Reduction In Minute Ventilation Research Articles

Reversal of Opioid-Induced Respiratory Depression in Healthy Volunteers: Comparison of Intranasal Nalmefene and Intranasal Naloxone.

An open-label, randomized, crossover study in healthy volunteers compared the reversal of remifentanil-induced respiratory depression by intranasal (IN) naloxone hydrochloride (4 mg) to IN nalmefene (2.7 mg) (NCT04828005). Subjects were administered a hypercapnic gas mixture which produces an elevation in minute ventilation (MV), a result of the ventilatory response to hypercapnia. Subjects breathed a hypercapnic gas mixture through a tight-fitting mask for an initial period of 46 min prior to a series of mask "holidays" introduced to reduce subject discomfort and encourage study completion. Ten minutes after initiating the hypercapnic gas mixture, a remifentanil bolus was administered, and an infusion continued for the study duration. Subjects were administered either naloxone or nalmefene 15 min after initiating the remifentanil infusion and MV monitored for 21 min followed by a mask holiday. Both nalmefene and naloxone produced a time-dependent reversal of remifentanil-induced reductions in MV measured 2.5-20 min post administration. At the primary endpoint (5 min post administration), nalmefene increases in MV (5.75 L/min) were nearly twice that produced by naloxone (3.01 L/min) (P < .0009); the point estimate favors nalmefene, demonstrating non-inferiority and superiority. In this model of opioid-induced respiratory depression, nalmefene has a more rapid onset of action than naloxone, which required 20 min to achieve a comparable reversal of respiratory depression. Both nalmefene and naloxone were well tolerated by healthy volunteers. This rapid onset of action may prove particularly valuable in an era when over 90% of fatalities are linked to synthetic opioid overdose.

Combined Use of Alkaline Agents With Low-Flow Extracorporeal Carbon Dioxide Removal in Carbon Dioxide Inhalation Models Preserving Inspiratory Efforts.

Low-flow extracorporeal CO 2 removal (ECCO 2 R), managed using a renal replacement platform, is useful in achieving lung-protective ventilation with low tidal volume. However, its capacity for CO 2 elimination is limited. Whether this system is valuable in reducing strong inspiratory efforts in respiratory failure is unclear. The combined use of alkaline agents with low-flow ECCO 2 R might be useful in hypercapnic subjects preserving inspiratory efforts. This study examined the effects of low-flow ECCO 2 R on respiratory status and investigated the effects of NaHCO 3 , trometamol, and saline on respiratory status during low-flow ECCO 2 R in CO 2 inhalation models. Although low-flow ECCO 2 R did not significantly change the respiratory rate (92.2% ± 24.3% [mean ± standard deviation] of that before ECCO 2 R), it reduced minute ventilation (MV) (78.9% ± 13.5% of that before ECCO 2 R). The addition of NaHCO 3 improved acidemia but did not change MV compared with that of the saline group (0.451 ± 0.026 L/min/kg body weight [BW] vs. 0.556 ± 0.138 L/min/kg BW, respectively). The addition of trometamol improved acidemia and reduced MV compared with that of the saline group (0.381 ± 0.050 L/min/kg BW vs. 0.556 ± 0.138 L/min/kg BW, respectively). The total amounts of CO 2 removed during ECCO 2 R in the NaHCO 3 group were lower than those in the saline and trometamol groups. The low-flow ECCO 2 R reduced MV in subjects preserving spontaneous breathing efforts with CO 2 overload. The addition of NaHCO 3 improved acidemia but did not change MV, whereas the addition of trometamol improved acidemia and reduced MV.

Pseudoxanthoma elasticum is associated with cardiocirculatory inefficiency.

Pseudoxanthoma elasticum (PXE) is a rare, genetic, metabolic disease characterized by dystrophic calcification of elastic fibres in the skin, retina and vascular wall. Data on cardiac involvement are inconsistent. Hence, we aimed to evaluate cardiorespiratory response to incremental cardiopulmonary exercise testing (CPET) in PXE. A total of 30 PXE patients (54.0 ± 11.2 years, 40.0% male) and 15 matched controls underwent symptom-limited incremental CPET. PXE patients presented an impaired peak work rate as compared to controls (84.2 ± 16.0% vs. 94.7 ± 10.4%, p = 0.03) that was accompanied by a lower peak oxygen uptake (in % predicted and mL/min/kg), reduced increments in oxygen uptake per increments of work rate (ΔV´O2/ΔWR, 8.4 ± 3.0 mL/min/W vs. 11.3 ± 4.9 mL/ min/W, p = 0.02), lower peak oxygen pulse (78.0 ± 12.3% vs. 90.6 ± 19.6%, p = 0.01) and reduced minute ventilation at peak exercise (V´E, 66.2 ± 16.8% vs. 82.9 ± 25.2%, p = 0.02). To summarize, we presently observed impairment in mainly cardiocirculatory parameters, whilst no substantial ventilatory limitation was detected. The potential implications of this finding for PXE management warrant further study.

Ventilatory Effects of Isoflurane Sedation via the Sedaconda ACD-S versus ACD-L: A Substudy of a Randomized Trial.

Devices used to deliver inhaled sedation increase dead space ventilation. We therefore compared ventilatory effects among isoflurane sedation via the Sedaconda ACD-S (internal volume: 50 mL), isoflurane sedation via the Sedaconda ACD-L (100 mL), and propofol sedation with standard mechanical ventilation with heat and moisture exchangers (HME). This is a substudy of a randomized trial that compared inhaled isoflurane sedation via the ACD-S or ACD-L to intravenous propofol sedation in 301 intensive care patients. Data from the first 24 h after study inclusion were analyzed using linear mixed models. Primary outcome was minute ventilation. Secondary outcomes were tidal volume, respiratory rate, arterial carbon dioxide pressure, and isoflurane consumption. In total, 151 patients were randomized to propofol and 150 to isoflurane sedation; 64 patients received isoflurane via the ACD-S and 86 patients via the ACD-L. While use of the ACD-L was associated with higher minute ventilation (average difference (95% confidence interval): 1.3 (0.7, 1.8) L/min, p < 0.001), higher tidal volumes (44 (16, 72) mL, p = 0.002), higher respiratory rates (1.2 (0.1, 2.2) breaths/min, p = 0.025), and higher arterial carbon dioxide pressures (3.4 (1.2, 5.6) mmHg, p = 0.002), use of the ACD-S did not significantly affect ventilation compared to standard mechanical ventilation and sedation. Isoflurane consumption was slightly less with the ACD-L compared to the ACD-S (-0.7 (-1.3, 0.1) mL/h, p = 0.022). The Sedaconda ACD-S compared to the ACD-L is associated with reduced minute ventilation and does not significantly affect ventilation compared to a standard mechanical ventilation and sedation setting. The smaller ACD-S is therefore the device of choice to minimize impact on ventilation, especially in patients with a limited ability to compensate (e.g., COPD patients). Volatile anesthetic consumption is slightly higher with the ACD-S compared to the ACD-L.

Effects of an asymmetrical high flow nasal cannula interface in hypoxemic patients

BackgroundOptimal noninvasive respiratory support for patients with hypoxemic respiratory failure should minimize work of breathing without increasing the transpulmonary pressure. Recently, an asymmetrical high flow nasal cannula (HFNC) interface (Duet, Fisher & Paykel Healthcare Ltd), in which the caliber of each nasal prong is different, was approved for clinical use. This system might reduce work of breathing by lowering minute ventilation and improving respiratory mechanics.MethodsWe enrolled 10 patients ≥ 18 years of age who were admitted to the Ospedale Maggiore Policlinico ICU in Milan, Italy, and had a PaO2/FiO2 < 300 mmHg during HFNC support with a conventional cannula. We investigated whether the asymmetrical interface, compared to a conventional high flow nasal cannula, reduces minute ventilation and work of breathing. Each patient underwent support with the asymmetrical interface and the conventional interface, applied in a randomized sequence. Each interface was provided at a flow rate of 40 l/min followed by 60 l/min. Patients were continuously monitored with esophageal manometry and electrical impedance tomography.ResultsApplication of the asymmetrical interface resulted in a −13.5 [−19.4 to (−4.5)] % change in minute ventilation at a flow rate of 40 l/min, p = 0.006 and a −19.6 [−28.0 to (−7.5)] % change at 60 l/min, p = 0.002, that occurred despite no change in PaCO2 (35 [33–42] versus 35 [33–43] mmHg at 40 l/min and 35 [32–41] versus 36 [32–43] mmHg at 60 l/min). Correspondingly, the asymmetrical interface lowered the inspiratory esophageal pressure–time product from 163 [118–210] to 140 [84–159] (cmH2O*s)/min at a flow rate of 40 l/min, p = 0.02 and from 142 [123–178] to 117 [90–137] (cmH2O*s)/min at a flow rate of 60 l/min, p = 0.04.The asymmetrical cannula did not have any impact on oxygenation, the dorsal fraction of ventilation, dynamic lung compliance, or end-expiratory lung impedance, suggesting no major effect on PEEP, lung mechanics, or alveolar recruitment.ConclusionsAn asymmetrical HFNC interface reduces minute ventilation and work of breathing in patients with mild-to-moderate hypoxemic respiratory failure supported with a conventional interface. This appears to be primarily driven by increased ventilatory efficiency due to enhanced CO2 clearance from the upper airway.

Enhanced extracorporeal carbon dioxide removal by acidification and metabolic control.

Extracorporeal carbon dioxide removal (ECCO<inf>2</inf>R) promotes protective ventilation in patients with acute respiratory failure, but devices with high CO<inf>2</inf> extraction capacity are required for clinically relevant impact. This study evaluates three novel low-flow techniques based on dialysate acidification, also combined with renal replacement therapy, and metabolic control. Eight swine were connected to a low-flow (350 mL/min) extracorporeal circuit including a dialyzer with a closed-loop dialysate circuit, and two membrane lungs on blood (ML<inf>b</inf>) and dialysate (ML<inf>d</inf>), respectively. The following 2-hour steps were performed: 1) ML<inf>b</inf>-start (ML<inf>b</inf> ventilated); 2) ML<inf>bd</inf>-start (ML<inf>b</inf> and ML<inf>d</inf> ventilated); 3) HLac (lactic acid infusion before ML<inf>d</inf>); 4) HCl-NaLac (hydrochloric acid infusion before ML<inf>d</inf> combined with renal replacement therapy and reinfusion of sodium lactate); 5) HCl-βHB-NaLac (hydrochloric acid infusion before ML<inf>d</inf> combined with renal replacement therapy and reinfusion of sodium lactate and sodium 3-hydroxybutyrate). Caloric and fluid inputs, temperature, blood glucose and arterial carbon dioxide pressure were kept constant. The total MLs CO<inf>2</inf> removal in HLac (130±25 mL/min), HCl-NaLac (130±21 mL/min) and HCl-βHB-NaLac (124±18 mL/min) were higher compared with ML<inf>bd</inf>-start (81±15 mL/min, P<0.05) and ML<inf>b</inf>-start (55±7 mL/min, P<0.05). Minute ventilation in HLac (4.3±0.9 L/min), HCl-NaLac (3.6±0.8 L/min) and HCl-βHB-NaLac (3.6±0.8 L/min) were lower compared to ML<inf>b</inf>-start (6.2±1.1 L/min, P<0.05) and ML<inf>bd</inf>-start (5.8±2.1 L/min, P<0.05). Arterial pH was 7.40±0.03 at ML<inf>b</inf>-start and decreased only during HCl-βHB-NaLac (7.35±0.03, P<0.05). No relevant changes in electrolyte concentrations, hemodynamics and significant adverse events were detected. The three techniques achieved a significant extracorporeal CO<inf>2</inf> removal allowing a relevant reduction in minute ventilation with a sufficient safety profile.

In-line miniature 3D-printed pressure-cycled ventilator maintains respiratory homeostasis in swine with induced acute pulmonary injury.

The COVID-19 pandemic demonstrated the need for inexpensive, easy-to-use, rapidly mass-produced resuscitation devices that could be quickly distributed in areas of critical need. In-line miniature ventilators based on principles of fluidics ventilate patients by automatically oscillating between forced inspiration and assisted expiration as airway pressure changes, requiring only a continuous supply of pressurized oxygen. Here, we designed three miniature ventilator models to operate in specific pressure ranges along a continuum of clinical lung injury (mild, moderate, and severe injury). Three-dimensional (3D)-printed prototype devices evaluated in a lung simulator generated airway pressures, tidal volumes, and minute ventilation within the targeted range for the state of lung disease each was designed to support. In testing in domestic swine before and after induction of pulmonary injury, the ventilators for mild and moderate injury met the design criteria when matched with the appropriate degree of lung injury. Although the ventilator for severe injury provided the specified design pressures, respiratory rate was elevated with reduced minute ventilation, a result of lung compliance below design parameters. Respiratory rate reflected how well each ventilator matched the injury state of the lungs and could guide selection of ventilator models in clinical use. This simple device could help mitigate shortages of conventional ventilators during pandemics and other disasters requiring rapid access to advanced airway management, or in transport applications for hands-free ventilation.

Intraoperative Management of a Severely Kinked Endotracheal Tube and Difficult Airway.

This figure is a lateral cervical radiograph of a nasally intubated 16-yr-old patient with Crouzon syndrome obtained after completion of cranial fossa surgery for Chiari malformation and returning to supine from a prone position. The standard endotracheal tube was severely kinked in the nasopharynx, as shown in the image, and the location of the kinking is indicated with a red arrow. This was likely caused by the warming of the endotracheal tube and the patient’s unique pharyngeal anatomy. The tracheal intubation of the patient was difficult, requiring 11 attempts due to midface hypoplasia, obesity, macroglossia, and cervical spine instability. After the start of surgery, elevated airway pressures and the inability to pass a suction catheter suggested kinking of the endotracheal tube. Due to extremely difficult intubation, endotracheal tube replacement was not attempted. Because the severely kinked endotracheal tube limited inspiratory and expiratory airflow, adequate tidal volume was achieved by increasing peak inspiratory pressure.1 Intermittent measurement of plateau pressure with an expiratory hold yielded additional information about the pressure at the alveoli. Because expiration was passive, increasing the expiratory time facilitated exhalation and reduced the risk of breath stacking.2 A helium–oxygen mixture can also be used to improve ventilation by reducing gas density, increasing the likelihood of maintaining laminar flow across the point of obstruction, and improving bulk flow.3 If the patient can tolerate permissive hypercapnia, a reduction in minute ventilation is also an option to minimize turbulent flow. The use of a wire-reinforced tube is often recommended to prevent endotracheal tube kinking in such a patient.The authors declare no competing interests.

Parameters of high-frequency jet ventilation using a mechanical lung model

High frequency jet ventilationis a mechanical lung ventilation method which uses a relatively high flow usually through an open system. This work examined the effect of high-frequency jet ventilation on respiratory parameters of an intubated patient simulated using a high-frequency jet ventilator attached to a ventilation monitor for measurements of ventilation parameters. The series of experiments altered specific parameters each time (respiratory rate, inspiratory-expiratory (I:E) ratio, and inspiratory pressure), under different lung compliances. A reduction of minute ventilation was observed alongside a rise in respiratory rate, with low airway pressures over the entire range of lung compliances. In addition, an I:E ratio of 2:1 to 1:1; and the tidal and minute volumes were directly related to the inspiratory pressure over all compliance settings. To conclude, the respiratory mechanics in high-frequency jet ventilation are very different from those of conventional rate ventilation in a lung model. Further studies on patients and/or a biological model are needed to investigate pCO2 and end-tidal carbon-dioxide during high-frequency jet ventilation.

Obesity elicits a sex‐specific attenuation of the daily rhythm in ventilation in mice chronically fed a high‐fat diet

To efficiently deal with changes in nutrient availability across the 24‐hr day, animals have evolved daily rhythms in energy metabolism and, consequently, a daily rhythm in ventilation to mediate metabolic gas exchange. Daily ventilatory rhythms have been implicated in a variety of respiratory diseases such as sleep apnea, due to time‐specific occurrence of symptoms. However, it is unknown how obese physiology and intermittent hypoxia (IH), two hallmarks of sleep apnea, influence the daily rhythm in ventilation. Here, we use a dietary mouse model of obesity to determine the extent to which ventilation rhythms are influenced by obese physiology and IH. Using whole‐body plethysmography, we found that obese mice chronically‐fed a high‐fat diet exhibit a dampened minute ventilation rhythm and decreased mean ventilation during the night‐time. The obesity‐associated reduction in minute ventilation was sex‐specific and resulted in part from a failure of female mice to increase minute ventilation in proportion to weight gain. Moreover, we found that 5 days of daytime IH exposure minimally affected the daily rhythm in minute ventilation. We conclude that the daily rhythm in minute ventilation is attenuated by obesity in a sex‐specific manner but largely unaffected by intermittent hypoxia. Taken together, these results have clinical implications for obesity‐associated respiratory diseases such as obstructive sleep apnea.

Intravenous vasopressin leads to greater haemodynamic and respiratory responses in spontaneously hypertensive SHR rats than in normotensive controls

Introduction Increased activity of vasopressinergic system has been implicated in pathophysiology of essential hypertension. Intravenous or central administrations of vasopressin (AVP) were shown to affect not only hemodynamics, but also ventilatory function in rats. Receptors for AVP have been found in the brainstem structures involved in the control of breathing and in the carotid bodies. We hypothesized that given the involvement of AVP in essential hypertension and control of ventilation, AVP may differently affect hemodynamics and ventilation in spontaneously hypertensive (SHR) and in normotensive Wistar-Kyoto (WKY) rats. Purpose In the study we investigated the effects of intravenously administered AVP on hemodynamic and respiratory parameters under hypertensive and normotensive conditions. Methods The study was performed in urethane-anesthetizes adult male normotensive WKY (n=7) and hypertensive SHR rats (n=7). We implanted catheters into the femoral artery and femoral vein for recording mean arterial blood pressure (MABP) and for intravenous infusions, respectively. Additionally, we recorded minute ventilation (MV), respiratory rate (RR) and end-tidal CO2 (ET-CO2) via tracheal tube. We also placed subcutaneous ECG electrodes for heart rate (HR) monitoring. After obtaining baseline parameters, the arterial chemoreflex was triggered pharmacologically with intravenous (i.v.) administration of potassium cyanide (KCN) (30 microg/100 microL). After stabilization of hemodynamic and respiratory parameters, rats received i.v. administration of AVP (10ng/100μL) and recordings continued. Results SHR rats had significantly higher resting MABP, HR and MV than WKY controls. Both increases in MABP and MV and decrease in ET-CO2 were significantly greater in SHR than in WKY rats in response to pharmacologically triggered peripheral chemoreflex. One minute after administration of KCN, MV remained elevated above baseline and ET-CO2 was below baseline in SHR rats, whereas all respiratory parameters were normal in WKY rats. In SHR rats administration of AVP resulted in significantly greater increase in MABP than in WKY controls and was accompanied by reduction in MV and RR but no changes in HR. In WKY rats AVP resulted in smaller MABP increase accompanied by insignificant changes in respiratory parameters or HR. Conclusions Our findings confirm increased sensitivity of arterial chemoreflex in urethane-anesthetized SHR rats and suggest that AVP-dependent pressor and respiratory responses are enhanced in spontaneously hypertensive rats.

The Effect of Nasal High Flow Therapy on Minute Ventilation in Chronic Obstructive Pulmonary Disease.

Nasal high-flow therapy (HFT) has been shown to improve daytime breathing mechanics in healthy adults as well as the lung function and quality of life in chronic obstructive pulmonary disease (COPD) patients. We hypothesized that improved breathing mechanics with HFT may further reduce minute ventilation (i.e. decreased work of breathing) during sleep in patients with COPD. In COPD participants we examined the dose effect of HFT (within night randomization of HFT level; 0, 10, 20 and 30L/min) on minute ventilation, oxyhemaglobin saturation and transcutaneous carbon dioxide during wake and sleep. We assessed overnight polysomnography with and without HFT on two separate nights. Paired t-tests were used to compare overnight sleep quality with and without HFT. The association between ventilatory variables and HFT level was assessed using regression analysis. During sleep, HFT decreased minute ventilation by 0.63±0.02L/min per 10L/min nasal airflow by reducing tidal volume (37±6mL per 10L/min; p<0.001) without affecting respiratory rate (p=0.9) or arterial CO2 (p=0.7). In contrast, during wakefulness reductions in minute ventilation (0.85±0.04L/min per 10L/min) was due to respiratory rate reduction along with prolongation in expiratory time. The reduction in minute ventilation is greater with higher dead-space volumes (r=0.50; p<0.02) and during wakefulness suggesting that ventilatory responses to HFT are mediated through a reduction in dead-space ventilation. The reduction in ventilation in response to HFT is large enough to reduce respiratory loads. Reducing respiratory loads may avert muscle fatigue, preserve respiratory function, or prevent development of respiratory failure.

Double-Triggering During Noninvasive Ventilation in a Simulated Lung Model.

Double-triggering is a well-recognized form of patient-ventilator asynchrony in noninvasive ventilation (NIV). This benchtop simulated lung study aimed to determine under which patient and device-specific conditions double-triggering is more prevalent, and how this influences the delivery of NIV. Two commonly used proprietary NIV devices were tested using a benchtop lung model. Lung compliance, airway resistance, respiratory effort, and breathing frequency were manipulated, and the frequency of double-triggering was assessed. A lung model of very low lung compliance (15 mL/cm H2O) was then used to assess the frequency of double-triggering when breathing frequency and respiratory effort were varied, along with basic NIV settings, including inspiratory pressure and expiratory pressure. Minute ventilation and total inspiratory work (as calculated by the simulated lung model) were also correlated with frequency of double-triggering. In both devices, double-triggering was observed with reduced lung compliance (P = .02 and P < .001 for the two devices, respectively). Reduced airway resistance was associated with double-triggering with the one device only (P = .02). Respiratory effort and breathing frequency were not independent predictors of double-triggering across all lung models. In the lung model of very low lung compliance, both devices showed increased double-triggering at a lower breathing frequency (P < .001 and P < .001), higher respiratory effort (P = .03 and P < .001), and greater pressure support (P = .044, P < .001). Importantly, double-triggering was associated with reduced minute ventilation (P = .007) with one device and increased inspiratory work (P < .001) with the other device. Both simulated-patient and device characteristics influenced the frequency of double-triggering in NIV, resulting in meaningful consequences in a simulated lung model.

Mechanisms of nasal high flow therapy in newborns.

In newborns, it is unclear how nasal high flow (NHF) generates positive airway pressure. In addition, the reported benefits of NHF such as reduction in work of breathing may be independent of airway pressure. The authors hypothesized that during NHF the area of leak and the flow determine airway pressure and that NHF can reduce the required minute ventilation to maintain gas exchange. In response to NHF, pressure was measured in the upper airways of 9 newborns and ventilation was measured in another group of 17 newborns. In a bench model, airway pressures were measured during NHF with different prong sizes, nare sizes, and flows. The airway pressures during 8 L/min NHF were greater when a larger cannula versus a smaller cannula was used (P < 0.05). NHF reduced minute ventilation in 16 of 17 neonates, with a mean decrease of 24% from a baseline of 0.66 L/min (SD 0.21) (P < 0.001), and was unrelated to changes in airway pressure; arterial oxygen saturation by pulse oximetry () and tissue CO2 were unchanged. In the bench model, the airway pressure remained <2 cmH2O when <50% of the “nare” was occluded by the prongs. As the leak area decreased, because of a smaller nare or a larger cannula, the airway pressure increased exponentially and was dependent on flow. In newborns NHF using room air substantially reduced minute ventilation without affecting gas exchange irrespective of a decrease or an increase of respiratory rate. NHF generates low positive airway pressure that exponentially increases with flow and occlusion of the nares.NEW & NOTEWORTHY In healthy newborns, nasal high flow (NHF) with room air reduced minute ventilation by one-fourth without affecting gas exchange but, in contrast to adults, produced variable response in respiratory rate during sleep. During NHF, pressure in the upper airways did not exceed 2 cmH2O at 8 L/min (3.4 L·min−1·kg−1) and was unaffected by opening of the mouth. NHF can generate higher pressure with larger prongs that decrease the leak around the cannula or by increasing the flow rate.

A CO2 removal system using extracorporeal lung and renal assist device with an acid and alkaline infusion.

The patients with respiratory failure need high tidal volume by mechanical ventilation, which lead to the ventilator-induced lung injury. We developed an extracorporeal lung and renal assist device (ELRAD), comprising acid infusion, membrane lung, continuous hemodiafiltration and alkaline infusion. To evaluate this system, we conducted in vivo studies using experimental swine which were connected to the new system. In vivo experiments consist of four protocols; baseline = hemodiafiltration only (no O2 gas flow to membrane lung); membrane lung = "Baseline" plus O2 gas flow to membrane lung; "Acid infusion" = "Membrane lung" plus continuous acid infusion; ELRAD = "Acid infusion" plus continuous alkaline infusion. We changed the ventilatory rate of the mechanical ventilation to maintain PCO2 at 50-55mmHg during the four protocols. The results showed that there was statistically no significant difference in the levels of pH, HCO3-, and base excess when each study protocol was initiated. The amount of CO2 eliminated by the membrane lung significantly increased by 1.6 times in the acid infusion protocol and the ELRAD protocol compared to the conventional membrane lung protocol. Minute ventilation in the ELRAD protocol significantly decreased by 0.5 times compared with the hemodiafiltration only protocol (P < 0.0001), the membrane lung (P = 0.0006) and acid infusion protocol (P = 0.0017), respectively. In conclusion, a developed CO2 removal system efficiently removed CO2 at low blood flow and reduced minute ventilation, while maintaining acid-base balance within the normal range.

Nasal high flow reduces minute ventilation during sleep through a decrease of carbon dioxide rebreathing

Nasal high flow (NHF) is an emerging therapy for respiratory support, but knowledge of the mechanisms and applications is limited. It was previously observed that NHF reduces the tidal volume but does not affect the respiratory rate during sleep. The authors hypothesized that the decrease in tidal volume during NHF is due to a reduction in carbon dioxide (CO2) rebreathing from dead space. In nine healthy males, ventilation was measured during sleep using calibrated respiratory inductance plethysmography (RIP). Carbogen gas mixture was entrained into 30 l/min of NHF to obtain three levels of inspired CO2: 0.04% (room air), 1%, and 3%. NHF with room air reduced tidal volume by 81 ml, SD 25 ( P < 0.0001) from a baseline of 415 ml, SD 114, but did not change respiratory rate; tissue CO2 and O2 remained stable, indicating that gas exchange had been maintained. CO2 entrainment increased tidal volume close to baseline with 1% CO2 and greater than baseline with 3% CO2 by 155 ml, SD 79 ( P = 0.0004), without affecting the respiratory rate. It was calculated that 30 l/min of NHF reduced the rebreathing of CO2 from anatomical dead space by 45%, which is equivalent to the 20% reduction in tidal volume that was observed. The study proves that the reduction in tidal volume in response to NHF during sleep is due to the reduced rebreathing of CO2. Entrainment of CO2 into the NHF can be used to control ventilation during sleep. NEW & NOTEWORTHY The findings in healthy volunteers during sleep show that nasal high flow (NHF) with a rate of 30 l/min reduces the rebreathing of CO2 from anatomical dead space by 45%, resulting in a reduced minute ventilation, while gas exchange is maintained. Entrainment of CO2 into the NHF can be used to control ventilation during sleep.

New insights into the timing and potential mechanisms of respiratory-induced cortical arousals in obstructive sleep apnea

A negative intrathoracic pressure threshold is one commonly proposed mechanism for triggering respiratory-induced arousals in obstructive sleep apnea (OSA). If so, they should occur during inspiration, shortly after maximal negative pressure swings. Alternatively, respiratory-induced arousals may occur throughout the respiratory cycle if other mechanisms also contribute. However, arousal timing has been minimally investigated. This study aimed to (1) determine the temporal relationship between respiratory-induced arousals and breathing phase and (2) characterize neuromuscular and load compensation responses prior to arousal. Fifty-one CPAP-treated OSA patients underwent a sleep physiology study with genioglossus and tensor palatini EMG, nasal mask/pneumotachograph, and epiglottic pressure. Transient CPAP reductions were delivered to induce respiratory-related arousals. Of 354 arousals, 65(60-70)%[mean(CI)] occurred during inspiration, 35(30-40)% during expiration. Nadir epiglottic pressure occurred 68(66-69)% into inspiration while inspiratory arousals had a uniform distribution throughout inspiration. Expiratory arousals occurred predominantly in early expiration. CPAP reductions initially reduced minute ventilation by ~2.5 liter/min, which was restored immediately prior to expiratory but not inspiratory arousals. Duty cycle just prior to arousal was greater for inspiratory versus expiratory arousals [0.20(0.18-0.21) vs. 0.13(0.11-0.15)Δbaseline, p = 0.001]. Peak tensor palatini EMG was higher for expiratory versus inspiratory arousals during prearousal breaths [7.6(5.8-9.6) vs. 3.7(3.0-4.5)%Δbaseline, p = 0.001], whereas genioglossus and tonic tensor palatini EMG were similar between arousal types. Over one third of respiratory-induced arousals occur during expiration. These findings highlight the importance of nonpressure threshold mechanisms of respiratory-induced arousals in OSA and suggest that expiratory arousals may be a novel marker of enhanced tensor palatini neuromuscular compensation.

Reductions in dead space ventilation with nasal high flow depend on physiological dead space volume: metabolic hood measurements during sleep in patients with COPD and controls.

Nasal high flow (NHF) reduces minute ventilation and ventilatory loads during sleep but the mechanisms are not clear. We hypothesised NHF reduces ventilation in proportion to physiological but not anatomical dead space.11 subjects (five controls and six chronic obstructive pulmonary disease (COPD) patients) underwent polysomnography with transcutaneous carbon dioxide (CO2) monitoring under a metabolic hood. During stable non-rapid eye movement stage 2 sleep, subjects received NHF (20 L·min-1) intermittently for periods of 5-10 min. We measured CO2 production and calculated dead space ventilation.Controls and COPD patients responded similarly to NHF. NHF reduced minute ventilation (from 5.6±0.4 to 4.8±0.4 L·min-1; p<0.05) and tidal volume (from 0.34±0.03 to 0.3±0.03 L; p<0.05) without a change in energy expenditure, transcutaneous CO2 or alveolar ventilation. There was a significant decrease in dead space ventilation (from 2.5±0.4 to 1.6±0.4 L·min-1; p<0.05), but not in respiratory rate. The reduction in dead space ventilation correlated with baseline physiological dead space fraction (r2=0.36; p<0.05), but not with respiratory rate or anatomical dead space volume.During sleep, NHF decreases minute ventilation due to an overall reduction in dead space ventilation in proportion to the extent of baseline physiological dead space fraction.

Anaesthetic management of robotic-assisted gynaecology surgery in the morbidly obese - A case series of 46 patients in a UK university teaching hospital.

Background and Aims:The evolution of robotic technology has enhanced the scope of laparoscopic surgery. Morbid obesity [body mass index (BMI) >40 kg/m2] due to significant physiological attributes presents a significant surgical and anaesthetic challenge. Robotic surgery in this subset of patients can present with its own problems due to surgical requirements of prolonged pneumoperitoneum and steep Trendelenburg position.Methods:We reviewed the anaesthetic management of 46 morbidly obese patients undergoing robotic-assisted laparoscopic gynaecology surgery. Patient characteristics, anaesthetic management, length of hospital stay (LOS), complications, and readmissions within 30 days were noted. Mean with standard deviation was used for statistical analysis.Results:The mean [standard deviation (SD)] weight and BMI were 121.2 (18.49) kg and 47.83 (7.89) kg/m2, respectively. The mean (SD) anaesthetic and surgical times were 229 (75.9) and 167.7 (62.7) min, respectively. The mean (SD) LOS was 1.57 (1.03) days. About 70% of patients were discharged on the first day after surgery. Six patients needed critical care support. There were two readmissions within 30 days.Conclusion:Good preparation, teamwork, and multidisciplinary input helped us to conduct complex robotic-assisted and long-duration surgery in morbidly obese patients with minimal complications.

Optimum support by high-flow nasal cannula in acute hypoxemic respiratory failure: effects of increasing flow rates

Limited data exist on the correlation between higher flow rates of high-flow nasal cannula (HFNC) and its physiologic effects in patients with acute hypoxemic respiratory failure (AHRF). We assessed the effects of HFNC delivered at increasing flow rate on inspiratory effort, work of breathing, minute ventilation, lung volumes, dynamic compliance and oxygenation in AHRF patients. A prospective randomized cross-over study was performed in non-intubated patients with patients AHRF and a PaO2/FiO2 (arterial partial pressure of oxygen/fraction of inspired oxygen) ratio of ≤300mmHg. A standard non-occlusive facial mask and HFNC at different flow rates (30, 45 and 60l/min) were randomly applied, while maintaining constant FiO2 (20min/step). At the end of each phase, we measured arterial blood gases, inspiratory effort, based on swings in esophageal pressure (ΔPes) and on the esophageal pressure-time product (PTPPes), and lung volume, by electrical impedance tomography. Seventeen patients with AHRF were enrolled in the study. At increasing flow rate, HFNC reduced ΔPes (p<0.001) and PTPPes (p<0.001), while end-expiratory lung volume (ΔEELV), tidal volume to ΔPes ratio (V T/ΔPes, which corresponds to dynamic lung compliance) and oxygenation improved (p<0.01 for all factors). Higher HFNC flow rate also progressively reduced minute ventilation (p<0.05) without any change in arterial CO2 tension (p=0.909). The decrease in ΔPes, PTPPes and minute ventilation at increasing flow rates was better described by exponential fitting, while ΔEELV, V T/ΔPes and oxygenation improved linearly. In this cohort of patients with AHRF, an increasing HFNC flow rate progressively decreased inspiratory effort and improved lung aeration, dynamic compliance and oxygenation. Most of the effect on inspiratory workload and CO2 clearance was already obtained at the lowest flow rate.