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
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
Not Specified
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
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