Clinical trial NCT04049240: Effect of HFNO on Spontaneous Ventilation in Obese Patients During Analgo-sedation for Vitrectomy
Official title: Effect of High-flow vs. Low-flow Nasal Oxygenation on Spontaneous Ventilation in Obese Adult Patients During Analgo-sedation for Vitrectomy, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Sedation Complication
Obesity
Hypoxic Respiratory Failure
Airway Obstruction, Nasal
Respiratory Insufficiency
Apnea
Keywords: Noninvasive Ventilation
Obesity
Moderate sedation
Adult
High-flow nasal oxygenation
Vitrectomy
Airway management
Lead sponsor: University of Split, School of Medicine
Sponsor class: OTHER
Collaborators: name: Clinical Hospital Centre Zagreb
First posted: 2019-08-08
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Investigators plan to conduct prospective, parallel group, randomized controlled clinical trial.

In total, 126 participants will be included in this trial. These participants are patients scheduled for outpatient analgo-sedation for vitrectomy.
Primary purpose: TREATMENT

Brief summary: Patients suffering from pathology of posterior eye chamber such as diabetic retinopathy, retinal detachment, traumatic eye injury, retained lens fragments, macular hole, pucker, dislocated intraocular lens after cataract surgery or vitreomacular traction are often subjected to pars plana vitrectomy (PPV). PPV is minimally invasive endo-microscopic operation usually performed in topical anesthesia combined with sub-Tenon or retrobulbar block done by surgeon, supplemented by intravenous analgo-sedation given by anesthesiologist.

Continuous infusion and dose adjustment of intravenous anesthetics applied should procure moderate sedation and preservation of patients' spontaneous ventilation. However, despite carefully applied anesthetics and standard low-flow nasal oxygenation (LFNO) (5 L/min O2 via nasal catheter), inadequate spontaneous breathing can occur leading to low blood oxygen level (hypoxia). Obese patients are susceptible to hypoxia and hypercapnia (high CO2 blood level) during analgo-sedation. Respiratory instability of obese patients is often associated to their subsequent circulatory instability (heart rate and blood pressure disorders).

On the other hand, high-flow nasal oxygenation (HFNO) is usually used during anesthesia induction when difficult maintenance of airway patency is expected, in intensive care units during weaning patients from mechanical respirator and in postanesthesia care units during awakening from anesthesia. It can deliver 20 to 70 L/min, up to 100% inspiratory fraction of O2 (FiO2) to patient. High oxygen/air flow produces 3-7 cmH2O of continuous pressure in patients' upper airways therefore providing better oxygenation. Oxygen/air mixture delivered by HFNO is humidified and heated, thus more comfortable to patient than dry and cold LFNO.

Aim of this study is to compare effect of HFNO to LFNO during intravenously applied standardized analgo-sedation given for PPV in obese adult patients.

Investigators hypothesize that obese patients, whose breathing pattern is preserved, receiving HFNO vs. LFNO during standardized analgo-sedation for PPV will be more respiratory and circulatory stable, preserving normal blood O2 and CO2 level, breathing pattern, heart rate and blood pressure.

Detailed description: Patients suffering from pathology of posterior eye chamber such as diabetic retinopathy, retinal detachment, traumatic eye injury, retained lens fragments, macular hole, pucker, dislocated intraocular lens after cataract surgery or vitreomacular traction are often subjected to pars plana vitrectomy (PPV).

PPV is minimally invasive micro-endoscopic surgery of posterior eye chamber. Patients usually receive analgo-sedation combined with topical anesthesia, which, depending on the type of surgery, precedes a regional, retrobulbar or sub-Tenon block. Although lower doses of intravenous anesthetics are carefully titrated in continuous infusion and standard, low - flow nasal oxygenation (LFNO) is applied, patients are prone to respiratory insufficiency. Obese patients are especially susceptible to bradypnoea, transitory apnoea, hypoxia and hypercapnia. Respiratory instability is then often followed by circulatory one presented by heart rate and blood pressure deflections from baseline values. It is known that higher anesthesia risk obese patients may suffer from serious complications due to respiratory issues during analgo-sedation, even fatal outcome may occur.

LFNO is applied at rate of 5 L/min O2 per nasal catheter, reaching inspiratory fraction of oxygen (FiO2) of 40%. High-flow nasal oxygenation (HFNO) is an innovative method of patient oxygenation that delivers warmed and moistened oxygen and air mixture with a flow rate of up to 70 L/min and up to 100% FiO2 via specially designed soft nasal cannula. It is known that 40 L/min of oxygen/air mixture delivered by HFNO provides 40% FiO2 applying continuous positive inspiratory pressure of 3-7 cmH2O which ensures continuous non-invasive support of patients' spontaneous ventilation and thus better oxygenation stability of the patient.

OBJECTIVE: The study aims to determine the effect of HFNO versus LFNO on the stability of spontaneous ventilation during standardized intravenous analgo-sedation for PPV in normal weight and obese patients.

HYPOTHESIS: Investigators hypothesize that administration of HFNO in comparison with LFNO in patients with preserved spontaneous breathing during the standard analgo-sedation procedure will contribute to better oxygenation maintenance and, consequently, greater peri-procedural safety of patients, especially in obese patients.

Investigators expect that HFNO will provide reduced bradypnoea intervals (bradypnoea \<12 breaths/min, FoB 1/min), longer maintenance of adequate oxygenation, shorter intervals of desaturation (peripheral blood oxygen saturation - SpO2≤92%), reducing hypercapnia (expiratory carbon-dioxide - expCO2≥45 mmHg) and less airway opening maneuvers performed by attending anesthesiologist (AOM). These will prevent partial respiratory insufficiency detected by low SpO2 accompanied by low or normal expiratory carbon-dioxide level (expCO2), and global respiratory insufficiency detected by decreased SpO2≤92% and increased expCO2≥45 mmHg.

Investigators plan to conduct prospective, parallel group, randomized controlled clinical trial. Trial will be managed according to principles of Declaration of Helsinki for scientific clinical research and will be planned and guided according to CONSORT guidelines (Consolidated Standards of Reporting Trials). The trial has been approved by Hospital's Ethic Committee.

The source of information are going to be 126 adult patients scheduled for PPV under analgo-sedation. Eligible participants will be interviewed and examined ambulatory by anesthesiologist, their ASA status, difficulty of airway management and body mass index (BMI) evaluated. After initial examination inclusive and exclusive criteria will be distinguished. Eligible participants who give voluntarily their written consent of participation will be included in this study. After that, participants will be assigned to equal normal weight (18\<BMI\<30 kg/m2), class I obesity (30≤BMI\<35 kg/m2) and class ≥II obesity (BMI≥35 kg/m2) groups. Each group will be randomized to intervention (HFNO) and control (LFNO) subgroup by computer random numbers generator. Randomization will be used until adequate number of participants in every subgroup is reached.

Interventions: intervention subgroups participants will be oxygenated via nasal cannula using high flow (40 L/min) of humidified and heated oxygen in air mixture (FiO2 40%). HFNO will be applied by oxygenator (AirVO™2, Fisher and Paykell, New Zealand, Technomedika, Croatia d.o.o.) during procedural analgo-sedation for PPV maintaining spontaneous breathing. In control subgroups, LFNO will be applied via nasal catheter (Bauerfeind d.o.o. Zagreb, Croatia) using standard low-flow oxygen (5 L/min, FiO2 40%). In both groups concentration of oxygen delivered depends on oxygen flow which is regulated by standard flow-regulator (flowmeter). Oxygen is delivered through pipelines from central hospital gas supply or from portable cylinder gas supply.

Anesthesia procedure will be uniformed for all participants. Integrated noninvasive monitoring of circulatory function (heart rate - EKG, intermittent mean arterial pressure - sphygmomanometer) will be set (Compact 7; Medical Econet GmbH, Germany). Respiratory vital functions: oxygenation (pulse oximeter), heart rate and expCO2 by using capnometer (Capnostream™35 Portable Respiratory Monitor, Medtronic, Belgium).

Every participant will have established intravenous infusion of 250 ml NaCl 0.9% via intravenous cannula regulated by continuous flow (Extension set/CONTROL-A-FLO Regulator 19 "Male Luer Lock Adapter", Baxter/Agmar d.o.o. United States of America/ Croatia).

Oxygenation (HFNO or LFNO) will be continuously administered before institution of analgo-sedation until patients' awakening. It will be started 3 minutes before analgo-sedation (preoxygenation), continued during analgo-sedation and procedure of PPV (perioperative oxygenation) and up to 5 minutes after PPV and until patient is awake (postprocedural oxygenation).

Induction of analgo-sedation will be instituted by droperidol 1.25 -2.5 mg bolus accompanied by continuous infusion of target remifentanyl concentration up to 0.05 mcg/kg/min. Intensity of sedation will be measured by Ramsay's sedation scale (RSS). Moderate sedation (RSS 4) is characterized by: purposeful response to verbal or tactile stimulation, no intervention required for airway patency maintenance, adequate spontaneous ventilation and sufficient cardiovascular function. Surgeon will apply topical local anesthetic on conjunctiva which is followed by regional anesthesia (sub-Tenon or retrobulbar block). Intravenous analgo-sedation will be administered via perfusor (B.Braun, Melsungen, Germany). Analgo-sedation will be discontinued immediately after end of PPV.

Control of nasopharyngeal airway is achieved by using oropharyngeal airway, if necessary. Oropharyngeal airway (Airway; Vigon-Medicpro d.o.o.) will be inserted after achieving moderate analgo-sedation and only if base of tongue is closing airway by dropping on posterior pharyngeal wall. Every manipulation of patients airway by anesthesiologist will be documented (insertion of airway, jaw thrust maneuver).

Measuring:

SpO2, expCO2, heart rate (fC) and respiratory rate (fD) will be measured continuously, and simultaneously continuously noted in 5 minutes intervals - T0=before oxygenation, T1=15 minutes after instituting LFNO or HFNO after beginning of analgo-sedation, T2=when patient is awake after oxygenation ends.

Noninvasive measurement SpO2 will be performed by indirect method using a pulse oximeter on the index finger of the left hand (Compact 7, Medical ECONET GmbH, Germany).

Blood pressure measuring and mean arterial pressure calculation will be repeated intermittently in 5 minutes intervals prior to-, during analgo-sedation and after patient is awaken. All measured parameters will be noted in identical intervals.

The data will be collected uniformly by three researchers: an anesthesiologist who interviews and examines patients ambulatory, an anesthesiologist designated for procedural analgo-sedation and an anesthesiologist who will collect the data after the completion of the analgo-sedation procedure.

The investigator in charge of the data collection will collect it from the pre-operative ambulatory list and the anesthesiologist list. The anesthesiology sheet will include all data from the trend table of the monitored vital parameters and from the simultaneously noted respiratory rate (fD) per minute and the expCO2.

The data will be collected through non-invasive measurements: peripheral blood oxygen saturation (SpO2), heart rate (fC), respiratory rate (fD), blood pressure (mean arterial pressure - MAP), carbon dioxide exhaled values before, in the stabilization and at the end of the analgo-sedation, i.e. 5 minutes after awakening of the patient.

A fourth researcher will be in charge of entering the collected data into the database. The statistician will analyze the data.

Basic data analyses will be performed by statistician. Sample size is determined by statistic computing web program: http://www.stat.ubc.ca/\~rollin/stats/ssize used statistic test Inference for Proportions:Comparing Two Independent Samples. Assessment of sample size is computed for two independent samples with assumption of clinically significant difference in patients' oxygenation: ≤88 and ≥99%. Statistical significance of difference will be inferred with 5% α-error, 50% β-error and study power 0.80.calculated size of sample is: 21 participant pro subgroup (total of 126 participants).

Possible biases and confounding variables could be caused by hypothermia of the participant and by sphygmomanometer pressure on the same arm where peripheral oxygenation level is measured. These difficulties can be bypassed by: adjustment of room temperature where analgo-sedation for PPV is performed and blood pressure measuring cuff placed on right arm (pulse oximeter placed on left index-finger).

Any possible event that may occur during analgo-sedation that causes deviation from the study protocol will be the reason for exclusion of the subjects from the study and the PPV will be continued under anesthesia according to the rules of good clinical practice.

Eligibility criteria: Inclusion Criteria:

* Normal weight and obese patients (18\<BMI\<30 kg/m2, 30≤BMI\<35 kg/m2, BMI≥35 kg/m2)
* Moderate intravenous analgo-sedation
* Pars plana vitrectomy

Exclusion Criteria:

* Higher anesthesia risk patients (ASA III)
* Conventional vitrectomy
* Diseases of peripheral blood vessels
* Hematological diseases
* Psychiatric diseases
* Sideropenic anemia
* Patient's refusal
* Ongoing chemotherapy or irradiation
* Remifentanyl and Xomolix allergies

Primary outcomes:
measure: Maintaining oxygenation above the level of hypoxemia. Measure: peripheral blood saturation (SpO2) before application of LFNO or HFNO.
timeFrame: Time 0=before oxygenation
measure: Maintaining oxygenation above the level of hypoxemia. Measure: peripheral blood saturation (SpO2) 15 minutes after institution of LFNO or HFNO.
timeFrame: Time 1=15 minutes after institution of LFNO or HFNO,
measure: Maintaining oxygenation above the level of hypoxemia. Measure: peripheral blood saturation (SpO2) 5 minutes after discontinuing analgo-sedation and oxygenation (LFNO and HFNO).
timeFrame: Time 2=5 minutes after discontinuing analgo-sedation and oxygenation (LFNO and HFNO).
Secondary outcomes:
measure: Maintaining of expiratory efficiency of spontaneous breathing below hypercapnia value. Measure: expiratory level of CO2 (expCO2) before oxygenation by LFNO or HFNO.
timeFrame: Time 0=before oxygenation by LFNO or HFNO
measure: Maintaining of expiratory efficiency of spontaneous breathing below hypercapnia value. Measure: expiratory level of CO2 (expCO2) 15 minutes after institution of LFNO or HFNO.
timeFrame: Time 1=15 minutes after institution of LFNO or HFNO
measure: Maintaining of expiratory efficiency of spontaneous breathing below hypercapnia value. Measure: expiratory level of CO2 (expCO2) 5 minutes after discontinuing analgo-sedation and oxygenation (LFNO or HFNO).
timeFrame: Time 2=5 minutes after discontinuing analgo-sedation and oxygenation (LFNO or HFNO).
measure: Maintaining of normopnoea and spontaneous ventilation: frequency of breathing Measure: frequency of breathing before oxygenation by LFNO or HFNO.
timeFrame: Time 0=before oxygenation by LFNO or HFNO.
measure: Maintaining of normopnoea and spontaneous ventilation: frequency of breathing Measure: frequency of breathing 15 minutes after institution of LFNO or HFNO.
timeFrame: Time 1=15 minutes after institution of LFNO or HFNO.
measure: Maintaining of normopnoea and spontaneous ventilation: frequency of breathing. Measure: frequency of breathing 5 minutes after discontinuing analgo-sedation and oxygenation (LFNO or HFNO).
timeFrame: Time 2=5 minutes after discontinuing analgo-sedation and oxygenation (LFNO or HFNO).
measure: Maintaining of normopnoea and spontaneous ventilation: frequency of bradypnoea during analgo-sedation and oxygenation by LFNO or HFNO (fBRP/min).
timeFrame: Procedure (From the start until the end of analgo-sedation and oxygenation by LFNO or HFNO.)
measure: Maintaining of normopnoea and spontaneous ventilation: frequency of desaturation during time of analgo-sedation and oxygenation by LFNO or HFNO.
timeFrame: Procedure (From the start until the end of analgo-sedation and oxygenation by LFNO or HFNO.)
measure: Maintaining of normopnoea and spontaneous ventilation: Duration of desaturation (DE/min) from the start until the end of analgo-sedation and oxygenation by LFNO or HFNO.
timeFrame: up to 1 minute (From the start until the end of analgo-sedation and oxygenation by LFNO or HFNO.)
measure: Measurement of procedural parameters: duration of analgo-sedation.
timeFrame: Procedure (From the start until the end of analgo-sedation.)
measure: Measurement of procedural parameters: duration of awakening (awaken patient).
timeFrame: up to 5 minutes
measure: Circulatory stability: heart rate before oxygenation by LFNO or HFNO
timeFrame: Time 0=before oxygenation by LFNO or HFNO
measure: Circulatory stability: heart rate 15 minutes after institution of LFNO or HFNO.
timeFrame: Time 1=15 minutes after institution of LFNO or HFNO.
measure: Circulatory stability: heart rate 5 minutes after discontinuing analgo-sedation and oxygenation (LFNO or HFNO).
timeFrame: Time 2=5 minutes after discontinuing analgo-sedation and oxygenation (LFNO or HFNO).
measure: Circulatory stability: mean arterial pressure before oxygenation by LFNO or HFNO
timeFrame: Time 0=before oxygenation by LFNO or HFNO.
measure: Circulatory stability: mean arterial pressure 15 minutes after institution of LFNO or HFNO
timeFrame: Time 1=15 minutes after institution of LFNO or HFNO.
measure: Circulatory stability: mean arterial pressure 5 minutes after discontinuing analgo-sedation and oxygenation (LFNO or HFNO).
timeFrame: Time 2=5 minutes after discontinuing analgo-sedation and oxygenation (LFNO or HFNO).
Other outcomes:
Locations:
city: Zagreb
country: Croatia
facility: University clinical hospital centre Zagreb
Study officials:
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