Respiratory Papers

Raidal et al, 2021

Bi-Level Positive Airway Pressure for Non-invasive Respiratory Support of Foals

Objective: To investigate the use of a commercial bi-level positive airway pressure (BiPAP) ventilator, designed for home care of people with obstructive respiratory conditions, for respiratory support of healthy foals with pharmacologically induced respiratory insufficiency

Results:

• Administration of supplementary oxygen alone or with BiPAP was associated with significantly increased PaO2 in comparison to results at all other sampling times and results following BiPAP were significantly greater than after O2 administration

• BiPAP was associated with significantly lower RR and significantly longer inspiratory and expiratory times at T2 than observed following O2 administration at this time

• FiO2 was higher during BiPAP than during O2 administration to foals

• Gas exchange and mechanics of breathing (increased tidal volume, decreased respiratory rate, and increased peak inspiratory flow) were improved during BiPAP relative to administration of supplementary oxygen alone or prior studies using continuous positive airway pressure, but modest hypercapnia was observed

  • Hypercapnia may be due to reduced respiratory drive, increased metabolic rate, hypoventilation due to sedation, or effects of equipment dead space

    • In this study, mask administration of O2 was likely associated with CO2 retention

    • Use of lower expiratory pressures did not prevent hypercapnia

• Results suggest that monitoring of alveolar ventilation, pressure-volume curves, and PEEPi might be important for effective NIV of foals and to better characterize the response of foals to respiratory support

Conclusion: BiPAP was an effective respiratory support strategy for healthy foals with pharmacologically induced respiratory insufficiency. BiPAP was associated with increased PaO2, more efficient gas exchange and changes in respiratory mechanics including increased tidal volume, decreased respiratory rate, and increased peak inspiratory flow. The technique preserved minute ventilation in the face of reduced ventilation observed at other times associated with sedation and recumbency, but was associated with modest increase in PaCO2. Clinical observations, pulse oximetry and monitoring of expired carbon dioxide was of limited benefit in identification of foals responding inappropriately to BiPAP and improved methods to assess and monitor respiratory function are required in foals

Floyd et al, 2021

Nasal high flow oxygen therapy in hospitalized neonatal foals

• Objective: To describe the use of high flow oxygen therapy (HFOT) in hospitalized neonatal foals

• Results:

  • 14 foals

  • Target starting respiratory gas flow rate of 40 L/min

    • Could not be achieved with 20 FR chest tubes initially used, limited to 25-35 L/min

    • Changed to 24 FR chest tubes to achieve a maximum flow rate of 60 L/min

  • Ensured chest tubes did not obstruct more than 50% of the nasal diameter to prevent obstruction to expiratory flow

  • Oxygen flow rate and oxygen concentration in the respiratory gas mix were based on arterial blood gas analysis

    • Specific FiO2 was not targeted

  • Median duration of use was 43 hours (range 2-93 hours)

  • Median flow rate of 0.7 L/kg/min (range 0.42-1.67)

  • 10/14 foals survived to discharge

    • 2 foals died

    • 2 foals were euthanized

  • Treatment was discontinued in two foals due to excessive activity

  • Mechanical ventilation was used in two foals following the use of HFOT

  • No significant complications associated with the technique recorded

  • Optiflow system used

  • HFOT did not significantly improve oxygenation but not all foals were hypoxemic at the initiation of HFOT and the majority had received traditional oxygen therapy prior to switching to HFOT

• Conclusion: This study provides preliminary information about the clinical use of HFOT in neonatal foals. This technique was well tolerated and no significant adverse effects were noted. Further study is required to evaluate efficacy and exact indications. HFOT shows promise as an intermediate means of providing respiratory support which may allow improved care for a wider group of neonatal foals

Harvey et al, 2021

Opsonization but not pretreatment of equine macrophages with hyperimmune plasma nonspecifically enhances phagocytosis and intracellular killing of Rhodococcus equi

Objective: To compare the effects of hyperimmune plasma (HIP) and normal plasma (NP) on phagocytosis and intracellular survival of virulent R. equi either as a pretreatment of alveolar macrophages (in the absence of opsonization) or when used as opsonins

Results:

• Concentrations of R. equi at T0 were significantly lower for AMs treated with HIP than those treated with media only but concentrations of R. equi for HIP did not differ significantly from NP

• Opsonization with either HIP or NP increased phagoyctosis by AMs and decreased intracellular survival or organisms in AMs

• Pretreating AMs with either HIP or NP without opsonizing R. equi had no effects on phagocytosis or intracellular replications

Conclusion: Opsonizing R. equi with either NP or HIP decreases intracellular survival of organisms in AMs, but the effect does not appear to be enhanced by using HIP. Mechanisms other than effects on AMs must explain any clinical benefits of using HIP over NP to decrease the incidence of R. equi pneumonia in foals

Berman et al, 2021

Comparison of thoracic ultrasonography and thoracic radiography to detect active infectious bronchopneumonia in hospitalized dairy calves

Objective: To estimate performances of thoracic ultrasonography (TUS) and thoracic radiography (TR) to detect active infectious bronchopneumonia (BP) in hospitalized dairy calves and to determine the best strategy for using these tests based on a panel diagnosis method (PDM). Performances of TUS and TR were hypothesized to be equivalent

Results:

• Interexpert agreement was moderate at 0.58

  • Diagnosis of active BP was consensual between 2 experts for 80% of the study sample

• Lung consolidation on TUS and presence of an alveolar pattern on TR were the most prevalent thoracic lesions and were both detected in calves with and without active BP

• TUS and TR failed to identify thoracic lesions in 3 and 2 calves with active BP, respectively

• Out of 19 calves with active BP, TUS and TR were positive for 16 and 17 calves, respectively

• The Se and Sp of TUS were 0.84 and 0.74, respectively

• The Se and Sp or TR were 0.89 and 0.58, respectively

• No significant difference was found in the Se and Sp of TUS and TR when analyzed alone, in series or in parallel

Conclusion: Thoracic ultrasonography or TR alone equally detected active BP in hospitalized dairy calves. Series or parallel analysis provided no additional benefits. Its ease of use and widespread accessibility support using TUS as a first-line test to detect active BP in hospitalized dairy calves

Sacks et al, 2021

Electrical impedance tomography to measure lung ventilation distribution in healthy horses and horses with left-sided cardiac volume overload

Objective: To describe and compare electrical impedance tomography (EIT) variables in horses with naturally occurring compensated and decompensated left-sided cardiac volume overload (LCVO) and compare them to a healthy cohort

Results:

• Compared to the healthy horses, the LCVO cohort had significantly less ventilated left (VAL) lung area, more ventilated right (VAR) lung area, smaller avg-max VdeltaZL_Line and VdeltaZL_Line

• Ventilation was observed to be estimated lower in the ventral and central-ventral lung regions and higher in the most dorsal lung regions in the horses with clinical signs of alveolar PE than in the horses with compensated LCVO

• Observation of EIT alterations were reflected by clinical signs in horses with decompensated LCVO and after administration of furosemide

• Observation that the left lung was more affected by LCVO was unexpected

  • in horses reversal flow might favor venous congestion and edema location in the left lung

  • Also may be due to the position of the heart, sitting cranio-ventrally and slightly left-sided within the thorax

    • Enlarged left atrium of horses with LCVO might compress the left mainstem bronchus, restricting the airway lumen and redirecting the gas toward the right lung

      • Less likely due to lack of inhomogeneity in inflation of the right and left lung units

• When assessing only the horses with decompensated LCVO, changes in accordance with the proposed slinky effect were observed

  • Less ventilation was detected in the ventral and central-ventral ROIs and more in the most dorsal ROI when compared to horses with compensated LCVO

Conclusion: EIT measurements of ventilation distribution showed less ventilation in the left lung of horses with LCVO and might be useful as an objective assessment of the ventilation effects of cardiogenic pulmonary disease in horses

Cohen et al, 2022

Association of pneumonia with concentrations of virulent Rhodococcus equi in fecal swabs of foals before and after intrabronchial infection with virulent R. equi

Hypothesis: Fecal concentration of virulent R. equi before IB infection with R. equi is positively associated with protection from pneumonia in foals

Results:

• Fecal concentrations of virulent R. equi (vapA) before IB infection were significantly lower in control foals that developed pneumonia than in healthy control foals or those gavaged with live virulent R. equi (LVRE)

• Two weeks after infection, fecal concentrations increased for pneumonic foals

• The foals that were gavaged with R. equi had a marked decrease in their fecal concentrations of virulent R. equi after IB infection

  • Don’t know if this was from enhanced clearance of R. equi from both the respiratory and intestinal tracts

Conclusion: Greater natural ingestion of LVRE might contribute to protection against pneumonia among foals

Cohen et al, 2022

Fecal concentration of Rhodococcus equi determined by quantitative polymerase chain reaction of rectal swab samples to differentiate foals with pneumonia from healthy foals

Objective: To evaluate the accuracy of qPCR of rectal swab samples to differentiate foals with pneumonia from healthy foals of similar age from the same environment

Results:

• The area under the ROC curve for qPCR of fecal swabs was 83.7%

• At a threshold of 14,883 copies of vapA per 100 ng fecal DNA, specificity of the assay was 83.0% and sensitivity was 79.5%

Conclusion: Although fecal concentrations of virulent R. equi are significantly higher in pneumonic foals than healthy foals of similar age in the same environment, qPCR of rectal swabs as reported here lacks adequate diagnostic accuracy for clinical use

Migliorisi et al, 2022

Hyponatremia in horses with septic pneumopathy

Objective: Describe admission plasma sodium concentration ([Na]) in horses with septic pneumopathy and evaluate any association of plasma [Na] with markers of systemic inflammtion

Results:

• 20/35 (57%) horses had hyponatremia

  • 14 had mild hyponatreima, 4 had moderate hyponatremia, and 2 had severe hyponatremia

  • When accounting for horses without pleural effusion, hyponatremia was present in 44% of cases

    • Loss of water into a third-space results in ADH release, water retention, and dilutional hyponatremia

• A higher proportion of horses with SIRS had hyponatremia

  • Hyponatremia in SIRS associated with altered expression of ion channels in nephrons under the influence of pro-inflammatory cytokines as well as nonosmotic ADH release, secondary to the action of pro-inflammatory mediators

• Hyponatremic patients had higher mean plasma fibrionogen concentration and higher rectal temperature than normonatremic horses

  • Fever and endogenous pyrogens are thought to induce nonosmotic release of ADH as a protective mechanism to retain more water and counteract insensible losses caused by the increased body temperature

  • Fibrinogen synthesized during inflammation after stimulation by IL-6 which has been linked to development of hyponatremia because of influence on ADH release

• Negative correlations were found between plasma [Na] and fibrinogen concentrations and between plasma [Na] and rectal temperature

• Presence of absence of pleural effusion did not influence severity of hyponatremia

• No difference was found in white blood cell or neutrophil counts between hyponatremic and normonatremic horses

• No association between prior usage of NSAIDs and frequency of hyponatremia at admission

• No association between albumin and sodium concentration

• Mean duration of hospitalization was longer in hyponatremic horses

• Most common aerobic isolates were Actinobacillus spp (31%), Streptococcus equi ssp zooepidemicus (31%), alpha-Streptococcus spp (25%), and R. equi (14%)

  • Anaerobes were isolated from (17%) and comprised Bacteroides spp, Fusobacterium necrophorum, Clostridium sordelli, and Prevotella spp

  • One horse was diagnosed with EMPF at necropsy

• Of the 35 horses in the study, 29 were discharged alive, 4 were euthanized, and 2 died in hospital

  • Both horses that died and 3 that were euthanized were hyponatremic at admission

• When evaluating [Na], direct ion selective electrode (dISE) methodology should be used to avoid interference from increased plasma protein or triglyceride concentrations

Conclusion: Hyponatremia at admission is associated with the presence of inflammation, SIRS, and with longer duration of hospitalization

Bevevino et al, 2023

Feasibility of a point-of-care ultrasound protocol for cardiorespiratory evaluation of horses in different clinical settings

Objective: a. Describe the windows of a POCUS protocol for cardiorespiratory assessment of horses (CRASH) b. Estimate the number of acoustic windows that can be acquired by a sonographer in training c. Estimate the time required to complete the protocol for specific groups of horses d. Describe the sonographic abnormalities detected in horses presented with cardiovascular, respiratory, or systemic disease

Results:

• The CRASH protocol could be performed in healthy and diseased horses in hospital, barn, and competition settings between 5.5 min (athletic horses) and 6.9 min (horses with clinical disease)

• Thoracic windows were obtained most consistently, followed by right parasternal long-axis echocardiographic windows

• For the cardiac windows, the 4-chamber long axis window was most consistently of good quality (92.5%) and the short axis at the level of the aorta had the lowest percentage of acceptable quality images in the normal (74.1%) and hospitalized (60%) groups

• For the athletic horses, the short axis at the level of the chordal attachments had the lowest percentage of acceptable quality images (78.7%) and the 2 chamber long axis window was most consistently of acceptable quality

• Frequently detected abnormalities were pleural fluid, lung consolidation, B-lines, and moderate-to-severe left-sided heart disease

Conclusion: The CRASH protocol was feasible using a pocket-sized ultrasound device in various groups of horses, could be completed rapidly in a variety of settings, and frequently identified sonographic abnormalities when evaluated by an expert sonographer. The diagnostic accuracy, observer agreement, and utility of the CRASH protocol merit further evaluation

Hepworth-Warren et al, 2023

Utility of serum amyloid A in monitoring clinical response to antimicrobial treatment in horses with bacterial pneumonia

Objective: To monitor SAA concentration in response to treatment and identify associations among SAA concentration, WBC and neutrophil counts, and fibrinogen in bacterial pneumonia in adult horses

Results:

• Geometric mean SAA concentration on day 0 was 537 ug/mL

• Geometric mean SAA concentration decreased significantly over time, peaking at day 2 and decreasing until discharge

  • SAA was normal (0 ug/mL) at the time or discharge in 40% of horses and decreased from admission in 94% of horses

• Plasma concentration of fibrinogen, neutrophil count, and WBC count did not change significantly over time

  • Hyperfibrinogenemia was present in 35% of horses on day 0

Conclusion: SAA concentration decreased significantly over the course of treatment and correlated with clinical improvement of pneumonia, whereas fibrinogen, neutrophil, and WBC counts did not

Boccardo et al, 2024

Blood gases, acid-base, and metabolic alterations in calves with bronchopneumonia diagnosed via clinical signs and thoracic ultrasonography: A cross-sectional study

Objective: To describe metabolic, arterial blood gas, and acid-base disorders in calves with bronchopneumonia (BP) diagnosed by thoracic ultrasound (TUS), Wisconsin score (WISC), and combinations of WISC and TUS

Results:

• WISC5: 71.9% healthy calves and 28.1% BP calves

• TUS1cm: 30.7% healthy calves and 69.3% BP calves

• TUS3cm: 51.1% healthy calves and 48.9% BP calves

• WISC5/TUS1cm: 26% healthy calves, 4.8% upper respiratory tract infection calves, 45.8% subclinical BP calves, 23.4% clinical BP calves

• WISC5/TUS3cm: 39.4% healthy calves, 11.7% upper respiratory tract infection calves, 32.5% subclinical BP calves, 16.5% clinical BP calves

• Variables that exhibited statistically significant differences between healthy and sick calves as classified with WISC5 included, Na+, blood glucose, and blood urea

• With TUS1cm, the statistically different variables included A-aO2, Na+, K+, blood glucose, blood creatinine, USI, and PON-1

• With WISC5+TUS1cm, the variables that exhibited statistically significant differences were Na+, K+, AG, blood glucose, blood urea, USI, SIG, and PON-1

• With WISC5+TUS3cm, only Na+, blood glucose, blood urea, and PON-1 showed statistically significant differences

• Oxygenation and acid-base variables were unaffected

• Glucose concentration in TUS-affected calves was significantly lower than in healthy calves

• Paraoxonase-1 was significantly lower in TUS-affected calves

• None of the variables highlighted clear distinctions in WISC-detected clinical and subclinical BP calves based on the combination of WISC and TUS

• Suggest that metabolic changes during an episode of BP diagnosed with WISC score or TUS1 or 3cm were less critical than other disease conditions

Conclusion: Clinical signs indicate minor systemic disorders compared to TUS. The abnormalities detected by ultrasonographic examination were moderate and did not deviate from normal reference ranges

Hallowell et al, 2024

An updated description of bacterial pneumonia in adult horses and factors associated with death

Objective: To describe the clinical presentation and bacterial isolates of adult horses with bacterial pneumonia and identify factors associated with death

Results:

• Historical risk factors were present for 60% of cases

  • History of travel (20%), general anesthesia (9.5%), esophageal obstruction (20%), other respiratory illness (12%)

• Median duration of clinical signs before presentation was 10.5 days

• Abnormal vital signs on intake were present for <50%

  • Fever present in 26%, tachycardia in 39%, and tachypnea in 44%

• 98% had one or more abnormality on ultrasound examination

  • Comet tails (68%), consolidation or abscessation (76%), pleural effusion (38%)

• The most common clinicopathologic abnormalities were hyperglycemia (66%), band neutrophilia (64%), hyperfibrinogenemia (52%), lymphopenia (44%), and hypoalbuminemia (44%)

• Most horses (58%) underwent at least 1 change of antimicrobial treatment and 67% received the highest priority critically important antimicrobials

• For cases in which TTW and pleural effusion samples were both submitted, bacterial growth was identical between samples in 27%, in 45% there was growth from the TTW sample but none from the pleural fluid, and in 27% some but not all of the organisms identified on TTW were also identified on pleural effusion

  • One case had growth of an organism on pleural effusion culture that was not identified on TTW culture

• Streptococcus zooepidemicus was the most isolated bacteria (44%), followed by E coli (19%), Kelbsiella spp (18%), other Streptococcus species (17%), and Bacillus spp (13%)

• Fusobacterium spp were the most common anaerobic isolates (11%)

• Antimicrobial susceptibility varied widely

• Complications were reported in 12% of cases

  • Laminitis in 3.7%, antimicrobial associated diarrhea in 1.9%, pneumothorax in 0.94%, and thrombophlebitis in 0.94%

• Survival to discharge was 73%

• Heart rate at presentation and higher creatinine increased the risk of death

• Higher lymphocyte count reduced risk

  • Could be that horses with higher lymphocyte counts have less circulating endotoxin and therefore less severe disease

Conclusion: Contrasting older literature, Fusobacterium spp. were the most common anaerobes. Streptococcus zoeepidemicus remained the most common isolate and was predictably susceptible to penicillin. Antimicrobial susceptibility was otherwise variable and broad applicability is limited as this was a single-center study. Increased risk of death associated with tachycardia and abnormally high serum creatinine concentration is consistent with previous studies

Raidal et al, 2024

Use of prototype bi-nasal prongs for noninvasive ventilation in foals

Objective: To compare bi-nasal prongs and masks for NIV in foals with pharmacologically induced respiratory insufficiency

Results:

• Bi-nasal prongs were well tolerated and required less manual positioning or monitoring compared to the mask

  • The mask had to be held in place manually by an assistant to minimize leaks during NIV and spirometry

• Partial pressure of carbon dioxide did not increase during NIV with bi-nasal prongs and was lower than observed with masks

  • Expiratory flow limitations may attenuate hypercapnia in foals during NIV and in this study expiratory flow limitations may have been ameliorated by the leaking of exhaled respiratory gases around the nasal prongs and reduced equipment dead space

• The expiratory Vt was approximately 75% of the inspiratory value, suggesting there was substantive leakage around the prongs

  • This is likely clinically acceptable

• Oxygenation and respiratory mechanics were improved in all foals and not different between device interfaces

Conclusion: Nasal prongs were well tolerated, had similar effects on respiratory function, and appeared to ameliorate hypercapnia observed previously during NIV in foals

What can high flow nasal oxygen deliver?

Heated and humidified medical gas at adjustable flow rates, up to 60 L/min, and FiO2, up to 100% via nasal cannulas

Proposed Benefits of High Flow Nasal Oxygen

Proposed that HFNOT improves pulmonary mechanics and reduces respiratory fatigue via reduction of anatomical dead space, provision of low-level PEEP, provision of constant FiO2 at rates corresponding to patient requirements and through improved patient tolerance

Reports in humans indicate that HFNOT decreases breathing frequency and work of breathing and reduces the need for escalation of respiratory support

Indications for High Flow Nasal Oxygen

• Current indications in dogs include acute respiratory failure associated with pulmonary parenchymal disease, upper airway obstruction and carbon monoxide intoxication

• Has also been advocated in certain conditions in cats and foals

Three Groups of Conditions that Can Result in Tissue Hypoxia

Those causing arterial hypoxemia

Those causing failure of the oxygen hemoglobin transport system without arterial hypoxemia

Those impairing the cells’ ability to utilize oxygen

Three Groups of Conditions that Can Result in Tissue Hypoxia - Those Causing Arterial Hypoxemia

Decreased FiO2

Alveolar hypoventilation

Gas diffusion impairment

V/Q mismatch

Cardiopulmonary shunt

Three Groups of Conditions that Can Result in Tissue Hypoxia - Those Causing Failure of the Oxygen Hemoglobin Transport System Without Arterial Hypoxemia

Anemia

Dyshemoglobinemia

Inadequate blood flow to tissues

Three Groups of Conditions that Can Result in Tissue Hypoxia - Those Impairing the Cells’ Ability to Utilize Oxygen

Cyanide toxicity

Low-Flow Oxygen

Deliver oxygen at a flow rate that is lower than the patient’s ventilatory requirements resulting in dilution of the concentration of inspired oxygen relative to the inspiratory flow

• Conventional oxygen therapy (COT)

High-Flow Oxygen

Can provide gas at a rate to match minute ventilation and therefore a stable and predictable FiO2

Flow By FiO2

25-45%

Flow By Flow Rate

6-8 L/min

Flow By Advantages

Utilizes readily available equipment

Flow By Limitations

Not appropriate for prolonged therapy

Wasteful

Flow By Indications

Triage and procedures

Initial stabilization

Oxygen Cage FiO2

21-60%

Oxygen Cage Advantages

Well tolerated

Allows eating and drinking

Oxygen Cage Limitations

Reduced access to patients

FiO2 rapidly decreases when doors opened

Larger patients

Oxygen Cage Indications

Patients that will not tolerate nasal oxygen or in which nasal oxygen is contraindicated

Face Mask FiO2

35-55%

Face Mask Flow Rate

1-6 L/min

Face Mask Advantages

Utilizes readily available equipment

Rebreathing at low rates

Face Mask Limitations

Not appropriate for prolonged therapy

FiO2 depends on fit of mask

Face Mask Indications

Triage and procedures

Initial stabilization

Risk of rebreathing

Nasal Prongs Flow Rate

50-150 ml/kg/min

Nasal Prongs Advantages

Easy to place

Well tolerated

Nasal Prongs Limitations

Poor patient tolerance at high flow rates

Not suitable for some facial conformations

Nasal Prongs Indications

Ongoing oxygen support in hospital

Nasal Catheter FiO2

30-60%

Nasal Catheter Flow Rate

50-150 ml/kg/min

Nasal Catheter Advantages

Well tolerated

Nasal Catheter Limitations

Poor patient tolerance at high flow rates

Harder to place

Nasal Catheter Indications

Ongoing oxygen support in hospital

CPAP FiO2

21-100%

CPAP Advantages

Reliable FiO2

Delivers PPEEP

Humidifies inhaled gases

CPAP Limitations

Often requires heavy sedation

Specific equipment

CPAP Indications

Hypoxemia despite oxygen support

Upper airway obstruction

HFNOT FiO2

21-100%

HFNOT Flow Rate

10-60 L/min

HFNOT Advantages

Reliable FiO2

Delivers PEEP

Humidified inhaled gases

HFNOT Limitations

Specific equipment

HFNOT Indications

Hypoxemia despite conventional oxygen therapy

Increased work of breathing

Mechanical Ventilation FiO2

21-100%

Mechanical Ventilation Advantages

Reliable FiO2

Delivers PEEP

Humidifies inhaled gases

Mechanical Ventilation Limitations

Specific equipment

High complication rate

High cost

Mechanical Ventilation Indications

Hypoventilation

Hypoxemia despite oxygen support

Increased work of breathing (fatigue)

Non-Invasive Ventilation

• Delivery of mechanical ventilation via techniques that do not require endotracheal intubation

• Improve gas exchange and reduce inspiratory effort through the generation of positive pressure within the airways, reducing upper airway obstruction and recruitment of alveoli

What are the two main modalities of non-invasive ventilation?

Continuous positive airway pressure (CPAP)

Non-invasive pressure support ventilation

Continuous Positive Airway Pressure (CPAP)

• May be performed using a tight-fitting mask or helmet with an expiratory valve connected to an oxygen source and gas blender or via a mechanical ventilator

• Significant increases in PaO2 have been demonstrated after CPAP administered by helmet in dogs and anesthetized cats

• Raidal et al compared the effect on respiration and ventilation in sedated foals treated with CPAP and mask oxygen

  • The effects of CPAP on arterial blood gas parameters were comparable to mask oxygen with modest increases in PaCO2 in almost all animals for both modalities

• Clinical use in veterinary patients is effective in providing a known level of PEEP and improving oxygenation

• Limited by the need for sedation or anesthesia to be tolerated in some patients and the high oxygen flow requirement to maintain PEEP

Non-Invasive Pressure Support Ventilation

• Requires a ventilator triggered by the patient's inspiratory effort to deliver a decelerated gas flow in order to generate and maintain two different pre-set pressures during inspiration and expiration

• Require nasal or oronasal (full face) masks which form an air seal

Invasive Mechanical Ventilation

• Indicated in the management of severe hypoventilation, severe hypoxemia despite oxygen supplementation, when there is excessive work of breathing, and when long term endotracheal intubation is required

• Provide oxygen support, conditioning of inspired gases, reduces the work of breathing, and can improve oxygenation via increasing airway and alveolar pressure and recruiting collapsed alveoli

• Heavy sedation or a light plane of anesthesia generally required

• Reported complications

  • Corneal and oral mucosal ulceration

  • Hypothermia

  • Positive fluid balance

  • Ventilator induced lung injury

  • Ventilator-associated pneumonia

  • Cardiovascular compromise

• Patients ventilated for primary hypoventilation have a better prognosis than those being treated for primary pulmonary pathology, in particular ARDS

What three variables does high flow nasal oxygen therapy allow modification of?

Percentage of oxygen delivered

The flow rate of gas

Gas temperature

Components of HFNOT Devices

• A high pressure source of oxygen and air

• An air-oxygen blender or high flow Venturi system

• A humidifying and heating system for conditioning the gas to optimal temperature and humidity

• A sterile water reservoir

• A non-condensing circuitry

• An interface

Clinically Relevant Features of HFNOT

• Provision of fixed concentrations of inspired gases

• Delivery of heated and humidified gases

• Generation of flow-dependent positive airway pressure

• Flushing of anatomical dead space

• Features result in increased patient comfort and compliance, provision of higher FiO2 compared to conventional oxygen therapy, maintenance of mucosal integrity and function, alveolar recruitment, and decreased work of breathing

FiO2 and Dead Space Washout with HFNOT

• Flow rates provided during HFNOT are able to match the peak inspiratory flow of the patient and thus reliably provide the set FiO2

  • FiO2 approaching 100% are able to be achieved without the need for endotracheal intubation

• Higher oxygen flow rates delivered during HFNOT compared to conventional oxygen therapy are proposed to "washout" CO2 from the anatomical dead space within the nasopharynx resulting in rebreathing

  • Results in improved FiO2, more efficient provision of minute ventilation, and decreased work of breathing

Positive Airway Pressure with HFNOT

• PEEP aims to prevent alveolar collapse and recruit atelectic lung, improving alveolar ventilation

• Providing higher flow rates to match intrinsic PEEP via CPAP reduces the work of breathing in patients with obstructive airway disease

• A study of human cardiac surgery patients demonstrated a positive linear relationship between flow rate and mean airway pressure during HFNOT, with peep ranging from 3.0-4.8 cmH2O at flow rates of 30-50 L/min

• Variations in the generation of airway pressure during HFNOT are due to patient differences, particularly the diameter of the nasal prongs relative to the patient's nares and whether or not the mouth is closed

  • Multiple prospective studies of adult humans treated with HFNOT have demonstrated that significant airway pressure generation only occurs when the patient's mouth is closed

Airway Resistance with HFNOT

• Nasopharynx warms and humidifies inspired gases by contact with its large surface area

  • Results in significant resistance to inspiratory flow

  • By matching or exceeding rates of inspiratory flow, HFNOT likely attenuates his effect and further reduces the work of breathing

• Pharyngeal distending pressure of up to 4 cm H2O can be achieved with HFNOT flow rates of 2 L/kg/min

  • Positive upper airway pressure may reduce airway resistance by stenting the soft palate and pharynx

  • Proposed that HFNOT stimulates airway stiffening and stenting by activation of the alae nasae muscle

• Cool, dry air during respiratory support has been shown to decrease pulmonary compliance and conductance in infants

  • Demonstrated to be associated with a protective bronchoconstrictive response, secondary to stimulation of mucsarinic receptors in the nasal mucosa

  • In Saslow et al, pulmonary compliance was higher in patients receiving HFNOT compared to CPAP, despite the lower PEEP

• Conditioning of inhaled gases by the nasal mucosa consumes energy

  • This energy is conceivably increased during supplementation of cool, dry gas during conventional oxygen therapy as well as during periods of respiratory distress and increased minute ventilation

Mucociliary Clearance with HFNOT

• Slow, turbulent airflow in the nasopharynx allows inspired air to be warmed to ~34*C and humidified to 100%

  • Creates optimal conditions for the functioning of cilia and maintenance of mucus composition

• Increased respiratory rates and open-mouth breathing in respiratory failure can affect airway humidification and conditioning of inspirated gas

  • HFNOT has been shown to reduce respiratory rates and effort and may be able to provide clinical improvement through the reduction in open mouth breathing

• In a canine model, provision of heated and humidified gas improved mucociliary function

Patient Comfort with HFNOT

• HFNOT is better tolerated and more comfortable than conventional oxygen therapy and non-invasive ventilation

  • Attributed to conditioning of inspired gas, correction of hypoxemia, increased alveolar recruitment, and the ability to eat and speak more readily

• Conditioning of gas

  • Maintains conditioning of inspired air and hydration of the airway mucosa so nasal passages aren't desiccated

• Device-patient interface

  • Non-invasive ventilation interfaces are associated with the development of skin lesions and patient discomfort

    • The interface of nasal CPAP requires secure fixing without leaks so the reported incidence of pressure ulcers ranges from 15-100%

  • Masks and helmets may interfere with eating and drinking

  • When compared to conventional nasal oxygen therapy patients, HFNOT patients experience decreased eye irritation and find it easier to eat

Indications for HFNOT in Human Medicine

Acute hypoxemic respiratory failure

Acute heart failure

Interstitial lung disease

Asthma

Carbon monoxide intoxication

Procedural sedation

Post-extubation

HFNOT for Acute Hypoxemic Respiratory Failure in People

• HFNOT is becoming the first-line therapy for acute hypoxemic respiratory failure in patients that fail to show an adequate response to conventional oxygen therapy and for whom immediate intubation is not indicated

  • Cross-over study demonstrated that this modality significantly reduced discomfort in critically ill patients with respiratory failure compared to conventional therapy

• FLORALI clinical trial

  • Compared conventional oxygen therapy (10 L/min or more via mask), HFNOT (50 L/min), and non invasive ventilation (8 hours or more/day with bilevel setting)

  • Included non-hypercapnic patients with acute hypoxemic respiratory failure (PaO2/FiO2 <300 mmHg), 84% of which had pneumonia

  • There was not significant difference in intubation rates between the 3 groups

  • Mortality was lower in the HFNOT group in the ICU and at 90 days

  • HFNOT was associated with a decreased intubation rate in a more severely affected subgroup of patients (PaO2/FiO2 <200 mmHg)

  • More than 75% of patients had thoracic radiographic changes consistent with a diagnosis of early ARDS

• Observational study evaluated the effect of HFNOT in ARDS

  • 45/51 patients who received HFNOT as a first line treatment had ARDS (PaO2/FiO2 137 mmHg) with 26/45 successfully treated with HFNOT alone

  • Patients who failed HFNOT had higher Simplified Acute Physiology Score II (SAPS II) scores in multivariate analysis

• HOT-ER trial

  • Aimed to determine if HFNOT compared to conventional oxygen therapy reduced the need for non-invasive ventilation or intermittent positive pressure ventilation in patients with acute respiratory distress presenting to a hospital emergency department

  • Hypoxemic (SpO2 92% or less) and tachypneic (respiratory rate 22 bpm or greater) adult patients were randomized to receive HFNOT or conventional oxygen therapy with need for mechanical ventilation as the primary outcome

  • HFNOT did not reduce the need for ventilation in this population

  • Adverse events were infrequent but 1/12 patients did not tolerate HFNOT

HFNOT for Acute Heart Failure in People

• HFNOT has been proposed to have hemodynamic effects that may aid in the management of acute heart failure and pulmonary edema

  • In particular, reducing pulmonary congestion via reductions in cardiac preload and afterload

• Roca et al performed echos in patients with NYHA class II heart failure during HFNOT delivered at flow rates of 20 L/min and 40 L/min with 21% FiO2

  • Significant reductions in inspiratory collapse of the inferior vena cava occurred relative to flow rate during HFNOT and normalized following discontinuation of therapy

• HFNOT may decrease afterload through the provision of PEEP and amelioration of sympathetic nervous system stimulation associated with hypoxia

• Makdee et al

  • Assessed the efficacy of HFNOT in the management of acute heart failure by comparing respiratory rates following HFNOT with conventional oxygen therapy in patients presenting to an emergency room with pulmonary edema

  • Patients were included if they had SpO2 <95% and respiratory rate >25 breaths per minute

  • HFNOT was associated with lower respiratory rates at 60 minutes after initiation of therapy but there was not difference in mortality, non-invasive ventilation or intubation between groups

• Prospective study compared HFNOT with conventional oxygen therapy in patients presenting to the emergency room with acute pulmonary edema

  • Conventional oxygen therapy group received oxygen via a nasal cannula at flow rates of >2 L/min while HFNOT was initiated at 45 L/min and FiO2 100%

  • Patients in both groups were treated to maintain SpO2 >93%

  • HFNOT resulted in greater improvement in respiratory rate, SpO2, lactate levels and arterial blood gas parameters compared with conventional therapy

• Osman et al

  • Comparing HFNOT to helmet CPAP in adult patients presenting to the emergency room with acute cardiogenic pulmonary edema

  • CPAP more effective in the very short term in improving dyspnea, hemodynamics, and respiratory parameters

HFNOT for Interstitial Lung Disease in People

• Group of pulmonary conditions that involve changes to the distal lung parenchyma

  • Subdivided into those with an identifiable etiology and those without

• Acute respiratory failure can complicate interstitial lung disease and is associated with a poor prognosis and high mortality rate

• Mechanical ventilation does not improve oxygenation in affected patients and is associated with a high incidence of barotrauma and a poor prognosis

• Horio et al

  • Cases of acute respiratory failure associated with interstitial lung disease

  • Commenced on HFNOT (FiO2 70-100% ; flow rate 40 L/min) while additional medical management was initiated and took effect

  • HFNOT was well-tolerated and weaned in accordance with improving oxygenation parameters until discharge at 21-26 days

  • All of the subjects demonstrated immediate improvement with the commencement of HFNOT after failing to respond to conventional oxygen therapy

• Retrospective study of patients with exacerbation of interstitial pneumonia

  • Grouped into pre-HFNOT and post-HFNOT cohorts based on the introduction of HFNOT at the hospital

  • Incorporation of HFNOT into the management of interstitial lung disease patients in this study resulted in lower in-hospital mortality, reduced requirement for sedation and analgesia and a lower incidence of discontinuation of oral intake

  • No difference in the incidence of complications

HFNOT for Asthma in People

• The cold and dry air provided via conventional oxygen therapy modalities may potentially exacerbate bronchoconstriction, promote airway inflammation, and impair mucociliary function

• Retrospective studies of pediatric status asthmaticus showed significant improvements in vital parameters, serum pH, and SpO2/FiO2 associated with HFNOT compared to conventional oxygen therapy

  • A pilot study supported these findings, demonstrating higher rates of pulmonary score improvement 2h after initiation of HFNOT compared to conventional oxygen therapy

• HFNOT has been associated with decreased intubation rates for severe pediatric asthma

• Improved patient outcomes have not been demonstrated

HFNOT for Carbon Monoxide Intoxication in People

• Carbon monoxide competitively and reversibly binds to hemoglobin with 250 times greater affinity than oxygen resulting in a marked anemic hypoxia despite a normal PaO2

• Treatment involves provision of high FiO2 to compete with carbon monoxide for hemoglobin binding sites and reduce the half-life of carboxyhemoglobin

• Prospective study of adults with carbon monoxide intoxication

  • Primary objective was to determine the mean half-life of COHb after HFNOT (FiO2 100%, T 37*C, 60 L/min) which was found to be 36.8 mins

• Another retrospective study identified a similar COHb half-life following HFNOT (41.1 min) but this was not found to be significantly different to that in patients receiving conventional oxygen therapy

  • There was a significant difference in COHb levels between treatment groups at 60 and 90 minutes

HFNOT for Procedural Sedation in People

• Oxygen desaturation, airway obstruction, and apnea are the most prevalent adverse events during procedural sedation

• Risk factors for hypoxemia during procedural sedation include high ASA physical status, reduced cardiopulmonary reserve, obesity, and prolonged procedural duration

• Meta-analysis evaluating the effect of HFNOT and conventional oxygen therapy during procedural sedation in adults and children

  • HFNOT reduced the risk of hypoxemia and increased minimum oxygen saturation

  • Reduction in hypoxemia persisted regardless of the procedure, FiO2, risk-profile of the patient, and mode of propofol administration

HFNOT Post-Extubation in People

• Post-extubation respiratory insufficiency is a known complication following weaning from invasive mechanical ventilation and may progress to acute respiratory failure which results in reintubation

• Conditions associated with post-extubation respiratory insufficiency include upper airway obstruction, decreased respiratory muscle function, atelectasis and increased work of breathing, and hemodynamic stability

• Zhu et al

  • Attempted to quantify the benefits of HFNOT for patients after planned extubation

  • HFNOT was associated with reduced post-extubation respiratory failure, decreased respiratory rates, and increased PaO2

  • No significant differences in reintubation rate, length of ICU and hospital stay, PaCO2, mortality, or severe adverse events were identified

• Meta-analysis

  • Compared HFNOT and non-invasive ventilation in patients after extubation

  • Initial use of HFNOT in the post-extubation period was not inferior to non-invasive ventilation in regards to the probability of reintubation, treatment failure, or mortality and was associated with a reduced probability of complications including cutaneous lesions and respiratory failure

• Multicenter randomized control trial comparing HFNOT to HFNOT in combination with non-invasive ventilation in patients at high risk of extubation failure

  • Included patients who successfully completed a spontaneous breathing trial after more than 24 hours intubation

  • Those in the combination group commenced non-invasive ventilation immediately after extubation with a minimum duration of 12h per day for the first 48h

  • HFNOT was administered between non-invasive ventilation sessions in the combined group and continuously in the HFNOT sole treatment group

  • Reintubation rate at day 7 was significantly higher in the HFNOT group compared to when the therapies were combined

  • Combination of HFNOT and non-invasive ventilation appeared to be more beneficial in patients with pre-exutubation hypercapnia, defined as PaCO2 > 45 mmHg

Complications and Considerations for HFNOT in People

• Complications are rare

• Complications include

  • Facial trauma

  • Abdominal distension

  • Aspiration

  • Epistaxis

  • Barotrauma

• Risk is lower than other non-invasive ventilation modalities

• Major concern during HFNOT is the risk of delayed intubation and mechanical ventilation in hypoxemic patients

• Kang et al

  • Evaluated if delaying intubation until failure of HFNOT adversely affected patient outcome

  • Categorized patients based on time at which intubation occurred - before (early) and after (late) 48 hours of HFNOT

  • Patients intubated after 48 hours had higher overall ICU mortality

• In a prospective observational study both patients and caregivers judged HFNOT to be more comfortable compared to conventional oxygen therapy

• Patients report less mouth dryness and improved breathlessness with HFNOT compared with facemask oxygen

• FLORALI trial reported higher patient discomfort after 1 h in patients failing HFNOT

• Lower temperatures with full humidification was associated with lower discomfort regardless of flow rate

• Cutaneous and mucosal ulceration of the nose, nasal septum, frenulum, and pinnae associated with friction between the skin and interface in prolonged HFNOT has been reported

  • Less significant than with NIV and CPAP

• Retrospective study evaluating complications associated with HFNOT in a pediatric ICU over 1 year

  • Pneumothoraxes

• Hodge and Prodhak

  • 3 life threatening occurrences of air leak syndrome associated with HFNOT in pediatrics

    • Pneumothorax

    • Pneumomediatstium

• Subcutaneous emphysema reported

• Tension pneumocephalus rare but has been associated with HFNOT

• Contraindications for HFNOT

  • Nasal, facial, and airway abnormalities that may affect nasal cannula fit and device function

    • Include epistaxis, basilar skull fractures, surgery to the nose and nasal obstruction

Predictors of HFNOT Treatment Failure in People

• Current literature indicates that around 30% of patients will fail treatment and require mechanical ventilation

• In patients with acute hypoxemic respiratory failure, an increased heart rate after 1 h of HFNOT was associated with intubation

• Hemodynamic instability, elevated SOFA score, thoracoabdominal asynchrony, significantly increased respiratory rate, and poor oxygenation have been associated with HFNOT failure

• ROX index was developed to predict success and failure of HFNOT

  • Index is the ratio of the pulse oximetry oxygen saturation over the fraction of inspired oxygen over the respiratory rate [(SpO2/FiO2/RR]

  • In a prospective study of 157 pneumonia patients treated with HFNOT, with FiO2 set to maintain SpO2 >92% and flow rate set at the clinician's discretion

    • Treatment failure was assessed based on respiration, oxygenation, and ventilatory parameters

    • Criteria for intubation and mechanical ventilation were decreased Glasgow Coma Scale score, hemodynamic instability, and persistent or worsening respiratory condition

    • A ROX index of 4.88 or greater measured after 12 hours of HFNOT was significantly associated with a lower risk of mechanical ventilation

  • In a multicenter prospective study ROX of 4.88 or greater measured at 2, 6, or 12h after HFNOT initiation was consistently associated with a lower risk of intubation

    • A ROX <2.85, <3.47, and <3.85 at 2, 6, and 12h of HFNOT initiation, respectively, were predictors of HFNOT failure

    • Patients who failed also demonstrated a lower increase in the values of the ROX index over the 12 h

HFNOT in Healthy Dogs

• Precision Flow system vs conventional nasal oxygen cannula in healthy dogs

  • Significantly higher increase in baseline PaO2 between the delivery methods but no difference in PaO2 achieved with HFNOT at different flow rates

  • No differences in transpulmonary pressure between baseline and any of the treatment methods or between any of the treatments, suggesting negligible generation of positive airway pressure

• Jagodich et al.

  • Optiflow/Airvo 2 system in a prospective randomized crossover study

  • Oxygen provided via conventional nasal cannula or HFNOT at a range of flow rates

  • Airway pressures generated by each system were comparable at equivalent flow rates

  • Only HFNOT at flow rates of 1-2 L/kg/min was able to maintain positive airway pressure and achieve CPAP in the majority of dogs

  • Both inspiratory and expiratory airway pressures significantly increased with increases in flow rate

• Harduin et al

  • Evaluated the impact of gas flow rate and temperature on tolerance of dogs receiving HFNOT during recovery from anesthesia

  • No effect of flow rate or temperature on vital parameters or tolerance and overall good tolerance

HFNOT in Hypoxemic Respiratory Failure in Dogs

• Keir et al

  • HFNOT in dogs with primary pulmonary hypoxemia

  • All dogs transitioned to HFNOT following failure of conventional oxygen therapy to maintain adequate oxygenation

  • A significant increase in mean PaO2 was achieved in association with a significant increase in oxygen flow rate

  • Four of the dogs had resolution of their hypoxemia following HFNOT

• Prospective pilot study of effectiveness and tolerance of HFNOT therapy in 11 dyspneic dogs

  • After 60 minutes of treatment with 100% FiO2 at a flow rate calculated to match minute ventilation there was a significant increase in mean PaO2 and resolution of hypoxemia in 5/8 dogs with PaO2 <80 mmHg prior to initiation of HFNOT

  • 6/11 dogs had a decrease in respiratory rate but only 2/11 were classified as not in respiratory distress base on the authors criteria

  • HFNOT was well tolerated

  • 6/11 dogs died as a result of cardiac arrest or euthanasia due to deteriorating clinical condition

    • 5/6 met criteria for intubation within 24h of admission

• Prospective study evaluating HFNOT in acute hypoxemic respiratory failure in 22 dogs

  • Significant improvements in dyspnea score and oxygen saturation were identified at all times points compared to baseline with a moderate correlation between HFNOT flow rate and PaO2

  • There was no significant difference in PaCO2 between conventional oxygen therapy and HFNOT

  • There was a moderate correlation between PaCO2 and HFNOT flow rate

  • 6/22 were intubated and ventilated after starting HFNOT and an additional 6/22 were euthanized due to required escalation of therapy

  • 10/22 survived to discharge

    • 8/22 avoided intubation and mechanical ventilation

HFNOT Post-Extubation in Dogs

• Jagodich et al

  • Brachycephalic dogs with signs of upper airway obstruction in the immediate post-anesthetic period

  • Dyspnea scores and respiratory rates improved over time with stable normoxemia despite decreasing FiO2 and flow rates

  • HFNOT was able to be discontinued in <12h in 3 dogs and all survived to discharge without requirement of reintubation

HFNOT in Carbon Monoxide Poisoning in Dogs

• Gazsi et al

  • Comparing mechanical ventilation and HFNOT in dogs with carbon monoxide poisoning following progression of clinical signs despite conventional oxygen therapy

    • The dog receiving HFNOT had marked improvement in FCOhb after 4 hours

    • The dog treated with mechanical ventilation had similar improvements in FCOHb and was weaned off the ventilator in the same time period

    • The calculated half-life of FCOHb was 167 min and 150 min in the dogs treated with HFNOT and IPPV, respectively

Complications of HFNOT in Dogs

• Increase in PaCO2 has been identified in dogs receiving HFNOT

• Aerophagia and gastric distension has been noted in dogs receiving HFNOT

• No cases of air leak syndrome have been identified but there was one dog with pre-existing pneumothorax that did not resolve until discontinuation of HFNOT

HFNOT in Horses

• Floyd et al

  • HFNOT in foals <36 hours old

  • No significant improvement in oxygenation with treatment was identified but not all foals were hypoxemic prior to initiation of HFNOT

  • Improvements in respiration pattern and decreased respiratory rates were observed

  • 10/14 survived to discharge

  • HFNOT was well tolerated in all patients

  • No significant complications noted but two foals required escalation to mechanical ventilation and HFNOT had to be discontinued in two foals due to excessive activity

  • No significant increase in mean PaCO2 was observed

    • A mild but insignificant decrease in PaCO2 was observed in many foals

What % of the opening of the nares should the nasal prongs occlude in HFNOT

~50% to facilitate generation of desired airway pressures while minimizing resistance to exhalation

HFNOT Device Set Up

• Patients should initially receive 100% FiO2 while stabilization occurs

  • This may then be titrated down based on patient oxygenation, aiming to maintain a SpO2 > 95% or PaO2 > 80 mmHg

  • Timely reduction of FiO2 to <60% is recommended due to concerns for oxygen toxicity associated with prolonged administration of high concentrations of oxygen

• Flow rates should be commenced at 1-2 L/kg/min or calculated to match the patients minute ventilation (respiratory rate x V_T)

  • A CPAP effect in dogs occurs at flow rates of 1-2 L/kg/min

  • A study assessing HFNOT protocol in human pediatric intensive care patients demonstrated more rapid weaning, decreased failure rates, and possibly decreased rate of escalation to positive pressure ventilation in patients initially treated with higher flow rates

    • These patients also received lower initial FiO2 and had a shorter length of stay in hospital despite longer duration of HFNOT

    • Higher flow rates may result in patient discomfort and aerophagia

• Temperature is initially set at 37*C but may be adjusted based on patient body temperature and comfort

HFNOT Weaning

• No weaning protocols available

• Consider similar criteria as used for weaning from other methods of oxygen support

  • Improvement in underlying condition

  • Decreased device settings

  • High likelihood of coping with de-escalated therapy (e.g. conventional oxygen therapy)

• Patients with stable respiration and oxygenation at <500 ml/kg/min FiO2 <40% will likely meet these criteria

• FiO2 should be reduced prior to reducing the flow rate

  • Reduction of 5-10% FiO2, followed by reassessment in 1-2 h is recommended

• In human adults, maintenance of stable respiratory parameters at 40% FiO2 should be achieved prior to flow weaning

• In neonates, it has been recommended that FiO2 be reduced to 30% prior to reductions in flow rate

• Respiratory rate, FiO2 and work of breathing should be stable for 12-24 h before commencing flow reduction

Escalation from HFNOT

• Escalation of treatment is recommended when there is no clinical improvement in 1-2h despite high flow rates and FiO2

• Failure to maintain adequate oxygenation despite HFNOT or persistent increased work of breathing are indication for positive pressure ventilation

• Mechanical ventilation is also indicated in cases of severe or progressive hypoventilation

Long et al, 2024

Bilateral diaphragmatic paralysis in a weanling donkey jack

Case description: A 5 month old miniature donkey jack presented for fever, cough, and increased respiratory rate and effort initially unresponsive to treatment with antimicrobials and anti-inflammatories

Clinical findings:

• No evidence of upper respiratory obstruction or bacterial pneumonia

• Serial arterial blood gas evaluations revealed hypercapnia and hypoxemia

• Diagnostic imaging was consistent with bilateral diaphragmatic paralysis

• Nasal swab for equine influenza type A (subtype H3N8) was positive

• Mildly decreased whole blood selenium concentration

Treatment and outcome:

• Recovered after treatment with anti-inflammatories and supportive care

Clinical relevance: This case documents the first report of diaphragmatic paralysis in a donkey, with concurrent equine influenza infection offering a possible causal factor. Bilateral diaphragmatic paralysis should be considered as a differential diagnosis for respiratory distress in donkeys, particularly when diagnostic testing or treatment trials do not support more common causes of respiratory disease in adult animals, such as lower airway disease, asthma, and pulmonary fibrosis

What % of patients admitted to the ICU and mechanically ventilated patients had ARDS?

10% of all patients admitted to the ICU

23% of mechanically ventilated patients

What is the % mortality for patients with severe ARDS?

46%

Berlin Definition - Timing

Within 1 week of a known clinical insult or new or worsening respiratory symptoms

Berlin Definition - Origin of Edema/Diagnostics

Respiratory failure not fully explained by cardiac failure or fluid overload. Need objective assessment (e.g. echocardiography) to exclude hydrostatic edema if no risk factor present

Bilateral opacities - not fully explained by effusions, lobar/lung collapse, or nodules (chest radiograph or computed tomography)

Berlin Definition - Mild ARDS

PaO2/FiO2 >200 mmHg and less than or equal to 300 mmHg with PEEP or CPAP 5cm H2O or more

Berlin Definition - Moderate ARDS

PaO2/FiO2 > 100 mmHg and less than or equal to 200 mmHg with PEEP 5 cm H2O or more

Berlin Definition - Severe ARDS

PaO2/FiO2 100 mmHg or less with PEEP 5cm H2O or more

Vet ALI/ARDS Definition - Timing

Acute onset (<72 hours) of tachypnea and labored breathing at rest

Known risk factors