Injection of dexmedetomidine into the paravertebral space (where the nerve for the chest section comes out of the vertebra) protects against lung injury during lung surgery when only one lung is being inflated by a breathing machine
ISRCTN | ISRCTN13000406 |
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DOI | https://doi.org/10.1186/ISRCTN13000406 |
Secondary identifying numbers | N/A |
- Submission date
- 15/05/2018
- Registration date
- 21/05/2018
- Last edited
- 22/02/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English summary of protocol
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
Contact information
Scientific
No.7 Weiwu Road, Zhengzhou City, Henan Province,China
Zhengzhou
450003
China
Study information
Study design | Randomized blinded single-centre study |
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Primary study design | Interventional |
Secondary study design | Randomised controlled trial |
Study setting(s) | Hospital |
Study type | Treatment |
Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
Scientific title | Paravertebral dexmedetomidine as an adjuvant to ropivacaine protects against lung injury in the non-ventilated lung during one-lung ventilation |
Study objectives | We hypothesized that paravertebral dexmedetomidine would alleviate lung injury as effectively as intravenous dexmedetomidine. |
Ethics approval(s) | Henan Provincial People's Hospital ethics committee, 18/09/2017 |
Health condition(s) or problem(s) studied | 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 |
Pharmaceutical study type(s) | |
Phase | Not Specified |
Drug / device / biological / vaccine name(s) | 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 study start date | 01/06/2016 |
Completion date | 01/03/2017 |
Eligibility
Participant type(s) | Patient |
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Age group | Adult |
Lower age limit | 18 Years |
Upper age limit | 65 Years |
Sex | Both |
Target number of participants | Six groups of 20 patients |
Key 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 |
Key exclusion criteria | 1. Hypertension 2. Diabetes mellitus 3. Heart diseases 4. Suggestive history of inflammation or coagulation dysfunction |
Date of first enrolment | 01/07/2016 |
Date of final enrolment | 01/02/2017 |
Locations
Countries of recruitment
- China
Study participating centre
China
Sponsor information
Hospital/treatment centre
No.7 Weiwu Road, Zhengzhou City, Henan Province
Zhengzhou
450003
China
https://ror.org/03f72zw41 |
Funders
Funder type
Not defined
No information available
No information available
No information available
Results and Publications
Intention to publish date | 01/08/2018 |
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Individual participant data (IPD) Intention to share | Yes |
IPD sharing plan summary | Available on request |
Publication and dissemination plan | Submitted to BMC Anesthesiology |
IPD sharing plan | The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication. |
Study outputs
Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
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Results article | results | 15/06/2018 | Yes | No |
Editorial Notes
22/02/2019: Internal review.
19/06/2018: Publication reference added.