Spontaneous Respiratory Activity Research Articles

Ultrasound guided transcutaneous phrenic nerve stimulation in critically ill patients: a new method to evaluate diaphragmatic function.

Diaphragm dysfunction is common in intensive care unit and associated with weaning failure and mortality. Diagnosis gold standard is the transdiaphragmatic or tracheal pressure induced by magnetic phrenic nerve stimulation. However, the equipment is not commonly available and requires specific technical skills. We aimed to evaluate ultrasound guided transcutaneous phrenic nerve stimulation for daily bedside assessment of diaphragm function by targeted electrical phrenic nerve stimulation. In this randomized cross-over study we compared a new method of ultrasound guided transcutaneous electrical phrenic nerve stimulation (SONOTEPS method) using a peripheral nerve stimulator, with the magnetic phrenic nerve stimulation. Intensive care unit adult patients under mechanical ventilation with a Richmond-Agitation-Sedation-Scale score of -4 or -5 were included. Each patient received the two methods of stimulation, in a randomized order. The primary outcome was the tracheal pressure (Ptrach) induced by stimulation. We analyzed 232 measures of Ptrach from 116 patients of whom 77 presented a diaphragm dysfunction (Ptrach < 11 cmH2O) and 50 a severe diaphragm dysfunction (Ptrach < 8 cmH2O). The Passing-Bablok regression showed no significant differences (intercept A of -0.03 [CI95:-0.83-0.52] and slope B of 0.98 [CI95:0.90-1.05]) between SONOTEPS method and magnetic stimulation which were positively correlated (R²=0.639). The mean bias was -1.08 (CI95 5.02, -7.18) cmH2O. The receiver operating curves showed an excellent performance for the diagnosis of diaphragm dysfunction and severe diaphragm dysfunction with respectively an area under curve of 0.90 (CI95 0.83-0.97) and 0.88 (CI95 0.82-0.95). This performance was not significantly affected by the body mass index or the presence of a neck catheter. The SONOTEPS method is a simple and accurate tool for bedside assessment of diaphragm function with ultrasound guided transcutaneous phrenic nerve stimulation in sedated patients with no or minimal spontaneous respiratory activity.

Predictive Hypoxemic Threshold for Tolerating the Apnea Test While Assessing Death by Neurological Criteria

Abstract Background The apnea test (AT) plays a vital role in diagnosing brain death by evaluating the absence of spontaneous respiratory activity. It entails disconnecting the patient from mechanical ventilation to raise the CO2 partial pressure and lower the pH. Occasionally, the AT is aborted because of safety concerns, such as hypoxemia and hemodynamic instability, to prevent worsening conditions. However, the exact oxygen partial pressure level needed before commencing AT, indicating an inability to tolerate the test, is still uncertain. This study seeks to determine pre-AT oxygen levels linked with a heightened risk of test failure. Methods We conducted a retrospective cohort study involving patients suspected of having brain death at the Tel Aviv Medical Center from 2010 to 2022. The primary outcome was defined as an arterial partial O2 pressure (PaO2) level of 60 mmHg or lower at the conclusion of the AT. This threshold is significant because it marks the point at which the saturation curve deflects, potentially leading to rapid deterioration in the patient’s oxygen saturation. Results Among the 70 patients who underwent AT, 7 patients met the primary diagnostic criteria. Patients with a PaO2 ≤ 60 mmHg at the conclusion of the AT exhibited a significantly lower initial median PaO2 of 243.7 mmHg compared with those with higher pre-AT PaO2 levels of 374.8 mmHg (interquartile range 104.65–307.00 and interquartile range 267.8–444.9 respectively, P value = 0.0041). Pre-AT PaO2 levels demonstrated good discriminatory ability for low PaO2 levels according to the receiver operating characteristic (ROC) curve, with an area under the curve of 0.76 (95% confidence interval 0.52–0.99). Conclusions PaO2 values at the conclusion of the AT are closely associated with PaO2 values at the beginning of the test. Establishing a cutoff value of approximately 300 mmHg PaO2 at the onset of AT may assist in avoiding saturation drops below 90%.

Impact of neonatal noninvasive resuscitation strategies on lung mechanics, tracheal pressure, and tidal volume in preterm lambs.

This study investigated the relationship between three respiratory support approaches on lung volume recruitment during the first 2 h of postnatal life in preterm lambs. We estimated changes in lung aeration, measuring respiratory resistance and reactance by oscillometry at 5 Hz. We also measured intratracheal pressure in subsets of lambs. The first main finding is that sustained inflation (SI) applied noninvasively (Mask SI; n = 7) or invasively [endotracheal tube (ETT) SI; n = 6] led to similar rapid lung volume recruitment (∼6 min). In contrast, Mask continuous positive airway pressure (CPAP) without SI (n = 6) resuscitation took longer (∼30-45 min) to reach similar lung volume recruitment. The second main finding is that, in the first 15 min of postnatal life, the Mask CPAP without SI group closed their larynx during custom ventilator-driven expiration, leading to intratracheal positive end-expiratory pressure of ∼17 cmH2O (instead of 8 cmH2O provided by the ventilator). In contrast, the Mask SI group used the larynx to limit inspiratory pressure to ∼26 cmH2O (instead of 30 cmH2O provided by the ventilator). These different responses affected tidal volume, being larger in the Mask CPAP without SI group [8.4 mL/kg; 6.7-9.3 interquartile range (IQR)] compared to the Mask SI (5.0 mL/kg; 4.4-5.2 IQR) and ETT SI groups (3.3 mL/kg; 2.6-3.7 IQR). Distinct physiological responses suggest that spontaneous respiratory activity of the larynx of preterm lambs at birth can uncouple pressure applied by the ventilator to that applied to the lung, leading to unpredictable lung pressure and tidal volume delivery independently from the ventilator settings.NEW & NOTEWORTHY We compared invasive and noninvasive resuscitation on lambs at birth, including or not sustained inflation (SI). Lung volume recruitment was faster in those receiving SI. During noninvasive resuscitation, larynx modulation reduced tracheal pressure from that applied to the mask in lambs receiving SI, while it led to increased auto-positive end-expiratory pressure and very large tidal volumes in lambs not receiving SI. Our results highlight the need for individualizing pressures and monitoring tidal volumes during resuscitation at birth.

Patient Self-Inflicted Lung Injury-A Narrative Review of Pathophysiology, Early Recognition, and Management Options.

Patient self-inflicted lung injury (P-SILI) is a life-threatening condition arising from excessive respiratory effort and work of breathing in patients with lung injury. The pathophysiology of P-SILI involves factors related to the underlying lung pathology and vigorous respiratory effort. P-SILI might develop both during spontaneous breathing and mechanical ventilation with preserved spontaneous respiratory activity. In spontaneously breathing patients, clinical signs of increased work of breathing and scales developed for early detection of potentially harmful effort might help clinicians prevent unnecessary intubation, while, on the contrary, identifying patients who would benefit from early intubation. In mechanically ventilated patients, several simple non-invasive methods for assessing the inspiratory effort exerted by the respiratory muscles were correlated with respiratory muscle pressure. In patients with signs of injurious respiratory effort, therapy aimed to minimize this problem has been demonstrated to prevent aggravation of lung injury and, therefore, improve the outcome of such patients. In this narrative review, we accumulated the current information on pathophysiology and early detection of vigorous respiratory effort. In addition, we proposed a simple algorithm for prevention and treatment of P-SILI that is easily applicable in clinical practice.

Accurate evaluation of mechanical ventilation and spontaneous respiratory activity

Maintenance of spontaneous effort during mechanical ventilation has long been recognized to improve oxygenation. Such effort has been considered beneficial because oxygenation is a key management aim. However, accumulating evidence indicates that spontaneous effort during mechanical ventilation may cause or worsen acute lung injury. Recently, effort-dependent lung injury has been termed as patient-self inflicted lung injury (P-SILI). This paper describes pathophysiological changes of ventilation-induced lung injury (VILI) induced by mechanical ventilation and spontaneous breathing, and the role of spontaneous breathing during mechanical ventilation in acute respiratory distress syndrome (ARDS). Studies have shown that spontaneous breathing is a double-edged sword, depending on the intensity of spontaneous breathing activity and the severity of lung injury. Future studies are needed to determine ventilator strategies minimizing injury.

The Cardiac Caval Index: Improving Noninvasive Assessment of Cardiac Preload.

Inferior vena cava (IVC) pulsatility quantified by the Caval Index (CI) is characterized by poor reliability, also due to the irregular magnitude of spontaneous respiratory activity generating the major pulsatile component. The aim of this study was to test whether the IVC cardiac oscillatory component could provide a more stable index (Cardiac CI-CCI) compared to CI or respiratory CI (RCI). Nine healthy volunteers underwent long-term monitoring in supine position of IVC, followed by 3 minutes passive leg raising (PLR). CI, RCI, and CCI were extracted from video recordings by automated edge-tracking and CCI was averaged over each respiratory cycle (aCCI). Cardiac output (CO), mean arterial pressure (MAP) and heart rate (HR) were also recorded during baseline (1 minutes prior to PLR) and PLR (first minute). In response to PLR, all IVC indices decreased (P < .01), CO increased by 4 ± 4% (P=.055) while HR and MAP did not vary. The Coefficient of Variation (CoV) of aCCI (13 ± 5%) was lower than that of CI (17 ± 5%, P < .01), RCI (26 ± 7%, P < .001) and CCI (25 ± 7%, P < .001). The mutual correlations in time of the indices were 0.81 (CI-RCI), 0.49 (CI-aCCI) and 0.2 (RCI-aCCI). Long-term IVC monitoring by automated edge-tracking allowed us to evidence that 1) respiratory and averaged cardiac pulsatility components are uncorrelated and thus carry different information and 2) the new index aCCI, exhibiting the lowest CoV while maintaining good sensitivity to blood volume changes, may overcome the poor reliability of CI and RCI.

Effects of early respiratory physiotherapy on spontaneous respiratory activity of preterm infants: study protocol for a randomized controlled trial

BackgroundTactile maneuvers stimulating spontaneous respiratory activity in preterm infants are recommended since birth, but data on how and how often these maneuvers are applied in clinical practice are unknown. In the last years, most preterm newborns with respiratory failure are preferentially managed with non-invasive respiratory support and by stimulating spontaneous respiratory activity from the delivery room and in neonatal intensive care unit (NICU), in order to avoid the risks of intubation and prolonged mechanical ventilation.MethodsPreterm infants with gestational age < 31 weeks not intubated in the delivery room and requiring non-invasive respiratory support at birth will be eligible for the study. They will be randomized and allocated to one of two treatment groups: (1) the study group infants will be subject to the technique of respiratory facilitation within the first 24 h of life, according to the reflex stimulations, by the physiotherapist. The newborn is placed in supine decubitus and a slight digital pressure is exerted on a hemithorax. The respiratory facilitation technique will be performed for about three minutes and repeated for a total of 4/6 times in sequence, three times a day until spontaneous respiratory activity is achieved; thus, no respiratory support is required; (2) the control group infants will take part exclusively in the individualized postural care program. They will perform the technique of respiratory facilitation and autogenous drainage.ObjectiveTo evaluate the efficacy of early respiratory physiotherapy in reducing the incidence of intubation and mechanical ventilation in the first week of life (primary outcome).DiscussionThe technique of respiratory facilitation is based on reflex stimulations, applied early to preterm infant. Slight digital pressure is exerted on a “trigger point” of each hemithorax, to stimulate the respiratory activity with subsequent increase of the ipsilateral pulmonary minute ventilation and to facilitate the contralateral pulmonary expansion. This mechanism will determine the concatenation of input to all anatomical structures in relation to the area being treated, to promote spontaneous respiratory activity and reducing work of breathing, avoiding or minimizing the use of invasive respiratory support.Trial registrationUMIN-CTR Clinical Trial UMIN000036066. Registered on March 1, 2019. Protocol 1. https://www.umin.ac.jp/ctr

Cell Type-Dependent Activation Sequence During Rhythmic Bursting in the PreBötzinger Complex in Respiratory Rhythmic Slices From Mice.

Spontaneous respiratory rhythmic burst activity can be preserved in the preBötzinger Complex (preBötC) of rodent medullary transverse slices. It is known, that the activation sequence of inspiratory neurons in the preBötC stochastically varies from cycle to cycle. To test whether the activation timing of an inspiratory neuron depends on its neurotransmitter, we performed calcium imaging of preBötC neurons using double-transgenic mice expressing EGFP in GlyT2+ neurons and tdTomato in GAD65+ neurons. Five types of inspiratory neurons were identified using the fluorescence protein expression and the maximum cross-correlation coefficient between neuronal calcium fluctuation and field potential. Regarding the activation sequence, irregular type putative excitatory (GlyT2-/GAD65-) neurons and irregular type glycinergic (GlyT2+/GAD65-) neurons tended to be activated early, while regular type putative excitatory neurons, regular type glycinergic neurons tended to be activated later. In conclusion, the different cell types define a general framework for the stochastically changing activation sequence of inspiratory neurons in the preBötC.

Role of the K+-Cl- Cotransporter KCC2a Isoform in Mammalian Respiration at Birth.

In central respiratory circuitry, synaptic excitation is responsible for synchronizing neuronal activity in the different respiratory rhythm phases, whereas chloride-mediated inhibition is important for shaping the respiratory pattern itself. The potassium chloride cotransporter KCC2, which serves to maintain low intraneuronal Cl– concentration and thus render chloride-mediated synaptic signaling inhibitory, exists in two isoforms, KCC2a and KCC2b. KCC2 is essential for functional breathing motor control at birth, but the specific contribution of the KCC2a isoform remains unknown. Here, to address this issue, we investigated the respiratory phenotype of mice deficient for KCC2a. In vivo plethysmographic recordings revealed that KCC2a-deficient pups at P0 transiently express an abnormally low breathing rate and a high occurrence of apneas. Immunostainings confirmed that KCC2a is normally expressed in the brainstem neuronal groups involved in breathing (pre-Bötzinger complex, parafacial respiratory group, hypoglossus nucleus) and is absent in these regions in the KCC2a–/– mutant. However, in variously reduced in vitro medullary preparations, spontaneous rhythmic respiratory activity is similar to that expressed in wild-type preparations, as is hypoglossal motor output, and no respiratory pauses are detected, suggesting that the rhythm-generating networks are not intrinsically affected in mutants at P0. In contrast, inhibitory neuromodulatory influences exerted by the pons on respiratory rhythmogenesis are stronger in the mutant, thereby explaining the breathing anomalies observed in vivo. Thus, our results indicate that the KCC2a isoform is important for establishing proper breathing behavior at the time of birth, but by acting at sites that are extrinsic to the central respiratory networks themselves.

An authentic animal model of the very preterm infant on nasal continuous positive airway pressure.

BackgroundThe surge in uptake of nasal continuous positive airway pressure (CPAP) for respiratory support in preterm infants has occurred in the absence of an authentic animal model. Such a model would allow investigation of research questions of physiological and therapeutic importance. We therefore aimed to develop a preterm lamb model of the non-intubated very preterm infant on CPAP.MethodsAfter staged exteriorisation and instrumentation, preterm lambs were delivered from anaesthetised ewes at 131 to 133 days gestation. Via a single nasal prong (4-mm internal diameter, 6- to 7-cm depth), positive pressure was delivered from the outset, with nasal intermittent positive pressure ventilation (NIPPV) used until transition to nasal CPAP was attempted, and periodically thereafter for hypoventilation. Caffeine and doxapram were used as respiratory stimulants. Gastric distension was prevented with an oesophageal balloon. Cardiorespiratory parameters and results of arterial blood gas analyses were monitored throughout the study period, which continued for 150 min after first transition to CPAP.ResultsTen preterm lambs were studied, at gestation 132 ± 1 days (mean ± SD) and birth weight 3.6 ± 0.45 kg. After stabilisation on NIPPV, transition to nasal CPAP was first attempted at 28 ± 11 min. There was transient respiratory acidosis, with gradual resolution as spontaneous respiratory activity increased. In the final hour, 79% ± 33% of time was spent on CPAP alone, with typical respiratory rates around 60 breaths per minute. PaCO2 at end-experiment was 58 ± 36 mmHg.ConclusionsNon-intubated preterm lambs can be effectively transitioned to nasal CPAP soon after birth. This animal model will be valuable for further research.

Weaning from extracorporeal membrane oxygenation: experience with dexmedetomidine in seven adult ARDS patients

Sedation in the ICU is a basic therapeutic procedure to increase tolerance of invasive treatments and reduce discomfort. Extracorporeal membrane oxygenation (ECMO) is a highly invasive treatment and prolonged sedation may be required. Patients undergoing ECMO represent a challenge with respect to sedation. Initially, deep sedation may be required to optimize ventilation and circuit-patient flows and to minimize oxygen consumption. The other critical phase is represented by weaning from ECMO support. Optimal sedation is not clearly defined, moreover there are no data on sedation practices with dexmedetomidine (DEX) in adult patients undergoing ECMO. In contrast to other sedatives, DEX has analgosedative effects without respiratory depression, and could be useful to facilitate spontaneous respiratory activity during recovery from sedation.

PPO.11 Perinatal mortality in Ireland: A national clinical audit

BackgroundPerinatal mortality has decreased in high-resource countries but cause of death, especially for stillbirths, is often unexplained. The Irish National Perinatal Epidemiology Centre (NPEC) established a national clinical audit on...

When to Promote Spontaneous Respiratory Activity in Acute Respiratory Distress Patients?

When to Promote Spontaneous Respiratory Activity in Acute Respiratory Distress Patients?

Can phrenic stimulation protect the diaphragm from mechanical ventilation-induced damage?

To the Editor: Mechanical ventilation is a prominent lifesaving treatment. It is, however, associated with an array of adverse effects, which include ventilator-associated pneumonias, volume-induced lung injury and, more recently identified, ventilator-induced diaphragm dysfunction (VIDD) [1–3]. VIDD combines diaphragm weakness with muscle fibre atrophy, remodelling and injury. Its mechanisms involve decreased protein synthesis, increased proteolysis, increased oxidative stress and mitochondrial dysfunction [2, 4]. Controlled mechanical ventilation appears to be the main, if not the sole, risk factor for VIDD, which in animal models is attenuated by the maintenance of respiratory efforts (assisted ventilatory modes) [2]. Although the corresponding human evidence is still lacking, this underlies the current notion that “clinicians should encourage persistent diaphragmatic activity” in patients receiving mechanical ventilation [2]. Diaphragm pacing has been proposed as a surrogate for spontaneous respiratory activity when the latter is not compatible with the condition of the patient [2, 5], but this approach has, seemingly, not yet been tested experimentally. Here we report a preliminary description of putative beneficial effects of diaphragm pacing in three mechanically ventilated sheep. Three female adult sheep (41, 32 and 34 kg), were anaesthetised (premedication: acepromazine 1.3 mg·kg−1 i.m. , 30 min before induction; induction: propofol 6 mg·kg−1 i.v. ; maintenance: continuous propofol 1–2 mg·kg−1·h−1, midazolam 0.3–2 mg·kg−1·h−1 and morphine 0.2–0.3 mg·kg−1·h−1; no paralysing agents), tracheotomised and mechanically ventilated with a minute ventilation ensuring normocapnia (Aisys, GE Healthcare, Datex Ohmeda, Madison, WI, USA). Additional oxygen was given to maintain transcutaneous-pulsed oxygen saturation >92%. Adequate fluid and nutritional support was provided and glycaemia controlled. Body temperature, heart rate and arterial pressure were monitored. Intradiaphragmatic phrenic nerve stimulation electrodes were inserted bilaterally in …

Bedside diagnosis of bilateral diaphragmatic paralysis

Dear Editor, Bilateral diaphragmatic paralysis (BDP) is a rare cause of respiratory failure that is quite challenging to diagnose [1]. Here we describe the cases of two children in whom BDP was easily detected at bedside once we used an esophagal probe equipped with sensors that measured the electrical activity of the diaphragm. A 3-year-old boy with complex congenital cardiopathy underwent a third surgery using the bidirectional Glenn anastomosis procedure. After extubation, he developed intense dyspnea. A commercially available feeding tube equipped with sensors (Edi 8-Fr catheter, Maquet Critical Care, Solna, Sweden) was installed to provide respiratory support using the neurally adjusted ventilatory assist mode (NAVA). This esophageal probe records electrical activity of the diaphragm via a Servo-I Ventilator (Maquet Critical Care, Solna, Sweden) using a standardized method [2]. The child regained spontaneous respiratory activity, but no electrical activity of the diaphragm could be found, thus evoking the diagnosis of BDP. This diagnosis was confirmed by a fluoroscopy. The child was completely liberated from noninvasive ventilation on the 18th postoperative day. A 9-month-old girl with an atrioventricular canal defect underwent a third surgery for mitral valve replacement. Over the next few days, she experienced two failed extubations. Echocardiographies showed good cardiac function. Laryngotracheal fibroscopy did not provide an explanatory diagnosis. A fluoroscopy of the diaphragm receiving pressure support ventilation was carried out by a radiologist who concluded that there were no components indicating diaphragmatic paralysis. A thoracic tomodensitometry showed systematized alveolar condensations reminiscent of non-specific ventilatory disorders. Two weeks after the valve replacement, a pacemaker was implanted because of a persistent complete atrioventricular block. Thereafter, the attending physician decided to try ventilatory support using the NAVA mode because of the good results we had obtained in other cases of challenging ventilation [3]. The respiratory rate and ventilator pressures were reduced in order to restore spontaneous respiratory activity. Nevertheless, the Edi catheter did not detect any electrical activity of the diaphragm. The diagnosis of BDP was then confirmed by an electromyography of the diaphragm with a phrenic nerve conduction study. After a left diaphragmatic plication, the child was free of all mechanical ventilation 3 weeks later. Bilateral diaphragmatic paralysis is a rare cause of respiratory distress that develops in various neuropathies and myopathies [1]. After cardiac surgery BDP is typically due to traction applied during the thoracic surgery [4]. Bilateral diaphragmatic paralysis is difficult to diagnose as there are no asymmetric movements, unlike unilateral diaphragmatic paralysis. Fluoroscopic imaging, although sensitive and specific for unilateral diaphragm paralysis, is frequently misinterpreted when diaphragmatic paralysis is bilateral. Currently, measurement of electrical activity of the diaphragm can be done at the bedside with a specific esophageal probe connected to a commercially available ventilator [5]. The position of this probe must be carefully checked using the positioning window and ECG signals. The absence of electrical activity of the diaphragm in a child with unexplained respiratory distress, where spontaneous breathing activity is present, strongly suggests the diagnosis of BDP.

Quantitative analysis of the excitability of hypoglossal motoneurons during natural sleep in the rat

We describe a novel approach to assess the excitability of hypoglossal motoneurons in rats during naturally occurring states of sleep and wakefulness. Adult rats were surgically prepared with permanently placed electrodes to record the EEG, EOG and neck EMG. A stimulating/recording miniature tripolar cuff electrode was implanted around the intact hypoglossal nerve and a head-restraining device was bonded to the calvarium. After a period of adaptation to head-restraint, the animals did not exhibit any sign of discomfort and readily transitioned between the states of wakefulness, NREM and REM sleep. There was no spontaneous respiratory or tonic activity present in the hypoglossal nerve during sleep or wakefulness. Hypoglossal motoneurons were activated by electrical stimulation of the hypoglossal nerve (antidromically) or by microstimulation directly applied to the hypoglossal nucleus. Microstimulation of hypoglossal motoneurons evoked compound action potentials in the ipsilateral hypoglossal nerve. The magnitude of their integrals tended to be higher during wakefulness (112.6%±15; standard deviation) and were strongly depressed during REM sleep (24.7%±3.4), compared to the integral magnitude during NREM sleep. Lidocaine, which was delivered using pressure microinjection to the microstimulation site, verified that the responses evoked in hypoglossal nerve can be affected pharmacologically. We conclude that this animal model can be utilized to study the neurotransmitter mechanisms that control the excitability of hypoglossal motoneurons during naturally occurring states of sleep and wakefulness.

Spinal and Pontine Relay Pathways Mediating Respiratory Rhythm Entrainment by Limb Proprioceptive Inputs in the Neonatal Rat

The coordination of locomotion and respiration is widespread among mammals, although the underlying neural mechanisms are still only partially understood. It was previously found in neonatal rat that cyclic electrical stimulation of spinal cervical and lumbar dorsal roots (DRs) can fully entrain (1:1 coupling) spontaneous respiratory activity expressed by the isolated brainstem/spinal cord. Here, we used a variety of preparations to determine the type of spinal sensory inputs responsible for this respiratory rhythm entrainment, and to establish the extent to which limb movement-activated feedback influences the medullary respiratory networks via direct or relayed ascending pathways. During in vivo overground locomotion, respiratory rhythm slowed and became coupled 1:1 with locomotion. In hindlimb-attached semi-isolated preparations, passive flexion-extension movements applied to a single hindlimb led to entrainment of fictive respiratory rhythmicity recorded in phrenic motoneurons, indicating that the recruitment of limb proprioceptive afferents could participate in the locomotor-respiratory coupling. Furthermore, in correspondence with the regionalization of spinal locomotor rhythm-generating circuitry, the stimulation of DRs at different segmental levels in isolated preparations revealed that cervical and lumbosacral proprioceptive inputs are more effective in this entraining influence than thoracic afferent pathways. Finally, blocking spinal synaptic transmission and using a combination of electrophysiology, calcium imaging and specific brainstem lesioning indicated that the ascending entraining signals from the cervical or lumbar limb afferents are transmitted across first-order synapses, probably monosynaptic, in the spinal cord. They are then conveyed to the brainstem respiratory centers via a brainstem pontine relay located in the parabrachial/Kölliker-Fuse nuclear complex.

Growth performance, feed utilization and non-specific immune response of gilthead sea bream (Sparus aurata L.) fed graded levels of a bioprocessed soybean meal

The objective of this study was to evaluate the effects of partial fish meal replacement by a bioprocessed soy product (BS) in juvenile gilthead sea bream over the course of a 3-month trial. A diet with fish meal as the sole protein source (FM) was compared to diets with 20% (BS20), 40% (BS40) and 60% (BS60) of replacement. The effects of diets on growth performance, feed utilization, gut integrity, liver structure and immune status were evaluated. Weight gain, feed efficiency, daily growth index and specific growth rate decreased at the highest level of BS, while feed intake increased. In fish from BS40 and BS60 groups, indices indicating growth in response to protein intake such as protein efficiency ratio and protein productive value were decreased significantly. Body composition did not differ among groups for all parameters analysed. As far as non-specific immune response is concerned, spontaneous respiratory burst activity of blood significantly decreased at BS20 and BS40 groups, while stimulated activity did not indicate any significant change. Serum myeloperoxidase levels and total bacteriolytic activity of complement increased significantly at the highest dietary inclusion of BS, compared to the control group, while serum lysozyme levels did not indicate significant changes. Liver structure was not affected at any level, but some alterations in intestinal morphology were observed in the distal intestine mainly in the BS60 group. Overall, FM replacement by BS affected negatively gilthead sea bream growth performance at the 60% level, protein efficiency from the 40% level and affected some indicators of the immune response.

Cerebral Arterial Air Embolism Associated with Mechanical Ventilation and Deep Tracheal Aspiration

Arterial air embolism associated with pulmonary barotrauma has been considered a rare but a well-known complication of mechanical ventilation. A 65-year-old man, who had subarachnoid hemorrhage with Glasgow coma scale of 8, was admitted to intensive care unit and ventilated with the help of mechanical ventilator. Due to the excessive secretions, deep tracheal aspirations were made frequently. GCS decreased from 8–10 to 4-5, and the patient was reevaluated with cranial CT scan. In CT scan, air embolism was detected in the cerebral arteries. The patient deteriorated and spontaneous respiratory activity lost just after the CT investigation. Thirty minutes later cardiac arrest appeared. Despite the resuscitation, the patient died. We suggest that pneumonia and frequent tracheal aspirations are predisposing factors for cerebral vascular air embolism.

Population calcium imaging of spontaneous respiratory and novel motor activity in the facial nucleus and ventral brainstem in newborn mice

The brainstem contains rhythm and pattern forming circuits, which drive cranial and spinal motor pools to produce respiratory and other motor patterns. Here we used calcium imaging combined with nerve recordings in newborn mice to reveal spontaneous population activity in the ventral brainstem and in the facial nucleus. In Fluo-8AM loaded brainstem-spinal cord preparations, respiratory activity on cervical nerves was synchronized with calcium signals at the ventrolateral brainstem surface. Individual ventrolateral neurons at the level of the parafacial respiratory group showed perfect or partial synchrony with respiratory nerve bursts. In brainstem-spinal cord preparations, cut at the level of the mid-facial nucleus, calcium signals were recorded in the dorsal, lateral and medial facial subnuclei during respiratory activity. Strong activity initiated in the dorsal subnucleus, followed by activity in lateral and medial subnuclei. Whole-cell recordings from facial motoneurons showed weak respiratory drives, and electrical field potential recordings confirmed respiratory drive to particularly the dorsal and lateral subnuclei. Putative facial premotoneurons showed respiratory-related calcium signals, and were predominantly located dorsomedial to the facial nucleus. A novel motor activity on facial, cervical and thoracic nerves was synchronized with calcium signals at the ventromedial brainstem extending from the level of the facial nucleus to the medulla–spinal cord border. Cervical dorsal root stimulation induced similar ventromedial activity. The medial facial subnucleus showed calcium signals synchronized with this novel motor activity on cervical nerves, and cervical dorsal root stimulation induced similar medial facial subnucleus activity. In conclusion, the dorsal and lateral facial subnuclei are strongly respiratory-modulated, and the brainstem contains a novel pattern forming circuit that drives the medial facial subnucleus and cervical motor pools.