Echographic Assessment of Diaphragmatic Function in Duchenne Muscular Dystrophy from Childhood to Adulthood.

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic muscle disorder. Respiratory muscle function is classically affected in this disease. Ultrasound recently emerged as a non-invasive tool to assess diaphragm function. However, there are only a few studies using diaphragm ultrasound (US) in DMD. PURPOSE: We aimed to assess diaphragm ultrasound patterns in DMD, their relationship with age and their association with home mechanical ventilation (HMV). METHODS: We included DMD patients followed at Raymond Poincaré Hospital who benefited from diaphragm ultrasound and pulmonary function tests. RESULTS: There were 110 DMD patients and 17 male sex-matched healthy subjects included. In all, 94% of patients were permanent wheelchair users. Median body mass index (BMI) was 18 kg/m2. DMD patients disclosed a reduced forced vital capacity (VC) (12% of predicted value), and 78% of patients were on HMV. In patients, right and left diaphragmatic motions on deep inspiration were reduced and end expiratory diaphragm thickness was borderline normal. In patients, right and left diaphragmatic thickening fractions (TF) were reduced 12.7% and 15.5%, respectively. Age and end expiratory thickness were significantly inversely associated (p = 0.005 for the right diaphragm, p = 0.018 for the left diaphragm). Diaphragm TF was significantly inversely associated with age (p = 0.001 for the right side, p < 0.0001 for the left side). Right and left inspiratory diaphragm motions were significantly inversely associated with age (p < 0.0001). CONCLUSION: This study describes the severity of diaphragm dysfunction in patients with DMD. Diaphragm US may be a non-invasive outcome measure for DMD.

Morbidity and Mortality of Crystalloids Compared to Colloids in Critically Ill Surgical Patients: A Subgroup Analysis of a Randomized Trial.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: The multicenter randomized Colloids versus Crystalloids for the Resuscitation of the Critically Ill (CRISTAL) trial was designed to test whether colloids altered mortality compared to crystalloids in the resuscitation of intensive care unit patients with hypovolemic shock. This preplanned analysis tested the same hypothesis in the subgroup of surgical patients. METHODS: The CRISTAL trial prospectively defined patients as critically ill surgical patients whenever they underwent emergency or scheduled surgery immediately before or within 24 h of intensive care unit admission and had hypovolemic shock. The primary outcome measure was death by day 28. Secondary outcome measures included death by day 90, the need for renal replacement therapy, or the need for fresh frozen plasma transfusion. RESULTS: There were 741 critically ill surgical patients, 356 and 385 in the crystalloid and colloid arm, respectively. Median (interquartile range) age was 66 (52 to 76) yr, and 484 (65.3%) patients were male. Surgery was unscheduled in 543 (73.3%) cases. Mortality by day 28 did not significantly differ for crystalloids 84 (23.6%) versus colloids 100 (26%; adjusted odds ratio, 0.86; 95% CI, 0.61 to 1.21; P = 0.768). Death by day 90 (111 [31.2%] vs. 122 [31.7%]; adjusted odds ratio, 0.97; 95% CI, 0.70 to 1.33; P = 0.919) did not significantly differ between groups. Renal replacement therapy was required for 42 (11.8%) patients in the crystalloids arm versus 49 (12.7%) in the colloids arm (P = 0.871). CONCLUSIONS: The authors found no survival benefit when comparing crystalloids to colloids in critically ill surgical patients.

Natural history of cardiac function in Duchenne and Becker muscular dystrophies on home mechanical ventilation.

Heart impairment is classical in dystrophinopathies and its management relies on medical drugs. Mechanical ventilation is used to treat respiratory failure, but can affect cardiac function. We aimed to investigate the natural history of cardiac function in patients with Duchenne (DMD) and Becker (BMD) muscular dystrophies on home mechanical ventilation (HMV).We reviewed the chart of DMD and BMD patients, followed in our institution, to obtain ventilation setting at HMV initiation and echocardiographic data at baseline and end follow up, as well as onset cardiac events and thoracic mechanical complication. We analyzed cumulative incidence of cardiac events as well as echocardiographic parameters evolution and its association with ventilation settings.We included 111 patients (101 DMD and 10 BMD). Median age was 21 years [18-26], median pulmonary vital capacity (VC) 15% of predicted [10-24]. All patients were on HMV and 46% ventilated using tracheostomy. After a median follow up of 6.3 years, we found a slight decrease of the left ventricular ejection fraction (LVEF) (45% at end follow up vs 50% at baseline P = .019) and a stabilization of the LV end diastolic diameter indexed (LVEDD indexed 29.4 mm/m vs 30.7 mm/m at end follow up, P = .17). Tidal volume (VT) level was inversely associated with the annual rate of the LVEF decline (r = -0.29, P = .025). Left atrium (LA) diameter decreased with mechanical ventilation (24 mm vs 20 mm, P = .039) and we found a reduction of systolic pulmonary pressure (35 mm Hg vs 25 mm Hg, P = .011). The cumulative incidence of cardiac events was 12.6%. Pneumothorax occurred in 4% of patients. Hypoxic arrest secondary to the presence of tracheal plugin occurred in 4% of patients with invasive ventilation.HMV is not harmful, decreases pulmonary pressure and may protect heart in dystrophinopathies, in addition with cardioprotective drugs. In patients with DMD and BMD on HMV, cumulative incidence of cardiac events remains moderate and incidence of pneumothorax is rare.

Prognostic Value of Initial Assessment of Residual Hypoventilation Using Nocturnal Capnography in Mechanically Ventilated Neuromuscular Patients: A 5-Year Follow-up Study.

BACKGROUND: Restrictive respiratory failure is a major cause of morbidity and mortality in neuromuscular diseases (NMD). Home mechanical ventilation (HMV) is used to treat hypoventilation, and its efficiency is mostly assessed by daytime blood gases or nocturnal oxygen saturation monitoring (SpO2). Non-invasive transcutaneous measure of CO2 (TcCO2) allows to directly assess nocturnal hypercapnia and to detect residual hypoventilation with a higher sensitivity than SpO2. We aimed to compare the prognostic value of nocturnal SpO2 and TcCO2 in ventilated adult NMD patients. METHODS: All consecutive capno-oximetries performed between 2010 and 2011 in ventilated adult NMD patients were analyzed retrospectively. Concomitant blood gas analysis and lung function data were collected. Patients on oxygen therapy were excluded. Nocturnal hypoxemia and hypercapnia (using four different definitions) at baseline were compared in their ability to predict mortality and respiratory events requiring ICU admission during follow-up. RESULTS: Data from 55 patients were analyzed (median age 28 [interquartile range: 25-36.5] years; 71% Duchenne muscular dystrophy; vital capacity 12 [7-27]% of predicted; 51% tracheostomy). Capno-oxymetry showed hypoxemia in 14.5% and hypercapnia in 12.7-41.8%, according to the used definition. Over a follow-up lasting up to 5 years (median 4.0 [3.6-4.5] years), we observed 12 deaths and 20 respiratory events requiring ICU admission. Hypercapnia was significantly associated with the study outcomes, with TcCO2 > 49 mmHg during ≥10% of the time being the best definition, while hypoxemia was not. CONCLUSION: Our data show for the first time that residual hypoventilation, assessed by capnometry, is significantly associated with negative outcomes in adult ventilated NMD patients, while oximetry is not. Accordingly, we suggest capnometry to be included in the systematic assessment of HMV efficiency in NMD patients. CLINICALTRIALSGOV IDENTIFIER: NCT02551406.

Emerging drugs for the treatment of sepsis.

INTRODUCTION: The incidence of sepsis, the systemic inflammatory response of the host to an infectious insult, has steadily increased over past decades. This trend is expected to continue. Sepsis is a leading cause of death and disability worldwide. Treatment relies on antibiotics associated to source control and supportive care. Major progress has been made in the understanding and overall management of sepsis. However, there is no specific treatment for sepsis. AREAS COVERED: We searched PubMed and the ClinicalTrials.gov site for English language reports of phase II and III clinical trials pertaining to the field of sepsis. The current review provides a summary of promising candidate treatments for sepsis. We broadly separated candidate drugs into three distinct categories: Blood purification techniques, immunomodulatory drugs and treatments targeting other systems including the heart, the endothelium or coagulation. EXPERT OPINION: Efforts to identify an efficient treatment for sepsis are hampered by the broad definition of the syndrome associated with major heterogeneity between patients affected by sepsis. The characterization of homogeneous groups of patients, through biological or clinical markers is unfortunately lacking. Current research remains active. Candidate drugs for sepsis include hemoperfusion with polymyxin B coated fibre devices, modulation of the immune system with treatments such as hydrocortisone, intravenous immunoglobulins, mesenchymal stem cells, GM-CSF or interferon gamma. Candidate drugs acting on the cardiovascular system include short acting beta 1 blockers, levosimendan or selepressin. Finally, promising strategies, involving monoclonal antibodies or protein antagonists, which selectively inhibit bacterial virulence factors are being assessed at the bedside. A much awaited and needed specific treatment for sepsis will hopefully soon emerge.

Peribulbar block in patients scheduled for eye procedures and treated with clopidogrel.

Our hypothesis was that the continuation of clopidogrel does not increase the risk of eye hemorrhage, compared to patients not treated with clopidogrel, when a peribulbar anesthesia is required. Our prospective case-control study enrolled two groups of 1,000 patients scheduled for intraocular eye surgery requiring a peribulbar block. Patients treated with clopidogrel were included in group A (1,000 patients). Patients who had never been treated with clopidogrel constituted the control group (group B, 1,000 patients). Hemorrhages were graded as follows: 1 = spot ecchymosis of eyelid and or subconjunctival hemorrhage; 2 = eyelid ecchymosis involving half the lid surface area; 3 = eyelid ecchymosis all around the eye, no increase in intraocular pressure; 4 = retrobulbar hemorrhage with increased intraocular pressure. Grade 1 hemorrhages were observed in 30 patients (3.0 %) in group A and in 20 patients (2.0 %) in group B. No grade 2, 3, or 4 hemorrhage was encountered. There was no significant difference in the grading of hemorrhage between the groups (p = 0.017). Clopidogrel was not associated with a significant increase in potentially sight-threatening local anesthetic complications.