PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY

Opioid analgesia is the primary pharmacologic intervention for managing pain in
hospitalized patients. Opioid therapy is indeed the gold standard for treatment
of post-surgical pain in hospital ward but also the majority of non-surgical
patients admitted in hospital are exposed to opioids. They can be administered
orally, by Patient Controlled Analgesia (PCA), by epidural or intrathecal
infusions, by intravenous or intramuscular analgesia. In recent years there
have been increasing concerns over unmonitored mortality and morbidity in
patients during opioid therapy for acute pain. Up to 80% of patients who
received opioid analgesics experience Opioid-Related Adverse Drug Events
(ORADEs). In post-surgical patients, ORADEs have been showed to significantly
increase patient*s hospital length of stay and related costs. Improper
patients* monitoring has been reported by the Joint Commission as one of the
main causes of ORADEs.
One of the major opioid side effects includes respiratory depression (RD),
which causes alveolar hypoventilation and hypoxemia. The reported incidence of
RD in post-surgical patients varied from 0.3% to 3.4% only considering
intervention rate (i.e. naxolone infusion), while it is reported up to 21% and
41% when including also prolonged oxygen desaturation and bradypnea episodes,
respectively. If detected early, most cases of opioid-related RD can be treated
with naloxone; however, severe cases can be fatal.
Respiratory Compromise is a state in which there is a high likelihood of
decompensation into respiratory depression, respiratory failure or death, but
in which specific interventions (enhanced monitoring and/or therapies) might
prevent or mitigate decompensation10. Detection of a patient*s Respiratory
Compromise status before progression can help avert unwarranted outcomes and
the possible need for critical care. Despite this, there are no universally
accepted guidelines to direct effective and safe assessment and monitoring
practices for patients receiving in-hospital opioid analgesia1. Current
standard of care for respiratory monitoring of hospital ward patients receiving
opioid therapy is intermittent documentation of oxygen saturation (SpO2) value
(e.g. performed at 4 to 6 hours intervals). Some centers perform continuous
SpO2 monitoring to patients considered at risk to develop RD, but the decision
is usually left to physician discretion. Respiratory rate (RR) is often
determined by clinician assessment though manual respiration counts9.
Typically, only some high-risk patients are monitored by capnography, a
technology that assesses real-time ventilation by continuous measuring of SpO2,
RR and the concentration of exhaled end tidal carbon dioxide (etCO2).
Pulse oximetry alone can lead to inaccurate assessment of patients* condition,
especially when supplemental oxygen is needed: the Anesthesia Patient Safety
Foundation recommended the use of continuous electronic monitoring of
oxygenation and ventilation for all patients undergoing opioid therapy in the
postoperative period and capnography monitoring when supplemental oxygen is
needed. Even at low respiratory rate, SpO2 could be maintained for a certain
period, thus delaying the RD detection. Many patients who breathe inadequately
at rest or during sleep may present normal or near-normal oxygen saturation
after they are awakened.
Growing evidence supports the use of capnography for earlier and more reliable
warnings of RD in postoperative patients in the general ward, compared with
pulse oximetry. It has been demonstrated that RD detected by capnography by
bradypnea is significantly higher than RD detected by oxygen desaturation in
post-surgical patients using PCA6, while there are no data in literature
related to capnography monitoring in non-surgical patients.

The purpose of this study is to improve the prediction of RD episode in
patients undergoing opioid therapy in the hospital ward (also known as the
General Care Floor) to guide clinicians and nursing staff in selecting the
at-risk patients who could more benefit from capnographic monitoring by:
- Deriving a score risk assessment tool in a derivation cohort;
- Evaluating the prognostic value of the score for the prediction of RD in an
internal validation cohort.

PRODIGY is a prospective, multi-center, post-market interventional,
international cohort study. The study will include consecutively enrolled
patients

NVT

Patients will be monitored during at least 24 hours by capnography and pulse
oxyon sensors. this is a common method