Physiology Regarding Apnoeic Oxygenation During Nasal Cannula Therapy at Different Flow Rates (PHARAO)

This study compares under controlled conditions if different flow rates affect apnoea time after induction of anaesthesia and how CO2 clearance is influenced. Furthermore, this study enables to quantify the effects of increased pCO2 on vital parameters (e.g. blood pressure, cardiac output, cerebral perfusion, etc.) The investigators will enroll patients undergoing elective surgery at the University Hospital of Bern, Switzerland.

Once anesthesia has been induced, apnoea will set it. During this period, the investigators will compare different methods of apnoeic oxygenation for a maximum of 15 or 30 minutes.

Before discharge, an interview will be conducted, assessing complications and patient satisfaction.

Study Overview

• Status: Completed
• Conditions: Apnoeic Oxygenation
• Intervention / Treatment: Drug: Oxygen 70l/min; Procedure: Videolaryngoscopy; Procedure: Jaw thrust; Drug: Oxygen 10 l/min; Drug: Oxygen 2l/min; Drug: oxygen 0.25l/min

Detailed Description

Eligible, consenting adults will be prepared for general anaesthesia in the usual way consisting of ECG, pulse-oximetry, NarcotrendTM, a venous cannula and an arterial line for continuous blood pressure monitoring. They will receive additional monitoring such as transcutaneous measurement of pCO2 and O2, NIRS, and thoracic electrical impedance tomography (EIT, PulmoVista® 500, Draeger, Luebeck, Germany).

Normal pre-oxygenation (until etO2 is > 90% or time > 3 minutes) will occur. Anaesthesia will be started (= "induction") using Propofol and Fentanyl, using NarcotrendTM to measure depth of anaesthesia. All patients will receive a standard dose of neuromuscular blockage to facilitate airway management and total intravenous anaesthesia will be installed. Using the train of four measurement (TOF) full neuromuscular blockage with Rocuronium will be confirmed every 30 seconds. If necessary, additional dosage of neuromuscular blockage will be administered.

After administration of Rocuronium, possibility of mask ventilation will be confirmed and the sealed envelope with the randomization will then be opened. As a study intervention, the assigned method (HFNCT 70 l/min with either jaw thrust or laryngoscopy, or 10 l/min or 2l/min with the standard nasal canula, or 0.25l/min delivery of oxgen via a tracheal tube) will be installed and mask ventilation discontinued starting the apnoea period. Nasopharyngoscopy (EF-N slim, Acutronic, Hirzel, Switzerland) will confirm upper airway patency. Blood gas analysis will be conducted: baseline awake, start of apnoea, first minute after apnoea start, and every 2 minutes thereafter with a maximum of 75ml 150 ml in total. Other measurements (ECG, pulse-oximetry, blood pressure, NIRS, thoracic EIT, NarcotrendTM, PtcO2, PtcCO2) will be measured continuously over the study period The study intervention will end when one of the following criteria (study end-points) is met: SpO2 <92%, PtcCO2 > 100 mmHg or time > 30 minutes.

When any of the end points is reached, patient-centred standard anaesthesia care will be continued, as planned for the case.

A post-operative interview will be conducted before discharge to evaluate injuries during airway management (bleeding, sore throat, hoarseness), pain, postoperative nausea and vomiting.

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3008
    • University Hospital Inselspital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• > 18 years
• Written informed consent
• Undergoing elective surgery
• Requiring general anesthesia

Exclusion Criteria:

• Any Indication for fibre optic intubation
• Expected impossible mask ventilation
• Known coronary heart disease
• Known heart failure, NYHA classification ≥ 2
• Therapy including β-receptor antagonists
• Arrhythmias in need of anti-arrhythmic therapy (e.g. implanted cardio defibrillator)
• Peripheral occlusive arterial disease, Fontaine ≥ 2b
• Known stenosis of the (common or internal) carotid or vertebral arteries
• BMI > 35kg/m2 and BMI < 16kg/m2
• Hyperkalaemia (K > 5.5 mmol/l)
• Known COPD Gold classification ≥ 2
• Known pulmonary arterial hypertension, systolic > 35mmHg
• Known obstructive sleep apnoea syndrome in need of therapy
• High risk of aspiration (requiring rapid sequence induction intubation)
• Increased intracranial pressure
• Intracranial surgery
• Limited knowledge of German language
• Absent power of judgement
• Anaemia, Hb < 100 g/l
• Pregnancy (pregnancy test in all female patients)
• Neuromuscular disorder
• Known or suspected cervical spine instability
• Nasal obstruction, impossibility of nasal ventilation (both sides patent)
• Allergies or contra-indications to one or more of the used anaesthesia agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control; These patients will receive HFNCT with oxygen 70l/min after induction of general anesthesia. Throughout the entire measurement period of 15 or 30 minutes, continuous videolaryngoscopy will be performed.	Drug: Oxygen 70l/min; HFNCT will be provided using OptiFlow by Fisher&Paykel.; Other Names: high flow; Procedure: Videolaryngoscopy; Continuous
Experimental: High flow; These patients will receive HFNCT with oxygen 70l/min after induction of general anesthesia. Throughout the entire measurement period of 15 or 30 minutes, jaw thrust will be performed.	Drug: Oxygen 70l/min; HFNCT will be provided using OptiFlow by Fisher&Paykel.; Other Names: high flow; Procedure: Jaw thrust; Continuous
Experimental: medium flow; These patients will receive oxygen 10l/min after induction of general anesthesia. Throughout the entire measurement period of 15 or 30 minutes, jaw thrust will be performed.	Procedure: Jaw thrust; Continuous; Drug: Oxygen 10 l/min; Medium flow will be applied with a humidifier (Hudson RCI) and a standard nasal cannula.; Other Names: medium flow
Experimental: low flow; These patients will receive oxygen 2l/min after induction of general anesthesia. Throughout the entire measurement period of 15 or 30 minutes, jaw thrust will be performed.	Procedure: Jaw thrust; Continuous; Drug: Oxygen 2l/min; Low flow will be applied with a humidifier (Hudson RCI) and a standard nasal cannula.; Other Names: low flow
Experimental: minimal flow; These patients will receive a standard tracheal tubes after induction of general anesthesia, with 100% Oxygen and Minimum-flow 0.25l/min. The measurement period is 15 or 30 minutes.	Drug: oxygen 0.25l/min; 0.25l/min of oxygen via an endotracheal tube; Other Names: minimal flow

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCO2 increase in kPa/min	pCO2 will be measured transcutaneously throughout the apnea period	15 or 30 minutes (maximum apnea time)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lowest Saturation	Lowest SpO2 in %	During apnea period (until end-point is met or max. 15 or 30 minutes)
Change in PaO2 in kPa	Blood gas analyses as well as transcutaneous measurement	During apnea period (until end-point is met or max. 15 or 30 minutes)
Change in cardiac output in L/min	Cardiac output will be measured using pulse pressure measurement	During apnea period (until end-point is met or max. 15 or 30 minutes)
Change in cerebral perfusion in %	Near infrared spectroscopy will be measured continuously	During apnea period (until end-point is met or max. 15 or 30 minutes)
Changes in end-expiratory lung impedance	To quantify atelectasis during apnoeic oxygenation	During apnoea time (until end-point is met or max. 15 or 30 minutes)
Change in invasive blood pressure	Measurement of change due to hypercarbia	During apnoea time (until end-point is met or max. 15 or 30 minutes)
Standard monitoring	3 pole ECG	During apnoea time (until end-point is met or max. 15 or 30 minutes)
Depth of anaesthesia	Using Narcotrend-EEG	During apnoea time (until end-point is met or max. 15 or 30 minutes)
Bilateral brain oxygenation	Using NIRS	During apnoea time (until end-point is met or max. 15 or 30 minutes)
Arterial blood gas analyses	pH	At 0, 1, 3, 5, 7, 9, 11, 13 and 15 minutes of apnoea or 0,1,3,5,7,9,13,15,17,19,21,23,25,27,29 and 30 min of apnoea.
Arterial blood gas analyses	pCO2 in mmhg	At 0, 1, 3, 5, 7, 9, 11, 13 and 15 minutes of apnoea or 0,1,3,5,7,9,13,15,17,19,21,23,25,27,29 and 30 min of apnoea.
Arterial blood gas analyses	pO2 in mmhg	At 0, 1, 3, 5, 7, 9, 11, 13 and 15 minutes of apnoea or 0,1,3,5,7,9,13,15,17,19,21,23,25,27,29 and 30 min of apnoea.
Arterial blood gas analyses	SaO2 in %	At 0, 1, 3, 5, 7, 9, 11, 13 and 15 minutes of apnoea or 0,1,3,5,7,9,13,15,17,19,21,23,25,27,29 and 30 min of apnoea.
Arterial blood gas analyses	Potassium in mmol	At 0, 1, 3, 5, 7, 9, 11, 13 and 15 minutes of apnoea or 0,1,3,5,7,9,13,15,17,19,21,23,25,27,29 and 30 min of apnoea.
Arterial blood gas analyses	Bicarbonate in mmol	At 0, 1, 3, 5, 7, 9, 11, 13 and 15 minutes of apnoea or 0,1,3,5,7,9,13,15,17,19,21,23,25,27,29 and 30 min of apnoea.
Postoperative questionnaire	Visual analogue scale (VAS) : pain, nausea, vomiting, feeling worried or anxious, feeling sad or depressed, injuries, discomfort, any complications	Morning of first postoperative day
Standard monitoring	Pulse oximetry SpO2 in %	During apnoea time (until end-point is met or max. 15 or 30 minutes)

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Investigators: Principal Investigator: Lorenz Theiler, PD MD, University Hospital of Bern

Publications and helpful links

General Publications

• Gustafsson IM, Lodenius A, Tunelli J, Ullman J, Jonsson Fagerlund M. Apnoeic oxygenation in adults under general anaesthesia using Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) - a physiological study. Br J Anaesth. 2017 Apr 1;118(4):610-617. doi: 10.1093/bja/aex036.
• Patel A, Nouraei SA. Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE): a physiological method of increasing apnoea time in patients with difficult airways. Anaesthesia. 2015 Mar;70(3):323-9. doi: 10.1111/anae.12923. Epub 2014 Nov 10.
• Riedel T, Burgi F, Greif R, Kaiser H, Riva T, Theiler L, Nabecker S. Changes in lung volume estimated by electrical impedance tomography during apnea and high-flow nasal oxygenation: A single-center randomized controlled trial. PLoS One. 2022 Sep 28;17(9):e0273120. doi: 10.1371/journal.pone.0273120. eCollection 2022.
• Theiler L, Schneeberg F, Riedel T, Kaiser H, Riva T, Greif R. Apnoeic oxygenation with nasal cannula oxygen at different flow rates in anaesthetised patients: a study protocol for a non-inferiority randomised controlled trial. BMJ Open. 2019 Jul 11;9(7):e025442. doi: 10.1136/bmjopen-2018-025442.

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2018
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: March 8, 2018
• First Submitted That Met QC Criteria: March 20, 2018
• First Posted (Actual): March 27, 2018

Study Record Updates

• Last Update Posted (Actual): February 3, 2021
• Last Update Submitted That Met QC Criteria: February 2, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Apnea
• Other Study ID Numbers: 2018-00293

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No