The effect of high-flow nasal oxygen flow rate on gas exchange in apnoeic patients: a randomised controlled trial.

High-flow nasal oxygen can be administered at induction of anaesthesia for the purposes of pre-oxygenation and apnoeic oxygenation. This intervention is claimed to enhance carbon dioxide elimination during apnoea, but the extent to which this occurs remains poorly quantified. The optimal nasal oxygen flow rate for gas exchange is also unknown. In this study, 114 patients received pre-oxygenation with high-flow nasal oxygen at 50 l.min-1. At the onset of apnoea, patients were allocated randomly to receive one of three nasal oxygen flow rates: 0 l.min-1; 70 l.min-1; or 120 l.min-1. After 4 minutes of apnoea, all oxygen delivery was ceased, tracheal intubation was performed, and oxygen delivery was recommenced when SpO2 was 92%. Mean (SD) PaCO2 rise during the first minute of apnoea was 1.39 (0.39) kPa, 1.41 (0.29) kPa, and 1.26 (0.38) kPa in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, respectively; p = 0.16. During the second, third and fourth minutes of apnoea, mean (SD) rates of rise in PaCO2 were 0.34 (0.08) kPa.min-1, 0.36 (0.06) kPa.min-1 and 0.37 (0.07) kPa.min-1 in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, respectively; p = 0.17. After 4 minutes of apnoea, median (IQR [range]) arterial oxygen partial pressures in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups were 24.5 (18.6-31.4 [12.3-48.3]) kPa; 36.6 (28.1-43.8 [9.8-56.9]) kPa; and 37.6 (26.5-45.4 [11.0-56.6]) kPa, respectively; p < 0.001. Median (IQR [range]) times to desaturate to 92% after the onset of apnoea in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, were 412 (347-509 [190-796]) s; 533 (467-641 [192-958]) s; and 531 (462-681 [326-1007]) s, respectively; p < 0.001. In conclusion, the rate of carbon dioxide accumulation in arterial blood did not differ significantly between apnoeic patients who received high-flow nasal oxygen and those who did not.

Carbon dioxide and MAPK signalling: towards therapy for inflammation.

Inflammation, although necessary to fight infections, becomes a threat when it exceeds the capability of the immune system to control it. In addition, inflammation is a cause and/or symptom of many different disorders, including metabolic, neurodegenerative, autoimmune and cardiovascular diseases. Comorbidities and advanced age are typical predictors of more severe cases of seasonal viral infection, with COVID-19 a clear example. The primary importance of mitogen-activated protein kinases (MAPKs) in the course of COVID-19 is evident in the mechanisms by which cells are infected with SARS-CoV-2; the cytokine storm that profoundly worsens a patient's condition; the pathogenesis of diseases, such as diabetes, obesity, and hypertension, that contribute to a worsened prognosis; and post-COVID-19 complications, such as brain fog and thrombosis. An increasing number of reports have revealed that MAPKs are regulated by carbon dioxide (CO2); hence, we reviewed the literature to identify associations between CO2 and MAPKs and possible therapeutic benefits resulting from the elevation of CO2 levels. CO2 regulates key processes leading to and resulting from inflammation, and the therapeutic effects of CO2 (or bicarbonate, HCO3-) have been documented in all of the abovementioned comorbidities and complications of COVID-19 in which MAPKs play roles. The overlapping MAPK and CO2 signalling pathways in the contexts of allergy, apoptosis and cell survival, pulmonary oedema (alveolar fluid resorption), and mechanical ventilation-induced responses in lungs and related to mitochondria are also discussed. Video Abstract.

Causes of hypercapnic respiratory failure: a population-based case-control study.

OBJECTIVE: There are no population-based data on the relative importance of specific causes of hypercapnic respiratory failure (HRF). We sought to quantify the associations between hospitalisation with HRF and potential antecedent causes including chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, and congestive cardiac failure. We used data on the prevalence of these conditions to estimate the population attributable fraction for each cause. METHODS: A case-control study was conducted among residents aged ≥ 40 years from the Liverpool local government area in Sydney, Australia. Cases were identified from hospital records based on PaCO2 > 45 mmHg. Controls were randomly selected from the study population using a cluster sampling design. We collected self-reported data on medication use and performed spirometry, limited-channel sleep studies, venous sampling for N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and sniff nasal inspiratory pressure (SNIP) measurements. Logistic regression analyses were performed using directed acyclic graphs to identify covariates. RESULTS: We recruited 42 cases and 105 controls. HRF was strongly associated with post-bronchodilator airflow obstruction, elevated NT-proBNP levels, reduced SNIP measurements and self-reported opioid medication use. There were no differences in the apnoea-hypopnea index or oxygen desaturation index between groups. COPD had the highest population attributable fraction (42%, 95% confidence interval 18% to 59%). CONCLUSIONS: COPD, congestive cardiac failure, and self-reported use of opioid medications, but not obstructive sleep apnea, are important causes of HRF among adults over 40 years old. No single cause accounts for the majority of cases based on the population attributable fraction.

Influence of graded hypercapnia on endurance exercise performance in healthy humans.

Military and/or emergency services personnel may be required to perform high-intensity physical activity during exposure to elevated inspired carbon dioxide (CO2). Although many of the physiological consequences of hypercapnia are well characterized, the effects of graded increases in inspired CO2 on self-paced endurance performance have not been determined. The aim of this study was to compare the effects of 0%, 2%, and 4% inspired CO2 on 2-mile run performance, as well as physiological and perceptual responses during time trial exercise. Twelve physically active volunteers (peak oxygen uptake = 49 ± 5 mL·kg-1·min-1; 3 women) performed three experimental trials in a randomized, single-blind, crossover manner, breathing 21% oxygen with either 0%, 2%, or 4% CO2. During each trial, participants completed 10 min of walking at ∼40% peak oxygen uptake followed by a self-paced 2-mile treadmill time trial. One participant was unable to complete the 4% CO2 trial due to lightheadedness during the run. Compared with the 0% CO2 trial, run performance was 5 ± 3% and 7 ± 3% slower in the 2% and 4% CO2 trials, respectively (both P < 0.001). Run performance was significantly slower with 4% versus 2% CO2 (P = 0.046). The dose-dependent performance impairments were accompanied by stepwise increases in mean ventilation, despite significant reductions in running speed. Dyspnea and headache were significantly elevated during the 4% CO2 trial compared with both the 0% and 2% trials. Overall, our findings show that graded increases in inspired CO2 impair endurance performance in a stepwise manner in healthy humans.

Transcutaneous CO2 monitoring as indication for inpatient non-invasive ventilation initiation in patients with amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) is characterized by profound muscle weakness, including diaphragmatic weakness resulting in hypercapnic respiratory failure. While non-invasive ventilation (NIV) is usually initiated in the home, patients presenting with hypercapnic respiratory failure may be at high risk of adverse outcomes with delays in treatment. We aim to describe the clinical utility of transcutaneous CO2 (TCO2 ) to assess the need for inpatient initiation of NIV. METHODS: Eight patients from the University of Michigan Pranger ALS clinic were directly admitted to the hospital for urgent initiation of NIV between May 2020-May 2021. A retrospective review of electronic medical records, including pre-hospital pulmonary function assessments, hospitalization blood gases, and NIV use metrics was performed. RESULTS: All eight patients had symptoms of respiratory insufficiency at time of admission, although not all patients had forced vital capacity (FVC) measurements that would identify need for NIV. All patients had measured TCO2 > 45 mmHg. Seven of eight patients had worsening hypercapnia after admission, indicating advanced respiratory failure. All patients were titrated to tolerance of continuous nocturnal NIV while in the hospital, with an average length of stay of 6.5 days (range, 3-8). All patients demonstrated compliance with NIV, >4 h, at post-hospital follow-up. DISCUSSION: Many current ambulatory measurements underestimate, or incompletely evaluate, respiratory dysfunction, and arterial blood gases are not typically readily available. Outpatient TCO2 measurements can serve as a useful screening tool to identify ALS patients who would benefit from inpatient initiation and titration of NIV.

Pre-oxygenation with facemask oxygen vs high-flow nasal oxygen vs high-flow nasal oxygen plus mouthpiece: a randomised controlled trial.

High-flow nasal oxygen used before and during apnoea prolongs time to desaturation at induction of anaesthesia. It is unclear how much oxygenation before apnoea prolongs this time. We randomly allocated 84 participants to 3 minutes of pre-oxygenation by one of three methods: 15 l.min-1 by facemask; 50 l.min-1 by high-flow nasal cannulae only; or 50 l.min-1 by high-flow nasal cannulae plus 15 l.min-1 by mouthpiece. We then anaesthetised and intubated the trachea of 79 participants and waited for oxygen saturation to fall to 92%. Median (IQR [range]) times to desaturate to 92% after pre-oxygenation with facemask oxygen, high-flow nasal oxygen only and high-flow nasal oxygen with mouthpiece, were: 309 (208-417 [107-544]) s; 344 (250-393 [194-585]) s; and 386 (328-498 [182-852]) s, respectively, p = 0.014. Time to desaturation after facemask pre-oxygenation was shorter than after combined nasal and mouthpiece pre-oxygenation, p = 0.006. We could not statistically distinguish high-flow nasal oxygen without mouthpiece from the other two groups for this outcome. Median (IQR [range]) arterial oxygen partial pressure after 3 minutes of pre-oxygenation by facemask, nasal cannulae and nasal cannulae plus mouthpiece, was: 49 (36-61 [24-66]) kPa; 57 (48-62 [30-69]) kPa; and 61 (55-64 [36-72]) kPa, respectively, p = 0.003. Oxygen partial pressure after 3 minutes of pre-oxygenation with nasal and mouthpiece combination was greater than after facemask pre-oxygenation, p = 0.002, and after high-flow nasal oxygen alone, p = 0.016. We did not reject the null hypothesis for the pairwise comparison of facemask pre-oxygenation and high-flow nasal pre-oxygenation, p = 0.14.

The impact of prehospital endotracheal intubation on mortality in traumatic brain injury.

INTRODUCTION: Our study aimed to evaluate whether prehospital endotracheal intubation (ETI) affects the mortality of individuals who sustain traumatic brain injury (TBI) compared with bag-valve mask (BVM) ventilation, as well as to test the interaction effect of ETI on study outcome according to carbon dioxide level. METHODS: Our retrospective study involving patients who experienced TBI between January 2019 and December 2020. The main exposure variable was the prehospital airway management technique (ETI vs. BVM) performed by emergency medical service technicians and the primary outcome was survival at hospital discharge and the secondary outcome was good functional recovery at hospital discharge and six-month survival. We performed multivariable logistic regression analysis and interaction analysis between the prehospital airway management and blood level of carbon dioxide for adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Of 562 eligible patients, 79 (14.1%) underwent ETI and 483 (85.9%) underwent BVM ventilation. After adjusting for possible confounders, TBI patients in the ETI group has a significantly lower likehood of survival to discharge than those in the BVM group (aOR 0.57 (0.41-0.73). In interaction analysis, the rates of survival to discharge and 6-month survival with ETI were significantly lower only in groups with hypocarbia (AOR 0.61 [95% CI 0.49-0.72] and AOR 0.82 [95% CI 0.65-0.99], respectively). CONCLUSION: Among individuals who experienced severe TBI, prehospital intubation did not have a significant effect on survival outcomes and good functional recovery. Patients exhibiting hypocarbia measured on hospital arrival demonstrated lower survival outcomes in the interaction analysis.

Error traps in pediatric one-lung ventilation.

With the advent of thoracoscopic surgery, the benefits of lung isolation in children have been increasingly recognized. However, because of the small airway dimensions, equipment limitations in size and maneuverability, and limited respiratory reserve, one-lung ventilation in children remains challenging. This article highlights some of the most common error traps in the management of pediatric lung isolation and focuses on practical solutions for their management. The error traps discussed are as follows: (1) the failure to take into consideration relevant aspects of tracheobronchial anatomy when selecting the size of the lung isolation device, (2) failure to execute correct placement of the device chosen for lung isolation, (3) failure to maintain lung isolation related to surgical manipulation and isolation device movement, (4) failure to select appropriate ventilator strategies during one-lung ventilation, and (5) failure to appropriately manage and treat hypoxemia in the setting of one-lung ventilation.

The association of acute hypercarbia and plasma potassium concentration during laparoscopic surgery: a retrospective observational study.

BACKGROUND: It is uncertain whether increases in PaCO2 during surgery lead to an increase in plasma potassium concentration and, if so, by how much. Hyperkalaemia may result in cardiac arrhythmias, muscle weakness or paralysis. The key objectives were to determine whether increases in PaCO2 during laparoscopic surgery induce increases in plasma potassium concentrations and, if so, to determine the magnitude of such changes. METHODS: A retrospective observational study of adult patients undergoing laparoscopic abdominal surgery was perfomed. The independent association between increases in PaCO2 and changes in plasma potassium concentration was assessed by performing arterial blood gases within 15 min of induction of anaesthesia and within 15 min of completion of surgery. RESULTS: 289 patients were studied (mean age of 63.2 years; 176 [60.9%] male, and mean body mass index of 29.3 kg/m2). At the completion of the surgery, PaCO2 had increased by 5.18 mmHg (95% CI 4.27 mmHg to 6.09 mmHg) compared to baseline values (P < 0.001) with an associated increase in potassium concentration of 0.25 mmol/L (95% CI 0.20 mmol/L to 0.31 mmol/L, P < 0.001). On multiple regression analysis, PaCO2 changes significantly predicted immediate changes in plasma potassium concentration and could account for 33.1% of the variance (r2 = 0.331, f(3,259) = 38.915, P < 0.001). For each 10 mmHg increment of PaCO2 the plasma potassium concentration increased by 0.18 mmol/L. CONCLUSION: In patients receiving laparoscopic abdominal surgery, there is an increase in PaCO2 at the end of surgery, which is independently associated with an increase in plasma potassium concentration. However, this effect is small and is mostly influenced by intravenous fluid therapy (Plasma-Lyte 148 solution) and the presence of diabetes. Trial registration Retrospectively registered in the Australian New Zealand Clinical Trials Registry (Trial Number: ACTRN12619000716167).

Preferential intracellular pH regulation is a common trait amongst fishes exposed to high environmental CO2.

Acute (<96 h) exposure to elevated environmental CO2 (hypercarbia) induces a pH disturbance in fishes that is often compensated by concurrent recovery of intracellular and extracellular pH (pHi and pHe, respectively; coupled pH regulation). However, coupled pH regulation may be limited at CO2 partial pressure (PCO2 ) tensions far below levels that some fishes naturally encounter. Previously, four hypercarbia-tolerant fishes had been shown to completely and rapidly regulate heart, brain, liver and white muscle pHi during acute exposure to >4 kPa PCO2  (preferential pHi regulation) before pHe compensation was observed. Here, we test the hypothesis that preferential pHi regulation is a widespread strategy of acid-base regulation among fish by measuring pHi regulation in 10 different fish species that are broadly phylogenetically separated, spanning six orders, eight families and 10 genera. Contrary to previous views, we show that preferential pHi regulation is the most common strategy for acid-base regulation within these fishes during exposure to severe acute hypercarbia and that this strategy is associated with increased hypercarbia tolerance. This suggests that preferential pHi regulation may confer tolerance to the respiratory acidosis associated with hypercarbia, and we propose that it is an exaptation that facilitated key evolutionary transitions in vertebrate evolution, such as the evolution of air breathing.

Postnatal development of diving physiology: implications of anthropogenic disturbance for immature marine mammals.

Marine mammals endure extended breath-holds while performing active behaviors, which has fascinated scientists for over a century. It is now known that these animals have large onboard oxygen stores and utilize oxygen-conserving mechanisms to prolong aerobically supported dives to great depths, while typically avoiding (or tolerating) hypoxia, hypercarbia, acidosis and decompression sickness (DCS). Over the last few decades, research has revealed that diving physiology is underdeveloped at birth. Here, I review the postnatal development of the body's oxygen stores, cardiorespiratory system and other attributes of diving physiology for pinnipeds and cetaceans to assess how physiological immaturity makes young marine mammals vulnerable to disturbance. Generally, the duration required for body oxygen stores to mature varies across species in accordance with the maternal dependency period, which can be over 2 years long in some species. However, some Arctic and deep-diving species achieve mature oxygen stores comparatively early in life (prior to weaning). Accelerated development in these species supports survival during prolonged hypoxic periods when calves accompany their mothers under sea ice and to the bathypelagic zone, respectively. Studies on oxygen utilization patterns and heart rates while diving are limited, but the data indicate that immature marine mammals have a limited capacity to regulate heart rate (and hence oxygen utilization) during breath-hold. Underdeveloped diving physiology, in combination with small body size, limits diving and swimming performance. This makes immature marine mammals particularly vulnerable to mortality during periods of food limitation, habitat alterations associated with global climate change, fishery interactions and other anthropogenic disturbances, such as exposure to sonar.

Limits and patterns of acid-base regulation during elevated environmental CO2 in fish.

Aquatic CO2 tensions may exceed 30-60 Torr (ca. 30,000-79,000 µatm, respectively; hypercarbia) in some environments inducing severe acid-base challenges in fish. Typically, during exposure to hypercarbia blood pH (pHe) is initially reduced and then compensated in association with an increase in plasma HCO3- in exchange for Cl-. Typically, intracellular pH (pHi) is reduced and recovery is to some degree coupled to pHe recovery (coupled pH regulation). However, during acute hypercarbia, pHe recovery has been proposed to be limited by an "apparent upper bicarbonate threshold", restricting complete pHe recovery to below 15 Torr PCO2. At PCO2 values beyond that which fish can compensate pHe, some fish are able to fully protect pHi despite large sustained reductions in pHe (preferential pHi regulation) and can tolerate PCO2 > 45 Torr. This review discusses pHe and pHi regulation during exposure to hypercarbia starting with modeling the capacity and theoretical limit to pHe compensation in 19 studies. Next, we discuss how fish compensate severe acute hypercarbia exposures beyond the putative limit of pHe compensation using preferential pHi regulation which has recently been observed to be common among fish subjected to severe hypercarbia. Finally, we consider the evolution of pH regulatory strategies in vertebrates, including how the presence of preferential pHi regulation in embryonic reptiles may indicate that it is an embryonic trait that is either lost or retained in adult vertebrates and may have served as an exaptation for key evolutionary transitions during vertebrate evolution.

Water pH limits extracellular but not intracellular pH compensation in the CO2-tolerant freshwater fish Pangasianodon hypophthalmus.

Preferentially regulating intracellular pH (pHi) confers exceptional CO2 tolerance on fish, but is often associated with reductions in extracellular pH (pHe) compensation. It is unknown whether these reductions are due to intrinsically lower capacities for pHe compensation, hypercarbia-induced reductions in water pH or other factors. To test how water pH affects capacities and strategies for pH compensation, we exposed the CO2-tolerant fish Pangasianodon hypophthalmus to 3 kPa PCO2  for 20 h at an ecologically relevant water pH of 4.5 or 5.8. Brain, heart and liver pHi was preferentially regulated in both treatments. However, blood pHe compensation was severely reduced at water pH 4.5 but not 5.8. This suggests that low water pH limits acute pHe but not pHi compensation in fishes preferentially regulating pHi Hypercarbia-induced reductions in water pH might therefore underlie the unexplained reductions to pHe compensation in fishes preferentially regulating pHi, and may increase selection for preferential pHi regulation.

Apnoeic oxygenation with high-flow nasal oxygen for laryngeal surgery: a case series.

Surgery under apnoeic conditions with the use of high-flow nasal oxygen is novel. Between November 2016 and May 2017, 28 patients underwent tubeless laryngeal or tracheal surgery under apnoeic conditions with high-flow nasal oxygen as the sole method of gas exchange. Patients received total intravenous anaesthesia and neuromuscular blocking agents for the duration of their surgery. The median (IQR [range]) apnoea time was 19 (15-24 [9-37]) min. Four patients experienced an episode of oxygen desaturation to a value between 85% and 90%, lasting less than 2 min in each case. Median (IQR [range]) end-tidal carbon dioxide (ETCO2 ) level following apnoea was 8.2 (7.2-9.4 [5.8-11.8]) kPa. The mean (SD) rate of ETCO2 increase was 0.17 (0.07) kPa.min-1 from an approximated baseline value of 5.00 kPa. Venous blood sampling from 19 patients demonstrated a mean (SD) partial pressure of carbon dioxide (PV CO2 ) of 6.29 (0.71) kPa at baseline and 9.44 (1.12) kPa after 15 min of apnoea. This equates to a mean (SD) PV CO2 rise of 0.21 (0.08) kPa.min-1 during this period. Mean (SD) pH was 7.40 (0.03) at baseline and 7.23 (0.04) after 15 min of apnoea. Mean (SD) standard bicarbonate was 26.7 (1.8) mmol.l-1 at baseline and 25.4 (1.8) mmol.l-1 at 15 min. We conclude that high-flow nasal oxygen under apnoeic conditions can provide satisfactory gas exchange in order to allow tubeless anaesthesia for laryngeal surgery.

Apneic Oxygenation Versus Low-Tidal-Volume Ventilation in Anesthetized Cardiac Surgical Patients: A Prospective, Single-Center, Randomized Controlled Trial.

OBJECTIVES: To compare the physiology of apneic oxygenation with low-tidal-volume (VT) ventilation during harvesting of the left internal mammary artery. DESIGN: Prospective, single-center, randomized trial. SETTING: Single-center teaching hospital. PARTICIPANTS: The study comprised 24 patients who underwent elective coronary artery bypass grafting surgery. INTERVENTIONS: Apneic oxygenation (apneic group: 12 participants) and low-VT ventilation (low-VT group: 12 participants) (2.5 mL/kg ideal body weight) for 15 minutes during harvesting of the left internal mammary artery. MEASUREMENT AND MAIN RESULTS: The primary endpoint was an absolute change in partial pressure of arterial carbon dioxide (PaCO2). Secondary endpoints were changes in arterial pH, pulmonary artery pressures (PAP), cardiac index, and pulmonary artery acceleration time and ease of surgical access. The mean (standard deviation) absolute increase in PaCO2 was 31.8 mmHg (7.6) in the apneic group and 17.6 mmHg (8.2) in the low-VT group (baseline-adjusted difference 14.2 mmHg [95% confidence interval 21.0-7.3], p<0.001). The mean (standard deviation) absolute decrease in pH was 0.15 (0.03) in the apneic group and 0.09 (0.03) in the low-VT group baseline-adjusted difference 0.06 [95% confidence interval 0.03-0.09], p<0.001. Differences in the rate of change over time between groups (time-by-treatment interaction) were observed for PaCO2 (p<0.001), pH (p<0.001), systolic PAP (p = 0.002), diastolic PAP (p = 0.023), and mean PAP (p = 0.034). Both techniques provided adequate ease of surgical access; however, apneic oxygenation was preferred predominantly. CONCLUSIONS: Apneic oxygenation caused a greater degree of hypercarbia and respiratory acidemia compared with low-VT ventilation. Neither technique had deleterious effects on PAP or cardiac function. Both techniques provided adequate ease of surgical access.

Intraoperative acidosis and hypercapnia during thoracoscopic repair of congenital diaphragmatic hernia and esophageal atresia/tracheoesophageal fistula.

BACKGROUND: Intraoperative hypercapnia and acidosis have been associated with thoracoscopic repair of both congenital diaphragmatic hernia and esophageal atresia/tracheoesophageal fistula. AIM: The aim of the present study was to investigate whether thoracoscopic repair of congenital diaphragmatic hernia or esophageal atresia/tracheoesophageal fistula was associated with acidosis and hypercapnia in a large group of neonates, and to analyze the effects of acidosis and hypercapnia on early postoperative outcomes. METHODS: We reviewed the charts of neonates who underwent open or thoracoscopic congenital diaphragmatic hernia or esophageal atresia/tracheoesophageal fistula repair (2004-2014). Patients with available intraoperative arterial gas values were included. Data (PaCO2 : mm Hg) were compared using paired/unpaired tests and are reported as difference [95% confidence interval]. RESULTS: Congenital diaphragmatic hernia: 187 neonates underwent open (n=153) or thoracoscopic (n=34) repair. Intraoperative arterial gas values were recorded in 96 open and in 23 thoracoscopic operations. Both groups had similar preoperative pH and PaCO2 , and developed intraoperative acidosis (open -0.08 [-0.11, -0.05] P<.001, thoracoscopic -0.14 [-0.24, -0.04] P=.01) and hypercapnia (open: 7.8 [3.2, 12.4], P=.002; thoracoscopic: 20.2 [-2.5, 43, P=.07). Intraoperatively, neonates undergoing thoracoscopic repair developed lower pH than those having open surgery (-0.06 [-0.01, -0.10] P=.018), but maintained similar levels of PaCO2 (-4.0 [-9.0, 4.4] P=.39). Esophageal atresia/tracheoesophageal fistula: 205 neonates underwent open (n=180) or thoracoscopic (n=25) repair. Intraoperative arterial gas values were recorded in 62 open and in 14 thoracoscopic operations. Both groups had similar preoperative pH and PaCO2 , and developed intraoperative acidosis (open: -0.09 [-0.14, -0.04], P<.001; thoracoscopic: 0.21 [-0.28, -0.14], P<.001) and hypercapnia (open: 9.2 [2.6, 15.7] P=.008; thoracoscopic: 15.2 [1.6, 28.7], P=.03). Intraoperatively, neonates undergoing thoracoscopic repair developed lower pH than those having open surgery (difference 0.08 [0.01, 0.15], P=.02) but maintained similar levels of PaCO2 (difference -1 [-9, 3], P=.35). CONCLUSION: Neonates undergoing operative repair of congenital diaphragmatic hernia and esophageal atresia/tracheoesophageal fistula develop intraoperative acidosis and hypercapnia, regardless of the approach used. However, this phenomenon is more severe during thoracoscopic repair. Novel modalities to reduce intraoperative gas derangements, particularly during thoracoscopic repair, need to be established.

Characterization of Na+ transport to gain insight into the mechanism of acid-base and ion regulation in white sturgeon (Acipenser transmontanus).

Freshwater fish actively take up ions via specific transporters to counter diffusive losses to their hypotonic environment. While much is known about the specific mechanisms employed by teleosts, almost nothing is known about the basal fishes, such as white sturgeon (Acipenser transmontanus) which may offer insight into the evolution of osmo- and ionoregulation in fishes. We investigated Na+ uptake in juvenile white sturgeon in the presence and absence of transporter inhibitors. We found that sturgeon acclimated to 100µmoll-1 Na+ have Na+ uptake kinetics typical of teleosts and that a Na+/H+ exchanger (NHE) is the predominant transporter for Na+ uptake. White sturgeon are tolerant to hypercarbia-induced respiratory acidoses and recover blood pH (pHe) at 1.5kPa PCO2 but not at higher PCO2 (6kPa PCO2) where they preferentially regulate intracellular pH (pHi). It was hypothesized that during exposure to hypercarbia Na+ uptake would increase at CO2 tensions at which fish were capable of pHe regulation but decrease at higher tensions when they were preferentially regulating pHi. We found that Na+ uptake did not increase at 1.5kPa PCO2, but at 6kPa PCO2 Na+ uptake was reduced by 95% while low water pH equivalent to 6kPa PCO2 reduced Na+ uptake by 71%. Lastly, we measured net acid flux during hypercarbia, which indicates that net acid flux is not associated with Na+ uptake. These findings indicate Na+ uptake in sturgeon is not different from freshwater teleosts but is sensitive to hypercarbia and is not associated with pHe compensation during hypercarbia.

JSA guideline for the management of malignant hyperthermia crisis 2016.

Malignant hyperthermia (MH) can be fatal if the crisis is not appropriately treated. It is an inherited disease usually triggered by the administration of volatile inhalational anesthetics and/or succinylcholine, a muscle relaxant. In a patient with suspected MH, the mechanism of calcium release from storage in the sarcoplasmic reticulum in the skeletal muscle is abnormally accelerated. Unexplained hypercarbia representing >55 mmHg of end-tidal carbon dioxide, tachycardia, and muscle rigidity (including masseter muscle rigidity) are early signs of the initiation of MH, because the metabolism is accelerated. The body temperature can rise by >0.5 °C/15 min and may reach ≥40 °C. Respiratory and metabolic acidosis, arrhythmia, cola-colored urine, increased levels of serum potassium, and tented T-waves on electrocardiogram are common and can lead to cardiac arrest. MH should be treated by discontinuation of the triggering agents, administration of intravenous dantrolene (initially 1 mg/kg), and reduction of the body temperature. Early diagnosis and sufficient dantrolene with body temperature reduction are essential to relieve the patient's MH crisis. This guideline in Japanese translation has been posted on the website: http://www.anesth.or.jp/guide/pdf/guideline_akuseikounetsu.pdf .

Control of lung ventilation following overwintering conditions in bullfrogs, Lithobates catesbeianus.

Ranid frogs in northern latitudes survive winter at cold temperatures in aquatic habitats often completely covered by ice. Cold-submerged frogs survive aerobically for several months relying exclusively on cutaneous gas exchange while maintaining temperature-specific acid-base balance. Depending on the overwintering hibernaculum, frogs in northern latitudes could spend several months without access to air, the need to breathe or the chemosensory drive to use neuromuscular processes that regulate and enable pulmonary ventilation. Therefore, we performed experiments to determine whether aspects of the respiratory control system of bullfrogs, Lithobates catesbeianus, are maintained or suppressed following minimal use of air breathing in overwintering environments. Based on the necessity for control of lung ventilation in early spring, we hypothesized that critical components of the respiratory control system of bullfrogs would be functional following simulated overwintering. We found that bullfrogs recently removed from simulated overwintering environments exhibited similar resting ventilation when assessed at 24°C compared with warm-acclimated control bullfrogs. Additionally, ventilation met resting metabolic and, presumably, acid-base regulation requirements, indicating preservation of basal respiratory function despite prolonged disuse in the cold. Recently emerged bullfrogs underwent similar increases in ventilation during acute oxygen lack (aerial hypoxia) compared with warm-acclimated frogs; however, CO2-related hyperventilation was significantly blunted following overwintering. Overcoming challenges to gas exchange during overwintering have garnered attention in ectothermic vertebrates, but this study uncovers robust and labile aspects of the respiratory control system at a time point correlating with early spring following minimal to no use of lung breathing in cold-aquatic overwintering habitats.