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Study of Melatonin on Sleep, Pain, and Confusion After Joint Replacement Surgery

Effects of Perioperative Melatonin on Sleep, Pain, and Confusion After Joint Replacement Surgery

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01505465
Enrollment
50
Registered
2012-01-06
Start date
2012-02-29
Completion date
2013-06-30
Last updated
2022-05-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Confusion, Delirium, Postoperative Pain, Sleep

Keywords

Total Knee Replacement, Pain, Confusion, Sleep

Brief summary

Pain, confusion, and breaks in normal sleep cycles have been challenges commonly faced by patients after undergoing joint surgeries. To address these issues, melatonin, an inexpensive over-the-counter supplement, has shown in previous to help manage sleep disorders, prevent and treat post-operative confusion in patients over 70 years of age, and reduce pain. The purpose of this study is to establish whether melatonin can aid in reducing pain and post-operative confusion and improve sleep quality after total knee replacement

Detailed description

Sleep disruption is a challenge commonly faced by patients and care providers in the perioperative period \[1,2\] and has been shown to affect postoperative performance after total knee arthroplasty \[3\] . Postoperative sleep disruption is likely influenced by environmental factors \[4\] and anesthetic exposure \[5,6\] and is known to be exacerbated by postoperative pain \[7\] . In a reciprocal manner, sleep disruption has been shown to exacerbate pain perception \[8,9\] . Melatonin is an inexpensive over-the-counter dietary supplement with an established safety profile \[10\] that has shown promise in managing sleep disorders and amelioration of chronic and acute pain. Evidence suggests that exogenous melatonin can be efficacious in improving sleep disruption in tracheostomized patients in the ICU \[11\] as well as those experiencing jet lag \[12,13\] . Previous studies have found conflicting results regarding the potential for melatonin to improve sleep and pain in the perioperative period \[14\] . These discrepancies may result from differences in surgical and anesthetic conditions, differences in melatonin dose and administration regimens, variations in study quality, different methods of assessing pain and sleep quality, and different patient populations. There is no consensus as to what dose, duration, and timing of melatonin administration in the perioperative period are most likely to improve sleep quality or quantity. This study was designed to explore the effect of a stable regimen of exogenous perioperative melatonin, administered over 6 consecutive nights, on postoperative pain, sleep quality, and sleep efficiency in patients undergoing total knee arthroplasty under regional anesthesia with sedation. To our knowledge, this study is the first to examine perioperative subjected sleep quality as well as sleep time and efficiency as measured by the validated objective tool of wrist actigraphy in this population. This study examined the hypotheses that sleep disruption occurs in the context of total knee arthroplasty performed under regional anesthesia with sedation and that perioperative melatonin can modulate pain and sleep disruption after total knee arthroplasty. 1. Gogenur I., Bisgaard T., Burgdorf S., et. al.: Disturbances in the circadian pattern of activity and sleep after laparoscopic versus open abdominal surgery. Surg Endosc 2009; 23: pp. 1026. 2. Kain Z.N., Caldwell-Andrews A.A.: Sleeping characteristics of adults undergoing outpatient elective surgery: a cohort study. J Clin Anesth 2003; 15: pp. 505. 3. Cremeans-Smith J.K., Millington K., Sledjeski E., et. al.: Sleep disruptions mediate the relationship between early postoperative pain and later functioning following total knee replacement surgery. J Behav Med 2006; 29: pp. 215. 4. Lane T., East L.A.: Sleep disruption experienced by surgical patients in an acute hospital. Br J Nurs 2008; 17: pp. 766. 5. Tung A., Mendelson W.B.: Anesthesia and sleep. Sleep Med Rev 2004; 8: pp. 213. 6. Nelson L.E., Guo T.Z., Lu J., et. al.: The sedative component of anesthesia is mediated by GABA(A) receptors in an endogenous sleep pathway. Nat Neurosci 2002; 5: pp. 979. 7. Wylde V., Rooker J., Halliday L., et. al.: Acute postoperative pain at rest after hip and knee arthroplasty: severity, sensory qualities and impact on sleep. Orthop Traumatol Surg Res 2011; 97: pp. 139. 8. Tiede W., Magerl W., Baumgartner U., et. al.: Sleep restriction attenuates amplitudes and attentional modulation of pain-related evoked potentials, but augments pain ratings in healthy volunteers. Pain 2010; 148: pp. 36. 9. Raymond I., Nielsen T.A., Lavigne G., et. al.: Quality of sleep and its daily relationship to pain intensity in hospitalized adult burn patients. Pain 2001; 92: pp. 381. 10. Dietary supplements: a framework for evaluating safety.2005.The National Academies Press Washington, DC 11. Bourne R.S., Mills G.H., Minelli C.: Melatonin therapy to improve nocturnal sleep in critically ill patients: encouraging results from a small randomised controlled trial. Crit Care 2008; 12: pp. R52. 12. Suhner A., Schlagenhauf P., Hofer I., et. al.: Effectiveness and tolerability of melatonin and zolpidem for the alleviation of jet lag. Aviat Space Environ Med 2001; 72: pp. 638. 13. Suhner A., Schlagenhauf P., Johnson R., et. al.: Comparative study to determine the optimal melatonin dosage form for the alleviation of jet lag. Chronobiol Int 1998; 15: pp. 655. 14. Andersen L.P., Rosenberg J., Gogenur I.: Perioperative melatonin: not ready for prime time. Br J Anaesth 2014; 112: pp. 7.

Interventions

DRUGMelatonin

5mg of melatonin will be taken by the subject for 3 nights prior and continuing 3 nights after surgery as tolerated.

DRUGPlacebo

5mg of placebo will be taken by the subject 3 nights prior to surgery and continuing 3 nights after surgery

Sponsors

Hospital for Special Surgery, New York
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No

Inclusion criteria

* Patients 18-90 years old undergoing elective, primary total knee replacement * American Society of Anesthesiologists (ASA) Physical Status I-III * Epidural anesthesia/Patient Controlled Analgesia candidate

Exclusion criteria

* Mental impairment * Pre-operative use of benzodiazepines, narcotics, or prescription/over-the counter (OTC) sleep aids * Pre-operative use of calcium channel blockers * Insomnia * Recent drug or alcohol abuse * Psychiatric disorders other than anxiety, including depression * Diabetes

Design outcomes

Primary

MeasureTime frameDescription
Perioperative Sleep Efficiency96 hours before surgery to 72 hours after surgerySleep time change from 96 hours before surgery to 72 hours after surgery

Secondary

MeasureTime frameDescription
Perioperative Effects of Melatonin on Post-operative Pain ScoresUp to postoperative day 3A difference in 25% in average pain score at each time point be considered clinically significant.
Melatonin Effects on Delirium During Post-operative Inpatient Stay Based on Clinical Assessment in Patients 65 and OlderUp to postoperative day 3A difference of 25% will be considered clinically important.
Melatonin Effects on Daytime ActivityUp to postoperative day 3A 20% difference will be considered clinically important.
Melatonin Effects on Patient Controlled Analgesia and Postoperative Narcotic UsageUp to 3 daysA 25% in narcotic usage will be considered clinically important

Countries

United States

Participant flow

Participants by arm

ArmCount
Study: Melatonin
Melatonin: 5mg of melatonin will be taken by the subject for 3 nights prior and continuing 3 nights after surgery as tolerated.
19
Control: Placebo
Placebo: 5mg of placebo will be taken by the subject 3 nights prior to surgery and continuing 3 nights after surgery
18
Total37

Baseline characteristics

CharacteristicControl: PlaceboTotalStudy: Melatonin
Age, Continuous61.4 years
STANDARD_DEVIATION 14.3
65.82 years
STANDARD_DEVIATION 40.05
70 years
STANDARD_DEVIATION 65.8
Race and Ethnicity Not Collected0 Participants
Region of Enrollment
United States
18 Participants37 Participants19 Participants
Sex: Female, Male
Female
6 Participants20 Participants14 Participants
Sex: Female, Male
Male
12 Participants17 Participants5 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
0 / 190 / 18
serious
Total, serious adverse events
0 / 190 / 18

Outcome results

Primary

Perioperative Sleep Efficiency

Sleep time change from 96 hours before surgery to 72 hours after surgery

Time frame: 96 hours before surgery to 72 hours after surgery

ArmMeasureValue (MEAN)
Study: MelatoninPerioperative Sleep Efficiency20 minutes
Control: PlaceboPerioperative Sleep Efficiency-55 minutes
Secondary

Melatonin Effects on Daytime Activity

A 20% difference will be considered clinically important.

Time frame: Up to postoperative day 3

Population: DATA NOT COLLECTED

Secondary

Melatonin Effects on Delirium During Post-operative Inpatient Stay Based on Clinical Assessment in Patients 65 and Older

A difference of 25% will be considered clinically important.

Time frame: Up to postoperative day 3

Population: DATA NOT COLLECTED

Secondary

Melatonin Effects on Patient Controlled Analgesia and Postoperative Narcotic Usage

A 25% in narcotic usage will be considered clinically important

Time frame: Up to 3 days

Population: DATA NOT COLLECTED

Secondary

Perioperative Effects of Melatonin on Post-operative Pain Scores

A difference in 25% in average pain score at each time point be considered clinically significant.

Time frame: Up to postoperative day 3

Population: DATA NOT COLLECTED

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026