Improving Perioperative Sleep Disorders

The Effect of Pregabalin on Perioperative Sleep Quality in Orthopedic Surgery Patients: a Prospective, Randomized, Controlled Study

In today's day of increasing surgical volume, perioperative sleep disorders are an issue that cannot be ignored. They are an important component of perioperative brain protection. Physiologically and psychologically, sleep disorders cause serious damage to patients. The application of pregabalin aims to improve the sleep quality of hand surgery patients, and its anti anxiety effect can also alleviate preoperative anxiety. At the same time, its analgesic mechanism is different from that of opioid drugs, which is also conducive to reducing the use of opioid drugs. Therefore, we propose the following hypothesis: for orthopedic patients with high incidence of postoperative pain and sleep disorders, the use of pregabalin will improve the perioperative sleep quality of such patients.To test the above hypothesis, our research group plans to conduct this prospective, randomized, positive control study.

Study Overview

• Status: Completed
• Conditions: Sleep Disorder
• Intervention / Treatment: Drug: Pregabalin; Drug: Zolpidem

Detailed Description

Perioperative sleep disorders mainly refer to the syndrome in which patients undergoing surgery experience disrupted sleep wake rhythms before and/or after surgery, leading to abnormal sleep quality or behavior during sleep. Clinical manifestations include fragmented sleep, easy awakening at night, difficulty falling asleep, insufficient sleep time, early bedtime, or disrupted sleep rhythm at least one day before or after surgery. The latest meta-analysis study indicates that the incidence of preoperative sleep disorders in surgical patients is as high as 60%. After surgery, about 60-70% of patients will have postoperative sleep disorder (PSD), and even 23% of patients will have sleep disorder until the fourth day after surgery. Among various surgeries, orthopedic surgery has a high incidence of PSD due to its long operation time and wide surgical range. In the study by Duan G and colleagues, the PSD incidence rate of spinal orthopedic surgery in orthopedics was 35.4%, and the PSD incidence rate of limb surgery was 27%.

Sleep disorders may lead to a range of complications, including cognitive impairment, delayed postoperative recovery, acute pain, and cardiovascular accidents. In the hospital environment, factors that lead to poor sleep include pain, anxiety, noise, interference from hospital staff, continuous ambient lighting, and uncomfortable beds; After completing the surgery, factors such as the size of the surgery, the use of opioid drugs, inflammatory mediators, the release of various hormones, and pain contribute to a high incidence of sleep disorders, with pain being the most common cause, and there is an interactive relationship between postoperative sleep disorders and pain. It is worth noting that patients with poor preoperative sleep quality have a higher probability of developing sleep disorders after surgery. Therefore, it is necessary to comprehensively consider these factors and take corresponding preventive measures to reduce the incidence of perioperative sleep disorders.

According to the sleep care guidelines, for postoperative patients entering the ICU, maintaining a quiet and dim environment and reducing interruptions in nighttime care activities are recommended to improve sleep quality and efficiency. A meta-analysis shows that the use of earplugs and eye masks also helps promote sleep in ICU patients. However, it is evident that this method is not suitable for patients who are admitted to regular multi person wards after surgery. Although in a meta-analysis, there was insufficient evidence to suggest that drug therapy can improve the quality or quantity of sleep in patients with poor postoperative sleep. Even compared to placebo or no treatment, there is no established drug category or specific drug that is superior to placebo or no treatment [6]. However, drug therapy is still widely used for patients with perioperative sleep disorders due to its convenience, strong feasibility, and high patient acceptance.

In current clinical practice, the main drugs used to address perioperative sleep disorders are sleeping pills and painkillers. Specifically, sleeping pills are mainly divided into first generation, second generation, and third generation sedative hypnotic drugs. These drugs mainly exert extensive inhibition on the central nervous system, causing it to transition from an excited state to an inhibited state. However, their effect on improving sleep structure is not satisfactory, especially the second-generation drugs - benzodiazepines, which can change the usual sleep pattern, prolong shallow sleep, shorten the duration of REM sleep, and delay the appearance of the first REM sleep. This change, which is similar to the postoperative sleep structure, is more detrimental to the improvement of patients' sleep, therefore the effect is not satisfactory. As for painkillers, opioids are the most commonly used class in clinical practice. Even though they have strong analgesic effects, they have been found to dose dependently inhibit REM and SWS sleep in normal volunteers and animal experiments. In addition, in Cronin AJ et al.'s study, postoperative patients suffered from severe sleep disorders even when avoiding opioid use and pain was well controlled. Therefore, the improvement of sleep in perioperative patients cannot be limited to the use of the above two drugs.

Pregabalin is a gabapentin class drug that inhibits the influx of calcium ions into the presynaptic membrane of neurons and reduces the release of excitatory neurotransmitters (including glutamate, aspartic acid, substance P, calcitonin gene-related peptide, norepinephrine, serotonin, dopamine, etc.) by binding to the α 2 δ pressure group containing voltage-gated calcium channels. Its analgesic, anti anxiety, and anticonvulsant effects are widely used in various clinical diseases. Pregabalin has been approved for the treatment of neuropathic pain and partial seizures in the United States and Europe. It can also be used for fibromyalgia in the United States and for the treatment of generalized anxiety disorder in Europe. While treating patients with this type of chronic disease, its effect on improving sleep has been discovered. Studies have found that pregabalin exhibits significant sleep improvement effects from the initial stage of medication, and its therapeutic efficacy is maintained throughout the entire treatment phase. Similar sleep improvement effects to alprazolam have also been found in normal healthy individuals. The mechanism by which pregabalin improves sleep is still unclear, and it is speculated to be related to its ability to reduce excitatory neurotransmitters. Currently, there is no relevant research on the impact of pregabalin on sleep quality in perioperative patients.

• Study Type: Interventional
• Enrollment (Actual): 215
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Sichuan Provincial People's Hospita

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18 years old ≤ Age ≤ 65 years old, gender unlimited.
• ASA level I-II.
• Plan to undergo elective total knee arthroplasty, total hip arthroplasty, and spinal vertebral body surgery.

Exclusion Criteria:

• Patients with preoperative sleep problems.
• Patients refuse to participate in the study.
• The patient has any allergies or contraindications to the drugs used in the study.
• The patient has a history of long-term use of medications such as pregabalin or gabapentin.
• The patient has a history of long-term use of any painkillers or sleeping pills.
• The patient has cognitive impairment and is unable to conduct visits and communication.
• The patient has a history of renal dysfunction or any other serious organ dysfunction.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pregabalin Group; The Pregabalin group started taking Pregabalin 75mg bid two days before surgery and Pregabalin 150mg bid from the day before surgery to three days after surgery	Drug: Pregabalin; Start taking 75mg bid of pregabalin two days before surgery, and take 150mg bid of pregabalin from one day before surgery to three days after surgery; Other Names: Pregabalin Capsules (Lerika)
Experimental: Zolpidem Group; Patients in the zolpidem group took zolpidem 10mg every night from two days before surgery to three days after surgery	Drug: Zolpidem; Take zolpidem 10mg qn from two days before surgery to three days after surgery; Other Names: Zolpidem Tartrate Tablets（Sinuosi）
No Intervention: Control group; Control group patients do not take any additional medication that affects sleep

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Athens Insomnia Scale	The Athens Insomnia Scale has a minimum score of zero and a maximum score of 24. When the score is greater than or equal to 6, it indicates the presence of sleep disorders, and the higher the score, the more severe the sleep disorders.	From the second day of medication to five days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pittsburgh Sleep Quality Index score	The total score range of the Pittsburgh Sleep Quality Index is 0-21 points. The higher the score, the worse the sleep quality. An index greater than or equal to 8 points is considered to have a sleep quality issue	On the 30th day after surgery
Hamilton Anxiety Scale (HAMA)	A total score of ≥ 29 on the Hamilton Anxiety Scale may indicate severe anxiety 21 points, there must be obvious anxiety; ≥ 14 points, there must be anxiety; Exceeding 7 points may indicate anxiety; If it is less than 7 points, there are no symptoms of anxiety.	Two days before surgery and five days after surgery
VAS score	Evaluate patient pain using VAS score five days after surgery	Five days after surgery
Perioperative opioid consumption	Perioperative opioid consumption, converted to morphine equivalent	Immediately after discharge
Postoperative hospitalization time	Postoperative hospitalization time	Immediately after discharge
The incidence of various adverse events	The incidence of various adverse events, including fatigue, drowsiness, dizziness, nausea and vomiting, blurred vision, and other psychological symptoms such as hallucinations, agitation, nightmares, depression, etc	Immediately after discharge
Patient satisfaction survey	The patient satisfaction survey during hospitalization is divided into four levels: very satisfied, relatively satisfied, relatively dissatisfied, and very dissatisfied.	Immediately after discharge
Hamilton Depression Scale（HAMD）	Hamilton Depression Scale total score<7: normal; A total score of 7-17 indicates possible depression; A total score of 17-24 points indicates the presence of depression; Total score>24: Severe depression。	Two days before surgery and five days after surgery

Collaborators and Investigators

• Sponsor: Mengchang Yang
• Investigators: Principal Investigator: Yang Mengchang, Doctor, Sichuan Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2024
• Primary Completion (Actual): November 30, 2024
• Study Completion (Actual): December 26, 2024

Study Registration Dates

• First Submitted: June 24, 2024
• First Submitted That Met QC Criteria: July 16, 2024
• First Posted (Actual): July 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 26, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Parasomnias; Sleep Wake Disorders; Calcium-Regulating Hormones and Agents; Sleep Aids, Pharmaceutical; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics; Neurotransmitter Agents; Membrane Transport Modulators; Hypnotics and Sedatives; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; GABA Agents; Anticonvulsants; Calcium Channel Blockers; GABA-A Receptor Agonists; GABA Agonists; Pregabalin; Zolpidem
• Other Study ID Numbers: Sleep disorders-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No