Ignite Creation Date:
2024-10-25 @ 7:59 PM
Last Modification Date:
2024-10-26 @ 3:42 PM
Study NCT ID:
NCT06637280
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-09-29
Brief Title:
High - Flow Nasal Cannula Versus Conventional Nasal Cannula During Endobronchial Ultrasound Procedure
Sponsor:
None
Organization:
None
Study Overview
Official Title:
HFNC Versus Conventional Nasal Cannula During EBUS Procedure a Randomised Controlled Trial
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
EBUS bronchoscopy is performed in most centers under local anesthesia and moderate sedation Both the bronchoscopy itself and the sedation can lead to decreased ventilation and a drop in oxygen saturation in the body Typically oxygen is administered during the procedure via a nasal cannula at a flow rate of 6lmin The aim of the study is to compare a new method - a nasal cannula with high flow - to the standard cannula The primary objective is to demonstrate that the new method is more effective at preventing desaturation during the procedure Patients will be randomized into two groups before bronchoscopy and monitored The bronchoscopy will be performed in the same way for both groups The only difference between the groups will be in the method of oxygen administration during EBUS bronchoscopy
Detailed Description:
Introduction
1 EBUS - bronchoscopy From a physiological point of view bronchoscopy is an introduction of a foreign body into the airway Response mechanisms include laryngospasm bronchospasm cough increased secretion of bronchial mucus and reduced depth of breathing Sympathetic response with increased heart rate and blood pressure is common even before the procedure while the patient is being prepared on the examination table The bronchoscope occupies 10 to 15 of the cross-sectional area in the major airways and increases air flow resistance Suction applied during the procedure causes air stealing through the working channel of the bronchoscope which reduces end inspiratory and expiratory volumes leading to alveolar de-recruitment with increased intrapulmonary shunting consequently
EBUS bronchoscopy is associated with prolonged procedure time increased airway contact a thicker instrument and multiple needle punctures through the tracheal andor bronchial wall All these factors cause additional stress to the patient and require additional local anesthesia and deeper level of sedation
2 Sedation Although topical anesthesia of the upper airways vocal cords trachea and bronchi enables a tolerable bronchoscopic procedure a moderate level of sedation during bronchoscopy is currently the golden standard Use of sedation facilitates the passage through the vocal cords inhibits airway protective reflexes and increases patient safety 23 In combination with physiological responses to bronchoscopy which increase oxygen demand sedatives used during bronchoscopy reduce respiratory drive and further compromise patients especially those with chronic diseases When it occurs hypoxemia can induce periprocedural arrythmias and ischemia therefore should be generally avoided and if encountered must be reverted quickly 4 An oxygenation strategy with appropriate oxygen supplementation is therefore required during most bronchoscopic procedures
3 Oxygen supplementation Low flow oxygen up to 6 liters per minute applied through a nasal catheter is the most often used method for oxygen supplementation during flexible bronchoscopy Inspired oxygen fraction FiO2 can reach up to 45 but cannot be reliably predicted and may not be enough in all cases
High flow nasal cannula HFNC a device first introduced in neonates and pediatric care is currently used in a wide range of indications in adult respiratory and critical care medicine 5-7 It is a relatively new method in bronchoscopy with several notable theoretical advantages over low flow oxygen via conventional nasal cannula CNC
High flow up to 60 liters per minute ensures a more stable FiO2 and better matches the increased patients inspiratory flow
High flow generates a small positive expiratory airway pressure up to 5 cm H2O which could stabilize the upper airways during sedation and have a beneficial effect in the lower airways
High flow reduces dead space in the upper airways and increases alveolar ventilation
CPAP and NIV can provide similar beneficial effects but their use is challenging because they require a close-fitting facial mask which limits the use of a bronchoscope aspiration of secretions from the upper airways pharynx or oral cavity and expectoration of sputum
4 Previous studies on HFNC
A recent meta-analysis which included six randomized controlled trials found that patients who underwent bronchoscopy with the use of HFNC experienced less hypoxemic events and desaturations had fewer procedural interruptions and pneumothorax compared to patients supplemented with CNC 10 The three studies which evaluated HFNC during EBUS all showed that HFNC is more effective than CNC during the procedure and that HFNC can be considered an alternative to CNC However the studies had several important limitations such as a low number of patients included with a historical control Takakuwa O et al a large difference in FiO2 between trial groups 2Lmin in the CNC vs 100 FiO2 and 70Lmin flow rate in the HFNC group Irfan et al and lack of assessment of CO2 levels during the procedure Ulcar et al Nevertheless conclusions suggested that HFNC is sufficiently safe and provides adequate oxygenation for most of bronchoscopy examinations including EBUS 89
5 Study questions
Our hypothesis is that HFNC provides better control over hypoxemia during EBUS-TBNA procedure than CNC The primary outcome of the study is therefore proportion of patients with successfully controlled hypoxemia during EBUS TBNA in each arm Secondary outcomes are incidence of complications in each arm number of hypoxemic events mean lowest oxygen saturation during procedure average saturation drop in saturation pulse rate blood pressure incidence of arrhythmia number of patients who experienced mild moderate or severe hypoxemia number of patients who required escalation of the support and which support is effective what are risk factors for desaturation
Methods
1 Study design and study population
The study is designed as multicenter randomized controlled prospective trial Study will enroll patients who need EBUS -TBNA procedure with sampling of mediastinal lymph nodes for diagnosis andor staging
Patients will be recruited from four university hospitals in Slovenia Croatia Portugal and Greece
Study was approved by The National Medical Ethics Committee of the Republic of Slovenia and registered as 0120-29420233
2 Recruitment consensus and randomization
Bronchoscopy coordinator will screen the scheduled patients and notify study investigator about eligible patients Study investigator will explain the study to eligible patients and obtain informed consents Inclusion and exclusion criteria will be checked on the day of examination from the data routinely obtained before procedure including laboratory data
Patients will be randomized in bronchoscopy suite according to allocation group written in sequentially numbered sealed and opaque envelopes Envelopes will be prepared by independent statistician on the basis of block randomization with the block size of 4
3 Bronchoscopy and sedation
Topical anesthesia with lidocaine will be provided routinely before insertion of the bronchoscope Patients will be sedated by bedside anesthesiologist by combination of midazolam fentanyl and propofol The depth of sedation will be assessed using Modified Observers Assessment of Alertness Sedation scale MOAAS The level of sedation will be maintained between 1 and 2 throughout the procedure Patients will be monitored by BIS monitor for further analysis and comparison
The standard group of patients will receive oxygen through double-prong nasal cannula with the oxygen flow set to 6 liters per minute which corresponds to FiO2 45 The HFNC group will receive mixture of oxygen and air at FiO2 45 with initial flow of 60 liters per minute pre-warmed to 37 degrees of Celsius Nasal cannula will be chosen according to the patients face size Before procedure patients from both groups will be tested with HFNC with the flow of 60 lmin if they are able tolerate it
EBUS bronchoscope will be inserted through the oral bite block by experienced bronchoscopist and the whole procedure will be conducted according to ERS recommendations After systematical evaluation of mediastinal and hilar lymph nodes EBUS TBNAs will be performed according to the individual procedure plan
Patients will be monitored by continuous pulse oximetry periodical blood pressure measurements ECG and BIS
4 Hypoxemia escalation protocol complications and termination criteria
Oxygen will be delivered to the patient according to the allocation group 6lmin O2 CNC or 45 FiO2 60 lmin HFNC If desaturation occurs defined as SpO290 for more than 10s the patients will be approached according to the escalation protocol Figure 1
1 jaw thrust maneuver
2 patients in CNC group will be switched to 45 FiO2 60 lmin HFNC
3 patients with 45 FiO2 60 lmin HFNC will be switched to 100 FiO2
4 patients with HFNC failure will be switched to advanced respiratory support balloon ventilation laryngeal mask intubation reversal of sedation
In the case of moderate hypoxemia there will be temporal suspension of the bronchoscopy but in the case of severe hypoxemia the termination of the procedure will be considered if there is no immediate improvement after escalation of ventilatory support
Procedure will be terminated also in the case of other severe adverse events as are hemodynamic instability myocardial ischemia or pneumothorax Resuscitation equipment will be prepared on dedicated medical cart inside the bronchoscopy suite Any patient with adverse event will be monitored until complete recovery Alderete score 9 or more
Complications relevant to the decisions and study outcomes are defined as 1
Desaturation 90 for more than 10s
Moderate desaturation 75 SpO2 90 less than 60s
Severe desaturation 75 or 75 SpO2 90 more than 60s
Tachycardia 100 or 25
Bradycardia 50 or -25
Hypertension 25
Hypotension 90mmHg or -25
5 Data collection
Demographic data of patients age gender height weight BMI STOP-BANG score ASA score and laboratory results lung function testing relevant for the study will be collected before the procedure During and after the procedure there will be continuous SpO2 pulse rate ECG or periodical blood pressure monitoring of vital signs and depth of the sedation BIS MOAAS The starting point of the procedure T0 is defined as the time immediately prior sedatives are given to the patient T1 is the time point where bronchoscope is inserted and Tend is the end of the procedure when bronchoscope is withdrawn Venous blood for pCO2 analysis will be drawn at T0 on the procedure table before sedation and at Tend withdrawal of the bronchoscope
Timing and duration of desaturation the lowest SpO2 and all treatment escalations will be recorded as well as other possible complications
6 Sample size
The protocol is designed to show a superiority of HFNC over CNC According to pulled data in recently published meta-analysis we expect a 12 desaturation rate in the HFNC group and a 34 desaturation rate in CNC group The sample size should be 112 with a confidence level alpha of 95 power 1-beta of 80 With expected drop out of 25 the final number of included participants is set to 150 A web-based application was used for sample size calculation httpsclincalccomstatssamplesizeaspx
7 Statistical analysis
Data will be collected in specially designed case report formulars CRF and analyzed by GraphPad Prism 95 software Boston MA Categorical variables will be presented as percentages and analyzed by chi-square test Numerical variables will be presented as mean and standard deviation or median and ranges Distribution will be tested by the Kolmogorov - Smirnov test and further analysis performed by t-test or Mann Whitney test depending on normality of distribution Two-sided p-value will be regarded as statistically significant if 005
8 Patient and public involvement
Patients and public were not involved in the study design
References
1 Mason KP Green SM Piacevoli Q International Sedation Task Force Adverse event reporting tool to standardize the reporting and tracking of adverse events during procedural sedation a consensus document from the World SIVA International Sedation Task Force Br J Anaesth 2012 Jan108113-20 doi 101093bjaaer407 PMID 22157446
2 Sazak H Tunç M Alagöz A Pehlivanoğ Lu P Demirci NY Alıcı İO et al Assessment of perianesthesic data in subjects undergoing endobronchial ultrasound-guided transbronchial needle aspiration Respir Care 2015604567-76
3 Douglas N Ng I Nazeem F Lee K Mezzavia P Krieser R et al A randomised controlled trial comparing high-flow nasal oxygen with standard management for conscious sedation during bronchoscopy Anaesthesia 2018732169-76
4 Du Rand IA Blaikley J Booton R Chaudhuri N Gupta V Khalid S et al British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults accredited by NICE Thorax 2013 Aug68 Suppl 1i1-44
5 Sreenan C Lemke RP Hudson-Mason A Osiovich H High-Flow Nasal Cannulae in the Management of Apnea of Prematurity A Comparison With Conventional Nasal Continuous Positive Airway Pressure Pediatrics Internet 2001 May 110751081-3 Available from httpsdoiorg101542peds10751081
6 Roca O Riera J Torres F Masclans JR High-Flow Oxygen Therapy in Acute Respiratory Failure Respir Care Internet 2010 Apr 1554408 LP - 413 Available from httprcrcjournalcomcontent554408abstract
7 Nishimura M High-Flow Nasal Cannula Oxygen Therapy Devices Respir Care Internet 2019 Jun 1646735 LP - 742 Available from httprcrcjournalcomcontent646735abstract
8 Takakuwa O Oguri T Asano T Fukuda S Kanemitsu Y Uemura T et al Prevention of hypoxemia during endobronchial ultrasound-guided transbronchial needle aspiration Usefulness of high-flow nasal cannula Respir Investig 2018565418-23
9 Irfan M Ahmed M Breen D Assessment of High Flow Nasal Cannula Oxygenation in Endobronchial Ultrasound Bronchoscopy A Randomized Controlled Trial J Bronchol Interv Pulmonol 2021282130-7
10 Su C-L Chiang L-L Tam K-W Chen T-T Hu M-C 2021 High-flow nasal cannula for reducing hypoxemic events in patients undergoing bronchoscopy A systematic review and meta- analysis of randomized trials PLoS ONE 1612 e0260716 httpsdoiorg101371journal pone0260716
1 EBUS - bronchoscopy From a physiological point of view bronchoscopy is an introduction of a foreign body into the airway Response mechanisms include laryngospasm bronchospasm cough increased secretion of bronchial mucus and reduced depth of breathing Sympathetic response with increased heart rate and blood pressure is common even before the procedure while the patient is being prepared on the examination table The bronchoscope occupies 10 to 15 of the cross-sectional area in the major airways and increases air flow resistance Suction applied during the procedure causes air stealing through the working channel of the bronchoscope which reduces end inspiratory and expiratory volumes leading to alveolar de-recruitment with increased intrapulmonary shunting consequently
EBUS bronchoscopy is associated with prolonged procedure time increased airway contact a thicker instrument and multiple needle punctures through the tracheal andor bronchial wall All these factors cause additional stress to the patient and require additional local anesthesia and deeper level of sedation
2 Sedation Although topical anesthesia of the upper airways vocal cords trachea and bronchi enables a tolerable bronchoscopic procedure a moderate level of sedation during bronchoscopy is currently the golden standard Use of sedation facilitates the passage through the vocal cords inhibits airway protective reflexes and increases patient safety 23 In combination with physiological responses to bronchoscopy which increase oxygen demand sedatives used during bronchoscopy reduce respiratory drive and further compromise patients especially those with chronic diseases When it occurs hypoxemia can induce periprocedural arrythmias and ischemia therefore should be generally avoided and if encountered must be reverted quickly 4 An oxygenation strategy with appropriate oxygen supplementation is therefore required during most bronchoscopic procedures
3 Oxygen supplementation Low flow oxygen up to 6 liters per minute applied through a nasal catheter is the most often used method for oxygen supplementation during flexible bronchoscopy Inspired oxygen fraction FiO2 can reach up to 45 but cannot be reliably predicted and may not be enough in all cases
High flow nasal cannula HFNC a device first introduced in neonates and pediatric care is currently used in a wide range of indications in adult respiratory and critical care medicine 5-7 It is a relatively new method in bronchoscopy with several notable theoretical advantages over low flow oxygen via conventional nasal cannula CNC
High flow up to 60 liters per minute ensures a more stable FiO2 and better matches the increased patients inspiratory flow
High flow generates a small positive expiratory airway pressure up to 5 cm H2O which could stabilize the upper airways during sedation and have a beneficial effect in the lower airways
High flow reduces dead space in the upper airways and increases alveolar ventilation
CPAP and NIV can provide similar beneficial effects but their use is challenging because they require a close-fitting facial mask which limits the use of a bronchoscope aspiration of secretions from the upper airways pharynx or oral cavity and expectoration of sputum
4 Previous studies on HFNC
A recent meta-analysis which included six randomized controlled trials found that patients who underwent bronchoscopy with the use of HFNC experienced less hypoxemic events and desaturations had fewer procedural interruptions and pneumothorax compared to patients supplemented with CNC 10 The three studies which evaluated HFNC during EBUS all showed that HFNC is more effective than CNC during the procedure and that HFNC can be considered an alternative to CNC However the studies had several important limitations such as a low number of patients included with a historical control Takakuwa O et al a large difference in FiO2 between trial groups 2Lmin in the CNC vs 100 FiO2 and 70Lmin flow rate in the HFNC group Irfan et al and lack of assessment of CO2 levels during the procedure Ulcar et al Nevertheless conclusions suggested that HFNC is sufficiently safe and provides adequate oxygenation for most of bronchoscopy examinations including EBUS 89
5 Study questions
Our hypothesis is that HFNC provides better control over hypoxemia during EBUS-TBNA procedure than CNC The primary outcome of the study is therefore proportion of patients with successfully controlled hypoxemia during EBUS TBNA in each arm Secondary outcomes are incidence of complications in each arm number of hypoxemic events mean lowest oxygen saturation during procedure average saturation drop in saturation pulse rate blood pressure incidence of arrhythmia number of patients who experienced mild moderate or severe hypoxemia number of patients who required escalation of the support and which support is effective what are risk factors for desaturation
Methods
1 Study design and study population
The study is designed as multicenter randomized controlled prospective trial Study will enroll patients who need EBUS -TBNA procedure with sampling of mediastinal lymph nodes for diagnosis andor staging
Patients will be recruited from four university hospitals in Slovenia Croatia Portugal and Greece
Study was approved by The National Medical Ethics Committee of the Republic of Slovenia and registered as 0120-29420233
2 Recruitment consensus and randomization
Bronchoscopy coordinator will screen the scheduled patients and notify study investigator about eligible patients Study investigator will explain the study to eligible patients and obtain informed consents Inclusion and exclusion criteria will be checked on the day of examination from the data routinely obtained before procedure including laboratory data
Patients will be randomized in bronchoscopy suite according to allocation group written in sequentially numbered sealed and opaque envelopes Envelopes will be prepared by independent statistician on the basis of block randomization with the block size of 4
3 Bronchoscopy and sedation
Topical anesthesia with lidocaine will be provided routinely before insertion of the bronchoscope Patients will be sedated by bedside anesthesiologist by combination of midazolam fentanyl and propofol The depth of sedation will be assessed using Modified Observers Assessment of Alertness Sedation scale MOAAS The level of sedation will be maintained between 1 and 2 throughout the procedure Patients will be monitored by BIS monitor for further analysis and comparison
The standard group of patients will receive oxygen through double-prong nasal cannula with the oxygen flow set to 6 liters per minute which corresponds to FiO2 45 The HFNC group will receive mixture of oxygen and air at FiO2 45 with initial flow of 60 liters per minute pre-warmed to 37 degrees of Celsius Nasal cannula will be chosen according to the patients face size Before procedure patients from both groups will be tested with HFNC with the flow of 60 lmin if they are able tolerate it
EBUS bronchoscope will be inserted through the oral bite block by experienced bronchoscopist and the whole procedure will be conducted according to ERS recommendations After systematical evaluation of mediastinal and hilar lymph nodes EBUS TBNAs will be performed according to the individual procedure plan
Patients will be monitored by continuous pulse oximetry periodical blood pressure measurements ECG and BIS
4 Hypoxemia escalation protocol complications and termination criteria
Oxygen will be delivered to the patient according to the allocation group 6lmin O2 CNC or 45 FiO2 60 lmin HFNC If desaturation occurs defined as SpO290 for more than 10s the patients will be approached according to the escalation protocol Figure 1
1 jaw thrust maneuver
2 patients in CNC group will be switched to 45 FiO2 60 lmin HFNC
3 patients with 45 FiO2 60 lmin HFNC will be switched to 100 FiO2
4 patients with HFNC failure will be switched to advanced respiratory support balloon ventilation laryngeal mask intubation reversal of sedation
In the case of moderate hypoxemia there will be temporal suspension of the bronchoscopy but in the case of severe hypoxemia the termination of the procedure will be considered if there is no immediate improvement after escalation of ventilatory support
Procedure will be terminated also in the case of other severe adverse events as are hemodynamic instability myocardial ischemia or pneumothorax Resuscitation equipment will be prepared on dedicated medical cart inside the bronchoscopy suite Any patient with adverse event will be monitored until complete recovery Alderete score 9 or more
Complications relevant to the decisions and study outcomes are defined as 1
Desaturation 90 for more than 10s
Moderate desaturation 75 SpO2 90 less than 60s
Severe desaturation 75 or 75 SpO2 90 more than 60s
Tachycardia 100 or 25
Bradycardia 50 or -25
Hypertension 25
Hypotension 90mmHg or -25
5 Data collection
Demographic data of patients age gender height weight BMI STOP-BANG score ASA score and laboratory results lung function testing relevant for the study will be collected before the procedure During and after the procedure there will be continuous SpO2 pulse rate ECG or periodical blood pressure monitoring of vital signs and depth of the sedation BIS MOAAS The starting point of the procedure T0 is defined as the time immediately prior sedatives are given to the patient T1 is the time point where bronchoscope is inserted and Tend is the end of the procedure when bronchoscope is withdrawn Venous blood for pCO2 analysis will be drawn at T0 on the procedure table before sedation and at Tend withdrawal of the bronchoscope
Timing and duration of desaturation the lowest SpO2 and all treatment escalations will be recorded as well as other possible complications
6 Sample size
The protocol is designed to show a superiority of HFNC over CNC According to pulled data in recently published meta-analysis we expect a 12 desaturation rate in the HFNC group and a 34 desaturation rate in CNC group The sample size should be 112 with a confidence level alpha of 95 power 1-beta of 80 With expected drop out of 25 the final number of included participants is set to 150 A web-based application was used for sample size calculation httpsclincalccomstatssamplesizeaspx
7 Statistical analysis
Data will be collected in specially designed case report formulars CRF and analyzed by GraphPad Prism 95 software Boston MA Categorical variables will be presented as percentages and analyzed by chi-square test Numerical variables will be presented as mean and standard deviation or median and ranges Distribution will be tested by the Kolmogorov - Smirnov test and further analysis performed by t-test or Mann Whitney test depending on normality of distribution Two-sided p-value will be regarded as statistically significant if 005
8 Patient and public involvement
Patients and public were not involved in the study design
References
1 Mason KP Green SM Piacevoli Q International Sedation Task Force Adverse event reporting tool to standardize the reporting and tracking of adverse events during procedural sedation a consensus document from the World SIVA International Sedation Task Force Br J Anaesth 2012 Jan108113-20 doi 101093bjaaer407 PMID 22157446
2 Sazak H Tunç M Alagöz A Pehlivanoğ Lu P Demirci NY Alıcı İO et al Assessment of perianesthesic data in subjects undergoing endobronchial ultrasound-guided transbronchial needle aspiration Respir Care 2015604567-76
3 Douglas N Ng I Nazeem F Lee K Mezzavia P Krieser R et al A randomised controlled trial comparing high-flow nasal oxygen with standard management for conscious sedation during bronchoscopy Anaesthesia 2018732169-76
4 Du Rand IA Blaikley J Booton R Chaudhuri N Gupta V Khalid S et al British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults accredited by NICE Thorax 2013 Aug68 Suppl 1i1-44
5 Sreenan C Lemke RP Hudson-Mason A Osiovich H High-Flow Nasal Cannulae in the Management of Apnea of Prematurity A Comparison With Conventional Nasal Continuous Positive Airway Pressure Pediatrics Internet 2001 May 110751081-3 Available from httpsdoiorg101542peds10751081
6 Roca O Riera J Torres F Masclans JR High-Flow Oxygen Therapy in Acute Respiratory Failure Respir Care Internet 2010 Apr 1554408 LP - 413 Available from httprcrcjournalcomcontent554408abstract
7 Nishimura M High-Flow Nasal Cannula Oxygen Therapy Devices Respir Care Internet 2019 Jun 1646735 LP - 742 Available from httprcrcjournalcomcontent646735abstract
8 Takakuwa O Oguri T Asano T Fukuda S Kanemitsu Y Uemura T et al Prevention of hypoxemia during endobronchial ultrasound-guided transbronchial needle aspiration Usefulness of high-flow nasal cannula Respir Investig 2018565418-23
9 Irfan M Ahmed M Breen D Assessment of High Flow Nasal Cannula Oxygenation in Endobronchial Ultrasound Bronchoscopy A Randomized Controlled Trial J Bronchol Interv Pulmonol 2021282130-7
10 Su C-L Chiang L-L Tam K-W Chen T-T Hu M-C 2021 High-flow nasal cannula for reducing hypoxemic events in patients undergoing bronchoscopy A systematic review and meta- analysis of randomized trials PLoS ONE 1612 e0260716 httpsdoiorg101371journal pone0260716
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None