Airway injury from the presence of endotracheal tubes and the association with subglottic secretion drainage: a prospective observational study.

PURPOSE: Laryngeal and tracheal injuries are known complications of endotracheal intubation. Endotracheal tubes (ETTs) with subglottic suction devices (SSDs) are commonly used in the critical care setting. There is concern that herniation of tissue into the suction port of these devices may lead to tracheal injury resulting in serious clinical consequences such as tracheal stenosis. We aimed to describe the type and location of tracheal injuries seen in intubated critically ill patients and assess injuries at the suction port as well as in-hospital complications associated with those injuries. METHODS: We conducted a prospective observational study of 57 critically ill patients admitted to a level 3 intensive care unit who were endotracheally intubated and underwent percutaneous tracheostomy. Investigators performed bronchoscopy and photographic evaluation of the airway during the percutaneous tracheostomy procedure to evaluate tracheal and laryngeal injury. RESULTS: Forty-one (72%) patients intubated with ETT with SSD and sixteen (28%) patients with standard ETT were included in the study. Forty-seven (83%) patients had a documented airway injury ranging from hyperemia to deep ulceration of the mucosa. A common tracheal injury was at the site of the tracheal cuff. Injury at the site of the subglottic suction device was seen in 5/41 (12%) patients. There were no in-hospital complications. CONCLUSIONS: Airway injury was common in critically ill patients following endotracheal intubation, and tracheal injury commonly occurred at the site of the endotracheal cuff. Injury occurred at the site of the subglottic suction port in some patients although the clinical consequences of these injuries remain unclear.

RéSUMé: OBJECTIF: Les lésions laryngées et trachéales sont des complications connues de l'intubation endotrachéale. Les sondes endotrachéales (SET) avec dispositifs d'aspiration sous-glottiques (DASG) sont couramment utilisées aux soins intensifs. On craint qu'une hernie tissulaire dans l'orifice d'aspiration de ces dispositifs n'entraîne des lésions trachéales, résultant en de graves conséquences cliniques telles qu'une sténose trachéale. Nous avons cherché à décrire le type et l'emplacement des lésions trachéales observées chez les patients gravement malades intubés et à évaluer les lésions au port d'aspiration ainsi que les complications hospitalières associées à ces lésions. MéTHODE: Nous avons mené une étude observationnelle prospective auprès de 57 patients gravement malades admis dans une unité de soins intensifs de niveau 3 qui ont été intubés par voie endotrachéale et ont subi une trachéostomie percutanée. Les chercheurs ont réalisé une bronchoscopie et une évaluation photographique des voies aériennes au cours de la trachéostomie percutanée afin d'évaluer les lésions trachéales et laryngées. RéSULTATS: Quarante et un (72 %) intubés par SET avec DASG et seize (28 %) patients avec SET standard ont été inclus dans l'étude. Quarante-sept (83 %) patients ont présenté une lésion documentée des voies aériennes allant de l'hyperémie à l'ulcération profonde de la muqueuse. Une lésion trachéale commune était localisée sur le site du ballonnet trachéal. Une lésion au site du dispositif d'aspiration sous-glottique a été observée chez 5/41 (12 %) patients. Il n'y a pas eu de complications à l'hôpital. CONCLUSION: Les lésions des voies aériennes étaient fréquentes chez les patients gravement malades après une intubation endotrachéale, et les lésions trachéales se produisaient généralement au site du ballonnet endotrachéal. Des lésions se sont produites au site de l'orifice d'aspiration sous-glottique chez certains patients, bien que les conséquences cliniques de ces lésions restent incertaines.

Novel Mutations and Decreased Expression of the Epigenetic Regulator TET2 in Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a lethal vasculopathy. Hereditary cases are associated with germline mutations in BMPR2 and 16 other genes; however, these mutations occur in <25% of patients with idiopathic PAH and are rare in PAH associated with connective tissue diseases. Preclinical studies suggest epigenetic dysregulation, including altered DNA methylation, promotes PAH. Somatic mutations of Tet-methylcytosine-dioxygenase-2 (TET2), a key enzyme in DNA demethylation, occur in cardiovascular disease and are associated with clonal hematopoiesis, inflammation, and adverse vascular remodeling. The role of TET2 in PAH is unknown. METHODS: To test for a role of TET2, we used a cohort of 2572 cases from the PAH Biobank. Within this cohort, gene-specific rare variant association tests were performed using 1832 unrelated European patients with PAH and 7509 non-Finnish European subjects from the Genome Aggregation Database (gnomAD) as control subjects. In an independent cohort of 140 patients, we quantified TET2 expression in peripheral blood mononuclear cells. To assess causality, we investigated hemodynamic and histological evidence of PAH in hematopoietic Tet2-knockout mice. RESULTS: We observed an increased burden of rare, predicted deleterious germline variants in TET2 in PAH patients of European ancestry (9/1832) compared with control subjects (6/7509; relative risk=6; P=0.00067). Assessing the whole cohort, 0.39% of patients (10/2572) had 12 TET2 mutations (75% predicted germline and 25% somatic). These patients had no mutations in other PAH-related genes. Patients with TET2 mutations were older (71±7 years versus 48±19 years; P<0.0001), were more unresponsive to vasodilator challenge (0/7 versus 140/1055 [13.2%]), had lower pulmonary vascular resistance (5.2±3.1 versus 10.5±7.0 Wood units; P=0.02), and had increased inflammation (including elevation of interleukin-1ß). Circulating TET2 expression did not correlate with age and was decreased in >86% of PAH patients. Tet2-knockout mice spontaneously developed PAH, adverse pulmonary vascular remodeling, and inflammation, with elevated levels of cytokines, including interleukin-1ß. Long-term therapy with an antibody targeting interleukin-1ß blockade resulted in regression of PAH. CONCLUSIONS: PAH is the first human disease related to potential TET2 germline mutations. Inherited and acquired abnormalities of TET2 occur in 0.39% of PAH cases. Decreased TET2 expression is ubiquitous and has potential as a PAH biomarker.

Risk stratification of acute pulmonary embolism.

Approximately 5% of pulmonary embolism (PE) cases present with persistent hypotension, obstructive shock, or cardiac arrest. Given the high short-term mortality, management of high-risk PE cases focuses on immediate reperfusion therapies. Risk stratification of normotensive PE is important to identify patients with an elevated risk of hemodynamic collapse or an elevated risk of major bleeding. Risk stratification for short-term hemodynamic collapse includes assessment of physiological parameters, right heart dysfunction, and identification of comorbidities. Validated tools such as European Society of Cardiology guidelines and Bova score can identify normotensive patients with PE and an elevated risk of subsequent hemodynamic collapse. At present, we lack high-quality evidence to recommend one treatment over another (systemic thrombolysis, catheter-directed therapy, or anticoagulation with close monitoring) for patients at elevated risk of hemodynamic collapse. Newer, less well-validated scores such as BACS and PE-CH may help identify patients at a high risk of major bleeding following systemic thrombolysis. The PE-SARD score may identify those at risk of major anticoagulant-associated bleeding. Patients at low risk of short-term adverse outcomes can be considered for outpatient management. The simplified Pulmonary Embolism Severity Index score or Hestia criteria are safe decision aids when combined with physician global assessment of the need for hospitalization following the diagnosis of PE.

Neurophysiological mechanisms of exertional dyspnea in post-pulmonary embolism syndrome.

Following pulmonary embolism (PE), a third of patients develop persistent dyspnea, which is commonly termed the post-PE syndrome. The neurophysiological underpinnings of exertional dyspnea in patients with post-PE syndrome without pulmonary hypertension (PH) are unclear. Thus, the current study determined if abnormally high inspiratory neural drive (IND) due, in part, to residual pulmonary gas-exchange abnormalities, was linked to heightened exertional dyspnea and exercise limitation, in such patients. Fourteen participants with post-PE syndrome (without resting PH) and 14 age-, sex-, and body mass index-matched healthy controls undertook pulmonary function testing and a symptom-limited cycle cardiopulmonary exercise test with measurements of IND (diaphragmatic electromyography), ventilatory requirements for CO2 (V̇e/V̇co2), and perceived dyspnea intensity (modified Borg 0-10 scale). Post-PE (vs. control) had a reduced resting transfer coefficient for carbon monoxide (KCO: 84 ± 15 vs. 104 ± 14%pred, P < 0.001) and peak oxygen uptake (V̇o2peak) (76 ± 14 vs. 124 ± 28%pred, P < 0.001). IND and V̇e/V̇co2 were higher in post-PE than controls at standardized submaximal work rates (P < 0.05). Dyspnea increased similarly in both groups as a function of increasing IND but was higher in post-PE at standardized submaximal work rates (P < 0.05). High IND was associated with low KCO (r = -0.484, P < 0.001), high V̇e/V̇co2 nadir (r = 0.453, P < 0.001), and low V̇o2peak (r = -0.523, P < 0.001). In patients with post-PE syndrome, exercise IND was higher than controls and was associated with greater dyspnea intensity. The heightened IND and dyspnea in post-PE, in turn, were strongly associated with low resting KCO and high exercise V̇e/V̇co2, which suggest important pulmonary gas-exchange abnormalities in this patient population.NEW & NOTEWORTHY This study is the first to show that increased exertional dyspnea in patients with post-pulmonary embolism (PE) syndrome, without overt pulmonary hypertension, was strongly associated with elevated inspiratory neural drive (IND) to the diaphragm during exercise, compared with healthy controls. The greater IND was associated with impairments in pulmonary gas exchange and significant deconditioning. Our results help to explain why many patients with post-PE syndrome report significant dyspnea at relatively low levels of physical activity.

Left Main Coronary Artery Compression in Pulmonary Arterial Hypertension: Percutaneous Treatment to Improve Symptoms.

A 51-year-old woman with pulmonary arterial hypertension presented with progressive chest pain and dyspnea. Computed tomography imaging showed significant enlargement of her main pulmonary artery (PA) and was suggestive of left main coronary artery (LMCA) compression by the PA. The patient underwent percutaneous coronary intervention, which confirmed the diagnosis and a stent was deployed to the LMCA. Three months after the procedure the patient has near resolution of her symptoms. LMCA compression by an enlarged PA is an important cause of chest pain in patients with pulmonary arterial hypertension and can be managed safely and effectively with percutaneous coronary intervention and stenting.

Une femme de 51 ans atteinte d'hypertension artérielle pulmonaire présentait des symptômes progressifs de dyspnée et de douleur thoracique. Les images de la tomographie par ordinateur ont révélé un élargissement de l'artère pulmonaire (AP) principale et indiquaient une compression de l'artère coronaire gauche principale (ACGP) par l'AP. L'intervention coronarienne percutanée subie par la patiente a confirmé le diagnostic, et une endoprothèse coronaire a été déployée à l'intérieur de l'ACGP. Les symptômes de la patiente avaient pratiquement disparu trois mois après l'intervention. La compression de l'ACGP par une AP élargie est une cause importante de douleur thoracique chez les patients atteints d'hypertension artérielle pulmonaire qui peut être traitée de façon sûre et efficace par une intervention coronarienne percutanée et une endoprothèse coronaire.

Evaluation of the Impact of an Echocardiographic Diagnosis of Pulmonary Hypertension on Patient Outcomes.

BACKGROUND: Although detection of elevated right ventricular systolic pressure (RVSP) on routine echocardiography is common, its clinical significance is underappreciated. The recent change in the hemodynamic definition of pulmonary hypertension (PH) lowering the threshold from mean pulmonary arterial pressure ≥ 25 mm Hg to > 20 mm Hg further clouds the picture. METHODS: A retrospective cohort study was performed on residents of the South East Local Health Integration Network (population 495,000), Ontario, Canada, who underwent transthoracic echocardiography at the Kingston Health Sciences Centre between February 19, 2013, and December 31, 2016. The index echocardiography from 9291 unique patients was obtained. RESULTS: A total of 2049 patients (22.1%) had an RVSP ≥ 40 mm Hg, 2040 patients (22.0%) had an RVSP ≥ 30 and < 40 mm Hg, but only 284 patients (3.1%) had a clinical diagnosis of PH. Although patients with an RVSP ≥ 40 mm Hg had the highest Charlson Comorbidity Index (CCI) (1.81 ± 0.05) and number of hospitalizations 1 year before the echocardiography (1.24 ± 0.03), patients with RVSP between 30 and 40 mm Hg also had significantly higher CCI (1.19 ± 0.04) and hospitalization (0.87 ± 0.03) compared with the CCI (0.84 ± 0.03) and hospitalization (0.65 ± 0.02) of patients with RVSP < 30 mm Hg (P < 0.0001). CONCLUSION: Despite the finding that an elevated RVSP ≥ 30 mm Hg is common and predicts adverse outcomes, most patients with elevated RVSP are not reported as having PH or investigated. The significance of the elevated RVSP is underappreciated.

CONTEXTE: Bien qu'une pression systolique ventriculaire droite (PSVD) élevée soit fréquemment mise en évidence au cours d'une échocardiographie systématique, sa portée clinique s'avère sous-estimée. La modification récente de la définition hémodynamique de l'hypertension pulmonaire (HP), faisant passer le seuil de la pression artérielle pulmonaire moyenne de ≥ 25 mmHg à > 20 mmHg, embrouille davantage la situation. MÉTHODOLOGIE: Une étude rétrospective a été réalisée au sein d'une cohorte de résidents du territoire du Réseau local d'intégration des services de santé du Sud-Est (population de 495 000 personnes) de l'Ontario (Canada) ayant subi une échocardiographie transthoracique au Centre des sciences de la santé de Kingston entre le 19 février 2013 et le 31 décembre 2016. L'échocardiographie de référence de 9 291 patients différents a été obtenue. RÉSULTATS: La PSVD était ≥ 40 mmHg chez 2 049 patients (22,1 %) et ≥ 30 et < 40 mmHg chez 2 040 patients (22,0 %), mais un diagnostic clinique d'HP n'avait été posé que chez 284 patients (3,1 %). L'indice de comorbidité de Charlson (ICC) le plus élevé (1,81 ± 0,05) et le plus grand nombre d'hospitalisations un an avant l'échocardiographie (1,24 ± 0,03) ont été notés chez les patients qui présentaient une PSVD ≥ 40 mmHg; néanmoins, les valeurs de ces paramètres se sont aussi révélées significativement plus élevées chez les patients affichant une PSVD allant de 30 à 40 mmHg (ICC : 1,19 ± 0,04; hospitalisations : 0,87 ± 0,03) comparativement aux patients présentant une PSVD < 30 mmHg (ICC : 0,84 ± 0,03; hospitalisations : 0,65 ± 0,02) (p < 0,0001). CONCLUSION: Malgré le fait qu'une PSVD élevée (≥ 30 mmHg) soit d'observation courante et prédictive de résultats cliniques défavorables, la plupart des cas ne sont pas signalés en tant que manifestation d'HP et ne font l'objet d'aucune investigation. La portée d'une PSVD élevée s'avère sous-estimée.

Traumatic Pulmonary Hypertension Secondary to Arteriovenous Fistula and Remote Gunshot Wound.

Pulmonary hypertension is a known complication of high-flow arteriovenous fistulas (AVFs). We present a case of a 58-year-old man who sustained a gunshot wound 6.5 years before presentation for worsening pulmonary hypertension (PH). After diagnostic workup, the PH was attributed to a gunshot-related AVF. Exercise capacity and echocardiographic parameters improved after successful ligation of the AVF. This case highlights a rare and correctable cause of PH that requires careful investigation and multidisciplinary expertise for treatment.

Noninvasive ventilation practice patterns for acute respiratory failure in Canadian tertiary care centres: A descriptive analysis.

BACKGROUND: The extent of noninvasive ventilation (NIV) use for patients with acute respiratory failure in Canadian hospitals, indications for use and associated outcomes are unknown. OBJECTIVE: To describe NIV practice variation in the acute setting. METHODS: A prospective observational study involving 11 Canadian tertiary care centres was performed. Data regarding NIV indication, mode and outcomes were collected for all adults (>16 years of age) treated with NIV for acute respiratory failure during a four-week period (between February and August 2011). Logistic regression with site as a random effect was used to examine the association between preselected predictors and mortality or intubation. RESULTS: A total of 330 patients (mean [± SD] 30±12 per centre) were included. The most common indications for NIV initiation were pulmonary edema (104 [31.5%]) and chronic obstructive pulmonary disease (99 [30.0%]). Significant differences in indications for NIV use across sites, specialty of ordering physician and location of NIV initiation were noted. Although intubation rates were not statistically different among sites (range 10.3% to 45.4%), mortality varied significantly (range 6.7% to 54.5%; P=0.006). In multivariate analysis, the most significant independent predictor of avoiding intubation was do-not-resuscitate status (OR 0.11 [95% CI 0.03 to 0.37]). CONCLUSION: Significant variability existed in NIV use and associated outcomes among Canadian tertiary care centres. Assignment of do-not-resuscitate status prevented intubation.

Pulmonary hypertension: Tortuous route to diagnosis.

A 47 year-old woman, on hemodialysis via an arteriovenous (AV) fistula, was assessed for severe dyspnea and presyncope secondary to pulmonary hypertension. Right heart catheterization confirmed a mean pulmonary arterial pressure of 85 mm Hg. She had a normal wedge pressure. Investigations revealed that the total high cardiac output AV fistula, 8.3 L/min, resulted in pulmonary arteropathy and increased pulmonary vascular resistance at 674 dyne.sec.cm(-5). The AV fistula was banded and Sildenafil was prescribed, which resulted in improvement of pulmonary hypertension within one week.

Cellular assessment of muscle in COPD: case studies of two males.

The objective of this paper is to provide an overview of the recent developments in muscle physiology and biochemistry in general, and with respect to chronic obstructive pulmonary disease (COPD) specifically. As a way of illustration, we have presented data on the remodeling that occurs in vastus lateralis in two patients with COPD (COPD #1, forced expiratory volume in one second/forced vital capacity [FEV(1)/FVC] = 63%; COPD #2, FEV(1)/FVC = 41%) exhibiting differences in muscle wasting as compared to healthy controls (CON; FEV(1)/FVC = 111 +/- 2.2%, n = 4). Type I fibers percentages were lower in both COPD #1 (16.7) and COPD #2 (24.9) compared to CON (57.3 +/- 5.2). Cross sectional area of the type I fibers of the patients ranged between 65%-68% of CON and for the type II subtypes (IIA, IIAX, IIX) between 74% and 89% (COPD #1) and 17%-32% (COPD #2). A lower number of capillary contacts were observed for all fiber types in COPD #1 but not COPD #2. Lower concentrations of adenosine triphosphate (ATP) (24%-26%) and phosphocreatine (18%-20%), but not lactate occurred in COPD. In contrast to COPD #1, who displayed normal glucose transporter content, GLUT1 and GLUT4 were only 71% and 54%, respectively of CON in COPD #2. Lower monocarboxylate contents were found for MCT1 in both COPD #1 (63%) and COPD #2 (41%) and for MCT4 (78%) in COPD #1. Maximal oxidative enzyme activities (V(max)) for COPD #2 ranged between 37% (succinic dehydrogenase) and 70% (cytochrome C oxidase) of CON. For the cytosolic enzymes, V(max) ranged between 89% (hexokinase) to 31% (pyruvate kinase) of CON. Depressions were also observed in V(max) of the Na(+)-K(+)-ATPase for COPD #1 (66% of CON) but not COPD #2 (92% of CON) while V(max) of the Ca(2+)-ATPase was near normal in COPD #1 (84% CON). It is concluded that disturbances can occur in muscle to a wide range of excitation, contraction and metabolic processes in COPD.

Organization of metabolic pathways in vastus lateralis of patients with chronic obstructive pulmonary disease.

The objective of this study was to determine whether patients with chronic obstructive lung disease (COPD) display differences in organization of the metabolic pathways and segments involved in energy supply compared with healthy control subjects. Metabolic pathway potential, based on the measurement of the maximal activity (V(max)) of representative enzymes, was assessed in tissue extracted from the vastus lateralis in seven patients with COPD (age 67 +/- 4 yr; FEV(1)/FVC = 44 +/- 3%, where FEV(1) is forced expiratory volume in 1 s and FVC is forced vital capacity; means +/- SE) and nine healthy age-matched controls (age 68 +/- 2 yr; FEV(1)/FVC = 75 +/- 2%). Compared with control, the COPD patients displayed lower (P < 0.05) V(max) (mol.kg protein(-1).h(-1)) for cytochrome c oxidase (COX; 21.2 +/- 2.0 vs. 28.7 +/- 2.2) and 3-hydroxyacyl-CoA dehydrogenase (HADH; 2.54 +/- 0.14 vs. 3.74 +/- 0.12) but not citrate synthase (CS; 2.20 +/- 0.16 vs. 3.19 +/- 0.5). While no differences between groups were observed in V(max) for creatine phosphokinase, phosphorylase (PHOSPH), phosphofructokinase (PFK), pyruvate kinase, and lactate dehydrogenase, hexokinase (HEX) was elevated in COPD (P < 0.05). Enzyme activity ratios were higher (P < 0.05) for HEX/CS, HEX/COX, PHOSPH/HADH and PFK/HADH in COPD compared with control. It is concluded that COPD patients exhibit a reduced potential for both the electron transport system and fat oxidation and an increased potential for glucose phosphorylation while the potential for glycogenolysis and glycolysis remains normal. A comparison of enzyme ratios indicated greater potentials for glucose phosphorylation relative to the citric acid cycle and the electron transport chain and glycogenolysis and glycolysis relative to beta-oxidation.