This document provides an overview of respiratory failure and acute respiratory distress syndrome (ARDS). It discusses the diagnosis of respiratory failure using blood gases and imaging tests. The pathophysiology of ARDS involves generalized lung inflammation that leads to pulmonary edema. Mechanical ventilation aims to improve gas exchange while avoiding lung damage, using low tidal volumes and optimizing positive end-expiratory pressure levels. The treatment of respiratory failure focuses on addressing the underlying cause, symptoms, and pathogenesis.
Acute respiratory distress syndrome (ARDS) occurs when fluid builds up in the tiny, elastic air sacs (alveoli) in your lungs. The fluid keeps your lungs from filling with enough air, which means less oxygen reaches your bloodstream. This deprives your organs of the oxygen they need to function.
Reexpansion pulmonary edema is a serious complication after sudden expansion of collapsed lung.Re-expansion pulmonary edema is an uncommon complication following drainage of a pneumothorax , pleural effusion or removal of any space occupying lesion.
The incidence referred is less than 1%, andmortality can reach up to 20%.
Acute respiratory distress syndrome (ARDS) occurs when fluid builds up in the tiny, elastic air sacs (alveoli) in your lungs. The fluid keeps your lungs from filling with enough air, which means less oxygen reaches your bloodstream. This deprives your organs of the oxygen they need to function.
Reexpansion pulmonary edema is a serious complication after sudden expansion of collapsed lung.Re-expansion pulmonary edema is an uncommon complication following drainage of a pneumothorax , pleural effusion or removal of any space occupying lesion.
The incidence referred is less than 1%, andmortality can reach up to 20%.
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Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
The increased availability of biomedical data, particularly in the public domain, offers the opportunity to better understand human health and to develop effective therapeutics for a wide range of unmet medical needs. However, data scientists remain stymied by the fact that data remain hard to find and to productively reuse because data and their metadata i) are wholly inaccessible, ii) are in non-standard or incompatible representations, iii) do not conform to community standards, and iv) have unclear or highly restricted terms and conditions that preclude legitimate reuse. These limitations require a rethink on data can be made machine and AI-ready - the key motivation behind the FAIR Guiding Principles. Concurrently, while recent efforts have explored the use of deep learning to fuse disparate data into predictive models for a wide range of biomedical applications, these models often fail even when the correct answer is already known, and fail to explain individual predictions in terms that data scientists can appreciate. These limitations suggest that new methods to produce practical artificial intelligence are still needed.
In this talk, I will discuss our work in (1) building an integrative knowledge infrastructure to prepare FAIR and "AI-ready" data and services along with (2) neurosymbolic AI methods to improve the quality of predictions and to generate plausible explanations. Attention is given to standards, platforms, and methods to wrangle knowledge into simple, but effective semantic and latent representations, and to make these available into standards-compliant and discoverable interfaces that can be used in model building, validation, and explanation. Our work, and those of others in the field, creates a baseline for building trustworthy and easy to deploy AI models in biomedicine.
Bio
Dr. Michel Dumontier is the Distinguished Professor of Data Science at Maastricht University, founder and executive director of the Institute of Data Science, and co-founder of the FAIR (Findable, Accessible, Interoperable and Reusable) data principles. His research explores socio-technological approaches for responsible discovery science, which includes collaborative multi-modal knowledge graphs, privacy-preserving distributed data mining, and AI methods for drug discovery and personalized medicine. His work is supported through the Dutch National Research Agenda, the Netherlands Organisation for Scientific Research, Horizon Europe, the European Open Science Cloud, the US National Institutes of Health, and a Marie-Curie Innovative Training Network. He is the editor-in-chief for the journal Data Science and is internationally recognized for his contributions in bioinformatics, biomedical informatics, and semantic technologies including ontologies and linked data.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
2. Introduction
• Respiratory failure is present whenever the respiratory system fails in the gas exchange function
• ‘hypoxaemic’ when oxygen tension values are lower than normal (PaO2 value is lower than the
normal for age and altitude)
• ventilatory’ when elimination of carbon dioxide is insufficient (PaCO2 of >45 mmHg)
• The most common causes are COPD exacerbation, asthma, and neuromuscular fatigue, leading to
dyspnoea, tachypnoea, tachycardia, use of accessory muscles of respiration, and altered
consciousness
• History taking and ABG analysis are the easiest ways to assess the nature of ARF, and treatment
should resolve the baseline pathology. In severe cases, mechanical ventilation is necessary as a
‘buying time’ therapy
3. • Acute hypoxaemic respiratory failure arising from widespread diffuse injury to the alveolar– capillary
membrane is termed acute respiratory distress syndrome (ARDS), which is the clinical and
radiographic manifestation of acute pulmonary inflammatory states
5. Diagnosis
• Blood gases
• The PaO2 and PaCO2 values obtained by blood gas analysis give immediate information for the
diagnosis and determination of the ‘nature’ (oxygenation or ventilatory) of respiratory failure.
6. Imaging
• CXR is one of the simplest examinations used to assess the cardiopulmonary status of patients.
detect pulmonary infiltrates, pneumothorax, and pleural effusions.
• CT scans allows a complete examination of the lung parenchyma, and quantitative analysis makes
it possible to determine the degree of aeration of each lung region such as localized pneumothorax,
pleural effusions, and bronchial and tracheal alterations, not shown on X- rays
• PET can quantify regional perfusion, ventilation, aeration, lung vascular permeability, oedema,
inflammatory cell and enzyme activity, and pulmonary gene expression
• Lung US is a bedside tool to assess the state of aeration and ventilation of the lung, the presence of
heterogeneity, and the temporal evolution of pathologies
• EIT monitors lung heterogeneities, the effects of ventilatory manoeuvres, and the physiological
effects of PEEP and tidal volume.
7. Haemodynamics
• Cardiac output and pulmonary wedge pressure may provide important informationfor diagnosis
• PACs or CVCs allow precise monitoring of the volaemic status, cardiac function, and the
haemodynamic effects of mechanical ventilation Central venous saturation (SvO2)
• Bedside echocardiography has become useful for the management of critically ill patients and as a
non- invasive diagnostic and monitoring tool for circulatory and respiratory failure fluid
responsiveness, haemodynamic management
8. Treatment of respiratory failure
• The treatment of respiratory failure includes therapies, with three different targets, namely:
1. ‘Symptoms’: with the aim of correcting the consequences of the underlying pathology causing
respiratory failure. This kind of therapy is very important when the consequences, e.g. hypoxaemia,
are life- threatening.
2. ‘Pathogenesis’: with the aim of interrupting the primary insult and clinical consequences, e.g.
corticosteroid administration.
3. ‘Aetiology’: with the aim of correcting the underlying pathology, e.g. antimicrobial administration to
treat bacterial pneumonia or surgery in the case of abdominal disease.
• treatments devoted to correct symptoms, as they allow the buying of time while awaiting resolution
of the underlying pathology
9. Acute respiratory distress syndrome
• Definition
• ‘The clinical pattern . . . Includes severe dyspnoea, tachypnoea, cyanosis that is refractory to
oxygen therapy, loss of lung compliance, and a diffuse alveolar infiltrate seen on chest X- ray (The
lancet, 1967)
• ARDS definition revolved around a combination of the presence of hypoxaemia (PaO2, FiO2),
radiographic infiltrates, low compliance, and wedge pressure - 1988
• In 1988, Murray et al. [31] proposed an approach based on the ‘lung injury score’ (LIS)
1. Chest roentgenogram.
2. Hypoxaemia (PaO2/ FiO2 ratio).
3. PEEP (when ventilated).
4. Respiratory system compliance.
Three levels of severity of lung injury are defined: (1) absence of ung injury (LIS = 0); (2) mild to moderate lung
injury (LIS = 0.1–2.5); and (3) severe lung injury (ARDS) (LIS >2.5).
12. Pathophysiology
• pulmonary or extrapulmonary origin, causes a generalized inflammatory response involving the
whole lung clinical and radiographic manifestation
• The process begins with the local production of cytokines by inflammatory cells, epithelial cells, and
fibroblast
• The progression of the lung injury has been divided into three phases: (1) exudative; (2)
proliferative; and (3) fibrotic.ts, which increases the alveolar– capillary barrier permeability.
13. Inflammatory pulmonary oedema
• CT images of the lung during the early phase of ARDS are characterized by three vertically
distributed compartments: the non- dependent regions, which are usually normally aerated; the
middle lung, characterized by ground- glass opacification; and the almost consolidated dependent
regions
• ‘ground- glass opacification’ means an ‘increase in lung attenuation, with preservation of bronchial
and vascular margins’
• Ground- glass opacification reflects an active inflammatory process, involving the interstitium, filling
of the alveolar space, and oedema, which corresponds to poorly aerated tissue
• ‘consolidation’ means a ‘homogeneous increase in lung attenuation that obscures bronchovascular
margins in which an air bronchogram may be present’.
14.
15. Potential for lung recruitment
• the severity of the overall lung injury may be expressed as the ratio of non- aerated lung tissue weight to
total lung weight at end- expiration (5 cmH2O PEEP).
• patients with higher amounts of lung oedema have higher percentages of potential recruitment
• Patients with a higher potential for lung recruitment have, however, higher amounts of collapsed tissue
• CT analysis is the only reliable method to measure the potential for lung recruitment at the bedside
• The best results have been obtained on combining PaO2/FiO2have been obtained on combining PaO2/FiO2
<150 mmHg (at 5 cmH2O PEEP), increased lung compliance, and decreased
dead space from 5 to 15 cmH2O PEEP (sensitivity 79%, specificity
81%)
16. CT: stress, strain, and homogeneity
• Strain is defined as the deformation of lung tissue (tidal volume to
FRC ratio) due to the application of transpulmonary pressure.
• The reactive force rising in the tissue is called stress.
• Lung homogeneity is evaluated by measurement of the strain
difference between contiguous structures
• . The amount of voxels in which this phenomenon may occur (called
‘stress risers’) increases with ARDS severity, while higher PEEP levels
may decrease this phenomenon.
17. Mechanical ventilation
• The goal of mechanical ventilation progressively shifted to the
improvement of gas exchange to avoid lung damage.
• Non-invasive support is considered for mild ARDS patients. However, it can
be extended to selected moderate ARDS patients (i.e. cognizant younger
patients, patients with a SAPS II score of <34 and patient with ARDS not
caused by Pneumonia
• Suggested markers for intubation are excessive transpulmonary pressure
swings, a rapid shallow breathing index higher than 105 breaths/min/L, and
monitored tidal volumes persistently >9.5 mL/kg of predicted body weight.
• CPAP delivered via a face mask has been associated with early
improvement of oxygenation, but it was not associated with a reduction of
intubation need or improved outcome
18. • In a recent trial, the intubation rate was significantly lower with high-
flow nasal cannula (HFNC) O2, compared to standard O2 or NIV, in
patients with PaO2/FiO2 ≤200 mmHg at enrolment.
• HFNC can generate low levels of PEEP in the upper airways, decrease
work of breathing, and reduce dead space
19. Invasive ventilation
• The setting of ventilator parameters involves the respiratory rate, VT, I:E ratio, and pressure.
• Studies showed improved arterial oxygenation at the cost of increased mean airway pressure and
intrinsic PEEP and decreased cardiac output
• In ALI/ARDS, extreme forms of manipulating the I:E ratio are not recommended; values between
0.5 and 1.5 are acceptable
• during spontaneous breathing, high respiratory rates increase oedema formation
• High-frequency oscillatory ventilation (HFOV) has been proposed as an alternative technique to
provide mechanical ventilation, using low VT and very high mean airway pressure, thus improving
oxygenation and minimizing inspiratory overdistension and end-expiratory lung collapse
• A recent meta-analysis suggested that HFOV may be of potential advantage in very severe ARDS
patients (PaO2/FiO2 <70 mmHg)
• The scientific community agrees on the use of low VT, as it provides less injury to the lung. The
debate is still open, however, on an adequate PEEP setting
20. Tidal volume and plateau pressure
• In clinical practice, VT is normalized on the patient’s predicted body
weight (PBW) from the patient’s height (VT/PBW) to avoid excessive
strain on the lung parenchyma
• VT values in the 6–12 mL/kg range
• tidal volume should be scaled to compliance using driving pressure
(∆P = Pplat – PEEP
21. Positive end-expiratory pressure
• It is still not clear what the best way is to set an adequate PEEP level
• Several methods have been proposed, according to lung mechanics, pressure–volume curve, and
hysteresis.
• in the ExPress trial, severe patients were defined according to PaO2 of 80% for at least 1 hour.
• the mortality rate in the high PEEP group is lower than that in the low PEEP group
• It sounds reasonable that high PEEP is effective in the most severe patients, characterized by
smaller baby lung and higher potential for lung recruitment
• , in patients with mild and moderate ARDS, higher PEEP seemed harmful.
• in patients with moderate to severe ARDS, high PEEP levels [16.4 cmH2O (16.0–16.7) at 1 hour;
11.6 cmH2O (11.2– 12.1) at 7 days] may carry more negative (barotrauma) than positive effects
• Intermediate levels, as the ones reported in the control groups of this trial [13.0 cmH2O (12.7–
13.3) at 1 hour; 9.6 cmH2O (9.3–10.0) at 7 days], may prevent both barotrauma and atelectasis
22. Prone position
• The prone position is suggested for ALI/ARDS patients in whom mechanical
ventilation has potentially injurious effects.
• the prone position has been proven and other physiological mechanisms have
been postulated: improvement of V/Q mismatch; recruitment of the most
dependent areas; shunt reduction; and less lung compression by the heart.
• prone positioning is able to prevent or delay the development of VILI
• A recent clinical RCT by Guerin et al. tested the effects of prone positioning on
mortality in patients with severe and persistent ARDS
• survival benefit in patients treated with the prone position, with a reduction in
mortality of nearly 50%
• Contraindications to prone positioning include the presence of an open
abdominal wound, unstable pelvic fracture, spinal lesions and instability, and
brain injury without monitoring of ICP. In addition, well-trained staff are required
for its safe implementation.
23. Artificial lungs
• If the aim is to treat life-threatening hypoxaemia, the indication is
high-flow veno-venous ECMO if the patient does not present with
severe car
• According to the Italian ECMOnet experience, intracranial
haemorrhage occurred in one patient out of 49.
• the SUPERNOVA study showed the possibility to reduce the intensity
of mechanical ventilation, but with a high and partially unexpected
risk of coagulation
24. Overall management of acute lung
injury/acute respiratory distress syndrome
• Prophylaxis for PE and venous thrombosis should be applied in all patients,
unless contraindicated
• Enteral nutrition is also important to prevent GI bleeding and to maintain
the normal barrier function of the mucosa
• Tight glycaemic control has been proven to reduce the number of multiple
organ failure in a population of post-operative patients treated with
intensive insulin, thus also improving ICU and hospital outc
• prevention of nosocomial or secondary infections and VAP, which are
responsible for the high mortality rate in ALI/ARDS patients
• the routine use of corticosteroids is not recommended in patients with
persistent ARDS
Editor's Notes
Kegagalan oksigenasi terjadi ketika nilai PaO2 lebih rendah dari nilai prediksi normal untuk usia dan ketinggian dan mungkin karena ketidakcocokan V/Q atau konsentrasi O2 yang rendah di udara inspirasi.
Kegagalan pernapasan hadir setiap kali sistem pernapasan gagal dalam fungsi pertukaran gas
'hipoksemia' ketika nilai tegangan oksigen lebih rendah dari normal (nilai PaO2 lebih rendah dari normal untuk usia dan ketinggian)
ventilasi' ketika eliminasi karbon dioksida tidak mencukupi (PaCO2 >45 mmHg)
Penyebab paling umum adalah eksaserbasi PPOK, asma, dan kelelahan neuromuskular, yang menyebabkan dispnea, takipnea, takikardia, penggunaan otot bantu pernapasan, dan penurunan kesadaran.
Anamnesis dan analisis ABG adalah cara termudah untuk menilai sifat GGA, dan pengobatan harus menyelesaikan patologi dasar. Dalam kasus yang parah, ventilasi mekanis diperlukan sebagai terapi 'membeli waktu'
Kegagalan pernapasan hipoksemia akut yang timbul dari cedera difus luas pada membran alveolar-kapiler disebut sindrom gangguan pernapasan akut (ARDS), yang merupakan manifestasi klinis dan radiografi dari keadaan inflamasi paru akut.
Hipoksia alveolus ditandai dengan penurunan fraksi O2 pada sisi alveolus unit paru. Konsentrasi O2 alveolar yang rendah dapat disebabkan oleh pernapasan pada tekanan barometrik yang berkurang atau menghirup campuran gas dengan FiO2 <21%. Namun, mekanisme yang paling relevan secara klinis adalah ketidakcocokan V/Q.
Nilai PaO2 dan PaCO2 yang diperoleh dengan analisis gas darah memberikan informasi langsung untuk diagnosis dan penentuan 'sifat' (oksigenasi atau ventilasi) gagal napas.
CXR adalah salah satu pemeriksaan paling sederhana yang digunakan untuk menilai status kardiopulmoner pasien. mendeteksi infiltrat paru, pneumotoraks, dan efusi pleura.
CT scan memungkinkan pemeriksaan parenkim paru secara lengkap, dan analisis kuantitatif memungkinkan untuk menentukan derajat aerasi setiap daerah paru seperti pneumotoraks lokal, efusi pleura, dan perubahan bronkial dan trakea, tidak ditunjukkan pada sinar-X.
PET dapat mengukur perfusi regional, ventilasi, aerasi, permeabilitas pembuluh darah paru-paru, edema, sel inflamasi dan aktivitas enzim, dan ekspresi gen paru.
Lung US adalah alat samping tempat tidur untuk menilai keadaan aerasi dan ventilasi paru-paru, adanya heterogenitas, dan evolusi temporal patologi
EIT memantau heterogenitas paru-paru, efek manuver ventilasi, dan efek fisiologis PEEP dan volume tidal.
Curah jantung dan tekanan baji paru dapat memberikan informasi penting untuk diagnosis
PACs atau CVCs memungkinkan pemantauan yang tepat dari status volemik, fungsi jantung, dan efek hemodinamik dari ventilasi mekanis Saturasi vena sentral (SvO2)
Ekokardiografi samping tempat tidur telah menjadi berguna untuk pengelolaan pasien sakit kritis dan sebagai alat diagnostik dan pemantauan non-invasif untuk kegagalan sirkulasi dan pernapasan, respons cairan, manajemen hemodinamik.
Penatalaksanaan gagal napas meliputi terapi, dengan tiga sasaran yang berbeda, yaitu:
1. 'Gejala': dengan tujuan mengoreksi konsekuensi dari patologi yang mendasari yang menyebabkan gagal napas. Terapi semacam ini sangat penting ketika konsekuensinya, mis. hipoksemia, yang mengancam jiwa.
2. 'Patogenesis': dengan tujuan untuk menghentikan gangguan primer dan konsekuensi klinis, mis. pemberian kortikosteroid.
3. 'Etiologi': dengan tujuan mengoreksi patologi yang mendasari, mis. pemberian antimikroba untuk mengobati pneumonia bakteri atau pembedahan dalam kasus penyakit perut.
perawatan yang ditujukan untuk memperbaiki gejala, karena memungkinkan pembelian waktu sambil menunggu resolusi patologi yang mendasarinya
'Pola klinis. . . Termasuk dispnea berat, takipnea, sianosis yang refrakter terhadap terapi oksigen, kehilangan komplians paru, dan infiltrat alveolar difus yang terlihat pada rontgen dada (The lancet, 1967)
Definisi ARDS berkisar pada kombinasi dari adanya hipoksemia (PaO2, FiO2), infiltrat radiografi, kepatuhan rendah, dan tekanan baji - 1988
Pada tahun 1988, Murray dkk. [31] mengusulkan pendekatan berdasarkan 'skor cedera paru-paru' (LIS)
Roentgenogram dada.
Hipoksemia (rasio PaO2/FiO2).
PEEP (bila berventilasi).
Kesesuaian sistem pernapasan.
Tiga tingkat keparahan cedera paru didefinisikan: (1) tidak adanya cedera paru (LIS = 0); (2) cedera paru ringan sampai sedang (LIS = 0,1-2,5); dan (3) cedera paru berat (ARDS) (LIS >2.5).
asal paru atau ekstrapulmoner, menyebabkan respons inflamasi umum yang melibatkan seluruh paru, manifestasi klinis dan radiografis
Prosesnya dimulai dengan produksi lokal sitokin oleh sel inflamasi, sel epitel, dan fibroblas
Perkembangan cedera paru dibagi menjadi tiga fase: (1) eksudatif; (2) proliferatif; dan (3) fibrotik, yang meningkatkan permeabilitas penghalang alveolar-kapiler.
Gambar CT paru-paru selama fase awal ARDS dicirikan oleh tiga kompartemen yang terdistribusi secara vertikal: daerah yang tidak bergantung, yang biasanya biasanya diangin-anginkan; paru-paru tengah, ditandai dengan kekeruhan ground-glass; dan wilayah ketergantungan yang hampir terkonsolidasi
'ground-glass opacification' berarti 'peningkatan redaman paru-paru, dengan pelestarian margin bronkial dan vaskular'
Kekeruhan ground-glass mencerminkan proses inflamasi aktif, yang melibatkan interstitium, pengisian ruang alveolar, dan edema, yang berhubungan dengan jaringan aerasi yang buruk.
'konsolidasi' berarti 'peningkatan homogen dalam redaman paru-paru yang mengaburkan margin bronkovaskular di mana bronkogram udara mungkin ada'.
keparahan cedera paru secara keseluruhan dapat dinyatakan sebagai rasio berat jaringan paru non-aerasi terhadap berat paru total pada akhir ekspirasi (5 cmH2O PEEP).
pasien dengan jumlah edema paru yang lebih tinggi memiliki persentase perekrutan potensial yang lebih tinggi
Namun, pasien dengan potensi rekrutmen paru yang lebih tinggi memiliki jumlah jaringan yang kolaps lebih tinggi
Analisis CT adalah satu-satunya metode yang dapat diandalkan untuk mengukur potensi perekrutan paru-paru di samping tempat tidur
Hasil terbaik diperoleh pada penggabungan PaO2/FiO2 diperoleh pada penggabungan PaO2/FiO2
<150 mmHg (pada 5 cmH2O PEEP), peningkatan komplians paru, dan penurunan
ruang mati dari 5 hingga 15 cmH2O PEEP (sensitivitas 79%, spesifisitas
81%)
Strain didefinisikan sebagai deformasi jaringan paru (volume tidal terhadap rasio FRC) karena penerapan tekanan transpulmoner.
Gaya reaktif yang meningkat dalam jaringan disebut stres.
Homogenitas paru dievaluasi dengan pengukuran perbedaan regangan antara struktur yang berdekatan
. Jumlah voxel di mana fenomena ini dapat terjadi (disebut 'peningkat stres') meningkat dengan keparahan ARDS, sementara tingkat PEEP yang lebih tinggi dapat menurunkan fenomena ini.
Tujuan ventilasi mekanis secara progresif bergeser ke perbaikan pertukaran gas untuk menghindari kerusakan paru-paru.
Dukungan non-invasif dipertimbangkan untuk pasien ARDS ringan. Namun, dapat diperluas ke pasien ARDS sedang yang dipilih (yaitu pasien yang lebih muda, pasien dengan skor SAPS II <34 dan pasien dengan ARDS yang tidak disebabkan oleh Pneumonia.
Penanda yang disarankan untuk intubasi adalah perubahan tekanan transpulmoner yang berlebihan, indeks pernapasan dangkal yang cepat lebih tinggi dari 105 napas/menit/L, dan volume tidal yang dipantau secara terus-menerus >9,5 mL/kg berat badan yang diperkirakan.
CPAP yang diberikan melalui masker wajah telah dikaitkan dengan peningkatan awal oksigenasi, tetapi tidak terkait dengan pengurangan kebutuhan intubasi atau peningkatan hasil.
Dalam percobaan baru-baru ini, tingkat intubasi secara signifikan lebih rendah dengan kanula hidung aliran tinggi (HFNC) O2, dibandingkan dengan O2 standar atau NIV, pada pasien dengan PaO2/FiO2 200 mmHg saat pendaftaran.
HFNC dapat menghasilkan PEEP tingkat rendah di saluran udara bagian atas, mengurangi kerja pernapasan, dan mengurangi ruang mati
Pengaturan parameter ventilator meliputi frekuensi pernapasan, VT, rasio I:E, dan tekanan.
Studi menunjukkan peningkatan oksigenasi arteri dengan mengorbankan peningkatan tekanan jalan napas rata-rata dan PEEP intrinsik dan penurunan curah jantung
Dalam ALI/ARDS, bentuk ekstrim dari manipulasi rasio I:E tidak direkomendasikan; nilai antara 0,5 dan 1,5 dapat diterima
selama pernapasan spontan, tingkat pernapasan yang tinggi meningkatkan pembentukan edema
Ventilasi osilasi frekuensi tinggi (HFOV) telah diusulkan sebagai teknik alternatif untuk memberikan ventilasi mekanis, menggunakan VT rendah dan tekanan jalan napas rata-rata sangat tinggi, sehingga meningkatkan oksigenasi dan meminimalkan overdistensi inspirasi dan kolaps paru akhir ekspirasi.
Meta-analisis baru-baru ini menunjukkan bahwa HFOV mungkin berpotensi menguntungkan pada pasien ARDS yang sangat parah (PaO2/FiO2 <70 mmHg)
Komunitas ilmiah menyetujui penggunaan VT rendah, karena memberikan lebih sedikit cedera pada paru-paru. Perdebatan masih terbuka, bagaimanapun, pada pengaturan PEEP yang memadai
Dalam praktik klinis, VT dinormalisasi berdasarkan prediksi berat badan (PBW) pasien dari tinggi badan pasien (VT/PBW) untuk menghindari ketegangan yang berlebihan pada parenkim paru.
Nilai VT dalam kisaran 6–12 mL/kg
volume tidal harus diskalakan agar sesuai dengan menggunakan tekanan penggerak (∆P = Pplat – PEEP
Masih belum jelas apa cara terbaik untuk mengatur level PEEP yang memadai
Beberapa metode telah diusulkan, menurut mekanika paru, kurva tekanan-volume, dan histeresis.
dalam percobaan ExPress, pasien parah didefinisikan menurut PaO2 80% selama minimal 1 jam.
angka kematian pada kelompok PEEP tinggi lebih rendah dari pada kelompok PEEP rendah
Kedengarannya masuk akal bahwa PEEP tinggi efektif pada pasien yang paling parah, ditandai dengan paru-paru bayi yang lebih kecil dan potensi perekrutan paru-paru yang lebih tinggi
, pada pasien dengan ARDS ringan dan sedang, PEEP yang lebih tinggi tampaknya berbahaya.
pada pasien dengan ARDS sedang hingga berat, kadar PEEP tinggi [16,4 cmH2O (16,0-16,7) pada 1 jam; 11,6 cmH2O (11,2– 12,1) pada 7 hari] dapat membawa lebih banyak efek negatif (barotrauma) daripada efek positif
Tingkat menengah, seperti yang dilaporkan dalam kelompok kontrol percobaan ini [13,0 cmH2O (12,7-13,3) pada 1 jam; 9,6 cmH2O (9,3-10,0) pada 7 hari], dapat mencegah barotrauma dan atelektasis
Posisi tengkurap disarankan untuk pasien ALI/ARDS yang ventilasi mekanisnya berpotensi menimbulkan efek merugikan.
posisi tengkurap telah terbukti dan mekanisme fisiologis lainnya telah didalilkan: peningkatan ketidakcocokan V/Q; perekrutan daerah yang paling tergantung; pengurangan shunt; dan lebih sedikit kompresi paru-paru oleh jantung.
posisi tengkurap mampu mencegah atau menunda perkembangan VILI
RCT klinis terbaru oleh Guerin et al. menguji efek dari posisi tengkurap pada kematian pada pasien dengan ARDS yang parah dan persisten
manfaat kelangsungan hidup pada pasien yang dirawat dengan posisi tengkurap, dengan penurunan angka kematian hampir 50%
Kontraindikasi untuk posisi tengkurap termasuk adanya luka perut terbuka, fraktur panggul yang tidak stabil, lesi tulang belakang dan ketidakstabilan, dan cedera otak tanpa pemantauan ICP. Selain itu, staf terlatih diperlukan untuk implementasi yang aman.
Jika tujuannya adalah untuk mengobati hipoksemia yang mengancam jiwa, indikasinya adalah ECMO vena-vena aliran tinggi jika pasien tidak datang dengan mobil yang parah.
Menurut pengalaman ECMOnet Italia, perdarahan intrakranial terjadi pada satu dari 49 pasien.
studi SUPERNOVA menunjukkan kemungkinan untuk mengurangi intensitas ventilasi mekanis, tetapi dengan risiko koagulasi yang tinggi dan sebagian tidak terduga
Profilaksis untuk PE dan trombosis vena harus diterapkan pada semua pasien, kecuali dikontraindikasikan
Nutrisi enteral juga penting untuk mencegah perdarahan GI dan untuk mempertahankan fungsi sawar normal dari mukosa
Kontrol glikemik yang ketat telah terbukti mengurangi jumlah kegagalan organ ganda pada populasi pasien pasca operasi yang diobati dengan insulin intensif, sehingga juga meningkatkan ICU dan rawat inap.
pencegahan infeksi nosokomial atau sekunder dan VAP, yang bertanggung jawab atas tingginya angka kematian pada pasien ALI/ARDS
penggunaan rutin kortikosteroid tidak dianjurkan pada pasien dengan ARDS persisten