Caffeine and Neurologic Recovery Following Surgery and General Anesthesia

NCT03577730 | Completed Early Phase 1 Results FDA Drug

• 1 other identifier: HUM00135919
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

The ongoing opioid epidemic is a public health crisis, and surgical patients are particularly vulnerable to opioid-dependency and related risks. Emerging data suggest that caffeine may reduce pain after surgery. Thus, the purpose of this study is to test whether caffeine reduces pain and opioid requirements after surgery. The investigators will also test whether caffeine improves mood and brain function (e.g., learning, memory) after surgery.

Conditions

Pain, Postoperative

Keywords

Opioid Use; Opioid Dependence; Opioid-Related Disorders; Opioid Abuse; Opioid-use Disorder; Pain; Pain, Postoperative; Cognitive Impairment; Delirium; Delirium on Emergence; Depression; Anxiety; Anxiety Disorders; Affect

Outcome Measures

Primary Outcomes (1)

• Cumulative Opioid Consumption: Postoperative Opioid Consumption, Oral Morphine Equivalents (mg)

  Postoperative opioid consumption, oral morphine equivalents (mg)

  through postoperative day 3

Secondary Outcomes (9)

• Acute Pain (Patient-reported) as Assessed by Visual Analogue Scale

  Data gathered from postoperative day 0-3. Final results were based on all values combined over this time period, per protocol.

• Acute Pain (Observer-reported) as Assessed by Behavioral Pain Scale

  Data gathered from postoperative day 0-3. Final results were based on all values combined over this time period, per protocol.

• Time Until Anesthetic Emergence

  Duration of time from surgical dressing completion to anesthetic emergence (min); generally expected to be between 10 and 60 minutes

• Number of Participants With Depression as Assessed by the Hospitalized Anxiety and Depression Scale (HADS-D)

  baseline through postoperative day 3

• Number of Participants With Anxiety as Assessed by the Hospitalized Anxiety and Depression Scale (HADS-A)

  baseline through postoperative day 3

Other Outcomes (9)

• Caffeine Intake: Number of Caffeinated Beverages (n) Consumed

  postoperative day 0-7

• Subacute Opioid Consumption: Postoperative Subacute Opioid Consumption, Oral Morphine Equivalents (mg)

  postoperative days 4-7

• Sleep Disturbances: Incidence (%) of New, Self-reported Sleep Disturbances

  postoperative days 0-3

Study Arms (2)

Experimental

EXPERIMENTAL

Prepared intravenous piggyback solution of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group.

Drug: Caffeine Citrate

Control

PLACEBO COMPARATOR

Prepared intravenous piggyback solution of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants who are randomized to this group.

Drug: Dextrose Water

Interventions

Caffeine Citrate DRUG

Prepared intravenous piggyback solutions of caffeine citrate (200 mg caffeine) will be directly delivered to the operating room prior to the surgery of enrolled participants.

Experimental

Dextrose Water DRUG

Prepared intravenous piggyback solutions of 5 percent dextrose water will be directly delivered to the operating room prior to the surgery of enrolled participants.

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult (\>/= 18 years old) undergoing non-cardiac, non-neurologic, non-major vascular surgery requiring general anesthesia

You may not qualify if:

• Emergency surgery
• Cognitive impairment precluding capacity for informed consent
• Uncontrolled cardiac arrhythmias
• Seizure disorders
• Preoperative opioid use
• Diabetes
• Liver failure
• Pregnancy
• Breastfeeding
• Severe visual or auditory impairment (may hinder cognitive function testing)
• Patients unable to speak English.

Sponsors & Collaborators

• University of Michigan: lead

Study Sites (1)

Michigan Medicine

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (19)

• Weiser TG, Haynes AB, Molina G, Lipsitz SR, Esquivel MM, Uribe-Leitz T, Fu R, Azad T, Chao TE, Berry WR, Gawande AA. Estimate of the global volume of surgery in 2012: an assessment supporting improved health outcomes. Lancet. 2015 Apr 27;385 Suppl 2:S11. doi: 10.1016/S0140-6736(15)60806-6. Epub 2015 Apr 26.

  PMID: 26313057 BACKGROUND

• Kundermann B, Krieg JC, Schreiber W, Lautenbacher S. The effect of sleep deprivation on pain. Pain Res Manag. 2004 Spring;9(1):25-32. doi: 10.1155/2004/949187.

  PMID: 15007400 BACKGROUND

• Vaurio LE, Sands LP, Wang Y, Mullen EA, Leung JM. Postoperative delirium: the importance of pain and pain management. Anesth Analg. 2006 Apr;102(4):1267-73. doi: 10.1213/01.ane.0000199156.59226.af.

  PMID: 16551935 BACKGROUND

• Lynch EP, Lazor MA, Gellis JE, Orav J, Goldman L, Marcantonio ER. The impact of postoperative pain on the development of postoperative delirium. Anesth Analg. 1998 Apr;86(4):781-5. doi: 10.1097/00000539-199804000-00019.

  PMID: 9539601 BACKGROUND

• Karp JF, Reynolds CF 3rd, Butters MA, Dew MA, Mazumdar S, Begley AE, Lenze E, Weiner DK. The relationship between pain and mental flexibility in older adult pain clinic patients. Pain Med. 2006 Sep-Oct;7(5):444-52. doi: 10.1111/j.1526-4637.2006.00212.x.

  PMID: 17014605 BACKGROUND

• Dolan R, Huh J, Tiwari N, Sproat T, Camilleri-Brennan J. A prospective analysis of sleep deprivation and disturbance in surgical patients. Ann Med Surg (Lond). 2016 Jan 6;6:1-5. doi: 10.1016/j.amsu.2015.12.046. eCollection 2016 Mar.

  PMID: 26909151 BACKGROUND

• Gan TJ, Habib AS, Miller TE, White W, Apfelbaum JL. Incidence, patient satisfaction, and perceptions of post-surgical pain: results from a US national survey. Curr Med Res Opin. 2014 Jan;30(1):149-60. doi: 10.1185/03007995.2013.860019. Epub 2013 Nov 15.

  PMID: 24237004 BACKGROUND

• Avidan MS, Maybrier HR, Abdallah AB, Jacobsohn E, Vlisides PE, Pryor KO, Veselis RA, Grocott HP, Emmert DA, Rogers EM, Downey RJ, Yulico H, Noh GJ, Lee YH, Waszynski CM, Arya VK, Pagel PS, Hudetz JA, Muench MR, Fritz BA, Waberski W, Inouye SK, Mashour GA; PODCAST Research Group. Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Lancet. 2017 Jul 15;390(10091):267-275. doi: 10.1016/S0140-6736(17)31467-8. Epub 2017 May 30.

  PMID: 28576285 BACKGROUND

• Pandharipande P, Cotton BA, Shintani A, Thompson J, Pun BT, Morris JA Jr, Dittus R, Ely EW. Prevalence and risk factors for development of delirium in surgical and trauma intensive care unit patients. J Trauma. 2008 Jul;65(1):34-41. doi: 10.1097/TA.0b013e31814b2c4d.

  PMID: 18580517 BACKGROUND

• Robinson TN, Raeburn CD, Tran ZV, Angles EM, Brenner LA, Moss M. Postoperative delirium in the elderly: risk factors and outcomes. Ann Surg. 2009 Jan;249(1):173-8. doi: 10.1097/SLA.0b013e31818e4776.

  PMID: 19106695 BACKGROUND

• Brummett CM, Waljee JF, Goesling J, Moser S, Lin P, Englesbe MJ, Bohnert ASB, Kheterpal S, Nallamothu BK. New Persistent Opioid Use After Minor and Major Surgical Procedures in US Adults. JAMA Surg. 2017 Jun 21;152(6):e170504. doi: 10.1001/jamasurg.2017.0504. Epub 2017 Jun 21.

  PMID: 28403427 BACKGROUND

• Saczynski JS, Marcantonio ER, Quach L, Fong TG, Gross A, Inouye SK, Jones RN. Cognitive trajectories after postoperative delirium. N Engl J Med. 2012 Jul 5;367(1):30-9. doi: 10.1056/NEJMoa1112923.

  PMID: 22762316 BACKGROUND

• Bickel H, Gradinger R, Kochs E, Forstl H. High risk of cognitive and functional decline after postoperative delirium. A three-year prospective study. Dement Geriatr Cogn Disord. 2008;26(1):26-31. doi: 10.1159/000140804. Epub 2008 Jun 24.

  PMID: 18577850 BACKGROUND

• Nelson AM, Battersby AS, Baghdoyan HA, Lydic R. Opioid-induced decreases in rat brain adenosine levels are reversed by inhibiting adenosine deaminase. Anesthesiology. 2009 Dec;111(6):1327-33. doi: 10.1097/ALN.0b013e3181bdf894.

  PMID: 19934879 BACKGROUND

• Gauthier EA, Guzick SE, Brummett CM, Baghdoyan HA, Lydic R. Buprenorphine disrupts sleep and decreases adenosine concentrations in sleep-regulating brain regions of Sprague Dawley rat. Anesthesiology. 2011 Oct;115(4):743-53. doi: 10.1097/ALN.0b013e31822e9f85.

  PMID: 21857500 BACKGROUND

• Osman NI, Baghdoyan HA, Lydic R. Morphine inhibits acetylcholine release in rat prefrontal cortex when delivered systemically or by microdialysis to basal forebrain. Anesthesiology. 2005 Oct;103(4):779-87. doi: 10.1097/00000542-200510000-00016.

  PMID: 16192770 BACKGROUND

• Pisani MA, Murphy TE, Araujo KL, Slattum P, Van Ness PH, Inouye SK. Benzodiazepine and opioid use and the duration of intensive care unit delirium in an older population. Crit Care Med. 2009 Jan;37(1):177-83. doi: 10.1097/CCM.0b013e318192fcf9.

  PMID: 19050611 BACKGROUND

• Litaker D, Locala J, Franco K, Bronson DL, Tannous Z. Preoperative risk factors for postoperative delirium. Gen Hosp Psychiatry. 2001 Mar-Apr;23(2):84-9. doi: 10.1016/s0163-8343(01)00117-7.

  PMID: 11313076 BACKGROUND

• Vlisides PE, Li D, McKinney A, Brooks J, Leis AM, Mentz G, Tsodikov A, Zierau M, Ragheb J, Clauw DJ, Avidan MS, Vanini G, Mashour GA. The Effects of Intraoperative Caffeine on Postoperative Opioid Consumption and Related Outcomes After Laparoscopic Surgery: A Randomized Controlled Trial. Anesth Analg. 2021 Jul 1;133(1):233-242. doi: 10.1213/ANE.0000000000005532.

  PMID: 33939649 BACKGROUND

MeSH Terms

Conditions

Pain, Postoperative; Opioid-Related Disorders; Pain; Cognitive Dysfunction; Delirium; Emergence Delirium; Depression; Anxiety Disorders

Interventions

caffeine citrate

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations; Signs and Symptoms; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders; Confusion; Neurobehavioral Manifestations; Nervous System Diseases; Behavioral Symptoms; Behavior

Results Point of Contact

• Title: Phillip Vlisides
• Organization: University of Michigan

pvliside@umich.edu

734-936-4280

Study Officials

• Phillip Vlisides, MD

  Assistant Professor of Anesthesiology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This will be a single-center, quadruple-blinded, pilot randomized controlled trial at the University of Michigan Health System.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Anesthesiology

Study Record Dates

• First Submitted: June 8, 2018
• First Posted: July 5, 2018
• Study Start: July 10, 2018
• Primary Completion: November 21, 2019
• Study Completion: January 17, 2020
• Last Updated: October 6, 2021
• Results First Posted: October 6, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)