Inadvertent severe hypercapnia during general anesthesia: drop-in oxygen saturation or electrocardiography changes; which one warns us earlier?

Background During general anesthesia especially when the nurse or anesthesiologist forgets to change manual to controlled mode after successful endotracheal intubation, capnography shows End-tidal Co2 above 20 mmHg after checking the place of the tracheal tube and will remain on the screen permanently. In this scenario, the patient receives a high concentration of oxygen, and Spo2 (oxygen saturation) does not drop for a long time which is too late to intervene. It has been all-time questionable which one of the cardiac dysrhythmias or Spo2 dropping occurs earlier. Results Medical records of seven deceased patients reviewed. All of them had electrocardiogram changes including premature ventricular contraction or bradycardia as a first warning sign. Oxygen saturation remains above 95% even with cardiac dysrhythmia. Conclusions Bradycardia and premature ventricular contraction were the first warning findings for severe hypercapnia during general anesthesia and occurred earlier than dropping oxygen saturation. Furthermore, the normal capnography waveform is more reliable than the End-tidal Co2 number for monitoring.

Value of variation of end-tidal carbon dioxide for predicting fluid responsiveness during the passive leg raising test in patients with mechanical ventilation: a systematic review and meta-analysis

Background The ability of end-tidal carbon dioxide (ΔEtCO2) for predicting fluid responsiveness has been extensively studied with conflicting results. This meta-analysis aimed to explore the value of ΔEtCO2 for predicting fluid responsiveness during the passive leg raising (PLR) test in patients with mechanical ventilation. Methods PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched up to November 2021. The diagnostic odds ratio (DOR), sensitivity, and specificity were calculated. The summary receiver operating characteristic curve was estimated, and the area under the curve (AUROC) was calculated. Q test and I2 statistics were used for study heterogeneity and publication bias was assessed by Deeks’ funnel plot asymmetry test. We performed meta-regression analysis for heterogeneity exploration and sensitivity analysis for the publication bias. Results Overall, six studies including 298 patients were included in this review, of whom 149 (50%) were fluid responsive. The cutoff values of ΔEtCO2 in four studies was 5%, one was 5.8% and the other one was an absolute increase 2 mmHg. Heterogeneity between studies was assessed with an overall Q = 4.098, I2 = 51%, and P = 0.064. The pooled sensitivity and specificity for the overall population were 0.79 (95% CI 0.72–0.85) and 0.90 (95% CI 0.77–0.96), respectively. The DOR was 35 (95% CI 12–107). The pooled AUROC was 0.81 (95% CI 0.77–0.84). On meta-regression analysis, the number of patients was sources of heterogeneity. The sensitivity analysis showed that the pooled DOR ranged from 21 to 140 and the pooled AUC ranged from 0.92 to 0.96 when one study was omitted. Conclusions Though the limited number of studies included and study heterogeneity, our meta-analysis confirmed that the ΔEtCO2 performed moderately in predicting fluid responsiveness during the PLR test in patients with mechanical ventilation.

Cardiac Arrest due to Carbon Dioxide Embolism During Laparoscopic Gynecologic Surgery of a Patient with Previous Abdominal Surgery: A Case Report

Catastrophic carbon dioxide (CO2) embolism is a rare, but potentially life-threatening, the complication of laparoscopic gynecologic surgery. We report the case of a healthy 53-year-old woman who developed CO2 embolism and cardiac arrest during laparoscopic surgery. She had a history of two cesarean sections and had extensive peritoneal adhesions. After placement of the trocar and insufflation of CO2, end-tidal CO2 dropped from 35 to 15 mm Hg, and the patient had a cardiovascular collapse. In this patient, CO2 embolism was diagnosed on the basis of a sudden decrease in end-tidal CO2, hypotension, and hypoxemia. The patient was managed quickly and aggressively. The patient recovered completely following the treatment for CO2 embolism, with no cardiopulmonary or neurological sequelae. There is an increased risk of catastrophic CO2 embolism during laparoscopic gynecologic surgery in patients with previous abdominal surgery. Therefore, the surgeon and anesthesiologist should remain vigilant to promote early detection of CO2 embolism.

The Clamping of End-Tidal Carbon Dioxide Does Not Influence Cognitive Function Performance During Moderate Hyperthermia With or Without Skin Temperature Manipulation

Increases in body temperature from heat stress (i.e., hyperthermia) generally impairs cognitive function across a range of domains and complexities, but the relative contribution from skin versus core temperature changes remains unclear. Hyperthermia also elicits a hyperventilatory response that decreases the partial pressure of end-tidal carbon dioxide (PetCO2) and subsequently cerebral blood flow that may influence cognitive function. We studied the role of skin and core temperature along with PetCO2 on cognitive function across a range of domains. Eleven males completed a randomized, single-blinded protocol consisting of poikilocapnia (POIKI, no PetCO2 control) or isocapnia (ISO, PetCO2 maintained at baseline levels) during passive heating using a water-perfused suit (water temperature ~ 49°C) while middle cerebral artery velocity (MCAv) was measured continuously as an index of cerebral blood flow. Cognitive testing was completed at baseline, neutral core-hot skin (37.0 ± 0.2°C-37.4 ± 0.3°C), hot core-hot skin (38.6 ± 0.3°C-38.7 ± 0.2°C), and hot core-cooled skin (38.5 ± 0.3°C-34.7 ± 0.6°C). The cognitive test battery consisted of a detection task (psychomotor processing), 2-back task (working memory), set-shifting and Groton Maze Learning Task (executive function). At hot core-hot skin, poikilocapnia led to significant (both p < 0.05) decreases in PetCO2 (∆−21%) and MCAv (∆−26%) from baseline, while isocapnia clamped PetCO2 (∆ + 4% from baseline) leading to a significantly (p = 0.023) higher MCAv (∆−18% from baseline) compared to poikilocapnia. There were no significant differences in errors made on any task (all p > 0.05) irrespective of skin temperature or PetCO2 manipulation. We conclude that neither skin temperature nor PetCO2 maintenance significantly alter cognitive function during passive hyperthermia.

Efficacy and Safety Testing of a COVID-19 Era Emergency Ventilator in a Healthy Rabbit Lung Model

Background: The COVID-19 pandemic revealed a substantial and unmet need for low-cost, easily accessible mechanical ventilation strategies for use in medical resource-challenged areas. Internationally, several groups developed non-conventional COVID-19 era emergency ventilator strategies as a stopgap measure when conventional ventilators were unavailable. Here, we compared our FALCON emergency ventilator in a rabbit model and compared its safety and functionality to conventional mechanical ventilation. Methods: New Zealand white rabbits (n = 5) received mechanical ventilation from either the FALCON or a conventional mechanical ventilator (Engström CarestationTM) for 1 hour each. Airflow and pressure, blood O2 saturation, end tidal CO2, and arterial blood gas measurements were measured. Additionally, gross and histological lung samples were compared to spontaneously breathing rabbits (n = 3) to assess signs of ventilator induced lung injury.Results: All rabbits were successfully ventilated with the FALCON. At identical ventilator settings, tidal volumes, pressures, and respiratory rates were similar between both ventilators, but the inspiratory to expiratory ratio was lower using the FALCON. End tidal CO2 was significantly higher on the FALCON, and arterial blood gas measurements demonstrated lower arterial partial pressure of O2 at 30 minutes and higher arterial partial pressure of CO2 at 30 and 60 minutes using the FALCON. However, when ventilated at higher respiratory rates, we observed a stepwise decrease in end tidal CO2. Poincaré plot analysis demonstrated small but significant increases in short-term and long-term variation of peak inspiratory pressure generation from the FALCON. Wet to dry lung weight and lung injury scoring between the mechanically ventilated and spontaneously breathing rabbits were similar. Conclusions: Although conventional ventilators are always preferable outside of emergency use, the FALCON ventilator safely and effectively ventilated healthy rabbits without lung injury. Emergency ventilation using accessible and inexpensive strategies like the FALCON may be useful for communities with low access to medical resources and as a backup form of emergency ventilation.

Tracheal Tube-Mounted Camera Assisted Intubation vs. Videolaryngoscopy in Expected Difficult Airway: A Prospective, Randomized Trial (VivaOP Trial)

Background: Tracheal intubation in patients with an expected difficult airway may be facilitated by videolaryngoscopy (VL). The VL viewing axis angle is specified by the blade shape and visualization of the larynx may fail if the angle does not meet anatomy of the patient. A tube with an integrated camera at its tip (VST, VivaSight-SL) may be advantageous due to its adjustable viewing axis by means of angulating an included stylet.Methods: With ethics approval, we studied the VST vs. VL in a prospective non-inferiority trial using end-tidal oxygen fractions (etO2) after intubation, first-attempt success rates (FAS), visualization assessed by the percentage of glottis opening (POGO) scale, and time to intubation (TTI) as outcome parameters.Results: In this study, 48 patients with a predicted difficult airway were randomized 1:1 to intubation with VST or VL. Concerning oxygenation, the VST was non-inferior to VL with etO2 of 0.79 ± 0.08 (95% CIs: 0.75–0.82) vs. 0.81 ± 0.06 (0.79–0.84) for the VL group, mean difference 0.02 (−0.07 to 0.02), p = 0.234. FAS was 79% for VST and 88% for VL (p = 0.449). POGO was 89 ± 21% in the VST-group and 60 ± 36% in the VL group, p = 0.002. TTI was 100 ± 57 s in the VST group and 68 ± 65 s in the VL group (p = 0.079). TTI with one attempt was 84 ± 31 s vs. 49 ± 14 s, p < 0.001.Conclusion: In patients with difficult airways, tracheal intubation with the VST is feasible without negative impact on oxygenation, improves visualization but prolongs intubation. The VST deserves further study to identify patients that might benefit from intubation with VST.

A PHASE IIA OPEN LABEL STUDY TO EVALUATE THE SAFETY, TOLERABILITY AND EFFICACY OF S-1226 ADMINISTERED BY NEBULIZATION IN SUBJECTS WITH CYSTIC FIBROSIS LUNG DISEASE

Rationale: There are approximately 35,000 people with Cystic Fibrosis (CF) in North America. This condition is characterized by impaired airway clearance resulting in chronic infection and bronchiectasis. Current airway clearance treatments include nebulized hypertonic saline and Recombinant Human DNase, which may be limited by bronchospasm and cost, respectively. S-1226, a novel biophysical therapeutic agent combines carbon dioxide (CO2) enriched air (a bronchodilator) with nebulized perflubron (PFOB), (a synthetic surfactant). They act synergistically to open airways, enhance mucus clearance, and increase blood oxygenation. We report preliminary results from a Phase II clinical trial. Methods: An open label, single-center, Phase IIa study of subjects (≥14 years) with mild-moderate (FEV1 40-80%) CF lung disease treated with multiple ascending doses of S-1226 (week one), followed by the highest tolerated dose for 5 consecutive days (week two). Each dose of S-1226 comprised three successive treatments of 3mL of perflubron nebulized (Circulaire II) for two-minutes with CO2 concentrations ranging from 4 to 12%. The oxygen concentration was maintained at ambient levels. Treatments were administered twice daily. Efficacy measurements included spirometry, lung clearance index (LCI), lung volumes, blood oxygenation (SPO2), sputum weight and the respiratory domain of quality of life (QOL) questionnaire (CFQ-R). Safety included adverse event (AE) and tolerance monitoring, vital signs, and assessment of end-tidal CO2. Results: We report preliminary data on safety and efficacy for six CF subjects. All subjects tolerated all doses of S-1226. There were 5 reported AEs in 3 subjects. All were mild and resolved spontaneously. End-tidal CO2 immediately after treatment was comparable to baseline. SpO2 (baseline 91-95%) rapidly improved in all subjects with treatment. Five of six subjects had improvements in their LCI. Three subjects that were compliant in collecting mucus showed increases of 14%, 29% and 64% over baseline. Percent predicted FEV1 response was variable, decreasing initially with return to baseline values at two weeks. Four of the six subjects reported improvements in CFQ-R scores, three of which showed a clinically important difference (> 4 points). An important observation was that S-1226 controlled irritant (but not productive) cough in all five subjects and at all concentrations of S-1226. Conclusions: All doses of S-1226 were safe and well tolerated. Treatments with up to 12% extrinsic CO2 over short periods of time did not result in an elevation of end-tidal CO2. The preliminary efficacy results, including overall improved oxygen saturation, CFQ-R scores, increased expectorated mucus and LCI values provide evidence for potential beneficial effects of S-1226 for CF lung disease but require larger trials and longer-term treatments to fully assess efficacy in CF.

The Dynamic Relationship Between Cortical Oxygenation and End-Tidal CO2 Transient Changes Is Impaired in Mild Cognitive Impairment Patients

Background: Recent studies have utilized data-based dynamic modeling to establish strong association between dysregulation of cerebral perfusion and Mild Cognitive Impairment (MCI), expressed in terms of impaired CO2 dynamic vasomotor reactivity in the cerebral vasculature. This raises the question of whether this is due to dysregulation of central mechanisms (baroreflex and chemoreflex) or mechanisms of cortical tissue oxygenation (CTO) in MCI patients. We seek to answer this question using data-based input-output predictive dynamic models.Objective: To use subject-specific data-based multivariate input-output dynamic models to quantify the effects of systemic hemodynamic and blood CO2 changes upon CTO and to examine possible differences in CTO regulation in MCI patients versus age-matched controls, after the dynamic effects of central regulatory mechanisms have been accounted for by using cerebral flow measurements as another input.Methods: The employed model-based approach utilized the general dynamic modeling methodology of Laguerre expansions of kernels to analyze spontaneous time-series data in order to quantify the dynamic effects upon CTO (an index of relative capillary hemoglobin saturation distribution measured via near-infrared spectroscopy) of contemporaneous changes in end-tidal CO2 (proxy for arterial CO2), arterial blood pressure and cerebral blood flow velocity in the middle cerebral arteries (measured via transcranial Doppler). Model-based indices (physio-markers) were computed for these distinct dynamic relationships.Results: The obtained model-based indices revealed significant statistical differences of CO2 dynamic vasomotor reactivity in cortical tissue, combined with “perfusivity” that quantifies the dynamic relationship between flow velocity in cerebral arteries and CTO in MCI patients versus age-matched controls (p = 0.006). Significant difference between MCI patients and age-matched controls was also found in the respective model-prediction accuracy (p = 0.0001). Combination of these model-based indices via the Fisher Discriminant achieved even smaller p-value (p = 5 × 10–5) when comparing MCI patients with controls. The differences in dynamics of CTO in MCI patients are in lower frequencies (<0.05 Hz), suggesting impairment in endocrine/metabolic (rather than neural) mechanisms.Conclusion: The presented model-based approach elucidates the multivariate dynamic connectivity in the regulation of cerebral perfusion and yields model-based indices that may serve as physio-markers of possible dysregulation of CTO during transient CO2 changes in MCI patients.