Behaviors and Mental Disorders

All Conditions

Nervous System Diseases

Symptoms and General Pathology

Neoplasms

Digestive System Diseases

Anxiety Disorders

Parasomnias

Pain, Postoperative

Dyssomnias

Pain

Colorectal Neoplasms

Mental Disorders

Psychotic Disorders

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Postoperative Complications

Neurologic Manifestations

Sleep Wake Disorders

Pharmaceutical Solutions

All Drugs and Chemicals

Adjuvants, Anesthesia

Central Nervous System Depressants

Psychotropic Drugs

Midazolam

Anesthetics

Hypnotics and Sedatives

Anti-Anxiety Agents

Anesthetics, Intravenous

Anesthetics, General

GABA Modulators

Neurotransmitter Agents

The intervention drug is midazolam oral solution at a dose of 7-10mg. The starting dosage is 7mg, with subsequent individual increases of 1mg up to a maximum dose of 10mg if patients do not achieve sleep within 30 minutes of administration. The individual dose wil be consistently maintained at the corresponding level every night until the surgery.

Placebo is a solution of midazolam oral solution that looks, tastes, and appears the same as the intervention drug, similar to the experimental group increment method.

Each individual administers the midazolam oral solution nightly from enrollment to the surgry.

Midazolam oral solution

Each individual administers placebo solution nightly from enrollment to the surgry.

Placebo

Sanqing Jin, MD

Yan Zhou, MD

sanqing Jin, MD

Previous studies have indicated a high incidence of sleep disturbances and anxiety symptoms in individuals with colorectal cancers prior to undergoing surgery, leading to worsened postoperative pain, slower recovery, and higher risk of chronic pain. The enhancement of sleep quality is intricately linked to reducing stress. Preoperative drugs that combine hypnosis and anti-anxiety have not been studied in colorectal cancer patients. Midazolam oral solution is safe and effective for short-term hypnotic and anti-anxiety effects in clinical preoperative settings. In the current randomized controlled clinical trial, 280 patients experiencing sleep disturbance or anxiety prior to colorectal cancer surgery will receive midazolam solution to assess its potential efficacy in reducing postoperative pain, expediting recovery, and decreasing the likelihood of chronic pain. Additionally, the study aims to explore the potential connections between midazolam administration and reductions in stress and inflammation.

Preoperative sleep disturbance and anxiety worsen postoperative pain for patients undergoing surgeries. Research indicates that a significant proportion of patients, ranging from 8.8% to 79.1%, experience disturbances in sleep or anxiety prior to surgery. These preoperative issues have been shown to have lasting and intricate effects on postoperative pain, fatigue, and depression. Therefore, it is imperative for clinical doctors to promptly identify preoperative sleep disturbances and anxiety in order to offer appropriate support to patients.

Colorectal cancer is the fifth leading cause of death in China, with nearly 40% of patients experiencing insomnia before surgery, consistent with our previous studies. A case-control study demonstrated a protective association between improved sleep quality and relief of postoperative pain in colorectal cancers. Furthermore, individuals undergoing laparoscopic colorectal surgery showed a higher likelihood of experiencing visceral pain compared to somatic pain. Acute visceral pain has the potential to progress into chronic visceral pain, resulting in behavioral manifestations such as anxiety, fear, and depression, which may persist and exacerbate into enduring chronic pain, ultimately impacting the individual's quality of life. Currently, studies have shown that disturbed preoperative sleep has become a significant predictor of both acute and chronic postoperative pain. Therefore, finding effective interventions to promote preoperative sleep is a continuing consideration for clinicians.

Pharmacological intervention is the primary approach for preoperative sleep disturbances or anxiety. Finding appropriate drug is a challenge that needs to be solved in the clinical practice. There is currently a lack of evidence-based medical guidelines regarding pharmacologic interventions for preoperative sleep disturbances and anxiety. Research has indicated that zolpidem can enhance sleep quality in patients prior to surgery, decrease the need for analgesics during the procedure, and alleviate postoperative pain. Nevertheless, there is a demand for agents that possess both short-term hypnotic and anxiolytic properties, whereas zolpidem solely exhibits hypnotic effects. Midazolam, a short-acting benzodiazepine, is often used before anesthesia for its short-term hypnotic and anxiolytic effects. Studies have found that midazolam oral solution is safe and effective for short-term use in clinical pre-surgical settings. There are no studies on using oral midazolam solution to improve sleep and reduce anxiety in colorectal cancer patients before surgery. Our previous research found that a dose of 7.2mg can effectively induce sleep with minimal side effects in 50% patients before surgery.

In summary, the present study intends to carry out a prospective,randomized,double-blind,placebo-controlled clinical study to investigate the hypothesis that preoperative oral midazolam solution could reduce acute postoperative pain, promote early recovery, and reduce the risk of chronic pain in patients with poor sleep or anxiety before colorectal cancer surgery. It is postulated that the potential benefits of preoperative oral midazolam solution may be attributed to decreased stress levels, and lowered inflammation markers.

Preoperative Oral Midazolam to Postoperative Pain Relief in Sleep Disturbance or Anxiety Patients With Colorectal Cancer

Effects of Preoperative Oral Mmidazolam on Postoperative Pain in Sleep Disturbance or Anxiety Patients Undergoing Laparoscopic Colorectal Cancer Resection- A Prospective, Randomized, Double-blind, Placebo-controlled Clinical Study

Peripheral blood being collected before surgery

NRS: Numerical Rating Scale, NRS pain score 0-3 for mild, 4-6 for moderate, 7-10 for severe; Moderate to severe pain: Mean NRS pain score ≥4; Mean NRS pain score: Mean pain is defined as the mean of NRS scores of the severest, lightest, average, and present pain within 24 hours using the Brief Pain Inventory Short version (BPIsf).

NRS: Numerical Rating Scale, NRS pain score 0-3 for mild, 4-6 for moderate, 7-10 for severe; Mean NRS pain score: Mean pain is defined as the mean of NRS scores of the severest, lightest, average, and present pain within 24 hours using the Brief Pain Inventory Short version (BPIsf).

The number of additional postoperative analgesics, by Patient-Controlled Analgesia or prescribed by doctors

QoR-15: 15-item Quality of Recovery scale; QoR-15 is a patient-reported measure, and is used to assess global recovery quality after surgery physiologically and psychologically. QoR-15 contents 15 items, which item is constructed by an 11-point numerical rating scale (for positive items, 0="none of the time"to 10="all of the time"; for negative items the scoring are reversed). The total scores are ranging from 0(extremely poor QoR) to 150 (excellent QoR).

Propofol is titrated for the purpose of achieving general anesthesia prior to colorectal cancer resection. Upon reaching the titration endpoint, indicated by an OAAS sedation score of 0, the dosage of propofol administered (in mg/kg) is documented.

OAAS：Observer's Assessment Alertness/Sedation scale

Following the surgical procedure, the patient is relocated to the Post-Anesthesia Care Unit (PACU). Patients may be transferred to the general ward once their postoperative resuscitation meets established standards. Incidence of PACU stays longer than 1 hour is recorded.

The quantity of supplementary analgesic medications administered in PACU

The incidence of axillary temperatures above 38℃ within 72 hours post-surgery is recorded.

Length of hospital stay after surgery：hospital stay time (days) from operation completion to actual hospital discharge

Medical costs from operation completion to actual hospital discharge

Incidence of unplanned reoperations within 30 Days after Surgery

Incidence of unplanned admissions within 30 Days after Surgery

The Brief Pain Inventory: to survey postoperative chronic pain after surgery

SF-36: The short form (SF)-36 is an instrument to survey postoperative health status.

Number of patients still taking pain medication on day 30 after surgery

Number of patients still taking pain medication on day 90 after surgery

The prevalence of post-traumatic stress disorder as measured by the PC-PTSD scale at 30 days following surgical procedures.

PC- PTSD：Primary Care Post traumatic Stress Disorder

The prevalence of post-traumatic stress disorder as measured by the PC-PTSD scale at 90 days following surgical procedures.

PC- PTSD：Primary Care Post traumatic Stress Disorder

The ratio of neutrophils to lymphocytes in peripheral blood on the first day after surgery

The ratio of neutrophils to lymphocytes in peripheral blood on the second day after surgery

The ratio of neutrophils to lymphocytes in peripheral blood on the third day after surgery

The ratio of platelets to lymphocytes in peripheral blood on the first day after surgery

The ratio of platelets to lymphocytes in peripheral blood on the second day after surgery

The ratio of platelets to lymphocytes in peripheral blood on the third day after surgery

C-reactive protein levels in peripheral blood on the first day after surgery

C-reactive protein levels in peripheral blood on the second day after surgery

C-reactive protein levels in peripheral blood on the third day after surgery

Spots Global Cancer Trial Database for midazolam oral solution