The Diversity of Intestinal Microbiota in Patients With Different Sedative-hypnotics Undergoing Mechanical Ventilation

Not Applicable

Withdrawn

• Conditions: Mechanical Ventilation; Intestinal Microbiota
• Interventions: Device: Mechanical Ventilation; Drug: Midazolam; Drug: Dexmedetomidine

• Registration Number: NCT03401736
• Lead Sponsor: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Brief Summary

Bidirectional communication between the CNS and the GI tract - the brain-gut axis - occurs both in health and disease.Patients with mechanical ventilation in ICU (ICU) often meet the necessary nutritional needs. These patients often appear varying degrees of intestinal flora imbalance, such as diarrhea, vomiting, abdominal distension and other complications, which exert negative effect on treatment and prolong hospitalization time.So far，whether the sedative drugs used for a long time in mechanically ventilated patients will affect the diversity of intestinal flora or not has not been reported.The effects of different sedative drugs on the intestinal flora diversity need further study.Therefore, this topic will used midazolam and dexmedetomidine to study the effect on the diversity of intestinal microbiota.Meanwhile，the research will provide a theoretical basis for rational use of mechanical ventilation and sedative drugs.

Detailed Description

There are a variety of normal microbial communities in the healthy human intestines, which maintain the physiological balance of the host. Under normal circumstances, there are about 104 intestinal microflora in the adult's intestines. The total number of genes is about 150 times the number of human genes. More and more studies have found that intestinal flora plays an important role in the occurrence of many human diseases. In recent years, the role of intestinal microflora in the brain axis has gradually been recognized and become a hot spot of research, and a new concept of the brain - gut axis is proposed.

The brain-gut axis is a bidirectional communication system between the central nervous system (CNS) and the gastrointestinal tract. Compared with ordinary mice, mild exposure to pressure can increase the level of corticosterone and adrenocorticotropic hormone in sterile mice, and this overreaction can be reversed by transplantation of normal rats' feces.Together, it is clear that the gut microbiota can be a key regulator of mood, cognition, pain, and obesity. Understanding microbiota-brain interactions is an exciting area of research which may contribute new insights into individual variations in cognition, personality, mood, sleep, and eating behavior.The abnormal expression of GABA (GABA) receptor in central nervous system is related to anxiety and depression. It is found that probiotics can regulate the expression of GABA receptor in the cerebral cortex through vagus nerve, thereby reducing anxiety and depression.5-HT signal system abnormalities may be associated with the pathophysiological changes of irritable bowel syndrome (IBS), while intestinal flora can affect the generation of neurotransmitter 5-HT in the intestine, resulting in changing of gastrointestinal motility and sensibility of internal organ. The above study means that the brain axis plays an important role in maintaining the diversity of intestinal microbiota.

It is essential that using sedatives to maintain the safety and comfort of the patient in ICU.Most patients also need receiving mechanical ventilation.Many patients in Intensive care unit appear varying degrees of intestinal microflora imbalance,especially received mechanical ventilation.So far,whether sedatives used for a long time in mechanically ventilated patients will affect the diversity of intestinal flora or not still not been reported. The effects of different sedative drugs on the intestinal flora diversity also need further study.Therefore, the topic will discuss the diversity of intestinal microbiota in patients with different sedative-hypnotics and mechanical ventilation.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-12-16
• Study First Submitted QC: 2018-01-16
• Study First Posted: 2018-01-17
• Study Start: 2018-03-01
• Primary Completion: 2020-10-31
• Study Completion: 2020-11-01
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-24
• Last Update Posted: 2021-09-28

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• patients who receive long-term (≥12 hours) mechanical ventilation after operation on admission to the ICU
• APACHEII score 12-20 points
• no receive other clinical trials in the near 3 months
• no acute infectious disease, psychosis or other disease
• volunteer people

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Exclusion Criteria

• known or suspected allergy to midazolam or Dexmedetomidine
• suspected pregnancy, gross obesity, hyperlipemia, moribund state
• history of alcoholism or intake of anti-anxiety drugs or hypnotics
• chronic renal failure
• coma by cranial trauma or neurosurgery or unknown etiology or status epilepticus
• unwillingness to provide informed consent by patients or their authorized surrogates following ICU admission.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group M：received midazolam	Mechanical Ventilation	Patients who requires the mechanical ventilation allocated to the midazolam group (group M) were treated with an infusion bolus of 0.05 mg/kg and continuous infusion of 0.04 to 0.20 mg/kg/hour, with the dosage adjusted to achieve the desired level of sedation.
Group D: received dexmedetomidine	Mechanical Ventilation	Patients who requires the mechanical ventilation allocated to the dexmedetomidine group (group D) received an infusion bolus of 1 ug/kg within 10 minutes and continuous infusion of 0.25 to 0.75 ug/kg/hour, with the dosage adjusted to achieve the desired level of sedation.All patients maintained BIS between 65\~85 and the Ramsay score was 3 to 4.
Group M：received midazolam	Midazolam	Patients who requires the mechanical ventilation allocated to the midazolam group (group M) were treated with an infusion bolus of 0.05 mg/kg and continuous infusion of 0.04 to 0.20 mg/kg/hour, with the dosage adjusted to achieve the desired level of sedation.
Group D: received dexmedetomidine	Dexmedetomidine	Patients who requires the mechanical ventilation allocated to the dexmedetomidine group (group D) received an infusion bolus of 1 ug/kg within 10 minutes and continuous infusion of 0.25 to 0.75 ug/kg/hour, with the dosage adjusted to achieve the desired level of sedation.All patients maintained BIS between 65\~85 and the Ramsay score was 3 to 4.

Primary Outcome Measures

Name	Time	Method
The changing trends of the diversity of Intestinal microbiota	Up to 1 year from the beginning of the study	Bacterial diversity revealed by 16S ribosomal RNA (rRNA) gene high-throughput sequencing (HTS).Feces were collected before operation from patients who had surgery.After the first collection, another was collected when the patient received mechanical ventilation more than 12 hours.

Secondary Outcome Measures

Name	Time	Method
duration of sedation	Time from achieving sedation until reaching full consciousness,up to 1 week.	BIS and Ramsay score were described by the anesthetist physician
Duration of mechanical ventilation	Up to 3 days from the beginning of the study	Duration of mechanical ventilation was described by the anesthetist physician
The changing trends of weight	Up to 1 month from the beginning of the study	The changing trends of weight was recorded in kilograms by the experimental assistant

Trial Locations

Locations (1)

Shanghai9 Hospital; 🇨🇳 Shanghai, Shanghai, China