Clinical trial NCT06512155: Improving Perioperative Sleep Disorders
Official title: The Effect of Pregabalin on Perioperative Sleep Quality in Orthopedic Surgery Patients: a Prospective, Randomized, Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Sleep Disorder
Lead sponsor: Sichuan Provincial People's Hospital
Sponsor class: OTHER
First posted: 2024-07-22
Enrollment: 215
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Athens Insomnia Scale
timeFrame: From the second day of medication to five days after surgery
Secondary outcomes:
measure: Pittsburgh Sleep Quality Index score
timeFrame: On the 30th day after surgery
measure: Hamilton Anxiety Scale (HAMA)
timeFrame: Two days before surgery and five days after surgery
measure: VAS score
timeFrame: Five days after surgery
measure: Perioperative opioid consumption
timeFrame: Immediately after discharge
measure: Postoperative hospitalization time
timeFrame: Immediately after discharge
measure: The incidence of various adverse events
timeFrame: Immediately after discharge
measure: Patient satisfaction survey
timeFrame: Immediately after discharge
measure: Hamilton Depression Scale（HAMD）
timeFrame: Two days before surgery and five days after surgery
Other outcomes:
Locations:
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospita
state: Sichuan
Study officials:
affiliation: Sichuan Provincial People's Hospital
name: Yang Mengchang, Doctor
role: PRINCIPAL_INVESTIGATOR
References: