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Background During induction of general anaesthesia a ‘cannot intubate, cannot oxygenate' (CICO) situation can arise, leading to severe hypoxaemia. Evidence is scarce to guide ventilation strategies for small-bore emergency front of neck airways that ensure effective oxygenation without risking lung damage and cardiovascular depression. Methods Fifty virtual subjects were configured using a high-fidelity computational model of the cardiovascular and pulmonary systems. Each subject breathed 100% oxygen for 3 min and then became apnoeic, with an obstructed upper airway. When arterial haemoglobin oxygen saturation reached 40%, front of neck airway access was simulated with various configurations. We examined the effect of several ventilation strategies on re-oxygenation, pulmonary pressures, cardiovascular function, and oxygen delivery. Results Re-oxygenation was achieved in all ventilation strategies. Smaller airway configurations led to dynamic hyperinflation for a wide range of ventilation strategies. This effect was absent in airways with larger internal diameter (≥3 mm). Intrapulmonary pressures increased quickly to supra-physiological values with the smallest airways, resulting in pronounced cardio-circulatory depression (cardiac output Conclusions Dynamic hyperinflation can be demonstrated for a wide range of front of neck airway cannulae when the upper airway is obstructed. When using small-bore cannulae in a CICO situation, ventilation strategies should be chosen that prevent gas trapping to prevent severe adverse events including cardio-circulatory depression.

BACKGROUND: Studies of pulmonary denitrogenation (pre-oxygenation) in obstetric populations have shown high flow nasal oxygen therapy (HFNO) is inferior to facemask techniques. HFNO achieves median end-tidal oxygen fraction (FE′O(2)) of 0.87 after 3 min. As HFNO prolongs safe apnoea times through apnoeic oxygenation, we postulated that HFNO would still extend safe apnoeic times despite the lower FE′O(2) after pre-oxygenation. METHODS: The Interdisciplinary Collaboration in Systems Medicine simulation suite, a highly integrated, high-fidelity model of the human respiratory and cardiovascular systems, was used to study the effect of varying FE′O(2) (60%, 70%, 80%, and 90%) on the duration of safe apnoea times using HFNO and facemask techniques (with the airway open and obstructed). The study population consisted of validated models of pregnant women in active labour and not in labour with BMI of 24, 35, 40, 45, and 50 kg m(−2). RESULTS: HFNO provided longer safe apnoeic times in all models, with all FE′O(2) values. Labour and increased BMI reduced this effect, in particular a BMI of 50 kg m(−2) reduced the improvement in apnoea time to 1.8–8.5 min (depending on the FE′O(2)), compared with an improvement of more than 60 min in the subject with BMI 24 kg m(−2). CONCLUSIONS: Despite generating lower FE′O(2), HFNO provides longer safe apnoea times in pregnant subjects in labour. Care should be taken when used in patients with BMI ≥50 kg m(−2) as the extension of the safe apnoea time is limited.

BackgroundHypoxaemia during general anaesthesia can cause harm. Apnoeic oxygenation extends safe apnoea time, reducing risk during airway management. We hypothesised that low-flow nasal oxygenation (LFNO) would extend safe apnoea time similarly to high-flow nasal oxygenation (HFNO), whilst allowing face-mask preoxygenation and rescue.MethodsA high-fidelity, computational, physiological model was used to examine the progression of hypoxaemia during apnoea in virtual models of pregnant women in and out of labour, with BMI of 24–50 kg m−2. Subjects were preoxygenated with oxygen 100% to reach end-tidal oxygen fraction (FE'O2) of 60%, 70%, 80%, or 90%. When apnoea started, HFNO or LFNO was commenced. To simulate varying degrees of effectiveness of LFNO, periglottic oxygen fraction (FgO2) of 21%, 60%, or 100% was configured. HFNO provided FgO2 100% and oscillating positive pharyngeal pressure.ResultsApplication of LFNO (FgO2 100%) after optimal preoxygenation (FE'O2 90%) resulted in similar or longer safe apnoea times than HFNO FE'O2 80% in all subjects in labour. For BMI of 24, the time to reach SaO2 90% with LFNO was 25.4 min (FE'O2 90%/FgO2 100%) vs 25.4 min with HFNO (FE'O2 80%). For BMI of 50, the time was 9.9 min with LFNO (FE'O2 90%/FgO2 100%) vs 4.3 min with HFNO (FE'O2 80%). A similar finding was seen in subjects with BMI ≥40 kg m−2 not in labour.ConclusionsThere is likely to be clinical benefit to using LFNO, given that LFNO and HFNO extend safe apnoea time similarly, particularly when BMI ≥40 kg m−2. Additional benefits to LFNO include the facilitation of rescue face-mask ventilation and ability to monitor FE'O2 during preoxygenation.

Supplemental Digital Content is available in the text., Objectives: Patients with coronavirus disease 2019 acute respiratory distress syndrome appear to present with at least two distinct phenotypes: severe hypoxemia with relatively well-preserved lung compliance and lung gas volumes (type 1) and a more conventional acute respiratory distress syndrome phenotype, displaying the typical characteristics of the “baby lung” (type 2). We aimed to test plausible hypotheses regarding the pathophysiologic mechanisms underlying coronavirus disease 2019 acute respiratory distress syndrome and to evaluate the resulting implications for ventilatory management. Design: We adapted a high-fidelity computational simulator, previously validated in several studies of acute respiratory distress syndrome, to: 1) develop quantitative insights into the key pathophysiologic differences between the coronavirus disease 2019 acute respiratory distress syndrome and the conventional acute respiratory distress syndrome and 2) assess the impact of different positive end-expiratory pressure, Fio2, and tidal volume settings. Setting: Interdisciplinary Collaboration in Systems Medicine Research Network. Subjects: The simulator was calibrated to represent coronavirus disease 2019 acute respiratory distress syndrome patients with both normal and elevated body mass indices undergoing invasive mechanical ventilation. Interventions: None. Measurements and Main Results: An acute respiratory distress syndrome model implementing disruption of hypoxic pulmonary vasoconstriction and vasodilation leading to hyperperfusion of collapsed lung regions failed to replicate clinical data on type 1 coronavirus disease 2019 acute respiratory distress syndrome patients. Adding mechanisms to reflect disruption of alveolar gas-exchange due to the effects of pneumonitis and heightened vascular resistance due to the emergence of microthrombi produced levels of ventilation perfusion mismatch and hypoxemia consistent with data from type 1 coronavirus disease 2019 acute respiratory distress syndrome patients, while preserving close-to-normal lung compliance and gas volumes. Atypical responses to positive end-expiratory pressure increments between 5 and 15 cm H2O were observed for this type 1 coronavirus disease 2019 acute respiratory distress syndrome model across a range of measures: increasing positive end-expiratory pressure resulted in reduced lung compliance and no improvement in oxygenation, whereas mechanical power, driving pressure, and plateau pressure all increased. Fio2 settings based on acute respiratory distress syndrome network protocols at different positive end-expiratory pressure levels were insufficient to achieve adequate oxygenation. Incrementing tidal volumes from 5 to 10 mL/kg produced similar increases in multiple indicators of ventilator-induced lung injury in the type 1 coronavirus disease 2019 acute respiratory distress syndrome model to those seen in a conventional acute respiratory distress syndrome model. Conclusions: Our model suggests that use of standard positive end-expiratory pressure/Fio2 tables, higher positive end-expiratory pressure strategies, and higher tidal volumes may all be potentially deleterious in type 1 coronavirus disease 2019 acute respiratory distress syndrome patients, and that a highly personalized approach to treatment is advisable.

ObjectivesPatients with COVID-19 Acute Respiratory Distress Syndrome (CARDS) appear to present with at least two distinct phenotypes: severe hypoxemia with relatively well-preserved lung compliance and lung gas volumes (Type 1) and a more conventional ARDS phenotype displaying the typical characteristics of the ‘baby lung’ (Type 2). We aimed to test plausible hypotheses regarding the pathophysiological mechanisms underlying CARDS, and to evaluate the resulting implications for ventilatory management.DesignWe adapted a high-fidelity computational simulator, previously validated in several studies of ARDS, to (a) develop quantitative insights into the key pathophysiologic differences between CARDS and conventional ARDS, and (b) assess the impact of different PEEP, FiO2 and tidal volume settings.SettingInterdisciplinary Collaboration in Systems Medicine Research Network.SubjectsThe simulator was calibrated to represent CARDS patients with both normal and elevated body mass indices undergoing invasive mechanical ventilation.Measurements and Main ResultsAn ARDS model implementing disruption of hypoxic pulmonary vasoconstriction and vasodilation leading to hyperperfusion of collapsed lung regions failed to replicate clinical data on Type 1 CARDS patients. Adding mechanisms to reflect disruption of alveolar gas-exchange due to the effects of pneumonitis, and heightened vascular resistance due to the emergence of microthrombi, produced levels of V/Q mismatch and hypoxemia consistent with data from Type 1 CARDS patients, while preserving close to normal lung compliance and gas volumes. Atypical responses to PEEP increments between 5 and 15 cmH2O were observed for this Type 1 CARDS model across a range of measures: increasing PEEP resulted in reduced lung compliance and no improvement in oxygenation, while Mechanical Power, Driving Pressure and Plateau Pressure all increased. FiO2 settings based on ARDSnet protocols at different PEEP levels were insufficient to achieve adequate oxygenation. Incrementing tidal volumes from 5 to 10 ml/kg produced similar increases in multiple indicators of ventilator induced lung injury in the Type 1 CARDS model to those seen in a conventional ARDS model.ConclusionsOur model suggests that use of standard PEEP/ FiO2 tables, higher PEEP strategies, and higher tidal volumes, may all be potentially deleterious in Type 1 CARDS patients, and that a highly personalized approach to treatment is advisable.

Background Apnoeic oxygenation can come close to matching the oxygen demands of the apnoeic patient but does not facilitate carbon dioxide (CO2) elimination, potentially resulting in dangerous hypercapnia. Numerous studies have shown that high-flow nasal oxygen administration prevents hypoxaemia, and appears to reduce the rate of increase of arterial CO2 partial pressure (PaCO2), but evidence is lacking to explain these effects. Methods We extended a high-fidelity computational simulation of cardiopulmonary physiology to include modules allowing variable effects of: (a) cardiogenic oscillations affecting intrathoracic gas spaces, (b) gas mixing within the anatomical dead space, (c) insufflation into the trachea or above the glottis, and (d) pharyngeal pressure oscillation. We validated this model by reproducing the methods and results of five clinical studies on apnoeic oxygenation. Results Simulated outputs best matched clinical data for model selection of parameters reflecting: (a) significant effects of cardiogenic oscillations on alveoli, both in terms of strength of the effect (4.5 cm H2O) and percentage of alveoli affected (60%), (b) augmented gas mixing within the anatomical dead space, and (c) pharyngeal pressure oscillations between 0 and 2 cm H2O at 70 Hz. Conclusions Cardiogenic oscillations, dead space gas mixing, and micro-ventilation induced by pharyngeal pressure variations appear to be important mechanisms that combine to facilitate the clearance of CO2 during apnoea. Evolution of high-flow oxygen insufflation devices should take advantage of these insights, potentially improving apnoeic gas exchange.

Apnea is common after induction of anesthesia and may produce dangerous hypoxemia, particularly in obese subjects. Optimal management of airway emergencies in obese, apneic subjects is complex and controversial, and clinical studies of rescue strategies are inherently difficult and ethically-challenging to perform.We investigated rescue strategies in various degrees of obesity, using a highly-integrated, computational model of the pulmonary and cardiovascular systems, configured against data from 8 virtual subjects (body mass index [BMI] 24–57 kg m-2). Each subject received pre-oxygenation with 100% oxygen for 3 min, and then apnea with an obstructed airway was simulated until SaO 2 reached 40%. At that time, airway rescue was simulated, opening of the airway with the provision of various patterns of tidal ventilation with 100% oxygen.Rescue using tidal ventilation with 100% oxygen provided rapid re-oxygenation in all subjects, even with small tidal volumes in subjects with large BMI. Overall, subjects with larger BMI pre-oxygenated faster and, after airway obstruction, developed hypoxemia more quickly.Our results indicate that attempts to achieve substantial tidal volumes during airway rescues are probably not worthwhile (and may be counter-productive); rather, it is the assurance of a high-inspired oxygen fraction that will prevent critical hypoxemia.

Background During induction of general anaesthesia, patients frequently experience apnoea, which can lead to dangerous hypoxaemia. An obstructed upper airway can impede attempts to provide ventilation. Although unrelieved apnoea is rare, it continues to cause deaths. Clinical investigation of management strategies for such scenarios is effectively impossible because of ethical and practical considerations. Methods A population-representative cohort of 100 virtual (in silico) subjects was configured using a high-fidelity computational model of the pulmonary and cardiovascular systems. Each subject breathed 100% oxygen for 3 min and then became apnoeic, with an obstructed upper airway, during induction of general anaesthesia. Apnoea continued throughout the protocol. When arterial oxygen saturation (Sao2) reached 20%, 40%, or 60%, airway obstruction was relieved. We examined the effect of varying supraglottic oxygen fraction (Fo2) on the degree of passive re-oxygenation occurring without tidal ventilation. Results Relief of airway obstruction during apnoea produced a single, passive inhalation (caused by intrathoracic hypobaric pressure) in all cases. The degree of re-oxygenation after airway opening was markedly influenced by the supraglottic Fo2, with a supraglottic Fo2 of 100% providing significant and sustained re-oxygenation (post-rescue Pao2 42.3 [4.4] kPa, when the airway rescue occurred after desaturation to Sao2 60%). Conclusions Supraglottic oxygen supplementation before relieving upper airway obstruction improves the effectiveness of simulated airway rescue. Management strategies should be implemented to assure a substantially increased pharyngeal Fo2 during difficult airway management.

Apnoea is common after induction of anaesthesia and may produce dangerous hypoxemia and hypercapnia, particularly in patients with a reduced functional residual capacity (FRC) (e.g. obese patients). We hypothesized that oxygen insufflation via an open airway may provide adequate oxygenation and CO2 clearance in a computational model of obese apnoeic patients. The study uses our highly-integrated computational model of pulmonary and cardiovascular systems, recently developed to include apnoeic state, deadspace gas-mixing and tracheal gas insufflation (Laviola, M et al. Conf Proc IEEE EMBC 2017, 337-340). Four subjects (BMI 23–60 kg/m2) were configured. Oxygen consumption was set at 3.3 mL/kg/min. Each subject was pre-oxygenated using FiO2 1.0 for 30 min. At the onset of apnoea, FRC was reduced by 50%. Apnoea persisted for 30 mins. Oxygen was delivered immediately above the glottis (30 L/min), with concentrations 0.21–1.0; the glottis remained open. Arterial pressures of O2 (PaO2) and CO2 (PaCO2) and O2 saturation (SaO2) were collected. In all subjects, reducing the FiO2 reduced the rate of rise of PaCO2 (by up 29%). All levels of FiO2 assured adequate oxygenation (Table 1) and no desaturation below 94% over 30 min. This study suggests that supraglottic gas delivery at 30 L/min facilitates CO2 removal and maintenance of oxygenation (even at low FiO2).

Introduction In Duchenne muscular dystrophy (DMD) the assessment of diaphragmatic function is crucial because respiratory muscle weakness can cause respiratory failure. We aimed to noninvasively assess diaphragmatic function in DMD by measuring diaphragmatic thickness by ultrasonography, under the hypothesis that the progressive decrease of lung function is related to alterations of diaphragmatic thickness. Methods Forty-four DMD patients and thirteen healthy controls were enrolled and subdivided into three age groups. Diaphragmatic thickness was measured during quiet breathing, inspiratory capacity, maximal inspiratory pressure and expiratory pressure maneuvers. Results In DMD, absolute values of diaphragmatic thickness were significantly lower than in controls in the majority of the manoeuvers and diaphragmatic thickness significantly decreased with age at end-expiration, remaining constant at end-inspiration and during maximal inspiratory pressure maneuvers. Comparing to controls, absolute values of diaphragmatic thickness and diaphragmatic thickness variations were significantly lower (p

Objective:Congenitaldiaphragmatichernia(CDH)consistsofanincompleteformation of the diaphragm and the subsequent herniation of abdominal bowels. Diaphragmatic defect can be repaired by primary closure or placing a patch. Respiratory follow up usually focuses on spirometric and clinical evaluation. The aim of the study was to assess thoraco-abdominal volumes in CDH patients and to verify whether the action of the diaphragm on the chest wall is altered leading to an asymmetric and asynchronous expansion of the different thoracoabdominal compartments. Patients and Methods: Total and compartmental chest wall volumes and asynchronies were measured by Opto-Electronic Plethysmography in 14 CDH patients (7M/7F, age 5 � 2 years, 12 left side operated) and in 9 age matched healthy subjects during quiet spontaneous breathing in supine position. Patients were divided in two groups: five patients with suture (group S) and nine patients with diaphragmatic patch (group P). Pulmonary function was assessedbyspirometryandspirometricparameterswereexpressedasZ-score.Results:Ingroup P abdominal contribution to tidal volume was lower than healthy controls and group S. Unlike controls, in both CDH groups the right side of pulmonary rib cage moved inward with a correspondentleft side expansionduringinspiration. IngroupS,thoraco-abdominal asynchronies were higher than in group P and controls, especially in the right side. Five patients belonging to group P had a spirometric obstructive pattern. Conclusions: In overall CDH patients a reduced action of the treated (left) hemi-diaphragm is evident. In patients treated by primary suture, a compensatory action of the right side allows to reach a normal total diaphragmatic displacement and a proper contribution of the whole diaphragm to tidal volume. In patients treated by diaphragmatic patch, instead, thoraco-abdominal asynchronies are prevented. Pediatr

Spinal muscular atrophy (SMA) is characterized by degeneration of motor neurons resulting in muscle weakness. For the mild type III form, a sub-classification into type IIIA and IIIB, based on age of motor impairment, was recently proposed. To investigate if SMA IIIA (more severe) and IIIB differ also in terms of respiratory function, thoracoabdominal kinematics was measured during quiet breathing, inspiration preceding cough and inspiratory capacity on 5 type IIIA and 9 type IIIB patients. Four patients with SMA II (more severe than types III) and 19 healthy controls were also studied. Rib cage motion was similar in SMA IIIB and controls. Conversely, in SMA IIIA and SMA II it was significantly reduced and sometime paradoxical during quiet breathing in supine position. Our results suggest that in SMA IIIA intercostal muscles are weakened and the diaphragm is preserved similarly to SMA II, while in SMA IIIB the action of all inspiratory muscles is maintained. Sub-classification of type III seems feasible also for respiratory function.

Electrical impedance tomography (EIT) is a promising modality for lung ventilation monitoring. It can provide information about the distribution of regional ventilation in predefined regions of interest (ROIs), as well as estimate several ventilatory parameters including tidal volume (VT) or end-expiratory lung volume (EELV). The approaches for calculation of VT and EELV are based on the values of global tidal variation (TV) and end-expiratory lung impedance (EELI) obtained by the means of functional EIT (fEIT). For reconstruction of fEIT data, a set of reference measurements, often called as a baseline frame, needs to be determined. The aim of the study is to show how setting of this baseline frame can influence the values of ROI, global TV and EELI and thus affect the estimation of VT and EELV and the evaluation of lung recruitment as such. In order to study the effect of the baseline frame selection, an animal study (pigs, n=3) was conducted. The animals were anaesthetized and mechanically ventilated. Four incremental steps in positive end-expiratory pressure (PEEP), each having a value of 0.5 kPa were performed to reach a total PEEP level of 2.5 kPa. Continuous EIT monitoring was done during this PEEP trial. The obtained data were reconstructed using baseline frames chosen manually at five different PEEP levels. The selection of the baseline frames resulted in different values of global TV and EELI. Thus, when estimating VT and EELV by means of fEIT, it is necessary to choose one common baseline frame for data reconstruction. However, the effect on the percentage values that express the distribution of regional ventilation is negligible and below clinical significance.

High frequency oscillatory ventilation (HFOV) is an alternative mode of mechanical ventilation. HFOV has been shown to provide adequate ventilation and oxygenation in acute respiratory distress syndrome (ARDS) patients and may represent an effective lung-protective ventilation in patients where conventional ventilation is failing. The aim of this study is to evaluate effects of continuous distending pressure (CDP) on variables that contribute to the oxygenation in healthy and ARDS lung model pigs. Methods. In order to simulate a lung disease, lung injury was induced by lavage with normal saline with detergent in three pigs. HFOV ventilation was applied before and after the lung lavage. CDP was stepwise increased by 2 cmH2O, until the maximum CDP (before the lung lavage 32 cmH2O and after the lung lavage 42 cmH2O) and then it was stepwise decreased by 2 cmH2O to the initial value. In this paper we analyzed the following parameters acquired during our experiments: partial pressure of oxygen in arterial bloo...

Background Lung function after lung transplantation (LTx) has been widely studied. On the contrary, the thoracoabdominal volume rearrangement after LTx has yet to be investigated. Methods Patients with cystic fibrosis and listed for double LTx at our institution were enrolled for the prospective study to explore the effects of LTx on the rearrangement of respiratory volumes in patients affected by cystic fibrosis, by utilizing the opto-electronic plethysmography (OEP), a noninvasive method to study the volume and motion of the human trunk. Rib cage and abdominal volumes were tested with OEP (OEP system, BTS, Milano, Italy). Results Eight patients were enrolled (male-to-female ratio: 1:3; mean age 29.3 ± 7.8 years). After LTx the volume changes analyzed with OEP revealed a significant decrease of the total lung capacity (TLC) as well as the functional residual capacity and residual volume when the chest wall volume was considered. Dividing the whole respiratory volume in the three compartments showed different trends. Conclusions We consider OEP a particularly useful device in patients with severe respiratory disease, in that it allows a noninvasive estimate of the volume change of the chest wall. This study demonstrates a significant reduction of thoracoabdominal volumes in patients affected by cystic fibrosis treated with bilateral LTx. Abdomen and upper rib cage were congruent with the volume reduction, while the lower rib cage showed an opposite tendency.

Expulsive maneuvers (EMs) caused by simultaneous contraction of diaphragm and abdominal muscles shift substantial quantities of blood from the splanchnic circulation to the extremities. This suggests that the diaphragm assisted by abdominal muscles might accomplish ventilation and circulation simultaneously by repeated EMs. We tested this hypothesis in normal subjects by measuring changes (Δ) in body volume (Vb) by whole body plethysmography simultaneously with changes in trunk volume (Vtr) by optoelectronic plethysmography, which measures the same parameters as whole body plethysmography plus the volume of blood shifts (Vbs) between trunk and extremities: Vbs = ΔVtr − ΔVb. We also measured abdominal pressure, pleural pressure, the arterial pressure wave, and cardiac output (Q̇c). EMs with abdominal pressure ∼100 cmH2O for 1 s, followed by 2-s relaxations, repeated over 90 s, produced a “stroke volume” from the splanchnic bed of 0.35 ± 0.07 (SD) liter, an output of 6.84 ± 0.75 l/min compared with a resting Q̇c of 5.59 ± 1.14 l/min. Refilling during relaxation was complete, and the splanchnic bed did not progressively empty. Diastolic pressure increased by 25 mmHg during each EM. Between EMs, Q̇c increased to 7.09 ± 1.14 l/min due to increased stroke volume and heart rate. The circulatory function of the diaphragm assisted by simultaneous contractions of abdominal muscles with appropriate pressure and duration at 20 min−1can produce a circulatory output as great as resting Q̇c, as well as ventilation. These combined functions of the diaphragm have potential for cardiopulmonary resuscitation. The abdominal circulatory pump can act as an auxiliary heart.