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Duchenne muscular dystrophy (DMD) is a fatal genetic neuromuscular disease. Lack of dystrophin in skeletal muscles leads to intrinsic weakness, injury, subsequent degeneration and fibrosis, decreasing contractile function. Dystropathology eventually presents in all inspiratory and expiratory muscles of breathing, severely curtailing their critical function. In people with DMD, premature death is caused by respiratory or cardiac failure. There is an urgent need to develop therapies that improve quality of life and extend life expectancy in DMD. Surprisingly, there is a dearth of information on respiratory control in animal models of DMD, and respiratory outcome measures are often limited or absent in clinical trials. Characterization of respiratory performance in murine and canine models has revealed extensive remodelling of the diaphragm, the major muscle of inspiration. However, significant compensation by extradiaphragmatic muscles of breathing is evident in early disease, contributing to preservation of peak respiratory system performance. Loss of compensation afforded by accessory muscles in advanced disease is ultimately associated with compromised respiratory performance. A new and potentially more translatable murine model of DMD, the D2.mdx mouse, has recently been developed. Respiratory performance in D2.mdx mice is yet to be characterized fully. However, based on histopathological features, D2.mdx mice might serve as useful preclinical models, facilitating the testing of new therapeutics that rescue respiratory function. This review summarizes the pathophysiological mechanisms associated with DMD both in humans and in animal models, with a focus on breathing. We consider the translational value of each model to human DMD and highlight the urgent need for comprehensive characterization of breathing in representative preclinical models to better inform human trials. What is the topic of this review?We review current understanding of the respiratory phenotype in Duchenne muscular dystrophy (DMD), a fatal genetic neuromuscular disease.What advances does it highlight?Diaphragm muscle dystropathology and contractile dysfunction present early in dystrophic disease, yet respiratory system performance is maintained by compensatory mechanisms until late‐stage advanced disease. Loss of compensation afforded by accessory muscles of breathing contributes to respiratory morbidity in canine and murine models of DMD, mirroring the human disease. The D2.mdx mouse appears convenient for the study of the complex respiratory phenotype associated with dystrophin deficiency, and assessments of new therapeutics in this model might be translatable to human DMD. [ABSTRACT FROM AUTHOR]

Abstract Duchenne muscular dystrophy (DMD) is a fatal genetic neuromuscular disease. Lack of dystrophin in skeletal muscles leads to intrinsic weakness, injury, subsequent degeneration and fibrosis, decreasing contractile function. Dystropathology eventually presents in all inspiratory and expiratory muscles of breathing, severely curtailing their critical function. In people with DMD, premature death is caused by respiratory or cardiac failure. There is an urgent need to develop therapies that improve quality of life and extend life expectancy in DMD. Surprisingly, there is a dearth of information on respiratory control in animal models of DMD, and respiratory outcome measures are often limited or absent in clinical trials. Characterization of respiratory performance in murine and canine models has revealed extensive remodelling of the diaphragm, the major muscle of inspiration. However, significant compensation by extradiaphragmatic muscles of breathing is evident in early disease, contributing to preservation of peak respiratory system performance. Loss of compensation afforded by accessory muscles in advanced disease is ultimately associated with compromised respiratory performance. A new and potentially more translatable murine model of DMD, the D2.mdx mouse, has recently been developed. Respiratory performance in D2.mdx mice is yet to be characterized fully. However, based on histopathological features, D2.mdx mice might serve as useful preclinical models, facilitating the testing of new therapeutics that rescue respiratory function. This review summarizes the pathophysiological mechanisms associated with DMD both in humans and in animal models, with a focus on breathing. We consider the translational value of each model to human DMD and highlight the urgent need for comprehensive characterization of breathing in representative preclinical models to better inform human trials.

Abstract Background The endotracheal cuff pressure depends on the airway pressure during positive-pressure ventilation. A high endotracheal cuff pressure may be related to intraoperative coughing, which can be detrimental during neurosurgery. We investigated the incidence of intraoperative coughing and its association with peak inspiratory pressure (PIP) during neurosurgery under general anesthesia without neuromuscular blockade. Methods This retrospective study divided 1656 neurosurgical patients who underwent total intravenous anesthesia without additional neuromuscular blockade after tracheal intubation into high (PIP > 21.6 cmH2O, n = 318) and low (PIP ≤ 21.6 cmH2O, n = 1338) PIP groups. After propensity score matching, 206 patients were selected in each group. Demographic, preoperative, surgical, and anesthetic data were collected retrospectively from electronic medical records and continuous ventilator, infusion pump, and bispectral index data from a data registry. Results Intraoperative coughing occurred in 30 (1.8%) patients, including 9 (0.5%) during the main surgical procedure. Intraoperative coughing was more frequent in the high PIP group than in the low PIP group before (14/318 [4.4%] vs. 16/1338 [1.2%], P

Background: The endotracheal cuff pressure depends on the airway pressure during positive-pressure ventilation. A high endotracheal cuff pressure may be related to intraoperative coughing, which can be detrimental during neurosurgery. We investigated the incidence of intraoperative coughing and its association with peak inspiratory pressure (PIP) during neurosurgery under general anesthesia without neuromuscular blockade. Methods: This retrospective study divided 1656 neurosurgical patients who underwent total intravenous anesthesia without additional neuromuscular blockade after tracheal intubation into high (PIP > 21.6 cmH2O, n = 318) and low (PIP ≤ 21.6 cmH2O, n = 1338) PIP groups. After propensity score matching, 206 patients were selected in each group. Demographic, preoperative, surgical, and anesthetic data were collected retrospectively from electronic medical records and continuous ventilator, infusion pump, and bispectral index data from a data registry. Results: Intraoperative coughing occurred in 30 (1.8%) patients, including 9 (0.5%) during the main surgical procedure. Intraoperative coughing was more frequent in the high PIP group than in the low PIP group before (14/318 [4.4%] vs. 16/1338 [1.2%], P < 0.001) and after (13/206 [6.3%] vs. 1/206 [0.5%], P = 0.003) propensity score matching. In multivariable logistic regression analysis after propensity score matching, a high PIP (odds ratio [95% confidence interval] 14.22 [1.81-111.73], P = 0.012), tidal volume divided by predicted body weight (mL/kg, 1.36 [1.09–1.69], P = 0.006), and surgical duration (min, 1.01 [1.00–1.01], P = 0.025) predicted intraoperative coughing. Conclusion: The incidence of intraoperative coughing was 1.8% in neurosurgical patients undergoing general anesthesia without neuromuscular blockade and might be associated with a high PIP. [ABSTRACT FROM AUTHOR]

Purpose: In children with acute respiratory distress syndrome receiving mechanical ventilation, the peak inspiratory pressure (PIP) is close to plateau pressure (P PLAT ) when inspiratory flow approaches zero. We aimed to evaluate the reliability of PIP to estimate P PLAT in infants with severe respiratory viral infection (SRVI), characterized by increased airway resistance, and the accuracy of an equational model to estimates P PLAT (eP PLAT ) based on PIP., Methods: This was a retrospective observational study including mechanically ventilated children (1 to 24 month old) with SRVI, whose respiratory mechanics measurements were performed to evaluate PIP and P PLAT. The measured P PLAT was compared with the result of the equation: eP PLAT  = PIP - [5.067 - (0.858 × static compliance) - (0.018 × inspiratory resistance) - (0.390 × pressure above positive-end expiratory pressure) + (4.989 × inspiratory time)]., Results: Thirty-seven patients were included, with a median age of 3 (2-5) months. They presented a high inspiratory and expiratory resistance (136 ± 43 and 168 ± 66 cmH 2 O/L/s, respectively) and a moderate reduction in static compliance: 0.75 ± 0.3 mL/kg/cmH 2 O. PIP overestimated P PLAT (33 ± 3 and 26 ± 5 cmH 2 O, p = 0.01), with a mean difference of 7.3 ± 4 cmH 2 O. Moreover, the Bland-Altman analysis demonstrated a mean difference between P PLAT and eP PLAT of 1.0 ± 4.0 cmH 2 O, with 95% limits of agreement of -6.9 and 8.8., Conclusions: A significant difference between PIP and P PLAT was observed in infants with SRVI. The equation model was inaccurate for estimating P PLAT based on PIP. Any estimation of P PLAT from PIP needs to consider the resistance component of the respiratory system., (© 2024 Wiley Periodicals LLC.)

Objective: To evaluate the performance (i.e., agreement between set and measured parameters) and safety (adverse events, device malfunctions, and ventilator alarms) of the fabian HFOi neonatal ventilator in volume guaranteed (VG) mode during conventional ventilation. To analyze the impact of leakage around the endotracheal tube and the set maximum allowed inflating pressure (Pmax)., Design: Prospective multicenter observational study., Methods: Clinical and ventilator data were collected from 71 infants receiving VG ventilation for ≥12 h in four neonatal intensive care units (NICUs). Ventilator settings, parameters, and alarms were downloaded with 0.5 Hz sampling rate., Results: Data from 4,341 h of ventilation were analyzed. The median (interquartile range, IQR) of the absolute difference between the target and measured expired tidal volume was 0.76 (0.51-1.16) mL/kg. It was less when leak was <50% (median 0.36, IQR: 0.25-0.64 mL/kg, p < .001) and even less when the required peak inflating pressure (PIP) was also below Pmax (median: 0.09 mL/kg, IQR: 0.00-0.16 mL/kg, p < .001). On NICUs setting Pmax higher, tidal volume was maintained significantly closer to target. In 56 patients VG was continued until extubation. Two ventilator malfunctions were reported, none of them resulting in patient harm. "Tidal volume not reached" alarm occurred 32 times hourly, usually lasting for <10 s., Conclusion: The fabian HFOi ventilator maintains tidal volume close to its target, particularly when leak is <50% and when PIP is below Pmax. In most patients VG can be continued until extubation. Despite frequent ventilator alarms, ventilator malfunctions occur very rarely., (© 2024 Wiley Periodicals LLC.)

A closed suction system is used to remove endotracheal secretions without interrupting the patient's ventilation. Closed suctioning may reduce adverse effects associated with suctioning with, for example, decreased clinical signs of hypoxemia and limited environmental, personnel, and patient contamination. However, it is not clear whether ventilation is maintained during the procedure. We aimed to determine the effects of endotracheal tube (ETT) size, suction catheter (SC) size, and SC length in the ETT on ventilation parameters measured during suction. Suction was performed on a test lung, ventilated with either volume-controlled continuous mandatory ventilation (VC-CMV) or pressure-controlled continuous mandatory ventilation (PC-CMV) using ETT sizes of 6.0–8.5 mm paired with SC sizes of 8–16 French gauge (Fr = 0.33 mm). Airway resistance (Raw), peak inspiratory pressure (PIP), positive end-expiratory pressure (PEEP), and expiratory minute volume (Vexp) were recorded for each ventilation episode by a HAMILTON- G5 ventilator. Here, Raw was considerably increased by insertion of the SC into the ETT. This Raw effect altered the PIP and Vexp. PIP was increased in VC-CMV because the ventilation area of the ETT was reduced, and Vexp was decreased in PC-CMV in relation to the size of the SC. PEEP decreased with application of the 16 Fr SC and 30 L/min flow rate in VC-CMV. We conclude that airway pressure and minute volume are not maintained during closed endotracheal suctioning with VC-CMV and PC-CMV, respectively. The degree of interference to ventilation is affected through selection of appropriate SC size and ventilation settings. [ABSTRACT FROM AUTHOR]

Ventilation during chest compressions can lead to an increase in peak inspiratory pressure. High inspiratory pressure can raise the risk of injury to the respiratory system and make it challenging to deliver the required tidal volume. The utilization of mechanical devices for chest compression has exacerbated this challenge. The aim of this narrative review was to summarize the different mechanical ventilation strategies applied during mechanical cardiopulmonary resuscitation (CPR). To this end, we searched the PubMed and BioMed Central databases from inception to January 2020, using the search terms "mechanical ventilation," "cardiac arrest," "cardiopulmonary resuscitation," "mechanical cardiopulmonary resuscitation," and their related terms. We included all studies (human clinical or animal-based research studies, as well as studies using simulation models) to explore the various ventilation settings during mechanical CPR. We identified 842 relevant articles on PubMed and 397 on BioMed Central; a total of 38 papers were judged to be specifically related to the subject of this review. Of this sample, 17 studies were conducted on animal models, 6 considered a simulated scenario, 13 were clinical studies (5 of which were retrospective), and 2 studies constituted literature review articles. The main finding arising from the assessment of these publications is that a high FIO2 must be guaranteed during CPR. Low-grade evidence suggests turning off inspiratory triggering and applying PEEP ≥ 5 cm H2O. The analysis also revealed that many uncertainties persist regarding the ideal choice of ventilation mode, tidal volume, the ventilation rate setting, and the inspiratory:expiratory ratio. None of the current international guidelines indicate the "best" mechanical ventilation strategy to apply during mechanical CPR. We propose an operating algorithm worthy of future discussion and study. Future studies specifically addressing the topics covered in this review are required. [ABSTRACT FROM AUTHOR]

Stroke volume variation (SVV) may be affected by ventilation settings. However, it is unclear whether positive‐end‐expiratory pressure (PEEP) affects SVV independently of the effect of driving pressure. We aimed to investigate the effect of driving pressure and PEEP on SVV under various preload conditions using beagle dogs as the animal model. We prepared three preload model, baseline, mild and moderate haemorrhage model. Mild and moderate haemorrhage models were created in nine anaesthetized, mechanically ventilated dogs by sequentially removing 10 mL/kg, and then an additional 10 mL/kg of blood, respectively. We measured cardiac output, stroke volume (SV), SVV, heart rate, central venous pressure, pulmonary capillary wedge pressure and the mean arterial pressure under varying ventilation settings. Peak inspiratory pressure (PIP) was incrementally increased by 4 cmH2O, from 9 cmH2O to 21 cmH2O, under PEEP values of 4, 8, and 12 cmH2O. The driving pressure did not significantly decrease SV under each preload condition and PEEP; however, significantly increased SVV. In contrast, the increased PEEP decreased SV and increased SVV under each preload condition and driving pressure, but these associations were not statistically significant. According to multiple regression analysis, an increase in PEEP and decrease in preload significantly decreased SV (P <.05). In addition, an increase in the driving pressure and decrease in preload significantly increased SVV (P <.05). Driving pressure had more influence than PEEP on SVV. [ABSTRACT FROM AUTHOR]

Background: Premature neonates are exposed to numerous painful procedures. Physiologic fluctuations in heart rate (HR), respiratory rate, and oxygen saturation are typically used to determine the response to pain. Neurally assisted ventilatory assist (NAVA) delivers inspiratory pressure in proportion to the electrical activity of the diaphragm (Edi). Since NAVA allows self-regulation of peak inspiratory pressures (PIP), there is apprehension that painful stimulus may increase respiratory drive and result in excessive PIP. This study evaluated changes in respiratory drive, measured by Edi, in response to a painful procedure (heel stick) to determine if there was excessive PIP delivered from the ventilator. Methods: Prospective, single-center study; subjects <32 weeks on NAVA/NIV NAVA requiring routine blood work via heel sticks. Vital signs were measured every 10 seconds for the first 2 minutes. PIP, Edi peak, and min were collected for the first ten breaths and then averaged at 1 and 2 minutes. Statistics were repeated measures ANOVA. Results: Fourteen subjects with gestational age 26.9+2 weeks and birth weight 994+318 grams. At study, the average age was 4.6+5 days, and weight was 948+305 grams. Following the heel stick, the first breath showed an increase in PIP and Edi peak but returned to baseline by the second breath. PIP increased again by the10th breath and at 1 and 2 minutes. HR increased after heel stick and remained elevated through the remainder of the study. There were no changes in tonic Edi, Edi min or other vital signs. Conclusion: Although the increase in PIP and Edi peak in response to heel stick pain was brief and limited, it is important always to set the PIP alarm limit appropriately to protect the lung from excessive pressures that may be generated during painful procedures. [ABSTRACT FROM AUTHOR]

Obesity affects respiratory and hemodynamic function in anesthetized patients. The aim of this study was to evaluate the influence of the body mass index (BMI) on pulmonary changes in a permanent 45° steep Trendelenburg position (STP) during robotic-assisted laparoscopic prostatectomy (RALP). 51 patients undergoing RALP under standardized anesthesia were included. Perioperative pulmonary function and oxygenation were measured in awake patients (T0), 20 min after the induction of anesthesia (T1), after insufflation of the abdomen in supine position (T2), after 30 min in STP (T3), when controlling Santorini's plexus in STP (T4), before awakening while supine (T5), and after 45 min in the recovery room (T6). Patient-specific and time-dependent factor on ventilation and predicted peak inspiratory pressure (PIP), driving pressure (Pdriv) and lung compliance (LC) in a linear regression model were calculated. PIP and Pdriv increased significantly after induction of capnoperitoneum (T2-4) (p < 0.0001). In univariate mixed effects models, BMI was found to be a significant predictor for PIP and Pdriv increase and LC decrease. Obese patients a BMI > 31 kg/m2 reached critical PIP values ≥ 35 cmH2O. Postoperative oxygenation represented by the PaO2/FiO2 ratio was significantly decreased compared to T0 (p < 0.0001). Obesity in combination with STP and capnoperitoneum during RALP has a profound effect on pulmonary function. Increased PIP and Pdriv and decreased LC are directly correlated with a high BMI. Changes in PIP, Pdriv and LC during RALP may be predicted in relation to patient's BMI for consideration in the preoperative setting. Trial registration number Z-2014-0387-6. Registered on 8 July 2014. [ABSTRACT FROM AUTHOR]

Background: Chest physiotherapy (CPT) and positioning of neonates has been used in many developed countries around the world to improve airway clearance and avoid lung complications, but the combined effect of both techniques is less documented. The objective of the study was to compare the effectiveness of chest physiotherapy in prone position versus conventional chest physiotherapy in ventilated neonates on respiratory outcomes. Methods: The study design was randomized controlled pilot study. Participants: 12 ventilated neonates fitting in Inclusion Criteria. They were randomly divided into two groups (n=6 in each group) using simple random sampling i.e. Experimental group (4female and 2male) (Chest Physiotherapy and Prone Positioning) and the Control group (3 females and 3males) (Conventional Chest Physiotherapy). Primary outcome measures were SpO2 saturation, Partial Pressure of Arterial Oxygen (PaO2) & Peak Inspiratory Pressure (P.I.P.). Outcomes were recorded Pre & Post of every 120 minutes session of Intervention twice daily with a gap of 6 hours for consecutive three days for the experimental group while for the control group, parameters were measured at the same time of the day. Result: Total 10 participants completed the study protocol. On comparison of three parameters in two groups using the unpaired t-test, we found that there was a significant difference (p< 0.05) in SpO2 and PaO2 in both groups but no difference ( p >0.05) in P.I.P. levels. Conclusion: Chest physiotherapy in the prone position for ventilated neonate concluded with a higher oxygen saturation (SpO2) and partial pressure of oxygen in the arterial blood (PaO2) when compared to conventional chest physiotherapy.