Condition category
Respiratory
Date applied
15/05/2018
Date assigned
21/05/2018
Last edited
19/06/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
During lung surgery, the entry of air is blocked to the diseased lung so that it is not moving during the operation. The healthy lung is supplied with air using a ventilator (breathing machine). In a small proportion of patients, the non-ventilated lung can become swollen and stop working properly in the days after surgery. The risk of death in these patients is high. This study aims to investigate whether injection of the sedative (consciousness-reducing) drug dexmedetomidine into the paravertebral space (space next to a vertebra where a nerve exits the spinal column) can reduce swelling, inflammation and cell death in the non-ventilated lung.

Who can participate?
Adults aged 18 to 65 years who are having surgery to remove lung cancer.

What does the study involve?
The patients will receive intravenous (by vein) saline (salt solution), intravenous dexmedetomidine, or paravertebral injections of the anaesthetic (sensation-blocking) drug ropivacaine alone or paravertebral ropivacaine in combination with one of three doses of dexmedetomidine. The cancer will be removed as usual and samples of the lung tissue containing the tumour will be tested for signs of swelling, inflammation and cell death.

What are the possible benefits and risks of participating?
There are no known additional risks or benefits to participating. Patients will receive surgery as usual. Ropivacaine and dexmedetomidine are safe and widely-used drugs.

Where is the study run from?
Henan Provincial People's Hospital

When is the study starting and how long is it expected to run for?
July 2016 to March 2017

Who is funding the study?
The Natural Science Foundation of China and Henan Province, the Science and Technology Project of Henan Province and the Medical Science Research Project of Henan Province

Who is the main contact?
Prefessor Jiaqiang Zhang
mazuizhang@163.com

Trial website

Contact information

Type

Scientific

Primary contact

Prof Jiaqiang Zhang

ORCID ID

Contact details

No.7 Weiwu Road
Zhengzhou City
Henan Province,China
Zhengzhou
450003
China

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Paravertebral dexmedetomidine as an adjuvant to ropivacaine protects against lung injury in the non-ventilated lung during one-lung ventilation

Acronym

Study hypothesis

We hypothesized that paravertebral dexmedetomidine would alleviate lung injury as effectively as intravenous dexmedetomidine.

Ethics approval

Henan Provincial People's Hospital ethics committee, 18/09/2017

Study design

Randomized blinded single-centre study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Acute lung injury following selective radical resection for pulmonary carcinoma

Intervention

In total, 120 patients who underwent elective radical resection of pulmonary carcinoma were randomly assigned to one of six groups (n=20): normal saline (C group), ropivacaine (R group), intravenous dexmedetomidine (Div group), 0.5 μg/kg paravertebral dexmedetomidine as an adjuvant to ropivacaine (RD0.5 group), 1.0 μg/kg paravertebral dexmedetomidine as an adjuvant to ropivacaine (RD1.0 group), or 2.0 μg/kg paravertebral dexmedetomidine as an adjuvant to ropivacaine (RD2.0 group). Thoracic paravertebral block (TPVB) was induced under ultrasound guidance (S-Nerve, Fujifilm Sonosite, Inc). TPVB was not administered in the C or Div groups. Patients in the C group received only normal saline as a control; patients in the R group received a total volume of 20 ml 0.5% ropivacaine for the TPVB (cat No. NATM, AstraZeneca, Sweden), with 10 ml injected at each puncture point; patients in the Div group received a total dosage of 0.5 μg/kg intravenous dexmedetomidine (cat No. 20160301, Jiangsu Nhwa Pharmaceutical Co., Ltd, China) over 10 min; and patients in the RD0.5, RD1.0 and RD2.0 groups received ropivacaine (final concentration of 0.5%) mixed with 0.5 μg/kg, 1.0 μg/kg and 2.0 μg/kg dexmedetomidine, respectively, as an adjuvant. Only one anesthesiologist who was blinded to the group allocation was involved in the preoperative management.

Intervention type

Drug

Phase

Drug names

dexmedetomidine, ropivacaine

Primary outcome measure

Lung injury score.
Method: The histological changes of the fixed lung tissue were evaluated by an independent pathologist who was blinded to the study protocols. The lung tissues were embedded in paraffin wax, sectioned (5 μm), and then stained with hematoxylin and eosin. The severity of lung injury was quantified using the 4-point scoring system, which included pulmonary interstitial edema, alveolar edema, alveolar congestion and neutrophil infiltration. Scoring standards were as follows: 0, no change or very mild changes; 1, mild changes; 2, moderate changes; and 3, severe changes. The average lung injury score from three adjacent slices was evaluated. The summation of four scores was recognized as the final lung injury score.
Time point: Immediately after the tumor tissue was excised

Secondary outcome measures

1. Hemodynamics (heart rate, mean arterial pressure) measured using the ECG monitor and invasive arterial pressure system. Time points: preoperative (Pre) - 15 min after admission to the operating room without any drug treatment, two-lung ventilation (TLV) - immediately before initiation of one-lung ventilation (OLV), OLV1 - 15 min after initiation of OLV, OLV2 - 30 min after initiation of OLV, OLV3 - immediately before the tumor tissue was excised
2. Apoptosis measured using a TUNEL assay employed according to the manufacturer’s protocol of an in situ cell death detection kit-POD (cat no. 11684817910; Roche, Basel, Switzerland). Apoptotic cells were indicated by brown-yellow granules in the cytoplasm. The number of apoptotic cells in random fields of view (magnification, x400) was calculated. The apoptosis index (AI; %) was expressed as follows: the number of apoptotic cells/the total number of cells x100. The slides were prepared immediately after tumor excision.
3. Inflammatory cytokines measured by enzyme-linked immunosorbent assay (ELISA). Lung tissues were prepared as 10% tissue homogenates and centrifuged at 3000 rpm at 4°C for 10 min. The supernatant was collected for further analysis. The concentrations of TNF-α and IL-6 in lung tissues were measured according to the manufacturer’s instructions using ELISA kits (Nanjing Keygen Biotech Co., Ltd.). Absorbance at 450 nm (OD 450) was determined using a microplate reader. The tissues were prepared immediately after tumor excision.


Overall trial start date

01/06/2016

Overall trial end date

01/03/2017

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. American Society of Anesthesiologists (ASA) physician status I or II
2. Aged 18-65 years
3. Scheduled for selective radical resection of pulmonary carcinoma

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Six groups of 20 patients

Participant exclusion criteria

1. Hypertension
2. Diabetes mellitus
3. Heart diseases
4. Suggestive history of inflammation or coagulation dysfunction

Recruitment start date

01/07/2016

Recruitment end date

01/02/2017

Locations

Countries of recruitment

China

Trial participating centre

Henan Provincial People's Hospital
450003
China

Sponsor information

Organisation

Henan Provincial People's Hospital

Sponsor details

No.7 Weiwu Road
Zhengzhou City
Henan Province
Zhengzhou
450003
China

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Not defined

Funder name

The Natural Science Foundation of China and Henan Province (U1404807)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Science and Technology Project of Henan Province (182102310167)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Medical Science Research Project of Henan Province (201602227)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Submitted to BMC Anesthesiology

IPD sharing statement:
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.

Intention to publish date

01/08/2018

Participant level data

Available on request

Basic results (scientific)

Publication list

2018 results in: https://www.ncbi.nlm.nih.gov/pubmed/29907082

Publication citations

Additional files

Editorial Notes

19/06/2018: Publication reference added.