Dimitri Leduc

Acute and long term respiratory damage following inhalation of ammonia.

A lifelong non-smoker who was the victim of a massive accidental exposure to anhydrous ammonia gas was followed up for 10 years. In the acute phase the patient presented with severe tracheobronchitis and respiratory failure, caused by very severe burns of the respiratory mucosa. After some improvement he was left with severe and fixed airways obstruction. Isotope studies of mucociliary clearance, computed tomography, and bronchography showed mild bronchiectasis. It is concluded that acute exposure to high concentrations of ammonia may lead to acute respiratory injury but also to long term impairment of respiratory function.

Flumazenil in mixed benzodiazepine/tricyclic antidepressant overdose: A placebo-controlled study in the dog☆

This study evaluates the cardiac and neurologic risks associated with the antagonization of the benzodiazepine component of mixed drug overdoses, when cyclic antidepressants are also implicated. Twenty-four mongrel dogs were anesthetized and ventilated. Electroencephalogram, electrocardiogram, and tidal carbon dioxide and arterial pressure were continuously recorded. Amitriptyline (1 mg/kg/min) associated with midazolam (1 mg/kg + 1 mg/kg/h) was infused in 12 of the dogs. Midazolam was replaced by saline in the other 12. Drug administration was continued until signs of cardiotoxicity (QRS prolongation greater than 120 milliseconds or sustained arrhythmias) occurred. At that moment, midazolam effects were suddenly reversed by administration of flumazenil 0.2 mg/kg in six dogs out of each group. Placebo was administered in the others. Reactions were observed for the next 120 minutes. Midazolam-induced sedation efficiently protects (P less than .02) against seizures due to amitriptyline toxicity. This protective effect is counteracted by flumazenil. Midazolam has limited influence on the cardiac toxic effects of amitriptyline. The bolus of flumazenil is, however, associated with a significant worsening of electrocardiogram disturbances, and two sudden deaths were recorded. The mechanism of this effect remains unclear, as it could be unrelated to the antagonization of midazolam sedation. Given the problem of extrapolating animal data to humans, these results suggest that bolus administration of high doses of flumazenil in mixed intoxication implicating benzodiazepine and cyclic antidepressants has the potential to precipitate convulsions and/or arrhythmias. A slowly titrated administration of the antidote, as usually recommended, could prevent these effects.

Expiratory flow limitation during exercise in COPD: detection by manual compression of the abdominal wall

Manual compression of the abdomen (MCA) during spontaneous expiration is a simple method for the detection of flow limitation in the chronic obstructive pulmonary disease (COPD) patients during resting breathing, based on comparison of flow/volume curves obtained during MCA with that of the preceding control breath. It was assessed whether this nonstandardized technique is also feasible during exercise. MCA was performed during resting breathing and constant-exercise work at one- and two-thirds maximal mechanical power output (W′max) in six normal subjects and 12 COPD patients. Changes in end-expiratory lung volume (EELV) were also studied. With the aid of inspection, abdominal palpation and lung auscultation, MCA could always be applied during expiration. Flow limitation was never detected in the six normal subjects, whereas four of the COPD patients were flow limited at rest, seven during exercise at one-third W′max and nine during exercise at two-thirds W′max. Expiratory flow limitation detected by MCA was always associated with an increase in EELV during exercise, indicating dynamic hyperinflation occurrence or increase. It is concluded that manual compression of the abdomen is a very simple and reliable method for the detection of flow limitation during exercise.

Mechanisms of the inspiratory action of the diaphragm during isolated contraction

The lung-expanding action of the diaphragm is primarily related to the descent of the dome produced by the shortening of the muscle fibers. However, when the phrenic nerves in dogs are selectively stimulated at functional residual capacity, the muscle insertions into the lower ribs also move caudally. This rib motion should enhance the descent of the dome and increase the fall in pleural pressure (DeltaPpl). To quantify the role of this mechanism in determining DeltaPpl during isolated diaphragm contraction and to evaluate the volume dependence of this role, radiopaque markers were attached to muscle bundles in the midcostal region of the muscle in six animals, and the three-dimensional location of the markers during relaxation at different lung volumes and during phrenic nerve stimulation at the same lung volumes was measured using computed tomography. From these data, accurate measurements of muscle length, dome displacement, and lower rib displacement were obtained. The values of dome displacement were then corrected for lower rib displacement, and the values of DeltaPpl corresponding to the corrected dome displacements were obtained using the measured relationship between DeltaPpl and dome displacement. The measurements showed that phrenic stimulation at all lung volumes causes a caudal displacement of the lower ribs and that this displacement, taken alone, contributes approximately 25% of the DeltaPpl produced by the diaphragm. To the extent that this lower rib displacement is itself caused by DeltaPpl, the lung-expanding action of the diaphragm during isolated contraction may therefore be viewed as a self-facilitating phenomenon.

Reflex inhibition of canine inspiratory intercostals by diaphragmatic tension receptors

1 Electrical stimulation of phrenic afferent fibres in the dog elicits a reflex inhibition of efferent activity to the inspiratory intercostal muscles. However, electrical stimulation has a poor selectivity, so the sensory receptors responsible for this inhibition were not identified. 2 In the present studies, cranial forces were applied during spontaneous inspiration to the abdominal surface of the central, tendinous portion of the canine diaphragm to activate tension mechanoreceptors in the muscle. Vagal afferent inputs were eliminated by vagotomy. 3 The application of force to the central tendon caused a graded, reflex reduction in inspiratory intercostal activity, especially in external intercostal activity. This reduction was commonly associated with a decrease in inspiratory duration and was invariably attenuated after section of the cervical dorsal roots. 4 In contrast, no change in inspiratory intercostal activity was seen when high frequency mechanical vibration was applied to the central tendon to stimulate diaphragmatic muscle spindles. 5 These observations provide strong evidence that tension receptors in the diaphragm, but not muscle spindles, induce reflex inhibition of inspiratory intercostal activity. The expression of this reflex probably involves supraspinal structures.

Effects of inflation on the coupling between the ribs and the lung in dogs

The coupling between the ribs and the lung in dogs increases with increasing rib number in the cranial part of the rib cage and then decreases markedly in the caudal part. The hypothesis was raised that this non‐uniformity is primarily related to differences between the areas of the lung subtended by the different ribs, and in the current study we tested this idea by assessing the effects of passive lung inflation. Thus, by causing a descent of the diaphragm, inflation would expand the area of the lung subtended by the caudal ribs and improve the coupling between these ribs and the lung. The axial displacements of the ribs and the changes in airway opening pressure (ΔPao) were measured in anaesthetized, pancuronium‐treated, supine dogs while loads were applied in the cranial direction to individual rib pairs at functional residual capacity (FRC) and after passive inflation to 10 and 20 cmH2O transrespiratory pressure. In agreement with the hypothesis, inflation caused an increase in ΔPao for ribs 9 and 10. The most prominent alteration, however, was a marked decrease in ΔPao for ribs 2–8; at 20 cmH2O, ΔPao for these ribs was only 30% of the value at FRC. Additional measurements indicated that this decrease in ΔPao results partly from the increase in diaphragmatic compliance but mostly from the reduction in outward rib displacement. This alteration in the pattern of rib motion should add to the decrease in muscle length to reduce the lung expanding action of the external intercostal muscles at high lung volumes.

Transbronchial Cryobiopsies for the Diagnosis of Diffuse Parenchymal Lung Diseases: Expert Statement from the Cryobiopsy Working Group on Safety and Utility and a Call for Standardization of the Procedure

Transbronchial cryobiopsies (TBCB) have recently been introduced as a promising and safer alternative to surgical lung biopsy in the diagnostic approach to diffuse parenchymal lung diseases (DPLD). Despite a substantial and expanding body of literature, the technique has not yet been standardized and its place in the diagnostic algorithm of DPLD remains to be defined. In part, this reflects concerns over the diagnostic yield and safety of the procedure, together with the rapid spread of the technique without competency and safety standards; furthermore, there is a substantial procedural variability among centers and interventional pulmonologists. We report this expert statement proposed during the third international conference on “Transbronchial Cryobiopsy in Diffuse Parenchymal Lung Disease” (Ravenna, October 27–28, 2016), which formulates evidence- and expert-based suggestions on the indications, contraindications, patient selection, and procedural aspects of the procedure. The following 5 domains were reviewed: (1) what is the role of TBCB in the diagnostic evaluation of DPLD: patient selection; (2) pathological considerations; (3) contraindications and safety considerations; (4) how should TBCB be performed and in what procedural environment; and (5) who should perform TBCB. Finally, the existence of white paper recommendations may also reassure local hospital credentialing committees tasked with endorsing an adoption of the technique.

Association of Cadmium Exposure With Rapidly Progressive Emphysema in a Smoker

Rapidly progressive emphysema developed in a 59 year old smoker after exposure to cadmium fumes in a factory. Very high levels of cadmium in air sampled at the workplace and in the patients blood, urine, and lung tissue confirmed massive exposure. These data strongly suggest an association between the patients cadmium exposure and the development of emphysema.

Effects of single-lung inflation on inspiratory muscle function in dogs.

After single‐lung transplantation (SLT) for emphysema, a hyperinflated (native) lung operates in parallel with a normal (transplanted) lung. The interpulmonary distribution of the changes in pleural pressure (ΔPpl) during breathing, however, is unknown. To approach the problem, two endotracheal tubes were inserted in the right and left main stem bronchi of anaesthetized dogs, one lung was passively inflated, and the values of inspiratory ΔPpl over the two lungs were assessed by measuring the changes in airway opening pressure (ΔPao) in the two tubes during occluded breaths. With single‐lung inflation, ΔPao decreased in both lungs, but the decrease in the inflated lung was invariably larger than in the non‐inflated lung; when transrespiratory pressure in the inflated lung was set at 30 cmH2O, ΔPao in this lung was 27.7 ± 2.0% of the value of functional residual capacity (FRC), whereas ΔPao in the non‐inflated lung was 74.4 ± 4.5% (P < 0.001). This difference was abolished after the ventral mediastinal pleura was severed. The ribs in both hemithoraces were displaced cranially with inflation, such that the displacement in the contralateral hemithorax was 75% of that in the ipsilateral hemithorax, and parasternal intercostal activity remained unchanged. These observations suggest that in patients with SLT for emphysema (1) the inspiratory ΔPpl over the transplanted lung are greater than those over the native lung and (2) this difference results primarily from the greater pressure‐generating ability of the inspiratory muscles, in particular the diaphragm, on the transplanted side.

Mechanism of the lung-deflating action of the canine diaphragm at extreme lung inflation

When lung volume in animals is passively increased beyond total lung capacity (TLC; transrespiratory pressure = +30 cmH(2)O), stimulation of the phrenic nerves causes a rise, rather than a fall, in pleural pressure. It has been suggested that this was the result of inward displacement of the lower ribs, but the mechanism is uncertain. In the present study, radiopaque markers were attached to muscle bundles in the midcostal region of the diaphragm and to the tenth rib pair in five dogs, and computed tomography was used to measure the displacement, length, and configuration of the muscle and the displacement of the lower ribs during relaxation at seven different lung volumes up to +60 cmH(2)O transrespiratory pressure and during phrenic nerve stimulation at the same lung volumes. The data showed that 1) during phrenic nerve stimulation at 60 cmH(2)O, airway opening pressure increased by 1.5 ± 0.7 cmH(2)O; 2) the dome of the diaphragm and the lower ribs were essentially stationary during such stimulation, but the muscle fibers still shortened significantly; 3) with passive inflation beyond TLC, an area with a cranial concavity appeared at the periphery of the costal portion of the diaphragm, forming a groove along the ventral third of the rib cage; and 4) this area decreased markedly in size or disappeared during phrenic stimulation. It is concluded that the lung-deflating action of the isolated diaphragm beyond TLC is primarily related to the invaginations in the muscle caused by the acute margins of the lower lung lobes. These findings also suggest that the inspiratory inward displacement of the lower ribs commonly observed in patients with emphysema (Hoovers sign) requires not only a marked hyperinflation but also a large fall in pleural pressure.