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Background  Evidence to date suggests that capnography monitoring during gastrointestinal endoscopic procedures (GEP) reduces the incidence of hypoxemia, but the association of capnography monitoring with the incidence of other adverse outcomes surrounding these procedures has not been well studied. Our aims were to estimate the incidence of pharmacological rescue events and death at discharge from an inpatient or outpatient hospitalization where GEP was performed with sedation, and to determine if capnography monitoring was associated with reduced incidence of these adverse outcomes.    Methods  This retrospective Premier Database analysis included medical inpatients and all outpatients undergoing GEP with sedation. Patients were grouped as follows: (1) pulse oximetry (SpO 2 ) only, (2) capnography only, (3) SpO 2  with capnography, and (4) neither SpO 2  nor capnography. Multivariable logistic regression and propensity-score matching were used to compare patients with capnography sensor use to patients with only SpO 2  sensor use. Outcome measures included the incidence of pharmacological rescue events, as defined by administration of naloxone and/or flumazenil, and death.    Results  Two hundred fifty eight thousand and two hundred sixty two inpatients and 3,807,151 outpatients were analyzed. For inpatients, capnography monitoring was associated with a 47% estimated reduction in the odds of death at discharge (OR: 0.53 [95% CI: 0.40–0.70];  P  < 0.0001) and a non-significant 10% estimated reduction in the odds of pharmacological rescue event at discharge (0.91 [0.65–1.3];  P  = 0.5661). For outpatients, capnography monitoring was associated with a 61% estimated reduction in the odds of pharmacological rescue event at discharge (0.39 [0.29, 0.52];  P  < 0.0001) and a non-significant 82% estimated reduction in the odds of death at discharge (0.18 [0.02, 1.99];  P  = 0.16).    Conclusions  In hospital medical inpatients and all outpatients undergoing GEP performed with sedation, capnography monitoring was associated with a reduced likelihood of pharmacological rescue events in outpatients and death in inpatients when assessed at discharge. Despite the limitations of the retrospective data analysis methodology, the use of capnography during these procedures is recommended.    Electronic supplementary material  The online version of this article (10.1186/s12871-017-0453-9) contains supplementary material, which is available to authorized users.

Capnography sensor use is associated with reduction of adverse outcomes during gastrointestinal endoscopic procedures with sedation administration