scholarly journals Accelerated hyaluronan concentration as the primary driver of morbidity and mortality in high-risk COVID-19 patients: with therapeutic introduction of an oral hyaluronan inhibitor in the prevention of “Induced Hyaluronan Storm” Syndrome

2020 ◽  
Author(s):  
Michael A. Mong ◽  
Jacob A. Awkal ◽  
Paul E. Marik
Keyword(s):  
Respiratory Failure ◽  
High Risk ◽  
Respiratory Distress ◽  
Cause Of Death ◽  
Research Effort ◽  
Morbidity And Mortality ◽  
Normal Lung ◽  
Lung Weight ◽  
Severe Respiratory Distress ◽  
Hyaline Membranes

AbstractTo date, the fundamental drivers of the morbidity and mortality in COVID-19 remain uncertain. Clinicians worldwide appear to be at a loss to know how to prevent and treat the severe respiratory distress in these patients effectively. Consequently, the fundamental mechanisms leading to death in high-risk patients need to be discovered and addressed with urgency. The post-mortem autopsy remains an essential part of both discovering the cause of death in a particular individual, but also in advancing the science and treatment of disease, especially in the case of novel pathogens such as SARS-CoV-2[2]. The goal of an autopsy is to discover the cause of death (COD) using a macro/microscopic investigation. Because lung weight is often affected by the cause of death and the last breath occurs very near if not now of death, the evaluation of the lungs is one of the starting points of any COD investigation[3]. A comprehensive search was performed to systematically review all reported autopsy findings in COVID-19 patients with respect to lung weights and histologic findings. We then compared these findings with the results of a targeted literature review of hyaluronan in relationship to acute respiratory distress syndrome (ARDS). In total, data from 38 autopsies were identified. From this group, 36 autopsies of COVID-19 patients were selected for detailed review and statistical analysis. The average lung weight of those who were determined to have died as a result of SARS-CoV-2 was 1994g approximately 3.7 times the normal lung weight. Hyaline membranes were consistently identified on histologic sections. A review of the literature reveals that markedly elevated lung weights and hyaline membranes and have been associated with the pathophysiology of ARDS since 1967. However, the key role key of hyaluronan in driving the morbidity and mortality of the condition has heretofore not been fully recognized. We propose that the induced hyaluronan storm syndrome or IHS, is the model that best addresses the heretofore perplexing respiratory failure that is the proximal cause of death. An aggressive research effort should be undertaken to discover why the majority of individuals who are exposed to the virus are minimally symptomatic, while a minority of high-risk individuals rapidly progress to respiratory failure and death.

Isolation of Human Surfactant from Amniotic Fluid and a Pilot Study of Its Efficacy in Respiratory Distress Syndrome

PEDIATRICS ◽  
1983 ◽  
Vol 71 (4) ◽  
pp. 473-482 ◽  
Author(s):  
Mikko Hailman ◽  
T. Allen Merritt ◽  
Howard Schneider ◽  
Benita L. Epstein ◽  
Frank Mannino ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Amniotic Fluid ◽  
Distress Syndrome ◽  
Very Low Birth Weight ◽  
Pulmonary Complications ◽  
Low Birth Weight Infants ◽  
Severe Respiratory Distress ◽  
Surfactant Administration

Isolation of a sterile, surface-active human surfactant complex from amniotic fluid is described. Its effects on respiratory failure of five very low-birth-weight infants (974 ± 61 g) with severe RDS were studied before and after surfactant administration and were compared with those of a similar group of untreated infants with severe respiratory distress syndrome (RDS). Human surfactant (60 mg/kg) in 3.5 mL of saline was given as a single bolus intratracheally 6 ± 1 hours after birth with the following effects: Pao2 increased from 69 ± 11 mm Hg to 239 ± 19 mm Hg within five minutes, and within 1 hour fraction of inspired oxygen (FiO2) decreased from 0.94 ± 0.03 to 0.49 ± 0.03, mechanical ventilator pressure requirements decreased significantly, PaCo2 dropped, and the pH increased. Air bronchograms on chest roentgenograms lessened within five hours. In four infants the beneficial effects lasted eight to 15 hours, and although thereafter their respiratory conditions deteriorated somewhat, the RDS was less severe than before surfactant administration, and there were no associated pulmonary complications. However, a fifth infant had severe respiratory failure after striking improvement that lasted fewer than three hours, and subsequent interstitial emphysema, bronchopulmonary dysplasia, and intraventricular hemorrhage occurred. There were no detectable side effects with surfactant administration, although a search for immunologic complications continues. Protease activity in lung effluent from the treated infants was lower during the first week of life than among the comparison group, suggesting a lessening of lung injury by surfactant treatment. RDS among patients treated with one dose of human surfactant tended to be milder overall than RDS among control subjects.

Pulmonary Hyaline Membranes: Killer or Protector

PEDIATRICS ◽  
1972 ◽  
Vol 49 (4) ◽  
pp. 639-640
Author(s):  
Toshio Fujikura
Keyword(s):  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Clinical Significance ◽  
Cause Of Death ◽  
Distress Syndrome ◽  
Postmortem Examination ◽  
Fibrinolytic Enzymes ◽  
Definite Evidence ◽  
Neonatal Deaths ◽  
Hyaline Membranes

It is unfortunate that the clinical significance of hyaline membranes has been overempha-sized in the respiratory distress syndrome. Membranes are confirmed always in neonatal deaths at postmortem examination and there is very little information regarding the membranes among surviving infants who have suffered from the syndrome. Although some investigators have tried to dissolve the membranes with fibrinolytic enzymes, there is no definite evidence that the membranes are responsible for the direct cause of death and the syndrome.

Amiloride impairs lung water clearance in newborn guinea pigs

1990 ◽  
Vol 68 (4) ◽  
pp. 1758-1762 ◽  
Author(s):  
H. O'Brodovich ◽  
V. Hannam ◽  
M. Seear ◽  
J. B. Mullen
Keyword(s):  
Respiratory Distress ◽  
Sodium Transport ◽  
Guinea Pigs ◽  
Normal Lung ◽  
Lung Water ◽  
Lung Weight ◽  
Transport Inhibitor ◽  
Lung Liquid ◽  
Dose Dependent ◽  
Water Clearance

To determine whether epithelial ion transport is physiologically important for lung water clearance after birth, the sodium transport inhibitor amiloride or its vehicle saline was given intratracheally to newborn full-term guinea pigs before the first breath. Guinea pigs given saline intratracheally breathed normally and had arterial O2 saturations (SaO2) greater than 94%. In contrast, guinea pigs that had an estimated 10(-4) M intra-alveolar concentration of amiloride had chest wall retractions and 88 +/- 3.6% (SD) SaO2 (P less than 0.01). Extravascular lung water (EVLW) per gram of dry lung weight 4 h after birth was significantly greater in newborns that received amiloride (8.3 +/- 1.1, n = 5) than in those that received saline (5.6 +/- 0.9, n = 7, P less than 0.01). The degree of perivascular fluid cuffing at 25 cmH2O inflation was quantitatively similar in amiloride- and saline-treated animals. The effect of amiloride was dose dependent. Intratracheal amiloride did not affect EVLW in 9-day-old guinea pigs. This study demonstrates that intratracheal amiloride before the first breath results in respiratory distress, hypoxemia, and an abnormally high EVLW. Epithelial sodium transport contributes normal lung liquid clearance after birth.

scholarly journals Meralgia Paraesthetica after Prone Position Ventilation in a Patient with COVID-19

2020 ◽  
Author(s):  
Lucio Marinelli ◽  
Laura Mori ◽  
Chiara Avanti ◽  
Filippo Cotellessa ◽  
Sabrina Fabbri ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Respiratory Distress ◽  
Prone Position ◽  
Distress Syndrome ◽  
Prone Positioning ◽  
Severe Respiratory Distress ◽  
Case Presentation ◽  
Burning Pain ◽  
Femoral Cutaneous Nerve ◽  
Meralgia Paraesthetica

Background and objectives: One of the most feared complications of COVID-19 is respiratory failure caused by acute respiratory distress syndrome. In order to improve oxygenation and survival, patients admitted to intensive care units and intubated may undergo prone position mechanical ventilation. Prolonged prone positioning may cause meralgia paraesthetica due to lateral femoral cutaneous nerve entrapment between the inguinal ligament and the anterior superior iliac spine. Reports of the first two cases have been recently published. Case presentation: We describe the case of a 52-year-old man with respiratory failure during COVID-19 infection, who underwent prone position ventilation for 16 hours a day over 19 days and developed persistent burning pain and dysaesthesia on the lateral surface of the thigh bilaterally, diagnosed as meralgia paraesthetica. Conclusion: This is the second report describing meralgia paraesthetica following prone position ventilation in COVID-19. Given the ongoing pandemic and the inevitability of more patients with severe respiratory distress requiring prone position ventilation, this disabling entrapment condition should be considered and possibly prevented.

Respiratory failure in infants due to spinal muscular atrophy with respiratory distress type 1

2006 ◽  
Vol 32 (11) ◽  
pp. 1851-1855 ◽  
Author(s):  
Alberto Giannini ◽  
Anna Maria Pinto ◽  
Giordano Rossetti ◽  
Edi Prandi ◽  
Danilo Tiziano ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Respiratory Distress ◽  
Spinal Muscular Atrophy ◽  
Muscular Atrophy

A homozygous variant in ABCA3 is associated with severe respiratory distress and early neonatal death

2021 ◽  
Author(s):  
Montaha Al‐Iede ◽  
Mariam Khanfar ◽  
Luma Srour ◽  
Raja Rabah ◽  
Mousa Al‐Abbadi ◽  
...  
Keyword(s):  
Respiratory Distress ◽  
Neonatal Death ◽  
Early Neonatal Death ◽  
Severe Respiratory Distress ◽  
Homozygous Variant

High risk medicolegal autopsies: is a full postmortem examination necessary?

2012 ◽  
Vol 66 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Eve Patricia Fryer ◽  
Zoe C Traill ◽  
Rachel E Benamore ◽  
Ian S D Roberts
Keyword(s):  
High Risk ◽  
Minimally Invasive ◽  
Cause Of Death ◽  
Drug Abusers ◽  
Minimally Invasive Approach ◽  
Invasive Approach ◽  
External Examination ◽  
Invasive Techniques ◽  
Cocaine Toxicity ◽  
Selection Of

AimsAiming to reduce the numbers of high risk autopsies, we use a minimally invasive approach. HIV/hepatitis C virus (HCV)-positive coronial referrals, mainly intravenous drug abusers, have full autopsy only if external examination, toxicology and/or postmortem CT scan do not provide the cause of death. In this study, we review and validate this protocol.Methods and results62 HIV/HCV-positive subjects were investigated. All had external examination, 59 toxicology and 24 CT. In 42/62, this minimally invasive approach provided a cause of death. Invasive autopsy was required in 20/62, CT/toxicology being inconclusive, giving a potential rather than definite cause of death. Autopsy findings provided the cause of death in 6/20; in the remainder, a negative autopsy allowed more weight to be given to toxicological results previously regarded as inconclusive. In order to validate selection of cases for invasive autopsy using history, external examination and toxicology, a separate group of 57 non-infectious full autopsies were analysed. These were consecutive cases in which there was a history that suggested drug abuse. A review pathologist, provided only with clinical summary, external findings and toxicology, formulated a cause of death. This formulation was compared with the original cause of death, based on full autopsy. The review pathologist correctly identified a drug-related death or requirement for full autopsy in 56/57 cases. In one case, diagnosed as cocaine toxicity by the review pathologist, autopsy additionally revealed subarachnoid haemorrhage and Berry aneurysm.ConclusionsThese findings support the use of minimally invasive techniques in high risk autopsies, which result in a two-thirds reduction in full postmortems.

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