Analgo-sedation is standard procedure in anesthesiology practice and is often given for colonoscopy in the setting of daily hospital. Ideally, patients should be sedated with preserved spontaneous breathing and adequate blood O2 saturation. To maintain adequate oxygenation, low-flow O2 (2-6 L/min) is usually delivered through standard nasal catheter which can provide inspired fraction (FiO2) of 40% (low-flow nasal oxygenation - LFNO). Coldness and dryness of LFNO applied may be uncomfortable to patient. Standardly applied intravenous anesthetics can lead to transient ceasing of breathing and O2 desaturation despite LFNO. Respiratory instability can also potentiate circulatory instability - undesirable changes in heart rate (HR) and blood pressure (BP). Unlike LFNO, high-flow heated and humidified nasal oxygenation (HFNO) is characterized by the oxygen-air mixture flow of 20 to 70 L/min up to 100% FiO2. Warm and humidified O2, delivered via soft, specially designed nasal cannula, is pleasant to patient. HFNO develops continuous positive pressure of 3 to 7 cmH2O in upper airway which enables noninvasive support to patient's spontaneous breathing thus prolonging time of adequate O2 saturation.

Aim of this study is to compare effect of HFNO and LFNO on oxygenation maintenance before, during and after standardized procedure of intravenous analgo-sedation in normal weight patients of ASA risk I, II and III.

Investigators hypothesize that application of HFNO compared to LFNO, in patients with preserved spontaneous breathing during procedural analgo-sedation, will contribute to maintaining of adequate oxygenation, consequentially adding to greater circulatory and respiratory patients' stability.

Investigators expect that patients who receive HFNO will better maintain adequate oxygenation regarding improved spontaneous breathing. Also patients will have shorter intervals of blood oxygen desaturation, less pronounced rise in blood CO2 level and lesser fall of blood O2 level, less change in HR and BP. Investigators will have to exactly estimate partial and global respiratory insufficiency (blood CO2 and O2 levels) associated with LFNO and HFNO, which will be done by blood-gas analysis of 3 arterial blood samples collected before, during and after analgo - sedation via previously, in local anesthesia, placed arterial cannula. Possible complications will be explained in written uniformed consent and by anesthesiologist.

Analgo-sedation is standard procedure in anesthesiology practice and is often given for diagnostic and procedural intervention in the setting of daily hospital. Institution of sedation and maintaining spontaneous breathing are main characteristics of analgo-sedation. Preservation of adequate patient oxygenation is set up by continuous administration of sedative anesthetic infusion which contributes to hemodynamic stability and by administration of oxygen. Patient oxygenation is implemented prior to analgo-sedation (preoxygenation), during analgo-sedation (periprocedural oxygenation) and during awakening from analgo-sedation (postprocedural oxygenation) usually via nasal cannula with application of low-flow (2-6 L/min) up to 40% of inspired fraction of oxygen (LFNO: low-flow nasal oxygenation, FiO2: inspiratory fraction of oxygen). Despite oxygenation administered, intravenously applied analgo-sedation yields to risk of transitory apnea accompanied by hypoxemia, hypoxia, hypercapnia and hemodynamic insufficiency. Anesthesia risk is classified as ASA classification by American Society of Anesthesiologist Physical Status Classification System: ASA I includes healthy patients without systemic disease, ASA II patients who have mild systemic disease without functional organ limitations and ASA III patients with one or more organ function insufficiency.

High-flow heated and humidified oxygenation (HFNO) delivered via soft, specially designed, nasal cannula is successfully used for preoxygenation of patient with predicted difficulty in ensuring airway patency. Unlike LFNO, HFNO is characterized by high flow of heated and humidified oxygen-air mixture (20-70 L/min) up to 100% FiO2. HFNO prolongs adequate oxygenation time in patients during retrograde endoscopic cholangiopancreatography. Also, HFNO could be alternative for noninvasive ventilation of patients with acute hypoxemic respiratory failure. According to previously mentioned statements, LFNO has significant limitations. Main characteristic of HFNO as innovative technique is supporting patients' spontaneous inspiration effort through high-flow of heated and humidified oxygen-air mixture. Higher inspiratory fraction of oxygen, positive end-expiratory pressure, decreasing of pharyngeal airway dead space and decreasing of airway resistance lead to improved maintaining of oxygenation combined with better patients' tolerance.

AIM of this study is to compare effect of HFNO and LFNO during standardized procedure of intravenous analgo-sedation on periprocedural oxygenation maintenance in normal weight patients of ASA I, II and III status.

Investigators hypothesized that application of HFNO compared to LFNO, in patients with preserved spontaneous breathing during procedural analgo-sedation, contributes to maintaining adequate oxygenation, consequently adding to greater peri-procedural circulatory and respiratory stability of these patients. Investigators expect that HFNO will ensure reduced bradypnoea intervals (frequency of breathing, FoB 1/min), longer maintenance of adequate oxygenation, shorter intervals of desaturation (SpO2 ≤ 92%), reducing hypercapnia (PaCO2 ≥ 6 kPa) and less airway - opening maneuvers performed by attending anesthesiologist (Aom). These will prevent partial respiratory insufficiency detected by low SpO2 or low PaO2 ≤ 11kPa accompanied by normal or low PaCO2 ≤ 6 kPa, and global respiratory insufficiency detected by decreased SpO2 ≤ 92% and PaO2 ≤ 11kPa with increased PaCO2 ≥ 6 kPa.

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 colonoscopy under analgo-sedation in the setting of daily outpatient gastroenterology ambulance. Eligible participants will be interviewed and examined ambulatory by anesthesiologist together with evaluation of ASA status, difficulty of airway management and body mass index (BMI). After initial examination inclusive and exclusive criteria will be distinguished. Eligible participants who give their written consent of participation will be included in this study. After that, participants will be assigned to equal ASA I, II or III risk class group. Each group will be randomized to intervention (HFNO) and control (LFNO) subgroup by random numbers generator. Randomization will be used until we reach adequate number of participants in every group.

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 colonoscopy with maintained 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 vital functions will be set: EKG - (heart rate/min), SpO2 (%), blood pressure (mmHg), respiratory rate (number of breaths/min) (Compact 7; Medical Econet GmbH, Germany).

Every participant will have established intravenous infusion of 250 ml NaCl 0.9% through 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).

Arterial cannula (REF30401, 20 G - 1,10 mm x 45 mm 49 ml, atraumatic needle tip, Medbar LTD, Izmir, Turkey) will be placed in radial artery in a previously anesthetized area with local anesthetic (EMLA).

Oxygenation (HFNO or LFNO) will be administrated in continuity until patients' awakening. It will be started 3 minutes before starting analgo-sedation (preoxygenation), continued during analgo-sedation and procedure of colonoscopy (perioperative oxygenation) and up to five minutes after colonoscopy and until patient is awake (postprocedural oxygenation).

Intravenous analgo-sedation will be started through continuous infusions of propofol and fentanyl. Induction of sedation will be guided by TCI (Target control Infusion) (B. Braun Melsungen, Germany) with initial target propofol concentration of 6 micrograms/minute. Expected time of induction with this concentration is 60-120 seconds. This target concentration allows hemodynamic and respiratory stability. Required analgesia will be simultaneously applied through slow continuous infusion in dose of 0.05 mcg/kg/min in order to preserve spontaneous breathing. Slow infusion will be applied through perfusor (B.Braun, Melsungen, Germany). Analgo-sedation will be discontinued immediately after end of the procedure.

Control of nasopharyngeal airway passage during procedure is achieved by using oropharyngeal airway, if necessary. Oropharyngeal airway (Airway; Vigon-Medicpro d.o.o.) will be inserted after achieving moderate 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).

Sampling: one milliliter of arterial blood will be collected as three consecutive samples from arterial cannula before, during and after analgo-sedation. Sample of arterial blood will be drawn from left radial or cubital artery.

Measurements: measurement of oxygenation will be done using two methods: indirect (noninvasive) method using pulse oxymeter (Compact 7, Medical ECONET GmbH, Germany) and direct (invasive) method from obtained arterial blood sample. Measurement of SpO2 and drawing arterial blood sample will be done simultaneously. Direct measurements of SpO2 and PaO2 will be measured in intervals of time. SpO2 will be measured on the left-hand index finger. Data will be uniformly collected through indirect - noninvasive (SpO2, heart rate, blood pressure, respiratory rate) and direct - invasive (arterial blood gas analysis - pH, PaO2, PaCO2, SaO2) measurements

Possible biases and confounding variables could be caused by hypothermia of participant, by sphygmomanometer cuff pressure on the same arm where blood samples are drawn and by prolonged time of arterial blood analysis. These difficulties can be bypassed by: adjustment of room temperature where analgo-sedation is performed, blood pressure measuring on opposite arm from where samples of blood are taken and by arterial blood gas analysis without delay.

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: ≤11 and ≥14.4 kPa with delta 4.4. 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).

Investigators expect no changes to methods after trial commencement. All potential unwanted events which may happen during analgo-sedation and colonoscopy that could cause deviation from this trial's protocol will be reason for exclusion of participant from this trial. If circumstances change, anesthesiologist responsible for application of anesthesia will carry out procedure in way which is in patients' best interest.

Inclusion Criteria:

• normal weight ASA I patient
• normal weight ASA II patient
• normal weight ASA III patient
• intravenous analgo-sedation
• elective colonoscopy
• colorectal tumors.

Exclusion Criteria:

• obese patients
• emergency colonoscopy
• diseases of peripheral blood vessels
• hematological diseases
• psychiatric diseases
• sideropenic anemia
• patients' refusal
• ongoing chemotherapy or irradiation
• propofol allergies
• fentanyl allergies.

Anesthesiologist who interviews and examines patients scheduled for colonoscopy under analgo-sedation will enroll eligible participants and will offer procedure explanation and possibility to sign uniformed written consent. Unique personal hospital admission number (UPHAN) will be assigned to all eligible participants. After that, they 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. 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.