocol for a prospective randomized controlled trial. ( Gasangwa, D; Marcantonio, ER; Mueller, A; O'Gara, B; Packiasabapathy, S; Patxot, M; Shaefi, S; Shankar, P; Subramaniam, B, 2018)
"Delirium is a side effect associated with narcotic analgesics, with a higher incidence in the elderly."	5.37	Oxycodone induced delirium and agitation in an elderly patient following total right knee arthroplasty. ( Crane, JH; Suda, KJ, 2011)
"To evaluate the effect of postoperative intravenous (IV) acetaminophen (paracetamol) vs placebo combined with IV propofol vs dexmedetomidine on postoperative delirium among older patients undergoing cardiac surgery."	5.30	Effect of Intravenous Acetaminophen vs Placebo Combined With Propofol or Dexmedetomidine on Postoperative Delirium Among Older Patients Following Cardiac Surgery: The DEXACET Randomized Clinical Trial. ( Banner-Goodspeed, V; Eikermann, M; Gallagher, J; Gasangwa, D; Marcantonio, ER; Mathur, P; Mueller, A; O'Gara, B; Packiasabapathy, S; Patxot, M; Shaefi, S; Shankar, P; Subramaniam, B; Talmor, D, 2019)
"The aim of this study was to determine whether the administration of liposomal bupivacaine decreased opioid use and delirium in patients sustaining a hip fracture."	4.31	Liposomal Bupivacaine Decreases Intravenous Opioid Use in Patients with Hip Fracture: A Modification to a Novel Pain Protocol. ( Donegan, D; Fryhofer, GW; Looby, S; Mehta, S; Stein, MK; Stevenson, KL, 2023)
"The inclusion of IV acetaminophen as part of a multimodal pain regimen led to fewer episodes of delirium in this study."	3.96	Delirium Reduced With Intravenous Acetaminophen in Geriatric Hip Fracture Patients. ( Connolly, KP; Kleinman, RS; Mehta, SN; Neuman, MD; Stevenson, KL, 2020)
"Scheduled intravenous acetaminophen administration is effective and feasible for the postoperative pain management of patients undergoing esophagectomy and may be associated with a lower incidence of anastomotic leakage and postoperative delirium."	3.96	Scheduled intravenous acetaminophen versus nonsteroidal anti-inflammatory drugs (NSAIDs) for better short-term outcomes after esophagectomy for esophageal cancer. ( Abe, T; Fukaya, M; Higaki, E; Hosoi, T; Ito, S; Kawakami, J; Komori, K; Nagino, M; Nakatochi, M; Shimizu, Y, 2020)
"Postoperative delirium is common among older cardiac surgery patients."	3.01	Scheduled Prophylactic 6-Hourly IV AcetaminopheN to Prevent Postoperative Delirium in Older CaRdiac SurgicAl Patients (PANDORA): protocol for a multicentre randomised controlled trial. ( Banner-Goodspeed, VM; Davis, R; Kelly, L; Khera, T; Marcantonio, ER; Mathur, PA; Mcgourty, M; Narayanan, S; Novack, L; Palihnich, K; Subramaniam, B; Talmor, D, 2021)
"Postoperative delirium is common in elderly cardiac surgery patients."	2.87	Dexmedetomidine and intravenous acetaminophen for the prevention of postoperative delirium following cardiac surgery (DEXACET trial): protocol for a prospective randomized controlled trial. ( Gasangwa, D; Marcantonio, ER; Mueller, A; O'Gara, B; Packiasabapathy, S; Patxot, M; Shaefi, S; Shankar, P; Subramaniam, B, 2018)
"Sepsis and acute liver failure are associated with severe endogenous intoxication."	1.72	Reactive Microgliosis in Sepsis-Associated and Acute Hepatic Encephalopathies: An Ultrastructural Study. ( Hayden, MR; Shulyatnikova, T; Tumanskyi, V, 2022)
"Delirium is a side effect associated with narcotic analgesics, with a higher incidence in the elderly."	1.37	Oxycodone induced delirium and agitation in an elderly patient following total right knee arthroplasty. ( Crane, JH; Suda, KJ, 2011)

Research

Studies (20)

Authors

Clinical Trials (20)

Trial Overview

Trial Outcomes

Duration of Delirium

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	4 (20.00)	29.6817
2010's	9 (45.00)	24.3611
2020's	7 (35.00)	2.80

Authors	Studies
Guo, J	1
Wang, T	1
Zheng, X	1
Long, Y	1
Wang, X	1
Zhang, Q	1
Liu, J	1
Zhang, G	1
Zha, J	1
Hou, Z	1
Zhang, Y	1
Shulyatnikova, T	3
Tumanskyi, V	3
Hayden, MR	3
Stevenson, KL	2
Stein, MK	1
Fryhofer, GW	1
Looby, S	1
Donegan, D	1
Mehta, S	1
Connolly, KP	1
Kleinman, RS	1
Neuman, MD	1
Mehta, SN	1
Kawakami, J	1
Abe, T	1
Higaki, E	1
Hosoi, T	1
Fukaya, M	1
Komori, K	1
Ito, S	1
Nakatochi, M	1
Nagino, M	1
Shimizu, Y	1
Shen, L	1
Tam, CW	1
Jones, MM	1
Hoyler, M	1
Ivascu, NS	1
Khera, T	1
Mathur, PA	1
Banner-Goodspeed, VM	1
Narayanan, S	1
Mcgourty, M	1
Kelly, L	1
Palihnich, K	1
Novack, L	1
Davis, R	1
Talmor, D	2
Marcantonio, ER	3
Subramaniam, B	4
Tung, EE	1
Litin, SC	1
Bundrick, JB	1
Greenberg, S	1
Murphy, GS	1
Avram, MJ	1
Shear, T	1
Benson, J	1
Parikh, KN	1
Patel, A	1
Newmark, R	1
Patel, V	1
Bailes, J	1
Szokol, JW	1
Shankar, P	3
Mueller, A	3
Packiasabapathy, S	2
Gasangwa, D	2
Patxot, M	2
O'Gara, B	2
Shaefi, S	2
Banner-Goodspeed, V	1
Gallagher, J	1
Mathur, P	1
Eikermann, M	1
Wanek, MR	1
Suzuki, Y	1
Shinada, K	1
Orime, N	1
Someya, T	1
Björkelund, KB	1
Hommel, A	1
Thorngren, KG	1
Gustafson, L	1
Larsson, S	1
Lundberg, D	1
Crane, JH	1
Suda, KJ	1
Chan, TY	1
Tam, HP	1
Lai, CK	1
Chan, AY	1
Osterhoudt, KC	1
Okumura, A	1
Fukumoto, Y	1
Hayakawa, F	1
Nakano, T	1
Higuchi, K	1
Kamiya, H	1
Watanabe, K	1
Morishima, T	1
Kain, ZN	1
Mayes, LC	1
Caldwell-Andrews, AA	1
Karas, DE	1
McClain, BC	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
PANDORA: Scheduled Prophylactic 6-hourly Intravenous Acetaminophen to Prevent Postoperative Delirium in Older Cardiac Surgical Patients[NCT04093219]	Phase 3	900 participants (Anticipated)	Interventional	2020-08-11	Recruiting
CEReBral AutorEgulation in Non-cardiac SuRgery and Relationship to Postoperative DeliriUm State - CERBERUS Trial[NCT06133842]		100 participants (Anticipated)	Observational	2023-12-31	Not yet recruiting
Dexmedetomidine and IV Acetaminophen for the Prevention of Postoperative Delirium Following Cardiac Surgery in Adult Patients 60 Years of Age and Older[NCT02546765]	Phase 4	140 participants (Actual)	Interventional	2015-10-31	Completed
Impact of Intrathecal Dexamethasone Administration for Elderly Patients With Proximal Femoral Fracture[NCT03856502]		60 participants (Actual)	Interventional	2012-11-11	Completed
Intravenous Lidocaine Infusion in the Management of Post-operative Pain in Colorectal Patients[NCT01836614]	Phase 1/Phase 2	0 participants (Actual)	Interventional	2015-01-31	Withdrawn (stopped due to Study was closed due to recommendations of performing a PK study first.)
Personalizing Perioperative Morphine Analgesia for Adolescents Undergoing Major Spine Surgeries[NCT01839461]		137 participants (Actual)	Observational	2009-07-31	Completed
Longitudinal Virtual Reality Use in Pediatric Surgical Procedures[NCT03832478]		0 participants (Actual)	Interventional	2019-01-01	Withdrawn (stopped due to Technical difficulty with sending device home with patients)
Does Anxiety in Children on the Day of Surgery Impact Compliance in the Ophthalmology Clinic?[NCT02704442]		82 participants (Anticipated)	Observational	2016-02-29	Recruiting
Developing and Testing the Effectiveness of Intelligent Customer-driven Solution for Pediatric Surgery Care on the Improvement of Outcomes of Parents and Their Children Undergoing Circumcision[NCT04174404]		160 participants (Anticipated)	Interventional	2019-11-01	Recruiting
Use of Handheld Audiovisual Devices to Treat Pediatric Preoperative Anxiety: A Randomized Control Trial.[NCT02286674]		200 participants (Actual)	Interventional	2014-11-30	Completed
A Randomized Controlled Trial to Compare Pain Medications in Children Undergoing Strabismus Surgery[NCT02789969]		128 participants (Anticipated)	Interventional	2016-04-30	Recruiting
The Effect of Pre Surgery Dog Visits on Post Surgery Consumption of Pain Medication[NCT00452738]		0 participants (Actual)	Interventional	2007-04-30	Withdrawn (stopped due to PI left university. Did not start study)
ROPIVACAINE WITH CLONIDINE FOR PEDIATRIC RECTUS SHEATH BLOCKS- THE MAGIC COMBINATION? - A Double Blinded Prospective Study[NCT02439281]		50 participants (Actual)	Interventional	2015-05-31	Terminated (stopped due to The patients were discharged on the day of the surgery.)
Genetic, Epigenetic, Psychosocial, and Biological Determinants of Post-surgical Pain After Pectus or Spine Surgery[NCT04031716]		600 participants (Anticipated)	Interventional	2018-07-06	Enrolling by invitation
Adaptive Care in the Perioperative Setting: An Observational Study[NCT03353129]		60 participants (Actual)	Observational	2017-08-15	Completed
A Pilot Study to Evaluate the Efficacy of Virtual Reality on Pre-Operative Anxiety and Induction of Anesthesia in a Children's Hospital[NCT03239743]		80 participants (Anticipated)	Interventional	2017-07-20	Recruiting
Intelligent Customer-driven Solution for Children and Their Parents Undergoing Children´s Day Surgery[NCT04277299]		40 participants (Actual)	Interventional	2020-08-12	Completed
Efficacy of an Educational Pop-Up Book in Preparing Children for Anesthesia: A Randomized Controlled Trial[NCT04796077]		148 participants (Actual)	Interventional	2020-08-26	Completed
The Effects of Operating Room Virtual Tour on Preoperative Anxiety, Emergence Delirium and Postoperative Behavioral Changes of Pediatric Patients: Prospective, Randomized, and Controlled Trial[NCT03172182]		86 participants (Actual)	Interventional	2017-08-01	Completed
Non-Interventional Pharmacogenetic Study of Patient / Proxy Controlled Analgesia in Children Undergoing Surgery[NCT01731873]		182 participants (Actual)	Observational	2012-01-17	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Duration of delirium will be analyzed, measured from 24 hours post-operation and daily until discharge. Additional measurements will be made at 1 month and 1 year after discharge. Delirium will be defined as an acute change in pre-operative baseline condition with additional features of inattention and either disorganized thinking and altered loss of consciousness, as defined by the Confusion Assessment Method (CAM). (NCT02546765)
Timeframe: Participants will be followed for the duration of the hospital stay, an average of 6 days, and at 1 month and 1- year following the date of surgery

Follow up Incidence of Cognitive Dysfunction

Intervention	days (Median)
Acetaminophen and Dexmedetomidine	1
Acetaminophen and Propofol	1
Placebo and Dexmedetomidine	1
Placebo and Propofol	3

The follow up incidence of cognitive dysfunction will be analyzed at 1 month after discharge. T-MoCA is Telephone Montreal Cognitive Assessment Scale (MOCA). The T-MoCA is scored out of 22. The minimum score is 0 (worst) and maximum score is 22 (best). T-MOCA is converted back to 30 (full MOCA) with the help of conversion algorithms to a full MOCA.Example: 19/22 converts back to 30 by performing the following equation: (19×30) ÷ 22. The total converted score is 25.9 or 26/30 which is considered in the normal range. (NCT02546765)
Timeframe: Patients will be assessed for cognitive dysfunction with T-MOCA at 1 month following the date of surgery

Hospital Length of Stay

Intervention	units on a scale (Median)
Acetaminophen and Dexmedetomidine	17
Acetaminophen and Propofol	18
Placebo and Dexmedetomidine	19
Placebo and Propofol	18

Defined by the number of days admitted in the hospital following the completion of surgery. (NCT02546765)
Timeframe: Measured in days admitted in the hospital, an average of 6 days

ICU Length of Stay

Intervention	days (Median)
Acetaminophen and Dexmedetomidine	8
Acetaminophen and Propofol	8
Placebo and Dexmedetomidine	9
Placebo and Propofol	8

Defined by the number of days admitted in the ICU prior to transfer to the general cardiac surgical floor (NCT02546765)
Timeframe: Measured in days admitted in the ICU, an average of 2 days

Incidence of Delirium

Intervention	hours (Median)
Acetaminophen and Dexmedetomidine	28.8
Acetaminophen and Propofol	30.3
Placebo and Dexmedetomidine	49.1
Placebo and Propofol	29.3

Incidence of delirium will be analyzed between patients treated with and without IV acetaminophen, measured from 24 hours post-operation and daily until discharge. Delirium will be defined as an acute change in pre-operative baseline condition with additional features of inattention and either disorganized thinking and altered loss of consciousness, as defined by the Confusion Assessment Method (CAM). (NCT02546765)
Timeframe: Participants will be followed for the duration of the hospital stay, an average of 5 days

Montreal Cognitive Assessment (MoCA)

Intervention	Participants (Count of Participants)
Acetaminophen and Dexmedetomidine	2
Acetaminophen and Propofol	4
Placebo and Dexmedetomidine	8
Placebo and Propofol	9

MoCA scores at discharge will be reported in order to assess the occurrence of postoperative cognitive decline. Blinded study staff trained in administering the assessments will collect the data. MoCA is scored on a scale from 0 [worst] to 30 [best]; ǂA MoCA score of 24 would be equivalent to an Mini-Mental State Examination (MMSE) of about 27 or 28. Depending on education and peak intellectual attainment, such a score could be consistent with being either cognitively normal, or having very early mild cognitive impairment. Certainly such a person would be capable of living independently in the community and managing most or all of their affairs. (NCT02546765)
Timeframe: On the day of discharge, an average of 6 days

Postoperative Opioid Consumption in Morphine Equivalents

Intervention	score on a scale (Median)
Acetaminophen and Dexmedetomidine	23
Acetaminophen and Propofol	24
Placebo and Dexmedetomidine	24
Placebo and Propofol	23

Defined by the amount of additional opioid (IV morphine or hydromorphone) and oral acetaminophen medications required in the first 48 hours postoperatively. Values will be converted to morphine equivalents for analysis. Total morphine equivalent is calculated as the sum of (fentanyl dose x 100)+(hydromorphone dose x 4)+morphine dose+(oxycodone dose x 1.5) (NCT02546765)
Timeframe: Participants will be followed for the first 48 hours postoperatively.

Severity of Delirium

Intervention	mcg (Median)
Acetaminophen and Dexmedetomidine	10050
Acetaminophen and Propofol	12611
Placebo and Dexmedetomidine	11382
Placebo and Propofol	12616

Severity of delirium will be analyzed, measured from 24 hours post-operation and daily until discharge. The worst severity experienced while in the hospital will be analyzed. Delirium will be defined as an acute change in pre-operative baseline condition with additional features of inattention and either disorganized thinking and altered loss of consciousness, as defined by the Confusion Assessment Method Severity Score (CAM-S, Confusion Assessment Method-Severity). range 0 [best/no delirium] to 19 [worst]; Minimal Clinical Important Difference (MCID) 2 points (NCT02546765)
Timeframe: Participants will be followed for the duration of the hospital stay, an average of 6 days

Average Pain Severity at the Umbilicus Laparoscopic Site

Intervention	units on a scale (Median)
Acetaminophen and Dexmedetomidine	10
Acetaminophen and Propofol	8
Placebo and Dexmedetomidine	6
Placebo and Propofol	9

Numeric Rating Pain Scores ( 0-10), will be obtained every 2 hours after PACU discharge up to 18 hours or until hospital discharge, whichever occurs first. The pain score of 0, means no pain, is a good outcome , and a pain score of 10 is excruciating pain, a very bad outcome. The average of these scores will be evaluated.The pain scores will not longer be documented after the numbness went away. (NCT02439281)
Timeframe: Logistic regression of the 4 th pain score assessment

Change in Anxiety Scores

Intervention	units on a scale (Median)
Ropivacaine Group	2
Ropivacaine/ Clonidine Group	1.5

The investigators hypothesize that patient postoperative anxiety scores are lower in the Ropivacaine/Clonidine group and postoperative anxiety scores decrease more in Ropivacaine /Clonidine Group, than in Ropivacaine Group. (NCT02439281)
Timeframe: 6 hours after block placement

Complications Rate

Intervention	units on a scale (Median)
Ropivacaine Group	30
Ropivacaine/ Clonidine Group	29

The investigators expect no difference in incidence of complications (e.g. oversedation, hypotension, bradycardia episodes, etc.). (NCT02439281)
Timeframe: until study completion

Duration of Analgesia at Umbilicus Instrument Site-How Many Minutes Passed From the Time When the Blocks Where Performed Until Patient Reported Pain at Umbilicus

Intervention	Participants (Count of Participants)
Ropivacaine/ Clonidine Group	1
Ropivacaine Group	1

The investigators hypothesize that rectus sheath injections with ropivacaine/ clonidine would result in longer duration of analgesia and decreased pain scores compared to ropivacaine alone. (NCT02439281)
Timeframe: indicated by the first request for pain medication at umbilicus site

Duration of Sensory Block (Paresthesia)

Intervention	minutes (Median)
Ropivacaine/ Clonidine Group	230
Ropivacaine Group	240

The investigators hypothesize that rectus sheath injections with ropivacaine and clonidine result in longer duration of sensory block (paresthesia) compared to ropivacaine alone. (NCT02439281)
Timeframe: Indicated by return of normal sensation (expected average of 12 hours after block placement).

Medication Consumption

Intervention	minutes (Median)
Ropivacaine/ Clonidine Group	823.5
Ropivacaine Group	540

Total intravenous morphine equivalents mg/kg (NCT02439281)
Timeframe: 18 hours after surgery

Satisfaction With Pain Control From Patient

Intervention	mg/kg (Median)
Ropivacaine/ Clonidine Group	0.20
Ropivacaine Group	0.22

The investigators hypothesize that rectus sheath injections with ropivacaine/ clonidine would result in better satisfaction with pain control. (NCT02439281)
Timeframe: Prior to hospital discharge (up to 24 hours after surgery)

acetaminophen and Delirium of Mixed Origin