The Effectivity of End-tidal CO2 and Oxygen Reserve Index (ORI) Monitoring in Sedation
Condition: Hypoxemia; Procedural Sedation; Hypercapnia; Apnea
MeSH terms: Hypoxia; Hypercapnia
Study type: Interventional

Summary: 
      Endoscopic procedures are commonly performed using sedation. As drug-induced respiratory
      depression is a major cause of sedation-related morbidity, pulse oximetry has been
      established as standart practice . However SpO2 does not completely reflect ventilation.
      Capnography is an additional monitoring parameter which demonstrates respiration activity
      breath by breath. Unfortunately, in the state of moderate or deep sedation during diagnostic
      or therapeutic procedures (e.g.ERCP or colonoscopies), regular breathing is often disturbed
      by moving, squeezing, coughing or changes between nose and mouth ventilation causing leakage
      and therefore artifacts or misinterpretation of data acquired with ETCO2. These problems
      often restrict the use of side-stream capnography in clinical practice, although the American
      Society of Anesthesiologists have suggested in their guidelines that extended monitoring with
      capnography 'should be considered'in deep sedation. The oxygen reserve index (ORI) is a new
      feature of multiple wavelength pulse oximetry that provides real-time visibility to
      oxygenation status in the moderate hyperoxic range (PaO2 of approximately 100-200 mm Hg). The
      ORI is an "index" with a unit-less scale between 0.00 and 1.00 that can be trended and has
      optional alarms to notify clinicians of changes in a patient's oxygen status. When utilized
      in conjunction with SpO2 monitoring the ORI may extend the visibility of a patient's oxygen
      status into ranges previously unmonitored in this fashion. The ORI may make pre-oxygenation
      visible, may provide early warning when oxygenation deteriorates, and may facilitate a more
      precise setting of the required FiO2 level. In this study we aimed to show effectivity of
      capnography and ORİ monitoring to avoid respiratory events and hypoxia in sedated endoscopic
      patients. In this study we targeted totally 300 sedated endoscopy patients. Patients will
      randomize to two groups. In Group I anaesthesiologis will be able to use all the monitoring,
      where as in Group II will be blinded for ORİ. We will apply pre-oxygenation to obtain long
      safe apnea time. Approximately 5 min pre-oxygenation (5L/min via nasal cannula) will be used
      to reach steady state in oxygen reserve. We defined hypoxemia ; SpO2<95% and severe hypoxemia
      SpO2≤90%, hypoventilation; rise10 mmHg in ETCO2 compare to baseline, ETCO2≤30 mmHg and flat
      capnography.
    

Detailed description: 
      Endoscopy constitutes a wide range of procedures with many indications.
      Esophagogastroduodenoscopy, colonoscopy, endoscopic retrograde cholangiopancreatography
      (ERCP), endoscopic ultrasonography (EUS), and enteroscopy comprise the most commonly
      performed procedures.

      There has been a considerable progress in the practice of sedation and anaesthesia for
      endoscopic procedures. The use of sedation reduces patient discomfort and anxiety while
      improving the technical quality of the procedure, and as a result, over 98% of clinicians
      have adopted the practice. The tremendous benefits of sedation are offset by heightened
      costs, increased patient discharge time, and cardiopulmonary complication risks.(1) It has
      been well accepted that the most important negative impact of sedation and anaesthesia is the
      compromise of respiratory function in the form of hypoxemia, hypoxia and alveolar
      hypoventilation. Recent analysis of procedural sedation has revealed an overall incidence of
      respiratory depression of 4,1%, with 1,1% of patients requiring assisted ventilation or
      reversal agents for respiratory depression.(2) Respiratory monitoring is a fundamental
      component of every anaesthetic regimen. Its major relevance for maintenance of homeostasis
      and patients' safety is recognized in its position as a mandatory element in national and
      international standards for anaesthetic monitoring. (3)Through the decades, advances in
      respiratory monitoring have reduced the incidence of anaesthetic morbidity and mortality and
      have opened a new era of safe anaesthetic practice. The inherent liabilities of putting
      patients under sedation have necessitated a large number of physiological monitoring systems
      in order to ensure patient comfort and safety. Currently American Society of
      Anaesthesiologist (ASA) guidelines recommend monitoring of pulse oximetry, blood pressure,
      heart rate, and end-tidal CO2; although important safeguards, these physiological
      measurements do not allow for the reliable assessment of patient sedation. Proper monitoring
      of patient state ensures procedure quality and patient safety; however no "gold-standard" is
      available to determine the depth of sedation, which is comparable to the anaesthesiologist's
      professional judgment. The 2010 House of Delegates of the American Society of
      Anaesthesiologists (ASA) amended its Standards for Basic Anaesthetic Monitoring to include
      mandatory exhaled end-tidal carbon dioxide (ETCO2) monitoring during both moderate and deep
      sedation to its existing requirement for endotracheal and laryngeal mask airway general
      anaesthesia. (4) Changes in the respiratory rate, visual inspection of the chest rise and
      pulse oximetry (SpO2) have been considered the most conventional and oldest non-invasive
      methods to determine changes in the ventilator status of patients.(5,6) However, derived
      respiratory rate alone cannot measure of ventilation. Clinical organization guidelines and
      growing body of studies suggest that respiratory rate alone is an inadequate measure of
      ventilation, as severe respiratory depression may develop in the presence of a normal
      respiratory rate.(7,8) Pulse oximetry (SpO2) is a non-invasive, reliable, and simple method
      for continuously monitoring the fractional arterial oxygen saturation and is essential
      component of respiratory monitoring. SpO2 is an estimate of SaO2 and it does not provide
      information about tissue oxygenation. Moreover SpO2 does not completely reflect
      ventilation.(9) Due to the S-shape of the oxygen dissociation curve, large changes in the
      partial oxygen tension (PaO2) may remain unnoticed over a period of time if monitoring is
      carried out with SpO2 alone.(10) If healthy subjects are pre-oxygenated with 100% oxygen and
      ventilate effectively and then become apneic, it may take up to 6 min for an adult before
      SpO2 drops below 90%. (11)

      Monitoring ETCO2 for the anaesthesiologists is far superior to the pulse oximeter for
      immediately detecting an obstructed airway, opiate induced apnea, or other airway problems
      that only much later may be detected by the pulse oximeter. As hypoventilation is directly
      reflected by an increase in arterial carbon dioxide tension (PaCO2), capnography suggests
      itself as an additional monitoring parameter, which furthermore demonstrates respiration
      activity breath by breath. (10,12,13) Monitoring ETCO2 is particularly important when
      anaesthesiologists provide moderate sedation for patients who are medically compromised, such
      as an ASA IV patient with severe chronic obstructive pulmonary disease who may retain high
      levels of CO2 during sedation or a morbidly obese, insulin-dependent diabetic patient with
      severe obstructive sleep apnea. Additionally, in the case of colonoscopy the
      anaesthesiologist's only option for managing severe discomfort in the moderately sedated
      patients is to deepen the level of sedation until the patient becomes unconsciousness, when
      monitoring ETCO2 may be deemed much more important. ASA believes that other less qualified,
      non-anaesthesiologist sedation practitioners need it even more than anaesthesiologists.(4)
      Some of the independent risk factors for hypoxemia described by Friedrich-Rust et al. are
      age, high body mass index, history of sleep apnea, standart monitoring group (without
      capnography), total dose of propofol and dose of ketamine.(14) Quader et al. found a
      significant difference in the detection of hypoxemic events in 247 patients undergoing an
      endoscopic procedure using capnography versus routine surveillance. When capnography was
      blinded to the health care provider, 69% of the patients developed hypoxemia compared to 46%
      when capnography was available to the provider (p<0.001).(15) Slagelse et al. explored if the
      addition of capnography to standard monitoring during endoscopy could reduce number, duration
      and level of hypoxia in 540 patients. They found that the number and total duration of
      hypoxia was reduced by 39,3 and 21,1% in the intervention group compared to the control group
      (p>0.05). (16) Actually in intubated patients or under stable conditions without oral leakage
      the measurement of end-tidal carbon dioxide tension in the exhaled air shows an adequate
      correlation with PaCO2.(10) Unfortunately, in the state of moderate or deep sedation during
      diagnostic or therapeutic procedures (e.g.ERCP or colonoscopies), regular breathing is often
      disturbed by moving, squeezing, coughing or changes between nose and mouth ventilation
      causing leakage and therefore artifacts or misinterpretation of data acquired with ETCO2.
      These problems often restrict the use of side-stream capnography in clinical practice,
      although the American Society of Anesthesiologists as well as the American Society of
      Gastrointestinal Endoscopy (ASGE) have suggested in their guidelines that extended monitoring
      with capnography 'should be considered'in deep sedation. (12,17) Furthermore, while breathing
      room air, alveolar hypoventilation can be easily detected with capnography as an increase in
      the ETCO2. Since the alveolar oxygen partial pressure decreases, it may lead to an immediate
      decrease of SpO2. However up to 35% of all hypoxemic events in patients undergoing endoscopic
      procedures occur with completely normal ventilation. In contrast, supplemental oxygen results
      in increased alveolar oxygen partial pressure despite the presence of hypoventilation. Rising
      ETCO2 and/or flattening of capnography indicates hypoventilation with hypoxia being a
      relatively late finding, especially in a patient receiving supplemental oxygen. (18) Arakawa
      et al. recently evaluated the masking effects of oxygen supplementation in SpO2 when alveolar
      ventilation develops during sedated endoscopy in 70 patients. They found that SpO2 was
      significantly higher in the oxygen supplementation group than in the group breathing room air
      (98.6 1,4% vs 93,1 p<0.001) at peak ETCO2, and oxygen supplementation caused SpO2 to be
      overestimated by greater than 5% when compared with room air. SpO2 at peak ETCO2 was reduced
      from the baseline before sedation for the oxygen supplementation and room air breathing
      groups by 0,5 1,1% and 4,1 3,1% respectively (p<0.001). (19) The patients breathing a FiO2 as
      little as 1 L/min via nasal cannula could be at risk for extreme hypercarbia and CO2 narcosis
      from inadequate breathing before patient's arterial hemoglobin oxygen saturation falls below
      90%. (20) Under these circumstances, it's the visual inspection of the chest that may alert
      the clinician on the presence of hypoventilation. Even capnography monitoring during
      neurosurgery has been reported by several studies as a non-reliable method to monitor CO2 due
      to its underestimation of the PaCO2. (6)

      Masimo Corporation has developed a new parameter for noninvasive monitoring by optical
      sensors, Oxygen Reserve index (ORI). The oxygen reserve index (ORI) is a new feature of
      multiple wavelength pulse oximetry that provides real-time visibility to oxygenation status
      in the moderate hyperoxic range (PaO2 of approximately 100-200 mm Hg). The ORI is an "index"
      with a unit-less scale between 0.00 and 1.00 that can be trended and has optional alarms to
      notify clinicians of changes in a patient's oxygen status. When utilized in conjunction with
      SpO2 monitoring the ORI may extend the visibility of a patient's oxygen status into ranges
      previously unmonitored in this fashion. The ORI may make pre-oxygenation visible, may provide
      early warning when oxygenation deteriorates, and may facilitate a more precise setting of the
      required FiO2 level.(21) The administration of high levels of inspired O2 before tracheal
      intubation (pre-oxygenation) is considered to be a routine practice as oxygen reserves are
      not always sufficient to prevent hypoxia during the duration of intubation.(22) The ORI may
      make this process visible, ensuring that the PaO2 is indeed rising in the presence of a
      constant maximal SpO2 level. The ORI may eventually become a performance indicator, attesting
      to the fact that pre-oxygenation has indeed been properly performed. Monitoring the ORI may
      be especially important in the presence of predictive risk factors for inadequate
      pre-oxygenation, which overlap with criteria predictive of difficult mask ventilation.(22) It
      may also be extremely important during pre-oxygenation before suctioning hypoxemic patients
      (23), during emergency rapid sequence induction, in obese patients, during intubation in the
      ICU, and especially in hypoxic patients who may require non-invasive ventilation before
      intubation.(21) The ORI may provide early warning of impending hypoxia before any changes in
      SpO2 occur. In anesthetized pediatric patients the mean time (±SD) from the start of the ORI
      alarm to a decrease in SpO2 below 98 % and from SpO2 98 to 90 % was 40 ± 523 and 52 ± 44 s,
      respectively. (24) In another recent trial in 103 anesthetized adult patients, ORI could be
      calculated ~91.5 % of monitored time, and was positively correlated with PaO2 values ≤240
      mmHg but not with PaO2 >240 mmHg. PaO2 was ≥150 mmHg in 96.5 % of ORI >0.54, and was >100
      mmHg for all ORI >0.24 (25)The early warning that the ORI provides before any decrease in
      SpO2 occurs may provide precious time for an earlier detection of the event and the provision
      of timely remedial measures.(21) Most of the studies about ETCO2 monitoring in moderate and
      deep sedation patients focused on the range of hypoxic events with or without ETCO2
      monitoring.
    

Intervention name(s): Oxygen Reserve Index, Masimo Corporation, USA.
Intervention type(s): Device
Intervention description(s): The oxygen reserve index (ORI) is a new feature of multiple wavelength pulse oximetry that provides real-time visibility to oxygenation status in the moderate hyperoxic range (PaO2 of approximately 100-200 mm Hg).
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Diagnostic
Keywords: sedation, end-tidal carbon dioxide, oxygen reserve index