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Background: Ataxic breathing (AB) is a well-known manifestation of opioid effects in animals and humans, but is not routinely included in monitoring for opioid-induced respiratory depression (OIRD). We quantified AB in normal volunteers receiving increasing doses of remifentanil. We used a support vector machine (SVM) learning approach with features derived from a modified Poincaré plot. We tested the hypothesis that AB may be found when bradypnea and reduced mental status are not present., Methods: Twenty-six healthy volunteers (13 female) received escalating target effect-site concentrations of remifentanil with a low baseline dose of propofol to simulate typical breathing patterns in drowsy patients who had received parenteral opioids. We derived respiratory rate (RR) from respiratory inductance plethysmography, mental alertness from the Modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S), and AB severity on a 0 to 4 scale (categories ranging from none to severe) from the SVM. The primary outcome measure was sensitivity and specificity for AB to detect OIRD., Results: All respiratory measurements were obtained from unperturbed subjects during steady state in 121 assessments with complete data. The sensitivity of AB for detecting OIRD by the conventional method was 92% and specificity was 28%. As expected, 69 (72%) of the instances not diagnosed as OIRD using conventional measures were observed to have at least moderate AB., Conclusions: AB was frequently present in the absence of traditionally detected OIRD as defined by reduced mental alertness (MOAA/S score of <4) and bradypnea (RR <8 breaths/min). These results justify the need for future trials to explore replicability with other opioids and clinical utility of AB as an add-on measure in recognizing OIRD., Competing Interests: Conflicts of interest, Funding: See Disclosures at the end of the article., (Copyright © 2024 International Anesthesia Research Society.)

Background: Opioid-induced respiratory depression (OIRD) is traditionally recognized by assessment of respiratory rate, arterial oxygen saturation, end-tidal CO2, and mental status. Although an irregular or ataxic breathing pattern is widely recognized as a manifestation of opioid effects, there is no standardized method for assessing ataxic breathing severity. The purpose of this study was to explore using a machine-learning algorithm for quantifying the severity of opioid-induced ataxic breathing. We hypothesized that domain experts would have high interrater agreement with each other and that a machine-learning algorithm would have high interrater agreement with the domain experts for ataxic breathing severity assessment., Methods: We administered target-controlled infusions of propofol and remifentanil to 26 healthy volunteers to simulate light sleep and OIRD. Respiration data were collected from respiratory inductance plethysmography (RIP) bands and an intranasal pressure transducer. Three domain experts quantified the severity of ataxic breathing in accordance with a visual scoring template. The Krippendorff alpha, which reports the extent of interrater agreement among N raters, was used to assess agreement among the 3 domain experts. A multiclass support vector machine (SVM) was trained on a subset of the domain expert-labeled data and then used to quantify ataxic breathing severity on the remaining data. The Vanbelle kappa was used to assess the interrater agreement of the machine-learning algorithm with the grouped domain experts. The Vanbelle kappa expands on the Krippendorff alpha by isolating a single rater-in this case, the machine-learning algorithm-and comparing it to a group of raters. Acceptance criteria for both statistical measures were set at >0.8. The SVM was trained and tested using 2 sensor inputs for the breath marks: RIP and intranasal pressure., Results: Krippendorff alpha was 0.93 (95% confidence interval [CI], 0.91-0.95) for the 3 domain experts. Vanbelle kappa was 0.98 (95% CI, 0.96-0.99) for the RIP SVM and 0.96 (0.92-0.98) for the intranasal pressure SVM compared to the domain experts., Conclusions: We concluded it may be feasible for a machine-learning algorithm to quantify ataxic breathing severity in a manner consistent with a panel of domain experts. This methodology may be helpful in conjunction with traditional measures to identify patients experiencing OIRD.

Background: Supplemental oxygen is administered during procedural sedation to prevent hypoxemia. Continuous flow oxygen, the most widespread method, is generally adequate but distorts capnography. Pulsed flow oxygen is novel and ideally will not distort capnography. We have developed a prototype oxygen administration system designed to try to facilitate end-tidal carbon dioxide (ETCO2) measurement. We conducted a volunteer study (ClinicalTrials.gov, NCT02886312) to determine how much nasal ETCO2 measurements vary with oxygen flow rate. We also conducted a clinical study (NCT02962570) to determine the median difference and limits of agreement between ETCO2 measurements made with and without administering oxygen., Methods: Both studies were conducted at the University of Utah and participants acted as their own control. Inclusion criteria were age 18 years and older with an American Society of Anesthesiologists physical status of I-III. Exclusion criteria included acute respiratory distress syndrome, pneumonia, lung or cardiovascular disease, nasal/bronchial congestion, pregnancy, oxygen saturation measured by pulse oximetry <93%, and a procedure scheduled for <20 minutes. For the volunteer study, pulsed and continuous flow was administered at rates from 2 to 10 L/min using a single sequence of technique and flow. The median absolute deviation from the median value was analyzed for the primary outcome of ETCO2. For the clinical study, ETCO2 measurements (the primary outcome) were collected while administering pulsed and continuous flow at rates between 1 and 5 L/min and were compared to measurements without oxygen flow. Due to institutional review board requirements for patient safety, this study was not randomized. After completing the study, measurements with and without administering oxygen were analyzed to determine median differences and 95% limits of agreement for each administration technique., Results: Thirty volunteers and 60 patients participated in these studies which ended after enrolling the predetermined number of participants. In volunteers, the median absolute deviation for ETCO2 measurements made while administering pulsed flow oxygen (0.89; 25%-75% quantiles: 0.3-1.2) was smaller than while administering continuous flow oxygen (3.93; 25%-75% quantiles: 2.2-6.2). In sedated patients, the median difference was larger during continuous flow oxygen (-6.8 mm Hg; 25%-75% quantiles: -12.5 to -2.1) than during pulsed flow oxygen (0.1 mm Hg; 25%-75% quantiles: -0.5 to 1.5). The 95% limits of agreement were also narrower during pulsed flow oxygen (-2.4 to 4.5 vs -30.5 to 2.4 mm Hg)., Conclusions: We have shown that nasal ETCO2 measurements while administering pulsed flow have little deviation and agree well with measurements made without administering oxygen. We have also demonstrated that ETCO2 measurements during continuous flow oxygen have large deviation and wide limits of agreement when compared with measurements made without administering oxygen.

Background: Gastric reflux leading to pulmonary aspiration is a frequent event in mechanically ventilated, gastric-fed patients, which can lead to ventilator-associated complications and pneumonia., Objectives: The objectives of this study were to determine the association between gastric reflux and aspiration using the presence of pepsin in oral or tracheal secretions as a marker of reflux or aspiration and to determine the association between the pH (range, 0-14) and the presence of pepsin in oral secretions., Methods: A descriptive correlational study was conducted in mechanically ventilated surgical or medical patients receiving gastric tube feedings. Oral secretions were suctioned hourly and tracheal secretions every 2 to 3 hours for 12-hour periods over 1 to 2 days in 15 patients., Results: There were 142 paired samples of oral tracheal secretions. A majority of samples (60%) had the same results, with 32% both pepsin-positive and 27% both pepsin-negative. The range of pH measurements was 4 to 8, with a mean of 6.3 ± 0.05. Ninety oral specimens had a pH of 4 to 6. Forty-seven of the oral specimens with pH measures between 4 and 6 (52%) were pepsin-positive. The correlation of pH percent pepsin-positive oral secretions was not significant., Conclusion: Aspiration events were more frequent than reflux events. Measurement of actual pepsin concentration to detect new reflux and aspiration events is recommended in future studies. Bedside pH measures of oral secretions are not a valid marker of gastric reflux.

Background: Undetected apnea can lead to severe hypoxia, bradycardia, and cardiac arrest. Tracheal sounds entropy has been proved to be a robust method for estimating respiratory flow, thus maybe a more reliable way to detect obstructive and central apnea during sedation., Methods: A secondary analysis of a previous pharmacodynamics study was conducted. Twenty volunteers received propofol and remifentinal until they became unresponsive to the insertion of a bougie into the esophagus. Respiratory flow rate and tracheal sounds were recorded using a pneumotachometer and a microphone. The logarithm of the tracheal sound Shannon entropy (Log-E) was calculated to estimate flow rate. An adaptive Log-E threshold was used to distinguish between the presence of normal breath and apnea. Apnea detected from tracheal sounds was compared to the apnea detected from respiratory flow rate., Results: The volunteers stopped breathing for 15 s or longer (apnea) 322 times during the 12.9-h study. Apnea was correctly detected 310 times from both the tracheal sounds and the respiratory flow. Periods of apnea were not detected by the tracheal sounds 12 times. The absence of tracheal sounds was falsely detected as apnea 89 times. Normal breathing was detected correctly 1,196 times. The acoustic method detected obstructive and central apnea in sedated volunteers with 95% sensitivity and 92% specificity., Conclusions: We found that the entropy of the acoustic signal from a microphone placed over the trachea may reliably provide an early warning of the onset of obstructive and central apnea in volunteers under sedation.

Background: Hypercapnia with hyperventilation shortens the time between turning off the vaporizer (1 MAC) and when patients open their eyes after isoflurane anesthesia by 62%., Methods: In the present study we tested whether a proportional shortening occurs with sevoflurane and desflurane., Results: Consistent with a proportional shortening, we found that hypercapnia with hyperventilation decreased recovery times by 52% for sevoflurane and 64% for desflurane (when compared with normal ventilation with normocapnia)., Conclusion: Concurrent hyperventilation to rapidly remove the anesthetic from the lungs and rebreathing to induce hypercapnia can significantly shorten recovery times and produce the same proportionate decrease for anesthetics that differ in solubility.

Background: Anesthetic clearance from the lungs and the circle rebreathing system can be maximized using hyperventilation and high fresh gas flows. However, the concomitant clearance of CO2 decreases PAco2, thereby decreasing cerebral blood flow and slowing the clearance of anesthetic from the brain. This study shows that in addition to hyperventilation, hypercapnia (CO2 infusion or rebreathing) is a significant factor in decreasing emergence time from inhaled anesthesia., Methods: We anesthetized seven pigs with 2 MACPIG of isoflurane and four with 2 MACPIG of sevoflurane. After 2 h, anesthesia was discontinued, and the animals were hyperventilated. The time to movement of multiple limbs was measured under hypocapnic (end-tidal CO2 = 22 mm Hg) and hypercapnic (end-tidal CO2 = 55 mm Hg) conditions., Results: The time between turning off the vaporizer and to movement of multiple limbs was faster with hypercapnia during hyperventilation. Emergence time from isoflurane and sevoflurane anesthesia was shortened by an average of 65% with rebreathing or with the use of a CO2 controller (P < 0.05)., Conclusions: Hypercapnia, along with hyperventilation, may be used clinically to decrease emergence time from inhaled anesthesia. These time savings might reduce drug costs. In addition, higher PAco2 during emergence may enhance respiratory drive and airway protection after tracheal extubation.

Background: To shorten emergence time after a procedure using volatile anesthesia, 78% of anesthesiologists recently surveyed used hyperventilation to rapidly clear the anesthetic from the lungs. Hyperventilation has not been universally adapted into clinical practice because it also decreases the Paco2, which decreases cerebral bloodflow and depresses respiratory drive. Adding deadspace to the patient's airway may be a simple and safe method of maintaining a normal or slightly increased Paco2 during hyperventilation., Methods: We evaluated the differences in emergence time in 20 surgical patients undergoing 1 MAC of isoflurane under mild hypocapnia (ETco2 approximately 28 mmHg) and mild hypercapnia (ETco2 approximately 55 mmHg). The minute ventilation in half the patients was doubled during emergence, and hypercapnia was maintained by insertion of additional airway deadspace to keep the ETco2 close to 55 mmHg during hyperventilation. A charcoal canister adsorbed the volatile anesthetic from the deadspace. Fresh gas flows were increased to 10 L/min during emergence in all patients., Results: The time between turning off the vaporizer and the time when the patients opened their eyes and mouths, the time of tracheal extubation, and the time for normalized bispectral index to increase to 0.95 were faster whenever hypercapnic hyperventilation was maintained using rebreathing and anesthetic adsorption (P < 0.001). The time to tracheal extubation was shortened by an average of 59%., Conclusions: The emergence time after isoflurane anesthesia can be shortened significantly by using hyperventilation to rapidly clear the anesthetic from the lungs and CO2 rebreathing to induce hypercapnia during hyperventilation. The device should be considered when it is important to provide a rapid emergence, especially after surgical procedures where a high concentration of the volatile anesthetic was maintained right up to the end of the procedure, or where surgery ends abruptly and without warning.

We have developed an easy-to-use, noninvasive piezoelectric sensor for quantitative monitoring of neuromuscular block. In a clinical evaluation with 23 patients, the piezo sensor was objectively compared to a mechanomyogram (MMG) for its ability to measure train-of-four (TOF) ratio from the adductor pollicis. After administration of succinylcholine (120-200 mg intravenously [i.v.]) to facilitate intubation, neuromuscular block was maintained with vecuronium by either boluses (1-2 mg i.v.) or an infusion (0.4-1.0 micrograms.kg-1.min-1 i.v.). Paired measurements were made of the TOF ratio from both sensors over a complete range of block levels (8%-100%). The difference in the TOF ratio measurement between the sensors showed a bias of 0.018. The SD of the difference between the sensors was +/- 0.129. The limits of agreement, which define the range in which 95% of the differences between the sensor measurements lie, were from -0.24 to 0.275. The sensitivity of the piezo sensor for detecting recovery based on a TOF ratio greater than 0.70 was shown to be 0.74 with specificity of 0.91. Under the conditions tested, the piezo sensor was not as accurate as the MMG. However, it was able to predict recovery of neuromuscular block with better accuracy than shown previously by manual evaluation of the TOF ratio, making it a reasonable, convenient alternative for quantitative monitoring of recovery from neuromuscular block.

The proliferation of monitors and alarms in the operating room may lead to increased confusion and misdiagnosis unless the information provided is better organized. Intelligent alarm systems are being developed to organize these alarms, on the assumption that they will shorten the time anesthesiologists need to detect and correct faults. This study compared the human response time (the time between the sounding of an alarm and the resolution of a fault) when anesthesiologists used a conventional alarm system and when they used an intelligent alarm system. In a simulated operating room environment, we asked 20 anesthesiologists to resolve seven breathing circuit faults as quickly as possible. Human response time was 62% faster, decreasing from 45 to 17 s, when the intelligent alarm system was used. The standard deviations in response time were only half as large for the intelligent alarm system. It appears that the computer-based neural network in the intelligent alarm system diagnosed faults more rapidly and consistently than did the anesthesiologists. This study indicates that breathing circuit faults may be more rapidly corrected when the anesthesiologist is guided by intelligent alarms.

These experiments were designed to test the hypothesis that increases in blood flow to the lower brainstem would be greater than forebrain regions during arterial hypercapnia. Total and regional cerebral blood flow (CBF) was measured via the tracer microsphere technique in seven anesthetized New Zealand white rabbits during normocapnia (arterial PCO2 congruent to 40 torr) and hypercapnia (arterial PCO2 congruent to 80 torr). During normocapnia average CBF was 0.77 ml/min/g, and regional measurements of blood flow indicated significantly greater flow to the cerebrum (0.86 ml/min/g) than either the medulla (0.52 ml/min/g) or the pons (0.49 ml/min/g). When arterial PCO2 was increased average CBF increased 113%, and a significant linear regression was calculated for arterial PCO2 vs CBF [CBF (ml/min/g) = 0.028 PCO2 (torr) - 0.502]. The distribution of blood flow within the brain was similar to normocapnia except that blood flow to the cerebellum was now greater than any other brain region (1.97 ml/min/g for the cerebellum compared to 1.66 ml/min/g for the cerebrum). Absolute increases in blood flow to the lower brainstem were equal to or less than other areas of the brain. We conclude that ponto-medullary blood flow does not increase disproportionate to other areas of the brain during hypercapnia, but some redistribution of CBF does occur in that cerebellar blood flow increased significantly more than the cerebrum, medulla, or pons.