UNASSIGNED: While widely measured, the time-varying association between exhaled end-tidal carbon dioxide (EtCO2) and out-of-hospital cardiac arrest (OHCA) outcomes is unclear.
UNASSIGNED: To evaluate temporal associations between EtCO2 and return of spontaneous circulation (ROSC) in the Pragmatic Airway Resuscitation Trial (PART).
UNASSIGNED: This study was a secondary analysis of a cluster randomized trial performed at multicenter emergency medical services agencies from the Resuscitation Outcomes Consortium. PART enrolled 3004 adults (aged ≥18 years) with nontraumatic OHCA from December 1, 2015, to November 4, 2017. EtCO2 was available in 1172 cases for this analysis performed in June 2023.
UNASSIGNED: PART evaluated the effect of laryngeal tube vs endotracheal intubation on 72-hour survival. Emergency medical services agencies collected continuous EtCO2 recordings using standard monitors, and this secondary analysis identified maximal EtCO2 values per ventilation and determined mean EtCO2 in 1-minute epochs using previously validated automated signal processing. All advanced airway cases with greater than 50% interpretable EtCO2 signal were included, and the slope of EtCO2 change over resuscitation was calculated.
UNASSIGNED: The primary outcome was ROSC determined by prehospital or emergency department palpable pulses. EtCO2 values were compared at discrete time points using Mann-Whitney test, and temporal trends in EtCO2 were compared using Cochran-Armitage test of trend. Multivariable logistic regression was performed, adjusting for Utstein criteria and EtCO2 slope.
UNASSIGNED: Among 1113 patients included in the study, 694 (62.4%) were male; 285 (25.6%) were Black or African American, 592 (53.2%) were White, and 236 (21.2%) were another race; and the median (IQR) age was 64 (52-75) years. Cardiac arrest was most commonly unwitnessed (n = 579 [52.0%]), nonshockable (n = 941 [84.6%]), and nonpublic (n = 999 [89.8%]). There were 198 patients (17.8%) with ROSC and 915 (82.2%) without ROSC. Median EtCO2 values between ROSC and non-ROSC cases were significantly different at 10 minutes (39.8 [IQR, 27.1-56.4] mm Hg vs 26.1 [IQR, 14.9-39.0] mm Hg; P < .001) and 5 minutes (43.0 [IQR, 28.1-55.8] mm Hg vs 25.0 [IQR, 13.3-37.4] mm Hg; P < .001) prior to end of resuscitation. In ROSC cases, median EtCO2 increased from 30.5 (IQR, 22.4-54.2) mm HG to 43.0 (IQR, 28.1-55.8) mm Hg (P for trend < .001). In non-ROSC cases, EtCO2 declined from 30.8 (IQR, 18.2-43.8) mm Hg to 22.5 (IQR, 12.8-35.4) mm Hg (P for trend < .001). Using adjusted multivariable logistic regression with slope of EtCO2, the temporal change in EtCO2 was associated with ROSC (odds ratio, 1.45 [95% CI, 1.31-1.61]).
UNASSIGNED: In this secondary analysis of the PART trial, temporal increases in EtCO2 were associated with increased odds of ROSC. These results suggest value in leveraging continuous waveform capnography during OHCA resuscitation.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT02419573.

OBJECTIVE: To evaluate the effectiveness of utilizing the integrated pulmonary index for capnography implementation during sedation administered by nurses.
METHODS: Cluster-randomized trial.
METHODS: Participants were enrolled from the interventional radiology department at an academic hospital in Canada. Nurses were randomized to either enable or disable the Integrated Pulmonary Index feature of the capnography monitor. Procedures were observed by a research assistant to collect information about alarm performance characteristics. The primary outcome was the number of seconds in an alert condition state without an intervention being applied.
RESULTS: The number of seconds in an alarm state without intervention was higher in the group that enabled the integrated pulmonary index compared to the group that disabled this feature, but this difference did not reach statistical significance. Likewise, the difference between groups for the total alarm duration, total number of alarms and the total number of appropriate alarms was not statistically significant. The number of inappropriate alarms was higher in the group that enabled the Integrated Pulmonary Index, but this estimate was highly imprecise. There was no difference in the odds of an adverse event (measured by the Tracking and Reporting Outcomes of Procedural Sedation tool) occurring between groups. Desaturation events were uncommon and brief in both groups but the area under the SpO2 90% desaturation curve scores were lower for the group that enabled the integrated pulmonary index.
CONCLUSIONS: Enabling the integrated pulmonary index during nurse-administered procedural sedation did not reduce nurses\' response times to alarms. Therefore, integrating multiple physiological parameters related to respiratory assessment into a single index did not lower the threshold for intervention by nurses.
UNASSIGNED: The time it takes to respond to capnography monitor alarms will not be reduced if the integrated pulmonary Iindex feature of capnography monitors is enabled during nurse-administered procedural sedation.
CONCLUSIONS: Results do not support the routine enabling of the integrated pulmonary index when nurses use capnography to monitor patients during procedural sedation as a strategy to reduce the time it takes to initiate responses to alarms.
UNASSIGNED: CONSORT.
UNASSIGNED: There was no patient or public contribution.
BACKGROUND: This study was prospectively registered at ClinicalTrials.gov (ID: NCT05068700).

BACKGROUND: Capnography is a quantitative and reliable method of determining the ventilatory status of patients. We describe the test characteristics of capnography obtained during Emergency Department triage for screening acidemia.
RESULTS: We performed an observational, pilot study of adult patients presenting to Emergency Department (ED) triage. The primary outcome was acidemia, as determined by the basic metabolic panel and/or blood gas during the ED visit. Secondary outcomes include comparison of estimated and measured respiratory rates (RR), relationships between end-tidal CO2 (EtCO2) and venous partial pressure of CO2, admission disposition, in-hospital mortality during admission, and capnogram waveform analysis. A total of 100 adult ED encounters were included in the study and acidemia ([Formula: see text] or [Formula: see text]) was identified in 28 patients. The measured respiratory rate (20.3 ± 6.4 breaths/min) was significantly different from the estimated rate (18.4 ± 1.6 breaths/min), and its area under the receiver operating curve (c-statistic) to predict acidemia was only 0.60 (95% CI 0.51-0.75, p = 0.03). A low end-tidal CO2 (EtCO2 < 32 mmHg) had positive (LR+) and negative (LR-) likelihood ratios of 4.68 (95% CI 2.59-8.45) and 0.34 (95% CI 0.19-0.61) for acidemia, respectively-corresponding to sensitivity 71.4% (95% CI 51.3-86.8) and specificity 84.7% (95% CI 74.3-92.1). The c-statistic for EtCO2 was 0.849 (95% CI 0.76-0.94, p = 0.00). Waveform analysis further revealed characteristically abnormal capnograms that were associated with underlying pathophysiology.
CONCLUSIONS: Capnography is a quantitative method of screening acidemia in patients and can be implemented feasibly in Emergency Department triage as an adjunct to vital signs. While it was shown to have only modest ability to predict acidemia, triage capnography has wide generalizability to screen other life-threatening disease processes such as sepsis or can serve as an early indicator of clinical deterioration.

Objective. The respiratory rate (RR) is considered one of the most informative vital signals. A well-validated standard for RR measurement in mechanically ventilated patient is capnography; a noninvasive technique for expiratory CO2measurements. Reliable RR measurements in spontaneously breathing patients remains a challenge as continuous mainstream capnography measurements are not available. This study aimed to assess the accuracy of RR measurement using electrical impedance tomography (EIT) in healthy volunteers and intensive care unit (ICU) patients on mechanical ventilation and spontaneously breathing post-extubation. Comparator methods included RR derived from both capnography and bioimpedance electrocardiogram (ECG) measurements.Approach. Twenty healthy volunteers wore an EIT belt and ECG electrodes while breathing through a capnometer within a 10-40 breaths per minute (BPM) range. Nineteen ICU patients underwent similar measurements during pressure support ventilation and spontaneously breathing after extubation from mechanical ventilation. Stable periods with regular breathing and no artefacts were selected, and agreement between measurement methods was assessed using Bland-Altman analysis for repeated measurements.Main result. Bland-Altman analysis revealed a bias less than 0.2 BPM, with tight limits of agreement (LOA) ±1.5 BPM in healthy volunteers and ventilated ICU patients when comparing EIT to capnography. Spontaneously breathing ICU patients had wider LOA (±2.5 BPM) when comparing EIT to ECG bioimpedance, but gold standard comparison was unavailable. RR measurements were stable for 91% of the time for capnography, 68% for EIT, and 64% of the ECG bioimpedance signals. After extubation, the percentage of stable periods decreased to 48% for EIT signals and to 55% for ECG bioimpedance.Significance. In periods of stable breathing, EIT demonstrated excellent RR measurement accuracy in healthy volunteers and ICU patients. However, stability of both EIT and ECG bioimpedance RR measurements declined in spontaneously breathing patients to approximately 50% of the time.

BACKGROUND: Understanding mechanisms of drug use decisions will inform the development of treatments for opioid use disorder (OUD). Decision-making experiments using neurobehavioral approaches require many trials or events of interest for statistical analysis, but the pharmacokinetics of most opioids limit dosing in humans.
OBJECTIVE: This experiment characterized the effects of repeated infusions of the ultra-short acting opioid remifentanil in people with OUD and physical opioid dependence.
METHODS: An inpatient study using a within-subjects, single-blind, escalating, within-session, pre-post design was conducted. Seven (3 female) subjects were maintained on oral oxycodone (40-60 mg, 4x/day = 160-240 total mg/day) for seven days prior to the dose-ranging session. Subjects received infusions of three ascending remifentanil doses (0.03, 0.1, 0.3 mcg/kg/infusion in 2 subjects; 0.1, 0.3, 1.0 mcg/kg/infusion in 5 subjects) every minute for 40 min per dose, with infusions administered over 5 s to model naturalistic delivery rates. End tidal carbon dioxide, respiration rate, oxygen saturation (SpO2) and heart rate were measured continuously. Blood pressure (BP), pupil diameter and self-reported drug effects were measured every 5 min.
RESULTS: Pupil diameter, SpO2 and systolic BP decreased, and ratings on prototypic subjective effects questionnaire items increased, as a function of remifentanil dose. The number of infusions held because of sedation or physiological parameters exceeding predetermined cutoffs also increased with dose.
CONCLUSIONS: This experiment established doses and procedures for the safe delivery of rapid, repeated remifentanil infusions to individuals with OUD and physical fentanyl dependence, which can be applied to the mechanistic study of opioid use decisions.

To assess the efficacy of an ECG-based method called thoracic impedance pneumography to reduce hypoxic events in endoscopy.
This was a single center, 1:1 randomized controlled trial.
The trial was conducted during the placement of percutaneous endoscopic gastrostomy (PEG).
173 patients who underwent PEG placement were enrolled in the present trial. Indication was oncological in most patients (89%). 58% of patients were ASA class II and 42% of patients ASA class III.
Patients were randomized in the standard monitoring group (SM) with pulse oximetry and automatic blood pressure measurement or in the intervention group with additional thoracic impedance pneumography (TIM). Sedation was performed with propofol by gastroenterologists or trained nurses.
Hypoxic episodes defined as SpO2 < 90% for >15 s were the primary endpoint. Secondary endpoints were minimal SpO2, apnea >10s/>30s and incurred costs.
Additional use of thoracic impedance pneumography reduced hypoxic episodes (TIM: 31% vs SM: 49%; p = 0.016; OR 0.47; NNT 5.6) and elevated minimal SpO2 per procedure (TIM: 90.0% ± 8.9; SM: 84.0% ± 17.6; p = 0.007) significantly. Apnea events >10s and > 30s were significantly more often detected in TIM (43%; 7%) compared to SM (1%; 0%; p < 0.001; p = 0.014) resulting in a time advantage of 17 s before the occurrence of hypoxic events. As a result, adjustments of oxygen flow were significantly more often necessary in SM than in TIM (p = 0.034) and assisted ventilation was less often needed in TIM (2%) compared with SM (9%; p = 0.053). Calculated costs for the additional use of thoracic impedance pneumography were 0.13$ (0.12 €/0.11 £) per procedure.
Additional thoracic impedance pneumography reduced the quantity and extent of hypoxic events with less need of assisted ventilation. Supplemental costs per procedure were negligible.
thoracic impedance pneumography, capnography, sedation, monitoring, gastrointestinal endoscopy, percutaneous endoscopic gastrostomy.

To determine the diagnostic accuracy of end-tidal carbon dioxide (ETCO2) detection using capnography for verifying the correct placement of nasogastric tubes (NGTs) among adult patients in hospital settings.
A prospective observational diagnostic study will be conducted. Patients ≥ 18-year-old and requiring the insertion of an NGT will be recruited using a convenience sampling method from 39 general medical and geriatric wards, intensive care units, accident and emergency departments, and subacute/rehabilitation/infirmary wards in 21 acute or subacute/convalescent/extended care hospitals. ETCO2 detection by sidestream capnography, which indicates an airway intubation of an NGT when a capnogram waveform or an ETCO2 level > 10mmHg (1.33 kPa) occurs, will serve as the index test. The reference standards will be the X-ray performed and pH value of gastric aspiration (pH ≤ 5.5) after the index test. Each participant will be included only once. Sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve of capnography will be calculated to assess the diagnostic performance of capnography. The variability in diagnostic accuracy in participants with different characteristics will be explored by using chi-squared or Fisher\'s exact tests. The time spent and the cost of the tests will be compared using the paired t-test. All statistical tests will be two-sided with a level of significance set at 0.05.
This study will provide evidence on the diagnostic accuracy of capnography in verifying NGT placement and its applicability to patients in hospitals settings, since this evidence is limited in the current literature. In addition, it will help identify the optimal combination of tests in verifying the correct placement of NGTs and inform the update of clinical practice guidelines and stakeholders\' decisions on the adoption of ETCO2 detection as a routine method for verifying NGT placement.
ClinicalTrials.gov ID: NCT05817864.

Describing the association of the peak inflation pressure (PIP) with end-tidal carbon dioxide (ETCO2) is a prerequisite for the development of closed loop ventilation in neonatal intensive care. We aimed to develop an in-vitro system to study this relationship.
A ventilator was connected to a test lung, supplied with a stable CO2 concentration from a cylinder. The PIP was altered and the change in ETCO2 per unit of PIP was calculated in three models mimicking respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD) and viral bronchiolitis.
The median (IQR) change in ETCO2 per unit of PIP was 0.23(0.13-0.38) kPa/cmH2O, using 138 paired measurements of PIP and ETCO2. The median (IQR) change in ETCO2 per unit of PIP, was higher when starting at an ETCO2 > 6 kPa [0.43(0.33-0.58) kPa/cmH2O] compared to starting at an ETCO2 < 6 kPa [0.14(0.08-0.20) kPa/cmH2O, p < 0.001]. The median (IQR) change in ETCO2 per unit of PIP, was larger in the model of RDS [0.33(0.13-0.51) kPa/cmH2O] compared to the BPD [0.23(0.13-0.33) kPa/cmH2O, p = 0.043] and the bronchiolitis models [0.15(0.10-0.31) kPa/cmH2O, p = 0.017].
The change in ETCO2 in response to increasing PIP was larger for higher ETCO2 values and in a model simulating neonatal RDS, compared to BPD and bronchiolitis.

Supplemental oxygen (SO) potentiates opioid-induced respiratory depression (OIRD) in experiments on healthy volunteers. Our objective was to examine the relationship between SO and OIRD in patients on surgical units.
This post-hoc analysis utilized a portion of the observational PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial dataset (202 patients, two trial sites), which involved blinded continuous pulse oximetry and capnography monitoring of postsurgical patients on surgical units. OIRD incidence was determined for patients receiving room air (RA), intermittent SO, or continuous SO. Generalized estimating equation (GEE) models, with a Poisson distribution, a log-link function and time of exposure as offset, were used to compare the incidence of OIRD when patients were receiving SO vs RA.
Within the analysis cohort, 74 patients were always on RA, 88 on intermittent and 40 on continuous SO. Compared with when on RA, when receiving SO patients had a higher risk for all OIRD episodes (incidence rate ratio [IRR] 2.7, 95% confidence interval [CI] 1.4-5.1), apnea episodes (IRR 2.8, 95% CI 1.5-5.2), and bradypnea episodes (IRR 3.0, 95% CI 1.2-7.9). Patients with high or intermediate PRODIGY scores had higher IRRs of OIRD episodes when receiving SO, compared with RA (IRR 4.5, 95% CI 2.2-9.6 and IRR 2.3, 95% CI 1.1-4.9, for high and intermediate scores, respectively).
Despite oxygen desaturation events not differing between SO and RA, SO may clinically promote OIRD. Clinicians should be aware that postoperative patients receiving SO therapy remain at increased risk for apnea and bradypnea.
Clinicaltrials.gov: NCT02811302, registered June 23, 2016.

Non-contact continuous respiratory rate monitoring is preferred for early detection of patient deterioration. However, this technique is under development; a gold standard respiratory monitor has not been established. Therefore, this prospective observational method comparison study aimed to compare the measurement accuracy of a non-contact continuous respiratory rate monitor, a microwave Doppler sensor positioned beneath the mattress, with that of other monitors.
The respiratory rate of intensive care unit patients was simultaneously measured using a microwave Doppler sensor, capnography, thoracic impedance pneumography, and a piezoelectric sensor beneath the mattress. Bias and 95% limits of agreement between the respiratory rate measured using capnography (standard reference) and that measured using the other three methods were calculated using Bland-Altman analysis for repeated measures. Clarke error grid (CEG) analysis evaluated the sensor\'s ability to assist in correct clinical decision-making.
Eighteen participants were included, and 2,307 data points were analyzed. The bias values (95% limits of agreement) of the microwave Doppler sensor, thoracic impedance pneumography, and piezoelectric sensor were 0.2 (- 4.8 to 5.2), 1.5 (- 4.4 to 7.4), and 0.4 (- 4.0 to 4.8) breaths per minute, respectively. Clinical decisions evaluated using CEG analyses were correct 98.1% of the time for the microwave Doppler sensor, which was similar to the performance of the other devices.
The microwave Doppler sensor had a small bias but relatively low precision, similar to other devices. In CEG analyses, the risk of each monitor leading to inadequate clinical decision-making was low.
UMIN000038900, February 1, 2020.