Ignite Creation Date:
2024-05-06 @ 3:10 PM
Last Modification Date:
2024-10-26 @ 1:44 PM
Study NCT ID:
NCT04546932
Status:
COMPLETED
Last Update Posted:
2020-09-14
First Post:
2020-08-20
Brief Title:
Lung-protective Mechanical Ventilation for Abdominal Laparoscopic Surgeries
Sponsor:
Vietnam Military Medical University
Organization:
Vietnam Military Medical University
Study Overview
Official Title:
Lung-protective Mechanical Ventilation for Patients Undergoing Abdominal Laparoscopic Surgeries A Randomized Controlled Trial
Status:
COMPLETED
Status Verified Date:
2020-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This was a double-blind randomized controlled clinical trial 62 patients were randomly assigned to receive either lung-protective ventilation LPV with a tidal volume Vt of 7 mlkg ideal body weight IBW 10 cmH2O positive end-expiratory pressure PEEP combined with regular recruitment maneuvers or conventional ventilation CV with a Vt of 10 mlkg IBW 0 cmH2O in PEEP and no recruitment maneuvers The primary endpoints were the intraoperative fluctuation of Cdyn and Cstat the intra- and postoperative changes in pulmonary oxygenation function including OI A-aO2 The secondary endpoints were the alteration on chest x-ray modified Clinical Pulmonary Infection Score mCPIS and the incidence of PPCs on the first postoperative day
Detailed Description:
Study population We performed a randomized double-blind controlled trial at Vietnam National Cancer Hospital from January 2020 to July 2020 The trial protocol was approved by the medical ethics committee of Vietnam Military Medical University and Vietnam National Cancer Hospital simultaneously written informed consent was obtained from all patients before inclusion
Randomization and blinding technique Participants were randomly assigned to receive either lung-protective ventilation LPV group or conventional ventilation CV group at a ratio of 11 The randomization was performed using the R program with the runif asinteger int and replace functions As a result a list of random numbers was created in each group The patients were numbered according to their orders of hospital registration and then were allocated into the group of their numbers The intervention protocol was stored in sealed opaque numbered envelopes An anesthesiologist who did not involve in the study set the ventilator in accordance with the protocol in the envelopes Another anesthetist who was in charge of the patient collected data during surgery The surgeons taking part in the procedures and patients were not informed of the ventilator setting Physicians in post-anesthesia care unit who were not responsible for intraoperative care carried out the postoperative evaluation The analysis of the postoperative chest X-ray was completed by a radiologist who was not involved in the study
Standard procedure All patients fasted for 12 hours before the procedure but still consumed clear water until 2 hours prior to surgery in order to avoid preoperative dehydration Participants were premedicated with intravenous midazolam 1-2 mg 30 minutes before the surgery In the operating room a radical arterial cannula was inserted to monitor invasive blood pressure collect blood gas sample and measure the pulse pressure variation PPV index to guide intraoperative fluid therapy The ASA standards for monitoring such as pulse oximeter capnography electrocardiography thermometer were applied prior to the insertion of an epidural catheter at level T7-T12 for postoperative analgesia
All patients received intravenous fentanyl 2 µgkg lidocaine 40 mg propofol 2 mgkg and rocuronium 1 mgkg for the induction Intubation was performed 90 seconds after the administration of muscle relaxant and then 8 mg dexamethasone was injected Anesthesia was maintained using sevoflurane of which the concentration was justified to achieve the end-tidal concentration within the range of 14-18 in oxygen and the PRST score less than 3 If the PRST score was greater than 3 then an additional bolus dose of 20-30 mg propofol and 25-50 µg fentanyl was injected along with increasing sevoflurane concentration On the contrary if signs of deep anesthesia were presented PRST score0 blood pressure decreased by more than 20 of the baseline values bradycardia then the sevoflurane concentration was cut down and 100 ml of crystalloid solution was rapidly infused within 2 minutes A bolus dose of 100-200 µg phenylephrine was added if the blood pressure was still less than 20 of the baseline value in spite of these above-mentioned steps Rocuronium was continuously infused at the rate of 10 µgkgmin The solution of bupivacaine 01 combined with fentanyl 2 µgml was infused via the epidural catheter at the rate of 5 mlhour after a loading dose of 5 ml prior to skin incision Normothermia was maintained during surgery The pneumoperitoneum was implemented by CO2 insufflation at a pressure of 12 mmHg with room temperature in all patients The intraoperative fluid was managed based on the goal-directed fluid therapy with a crystalloid solution In brief no additional fluids were provided if PPV was lower than 10 otherwise additional boluses of 250 ml ringer lactate solution were given over 10-15 minutes After each bolus dose PPV was re-assessed and further bolus was administered until reaching a PPV of lower than 10
Intravenous 8 mg ondansetron was injected 30 minutes before the end of surgery to prevent postoperative nausea and vomiting Rocuronium infusion was stopped 30 minutes before abdominal closure The neuromuscular blockade was reversed in the postoperative care unit using intravenous neostigmine 40-60 µgkg combined with atropine 05 mg Patients were extubated when they met the extubation criteria spontaneous tidal volume 6 mlkg and respiratory rate 12-20 breathminute SpO295 normocarbia body temperature 350C positive gag reflexes and ability to follow a verbal command hemodynamic stability without vasopressor support and ability to lift their heads and hold for 30 seconds 23 Postoperative epidural analgesia for 48 hours was executed using bupivacaine 01 combined with fentanyl 2 µgml at a speed of infusion 5-10 mlhour to maintain a visual analogue scale VAS score 3 If the score was greater than 3 then a bolus dose 5 ml of the anesthetic solution was provided along with an increase in the speed of infusion After extubation patients were oxygenated via nasal cannula 3-5 mlminute 1 mlminute raises the FiO2 by 3 to keep the SpO295
Ventilation protocol Mechanical ventilation protocol was performed on the anesthesia machine GE healthcare carestation 620 The patients ideal body weight was predefined according to formula 455 091heightcm-1524 for women or 50 091heightcm-1524 for men In both groups the mechanical ventilation was set up at the volume-controlled mode inspiration to expiration ratio of 12 After being lifted to 100 in the induction period FiO2 was maintained at the level of 40 until extubation Respiratory rate starting with 18 breathsminute was justified to keep the end-tidal carbon dioxide EtCO2 in the normal range of 35-40 mmHg In the CV group the tidal volume was set at 10 mlkg IBW without PEEP and RM In contrast in the LPV group patients were provided with a tidal volume of 7 mlkg IBW and an intraoperative 10 cmH2O in PEEP Simultaneously in the LPV group alveoli were recruited applying a stepwise increase in PEEP from 4 to 10 cmH2O for 3 breaths 10 to 15 cmH2O for 3 breaths and 15 to 20 cmH2O for 10 breaths with maximum PIP 50 cmH2O 24 The recruitment maneuvers were performed right after intubation 30 minutes after CO2 insufflation then every hour and finally before extubation
Data source and collection The demographic characteristics including age gender height weight BMI ASA physical status and history of coexisting diseases and smoking were recorded Vital signs heart rate blood pressure SpO2 EtCO2 core temperature were also recorded at 15 minutes intervals throughout the surgery The volume of intravenous infusion crystalloid colloid solution blood loss urine output total dose of anesthetics fentanyl and muscle relaxant were recorded as well The dynamic compliance Cdyn was measured directly on the ventilator while the static compliance Cstat was calculated in accordance with the pre-defined formula as Vtplateau pressure of the respiratory system - PEEP with the plateau pressure measured during the normal ventilation setting using an inspiratory pause at 10 of the inspiratory time Both types of pulmonary compliance were recorded at H0 after intubation H1 30 minutes after pneumoperitoneum H2 1 hour after pneumoperitoneum H3 2 hours after pneumoperitoneum Hkt 10 minutes after pneumoperitoneum stopped and Hro before extubation Arterial blood samples were withdrawn from the radical arterial cannula for blood gas analysis before induction 1 hour after pneumoperitoneum and day 1 after operation The pulmonary oxygenation index OI and the alveolar-arterial oxygen gradient A-aO2 was calculated respectively as OI PaO2FiO2 and A-aO2 PB-PH2OFiO2 -PaCO2R - PaO2 where PB atmospheric pressure was 760 mmHg PH2O saturated vapor pressure at room temperature was 47 mmHg and the R respiration quotient was 08 SpO2 in the first postoperative day was measured in the room air the nasal oxygen catheter was removed for 10 min with the patient in bed If SpO2 dropped to lower than 90 the measurement was stopped and the supplemental oxygen was immediately re-provided via the nasal cannula
Pre- and postoperative day 1 chest radiography was obtained at the bedside and was analyzed in a blinded way by a radiologist who did not get involved in the study Pathological chest X-ray was defined as the presence of at least one of the following an increase in thickness of the interstitium atelectasis pleural effusion localized or diffused infiltrates and other chest radiological alterations
Modified Clinical Pulmonary Infection Score mCPIS The modified original version of the Clinical Pulmonary Infection Score described by pelosi et al 2008 was applied in the first postoperative day
Incidence of postoperative pulmonary complications PPCs PPCs were defined by the European Perioperative Clinical Outcome EPCO definitions
Primary and secondary endpoints Our hypothesis was that the intraoperative lung-protective ventilation strategy could improve the pulmonary mechanics oxygenation function and ameliorate early postoperative pulmonary complications The primary endpoints were the intraoperative fluctuation of Cdyn and Cstat the intra- and postoperative changes in pulmonary oxygenation function including OI A-aO2 The secondary endpoints were the alteration on chest x-ray mCPIS and the incidence of PPCs on the first postoperative day
Statistical analysis The sample size was calculated in accordance with the formula n 2Cδ2 1 with δµ1-µ2σ where n is the sample size in each group µ1 mean of OI in the LPV group µ2 mean of OI in the CV group σ is the common standard deviation and c 79 for 80 power Based on the study of Xin Pi 2015 whose primary outcome was the OI after 2 hours of ventilation in the two groups was 38221 8803 µg and 45010 7029 µg respectively Replacing µ138221 µ245010 σ8803 in the formula n was equal to 275 for each group which represented that the minimum sample size for each group was at least 28 patients
Statistical analysis was completed using SPSS software version 200 IBM USA on an intention-to-treat basis Whether variables distributed normally was tested with the Kolmogorov-Smirnov and Shapiro-Wilk test Continuous variables were compared applying either Students t-test or the Mann-Whitney U test depending on the characteristics of the distribution of the variable and consequently were presented as mean SD or median and interquartile range 25-75 as appropriate As for categorical variables the χ2 test was employed for comparison and the Fisher exact test was used for small frequencies All the tests were two-tailed and statistical significance was accepted at p005
Randomization and blinding technique Participants were randomly assigned to receive either lung-protective ventilation LPV group or conventional ventilation CV group at a ratio of 11 The randomization was performed using the R program with the runif asinteger int and replace functions As a result a list of random numbers was created in each group The patients were numbered according to their orders of hospital registration and then were allocated into the group of their numbers The intervention protocol was stored in sealed opaque numbered envelopes An anesthesiologist who did not involve in the study set the ventilator in accordance with the protocol in the envelopes Another anesthetist who was in charge of the patient collected data during surgery The surgeons taking part in the procedures and patients were not informed of the ventilator setting Physicians in post-anesthesia care unit who were not responsible for intraoperative care carried out the postoperative evaluation The analysis of the postoperative chest X-ray was completed by a radiologist who was not involved in the study
Standard procedure All patients fasted for 12 hours before the procedure but still consumed clear water until 2 hours prior to surgery in order to avoid preoperative dehydration Participants were premedicated with intravenous midazolam 1-2 mg 30 minutes before the surgery In the operating room a radical arterial cannula was inserted to monitor invasive blood pressure collect blood gas sample and measure the pulse pressure variation PPV index to guide intraoperative fluid therapy The ASA standards for monitoring such as pulse oximeter capnography electrocardiography thermometer were applied prior to the insertion of an epidural catheter at level T7-T12 for postoperative analgesia
All patients received intravenous fentanyl 2 µgkg lidocaine 40 mg propofol 2 mgkg and rocuronium 1 mgkg for the induction Intubation was performed 90 seconds after the administration of muscle relaxant and then 8 mg dexamethasone was injected Anesthesia was maintained using sevoflurane of which the concentration was justified to achieve the end-tidal concentration within the range of 14-18 in oxygen and the PRST score less than 3 If the PRST score was greater than 3 then an additional bolus dose of 20-30 mg propofol and 25-50 µg fentanyl was injected along with increasing sevoflurane concentration On the contrary if signs of deep anesthesia were presented PRST score0 blood pressure decreased by more than 20 of the baseline values bradycardia then the sevoflurane concentration was cut down and 100 ml of crystalloid solution was rapidly infused within 2 minutes A bolus dose of 100-200 µg phenylephrine was added if the blood pressure was still less than 20 of the baseline value in spite of these above-mentioned steps Rocuronium was continuously infused at the rate of 10 µgkgmin The solution of bupivacaine 01 combined with fentanyl 2 µgml was infused via the epidural catheter at the rate of 5 mlhour after a loading dose of 5 ml prior to skin incision Normothermia was maintained during surgery The pneumoperitoneum was implemented by CO2 insufflation at a pressure of 12 mmHg with room temperature in all patients The intraoperative fluid was managed based on the goal-directed fluid therapy with a crystalloid solution In brief no additional fluids were provided if PPV was lower than 10 otherwise additional boluses of 250 ml ringer lactate solution were given over 10-15 minutes After each bolus dose PPV was re-assessed and further bolus was administered until reaching a PPV of lower than 10
Intravenous 8 mg ondansetron was injected 30 minutes before the end of surgery to prevent postoperative nausea and vomiting Rocuronium infusion was stopped 30 minutes before abdominal closure The neuromuscular blockade was reversed in the postoperative care unit using intravenous neostigmine 40-60 µgkg combined with atropine 05 mg Patients were extubated when they met the extubation criteria spontaneous tidal volume 6 mlkg and respiratory rate 12-20 breathminute SpO295 normocarbia body temperature 350C positive gag reflexes and ability to follow a verbal command hemodynamic stability without vasopressor support and ability to lift their heads and hold for 30 seconds 23 Postoperative epidural analgesia for 48 hours was executed using bupivacaine 01 combined with fentanyl 2 µgml at a speed of infusion 5-10 mlhour to maintain a visual analogue scale VAS score 3 If the score was greater than 3 then a bolus dose 5 ml of the anesthetic solution was provided along with an increase in the speed of infusion After extubation patients were oxygenated via nasal cannula 3-5 mlminute 1 mlminute raises the FiO2 by 3 to keep the SpO295
Ventilation protocol Mechanical ventilation protocol was performed on the anesthesia machine GE healthcare carestation 620 The patients ideal body weight was predefined according to formula 455 091heightcm-1524 for women or 50 091heightcm-1524 for men In both groups the mechanical ventilation was set up at the volume-controlled mode inspiration to expiration ratio of 12 After being lifted to 100 in the induction period FiO2 was maintained at the level of 40 until extubation Respiratory rate starting with 18 breathsminute was justified to keep the end-tidal carbon dioxide EtCO2 in the normal range of 35-40 mmHg In the CV group the tidal volume was set at 10 mlkg IBW without PEEP and RM In contrast in the LPV group patients were provided with a tidal volume of 7 mlkg IBW and an intraoperative 10 cmH2O in PEEP Simultaneously in the LPV group alveoli were recruited applying a stepwise increase in PEEP from 4 to 10 cmH2O for 3 breaths 10 to 15 cmH2O for 3 breaths and 15 to 20 cmH2O for 10 breaths with maximum PIP 50 cmH2O 24 The recruitment maneuvers were performed right after intubation 30 minutes after CO2 insufflation then every hour and finally before extubation
Data source and collection The demographic characteristics including age gender height weight BMI ASA physical status and history of coexisting diseases and smoking were recorded Vital signs heart rate blood pressure SpO2 EtCO2 core temperature were also recorded at 15 minutes intervals throughout the surgery The volume of intravenous infusion crystalloid colloid solution blood loss urine output total dose of anesthetics fentanyl and muscle relaxant were recorded as well The dynamic compliance Cdyn was measured directly on the ventilator while the static compliance Cstat was calculated in accordance with the pre-defined formula as Vtplateau pressure of the respiratory system - PEEP with the plateau pressure measured during the normal ventilation setting using an inspiratory pause at 10 of the inspiratory time Both types of pulmonary compliance were recorded at H0 after intubation H1 30 minutes after pneumoperitoneum H2 1 hour after pneumoperitoneum H3 2 hours after pneumoperitoneum Hkt 10 minutes after pneumoperitoneum stopped and Hro before extubation Arterial blood samples were withdrawn from the radical arterial cannula for blood gas analysis before induction 1 hour after pneumoperitoneum and day 1 after operation The pulmonary oxygenation index OI and the alveolar-arterial oxygen gradient A-aO2 was calculated respectively as OI PaO2FiO2 and A-aO2 PB-PH2OFiO2 -PaCO2R - PaO2 where PB atmospheric pressure was 760 mmHg PH2O saturated vapor pressure at room temperature was 47 mmHg and the R respiration quotient was 08 SpO2 in the first postoperative day was measured in the room air the nasal oxygen catheter was removed for 10 min with the patient in bed If SpO2 dropped to lower than 90 the measurement was stopped and the supplemental oxygen was immediately re-provided via the nasal cannula
Pre- and postoperative day 1 chest radiography was obtained at the bedside and was analyzed in a blinded way by a radiologist who did not get involved in the study Pathological chest X-ray was defined as the presence of at least one of the following an increase in thickness of the interstitium atelectasis pleural effusion localized or diffused infiltrates and other chest radiological alterations
Modified Clinical Pulmonary Infection Score mCPIS The modified original version of the Clinical Pulmonary Infection Score described by pelosi et al 2008 was applied in the first postoperative day
Incidence of postoperative pulmonary complications PPCs PPCs were defined by the European Perioperative Clinical Outcome EPCO definitions
Primary and secondary endpoints Our hypothesis was that the intraoperative lung-protective ventilation strategy could improve the pulmonary mechanics oxygenation function and ameliorate early postoperative pulmonary complications The primary endpoints were the intraoperative fluctuation of Cdyn and Cstat the intra- and postoperative changes in pulmonary oxygenation function including OI A-aO2 The secondary endpoints were the alteration on chest x-ray mCPIS and the incidence of PPCs on the first postoperative day
Statistical analysis The sample size was calculated in accordance with the formula n 2Cδ2 1 with δµ1-µ2σ where n is the sample size in each group µ1 mean of OI in the LPV group µ2 mean of OI in the CV group σ is the common standard deviation and c 79 for 80 power Based on the study of Xin Pi 2015 whose primary outcome was the OI after 2 hours of ventilation in the two groups was 38221 8803 µg and 45010 7029 µg respectively Replacing µ138221 µ245010 σ8803 in the formula n was equal to 275 for each group which represented that the minimum sample size for each group was at least 28 patients
Statistical analysis was completed using SPSS software version 200 IBM USA on an intention-to-treat basis Whether variables distributed normally was tested with the Kolmogorov-Smirnov and Shapiro-Wilk test Continuous variables were compared applying either Students t-test or the Mann-Whitney U test depending on the characteristics of the distribution of the variable and consequently were presented as mean SD or median and interquartile range 25-75 as appropriate As for categorical variables the χ2 test was employed for comparison and the Fisher exact test was used for small frequencies All the tests were two-tailed and statistical significance was accepted at p005
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None