Pars plana vitrectomy is minimally invasive endoscopic procedure which is usually performed in moderate analgo-sedation given by anesthesiologist combined with topical anesthesia and retrobulbar or Subtenon block performed by surgeon. Intravenously applied anesthetics can often lead to slower breathing rate or cessation of breathing which introduces risk of low blood oxygen level despite careful adjustment of anesthetics' dose and application of standard low-flow nasal oxygenation (LFNO). Respiratory instability is often accompanied by circulatory instability manifested by disturbances of heart rate and blood pressure. LFNO provides maximally 40% inspired fraction of oxygen and can cause discomfort of a patient due to coldness and dryness of inspired gas.

On the other hand, high-flow nasal oxygenation (HFNO) can bring up to 100% of inspired oxygen fraction to patient, providing noninvasive pressure support of 3-7 cmH2O in patients' upper airway which ensures better oxygenation especially in higher anesthesia risk patients. Because of carrying warmed and humidified air/oxygen mixture via soft nasal cannula, HFNO is better tolerated by patients.

In this trial investigators will compare effect of HFNO to LFNO during intravenously applied standardized analgo-sedation given for vitrectomy in normal weight patients of low and high anesthesia risk.

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

Pars plana vitrectomy (PPV) is minimally invasive micro-endoscopic surgery of posterior eye chamber. Most often patients receive combination of loco-regional anesthesia (topical anesthetic plus retrobulbar or Subtenon block), performed by a surgeon, and moderate analgo-sedation, performed by an anesthesiologist. Although applied intravenous anesthetics are short-acting, carefully titrated and continuously infused, anesthesia can lead to cessation of adequate spontaneous patients' breathing detected as bradypnoea, hypoxia and hypercapnia reflecting respiratory instability of patient. Respiratory instability is accompanied by circulatory one, reflected in heart rate and blood pressure deflections from baseline values. Usually, before, during and after analgo-sedation until patient is awaken, low-flow nasal oxygenation (LFNO) of 2-6 L/min O2 is applied through nasal catheter providing maximum inspiratory fraction of oxygen (FiO2) of 40%. Beside coldness and dryness of LFNO (therefore causing discomfort to patient), LFNO is often inadequate to prevent respiratory instability manifested as hypoxia and hypercapnia and subsequent circulatory disturbances.

Anesthesia risk is classified by American Society of Anesthesiologists Physical Status Classification System (ASA classification system) where patients of ASA class I anesthesia risk are generally healthy without systemic disease, patients deployed to ASA class II group have mild disease, having no functional impairment, higher risk ASA III patients have one or more significant organ function impairment.

High-flow nasal oxygenation (HFNO) delivers to patient high flow heated and humidified oxygen/air mixture (up to 70 L/min, up to 100% FiO2) using soft nasal cannula. HFNO produces 3-7 cmH2O of positive end-expiratory pressure therefore supporting patients breathing effort and providing apnoeic oxygenation, decreasing pharyngeal airway dead space and resistance. The patients find HFNO more comfortable as delivered gas is heated and humidified. HFNO is usually used for oxygenation of patients with predicted difficult oroendotrachial intubation prior to anesthesia, in process of awakening from anesthesia in postanesthesia care units and during process of weaning from mechanical respiratory support in intensive care units.

Goal of this trial is to compare effect of HFNO and LFNO on oxygenation maintenance during standardized procedure of intravenous analgo-sedation in normal weight ASA I, II and III risk class patients for elective PPV.

Investigators hypothesize that application of HFNO compared to LFNO in patients with preserved spontaneous breathing during procedural analgo-sedation for PPV contributes to maintaining adequate oxygenation, consequently adding to greater patients periprocedural respiratory and circulatory stability. 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 ASA I, II and III risk class group. 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 (Subtenon 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.

Inclusion Criteria:

• normal weight ASA patients of risk class I, II and III
• moderate intravenous analgo-sedation
• pars plana vitrectomy

Exclusion Criteria:

• Conventional vitrectomy
• Obese
• Diseases of peripheral blood vessels
• Hematological diseases
• Psychiatric diseases
• Sideropenic anaemia
• Patient's refusal
• Ongoing chemotherapy or irradiation
• Remifentanyl and Xomolix allergies

Anesthesiologist who interviews and examines patients scheduled for PPV under analgo-sedation will enroll eligible participants and offer procedure explanation with possibility to sign uniformed written consent. Unique personal hospital admission number (UPHAN) will be assigned to all eligible participants. Participants will be randomized to control or intervention group by using random numbers generator. Anesthesiologist who implements anesthesia will receive nontransparent envelope with assigned intervention provided by independent investigator and will not decide which participant will receive LFNO or HFNO. However, attending anesthesiologist and participants will unavoidably be aware of type of oxygenation applied. Collected data are objective measures. Investigator who collects data after procedure will be unaware of study protocol and will enter data to formatted database. Participants' data will be noted under UPHAN. Outcome assessors will be unaware of intervention applied.