Updated: Aug 30
Each year, all senior engineering students at the University of Arizona must take this course to graduate. The course introduces the students to all of the steps that typically are part of an engineering project. The format is very similar to the Small Business Innovative Research type projects that each of the government departments (e.g., NASA, Air Force, Army, etc.) use to develop applied research and product development.
Sponsors, such as Raytheon, Caterpiller, IBM, and many others identify projects that would yield useful information for the company, but also recognize that this is an investment that helps with recruiting as well. I graduated from the UA in engineering and have served for several years as a judge on Design Day in May. I became interested as a sponsor when trying to better understand some of the issues that affect our gastrointestinal system.
I found that there was a huge amount of research on-going on the microbiome, but there was almost as large of a gap between the research and clinical applications, or therapies. Dr. Bonnie Hurwitz is an Associate Professor in the Department of Bio-systems, College of Agriculture and Life Sciences. I have teamed up with her to develop tools using the CAPSTONE Seniors Project that could be used to move the research over to the clinical side using bioinformatics tools described below.
We completed hour ZOOM speeding interviewing of the 16 students who expressed interest in becoming part of the team and have sent out our invites. There are several superstar candidates. We will now have to wait and see how things go this week as classes get underway.
Bioinformatics involves the analysis of high throughput sequence and molecular data for study of cancer genomes. The Bioinformatics Shared Resource (BISR) provides comprehensive analysis of genomic and proteomic data to University of Arizona Cancer Center members in support of their research. This contribution can result in short- or long-term projects, ranging from one day to many months, depending on the nature and extent of the support required.
The Shared Resource provides all levels of support from experimental design to analysis and publication of these data and development of grant applications. BISR staff works with researchers to select the data analysis approach that would help answer the research question. The resource assists in providing information about cancer data resources and utilization of bioinformatics pipelines and analytical tools for research projects. BISR also provides cohort identification in public clinically annotated molecular data for hypothesis generation. The goal is to provide assistance with data analysis that will lead to testable hypotheses and fundamentally important discoveries in cancer research.
The BISR specializes in the biological interpretation of data that may lead to a new understanding of cancer biology and the discovery of new diagnostic markers, risk genetic markers, and drug targets. The staff is well prepared to perform all of these types of analysis.
The Bioinformatics Shared Resource at The University of Arizona provides support in the following areas:
Analysis of genome data (e.g. gene expression, non-coding RNAs, CGH, next gen sequence analysis), proteomics, and other types of molecular data sets of cancer cells and tissues
Analysis of cancer molecular and clinical annotated datasets from public resources. NIH-TCGA (Cancer Genome Atlas) project, Cosmic (Catalogue of somatic mutations in Cancer), CCLE (Cancer Cell Line Encyclopedia), NIH LINCS project (Library of Network-based Cellular Signatures), NCBI GEO datasets and any other public resource.
Application of broad range of statistical and computational approaches for integrative analysis of molecular data with clinical parameters and correlating molecular profiles to patient attributes and outcome.
Support for pathway analysis, data visualization, systems biology analysis, analysis of genetic vulnerabilities for drug targeting and predictive patterns for outcome.
Assist in generation of preliminary data for development of grant applications and supporting bioinformatics data for publications.
Bioinformatics support for Cancer Center projects and other Shared Resources in the form of molecular databases, genome databases, and data sharing tools.
2020-21 Capstone Project Overview
Patients requiring ventilation due to severe COVID-19 infection are at a significant risk of death by secondary infections of the lung (CDC Clinical Guidance for Management of COVID-19 Disease). Even before the COVID-19 pandemic, ventilator acquired pneumonia was a significant health problem worldwide with cases now spiking due to COVID-19. When secondary infection arises, as in most critically ill COVID-19 patients, clinicians need to diagnose the causative organism and prescribe appropriate therapy as fast as possible. Recent developments in metagenomic next-generation sequencing (mNGS) make it possible to diagnose pathogens of viral, bacterial, or fungal origin within 12 hours (as opposed to days for culture) for a few hundred dollars per patient. In addition, while identifying the pathogens responsible for secondary pneumonia, mNGS can simultaneously confirm the primary cause of diseases such as SARS-CoV-2, including mutations signifying the emergence of novel strains of the virus. Engineering design students will use mNGS data from ventilated patients for secondary infection to develop statistical correlations with markers, visualizations, and a tool for measuring and monitoring the microbiome from extratracheal exudate. This tool could ultimately provide clinicians with data they need to make an accurate diagnosis, and offer personalized antibiotic therapy, days before symptoms of secondary infection arise. The project will leverage the 2019-20 Engineering Design Project work on metagenomic development for assessing data for the gut microbiota. And the results from this project can be further extrapolated to increase capabilities in out-years.
UNDERSTANDING VENTILATOR BASICS AND VENTILATOR WAVEFORMS
Mechanical ventilators provide support for patients by relieving the some or all of the work of breathing and allowing the body to heal when disease or trauma has caused normal functions to fail. This can be failure of the cardiopulmonary systems or failure of other body systems. Support can be accomplished in several ways: by helping eliminate carbon dioxide (CO2), by aiding in oxygenation, by taking over the work of breathing, and by recruiting or maintaining alveolar units.
Ventilator waveforms and loops are part of the standard monitoring package for all ICU ventilators but understanding what is being displayed can sometimes be difficult. This article will provide a look at many of the basic ventilator settings and examine how various waveforms and loops can be used to evaluate the effectiveness of mechanical ventilation in supporting the patient. The focus will be on the invasive approach to ventilation in adult patients where an artificial airway is used to provide an interface between the patient and the ventilator.
MECHANICAL VENTILATION BASICS
Breaths delivered by a mechanical ventilator are defined by four phases: the trigger phase (how the breath is initiated), the inspiratory phase (mainly dealing with the flow of gas into the lungs, or how the breath gets delivered), the cycle phase (how inspiration ends and expiration begins), and the expiratory phase (mainly dealing with the baseline pressure during the period between breaths). Many aspects of these four phases can be altered by changing settings on the ventilator and by use of waveforms the optimum settings can be achieved the best way to ventilate a patient and reduce asynchrony (this occurs when the actions of the ventilator and the actions of the patient are not working in harmony).
The trigger can occur by the patient’s inspiratory (negative) pressure reaching a set point or by the patient’s inspiratory flow reaching a set point. A third trigger is time-based on the setting for the respiratory rate. If the patient does not trigger any breaths, the ventilator will deliver breaths based on time. For example: with a rate or frequency set at 10 breaths per minute (BPM) in a patient who is not making any efforts to breath, a breath will be given every 6 seconds to achieve 10 BPM.
Inspiratory flow delivered by the ventilator is most often either a square flow pattern where flow is at a set value (LPM) and constant or a decelerating (or ramp) flow pattern where flow starts at a high level then tapers down with no preset value for peak flow.
Newer generations of ventilators can also provide a combination of fixed and variable flows in the use of dual modes such as volume-assured pressure support and pressure augmentation. The cycle phase is a function of the preset inspiratory time and preset tidal volume (or flow over time to deliver a targeted tidal volume). The baseline pressure may be zero (pressure is not elevated between breaths) or elevated above zero to a positive pressure that is held in the lungs by the action of the exhalation valve in the ventilator. When pressure is added it is called Continuous Positive Airway Pressure (CPAP) when providing noninvasive support or Positive End-Expiratory Pressure (PEEP) when providing invasive support (ie the patient has an endotracheal tube or tracheostomy tube).
For most patients receiving invasive mechanical ventilation, either a preset tidal volume is used (called volume-controlled ventilation, VC) or a preset pressure is used (called pressure-controlled ventilation, PC) to deliver a breath. Note: inspiratory flow in VC can be selected by the operator to be either square or decelerating. Inspiratory flow in PC is always decelerating- a square flow pattern cannot be selected.
Either of these controls can be set up using a continuous mandatory ventilation (CMV) or intermittent mandatory ventilation (IMV). With the CMV approach anytime the patient triggers the ventilator to get a breath the ventilator delivers the breath by either giving the preset volume in VC or the preset pressure in PC. In CMV, no purely spontaneous breaths occur.
With the IMV approach the patient can breathe spontaneously in between the mandatory breaths then when time comes for a mandatory breath to occur the ventilator will provide the mandatory breath. Patient effort can result in variations in the spontaneous breaths. So the basic approach to give a breath can be given by four basic modes: VC-CMV, VC-IMV, PC-CMV, or PC-IMV. (See Figure 1.)
Positive end expiratory pressure (PEEP) is an available option that can be added to any of these four approaches. When PEEP is added, the patient does not exhale at the end of exhalation or back to a zero pressure baseline, but instead exhalation is ended with early so that there is a positive pressure in the airways. This increases the patient’s functional residual capacity (FRC), aids in oxygenation by keeping alveoli open and reduce a patient’s work of breathing.
Pressure support ventilation (PSV) is another option is available for either VC-IMV or PC-IMV (either with or without adding PEEP). PSV provides an extra boost of flow to all spontaneous breaths to reach a preset pressure. This helps increase the spontaneous tidal volume, helps overcome the resistance of the artificial airway, and reduces the patient’s work of breathing.
Beyond the basic modes, dual-modes are also available such as volume-assured pressure support and pressure augmentation which combines a preset volume “target” with a pressure approach to achieve the targeted volume. With changing compliance (in essence, the ease to which the lungs are inflated) the pressure used to reach the volume will adjust.
As the lungs get stiffer or less compliant (for example in worsening pneumonia or when fibrotic changes occur), volume will tend to drop at a given pressure so the ventilator will adjust the pressure upward to maintain the preset volume. As lungs get less stiff or have increasing compliance, volume will tend to increase at a given pressure so the ventilator will decrease pressure to bring the volume back toward the preset targeted volume. The adjustment in pressure due to changing compliance will occur over time and safeguards are set by the operator to avoid having pressure get too high.
Care providers order some of the settings needed to establish mechanical ventilation. Beyond the ordered settings, respiratory therapists establish other settings to reduce asynchrony, place alarm limits (high and/or low alarm settings), use of humidification or heat and moisture exchangers, etc. Most often the provider will order the control approach, the mode, the desired tidal volume (for VC) or inspiratory pressure (for PC), the rate or frequency (f), the desired inspired oxygen level, added PEEP, and [–] if in the IMV mode added pressure support. For example, there may be an order for volume controlled continuous mandatory ventilation with a tidal volume of 400 mL, frequency of 12 BPM, 60% oxygen for each breath, and the addition of 8 cmH2O PEEP. In an abbreviated form this would be:
VC-CMV, VT 400 mL, f-12, FiO2 .60, + 8 cmH2O PEEP
Here is an example of an order for pressure-controlled intermittent mandatory ventilation with a peak inspiratory pressure of 20 cmH2O, frequency of 14 BPM, 40% oxygen for each breath, the addition of 5 cmH2O PEEP and 5 cmH2O pressure support:
PC-IMV, PIP 20, f-14, FiO2 .40, + 5 cmH2O PEEP, +5 PS
All other settings necessary for safe and effective ventilation are determined by the respiratory therapist involved with the patient’s care.
VENTILATOR WAVEFORMS: SCALARS
Scalars provide a basic look at changes in the variables of flow, pressure, and volume over time. They can be displayed alone or in combination (either 2 or all 3) on the ventilator screen. During the time of a breath, all 3 of these variable occur simultaneously. With selection of a slow “sweep” speed, several breaths can be displayed on the screen and trends in ventilation can be examined over time. A fast sweep speed will show much fewer breaths (perhaps even just one breath) and more details can be examined for the breath delivery. Many ventilators will give the operator an option to “freeze” the display and look at the flow, pressure, and/or time scalars without having the ventilator update and change the screen for subsequent breaths. Otherwise, the screen will update the view on the screen over time.
Ventilator graphics in the form of scalars and loops allow for a visual assessment of the patient-ventilator system and can help uncover problems that should be addressed. Spending time studying examples such as those shown in this article can help sharpen the skills needed to recognize problems. Adjustments to the variables such as sensitivity, inspiratory flow and volume, pressure support, PEEP, breath rate, and other settings can reduce work of breathing, decrease possible damage caused by mechanical ventilation, and make the patient more comfortable.
This article has touched on some of the basics of ventilation an ventilator waveforms; there are excellent textbooks, web-based teaching materials, and publications from the ventilator manufacturers that go deeper in showing what graphics can do to help effectively and safely ventilate a patient.
Bill Pruitt, RRT, CPFT, AE-C, FAARC is a senior instructor and director of clinical education in the department of Cardiorespiratory Sciences, College of Allied Health Sciences, at the University of South Alabama in Mobile. He is also currently an elected member of the Board of Directors for the National Asthma Educator Certification Board (NAECB). For more information, contact editor@RTmagazine.com.
SOURCES FOR MORE INFORMATION
Cairo, JM. (2016) Pilbeam’s Mechanical Ventilation, Physiological and Clinical applications. 6th ed. Ch 9.
Gentile MA. Cycling of the mechanical ventilator breath. Respiratory Care. 2011 Jan 1;56(1):52-60.
MacIntyre NR. Patient-ventilator interactions: optimizing conventional ventilation modes. Respiratory Care. 2011 Jan 1;56(1):73-84.