Physiol. Res. 70 (Suppl. 4): S567-S583, 2021 https://doi.org/10.33549/physiolres.

934767

REVIEW
This paper is dedicated to the 70th anniversary of the founding
of Physiologia Bohemoslovaca (currently Physiological Research)

Aspiration Syndromes and Associated Lung Injury: Incidence,

Pathophysiology and Management

Petra KOSUTOVA1, Pavol MIKOLKA1

1
Biomedical Center Martin and Department of Physiology, Jessenius Faculty of Medicine in
Martin, Comenius University in Bratislava, Martin, Slovakia

Received September 20, 2021

Accepted November 5, 2021

Summary Key words

Aspiration is a common condition affecting healthy or sick Aspiration syndromes • Aspiration pneumonitis • Aspiration
patients which could create an acute or chronic inflammatory pneumonia • Acute lung injury • Pathophysiology
reaction in the lungs. Aspiration syndromes could be categorized
according to a content entering the respiratory system into Corresponding author
bacterial aspiration pneumonia with the gastric or oropharyngeal Pavol Mikolka, Biomedical Center Martin and Department of
bacteria entering, aspiration chemical pneumonitis with bacteria- Physiology, Jessenius Faculty of Medicine in Martin, Comenius
freegastric acid aspiration, or aspiration of a foreign body which University in Bratislava, Mala Hora 4C, SK-03601 Martin, Slovakia.
causes an acute pulmonary emergency. There are differences in E-mail: [email protected]
the clinical presentation of volume-dependent aspirations
(microaspiration and macroaspiration): the higher is the volume Introduction
of aspiration, the greater is the injury to the patient and more
serious are the health consequences (with 70 % mortality rate Aspiration represents a great danger for patients.
for hospitalized patients). Aspiration syndromes can affect both In aspiration, a material, either liquid or even a foreign
the airways and pulmonary parenchyma, leading to acute lung object passes from the mouth or the upper part of the
injury, increased hospitalization rate and worse outcomes in gastrointestinal tract into the lungs. Aspiration syndromes
critically ill patients. Impaired alveolar-capillary permeability, occur more frequently than reported, in many cases, the
oedema formation, neutrophilic inflammatory response and disease is not recognized (unwitnessed). Aspiration
pulmonary surfactant inactivation lead to reduced lung symptoms are classified based on three main
compliance and loss of aerated lung tissue and give rise to characteristics: infectiousness of the inoculum, its
hypoxemia and respiratory failure. This review discusses the volume, and acuity of the onset of the clinical syndrome
effect of aspiration events on the pulmonary tissue. The main (Son et al. 2017).
focus is to distinguish the differences between bacterial and Aspiration pneumonitis and aspiration
chemical pneumonia, their clinical presentation and symptoms, pneumonia are two important manifestations of
risk factors of developing the changes, possibilities of diagnostics macroaspiration that cause abrupt changes in the patients'
and management as well as prevention of aspirations. Because of conditions (Marik 2001). The most affected are
a risk of serious lung damage after the aspiration, hospitalized and critically ill patients where the mortality
pathophysiology and processes leading to lung tissue injury are rate could be 70 % in large volume and low pH aspirates
discussed in detail. Data sources represent a systematic literature (DeLegge 2002, DiBardino and Wunderink 2015). The
search using relevant medical subject headings. aspiration syndromes can be difficult to distinguish.
Clinical presentation and disease management are
S568 Košutová and Mikolka Vol. 70

affected by various variables, such as bacterial virulence, misdirection of oropharyngeal or gastric contents into the
risk of repeated events, and the site of acquisition larynx and lower respiratory tract, can be a dangerous
(nursing home, hospital, or community) (Mandell and phenomenon (Marik 2001). Various materials can be
Niederman 2019). They also differ in terms of providing aspirated, such as bacteria, nasal secretions or saliva,
the appropriate treatment for each of the conditions. In toxic substances, liquids and food, or gastric contents
addition, aspiration syndromes are recognized as (Son et al. 2017, Zaloga 2002). Aspiration syndrome
an independent risk factor for the subsequent occurs more frequently than is recorded, and the disease
development of acute respiratory distress syndrome is often misdiagnosed. In hospitalized and
(ARDS), a life-threatening condition characterized by institutionalized patients with predisposing disorders,
diffuse lung damage, inflammation, oedema formation, early detection of this complication and efficient
and surfactant dysfunction leading to respiratory failure preventive measures will considerably minimize the
(Mokrá 2020, Raghavendran and Napolitano 2011, severity of health complications and mortality associated
Zaloga 2002). with aspiration syndromes (Petroianni et al. 2006).
We systematically searched NCBI, Scopus, Web Aspiration syndrome may occur due to (1) airway
of Science, and Cochrane Library databases of 'aspiration syndromes such as chronic cough, exacerbation of
pneumonia, aspiration pneumonitis, ARDS, acute lung asthma/bronchospasm or bronchiolitis obliterans in lung
injury' from inception to 14 July 2021. Data sources transplantation, (2) lung parenchymal syndromes such as
included scientific reviews and original research exacerbation of fibrotic lung disease or aspiration
publications from the human and veterinary literature. All pneumonitis, (3) bacterial pneumonia such as community
reviews and studies that added some information to the or hospital-acquired, ventilator-associated or aspiration
understanding of aspiration syndromes were included. pneumonia (Son et al. 2017). However, only bacterial
Finally, we aimed to summarize a current evidence types of pneumonia and acute circumstances are
surrounding the clinical presentation, pathophysiology, infectious. The summary is shown in Table 1.
diagnosis, treatment, risks and prevention of aspiration There are three particular classifications of
syndromes. aspiration syndromes that are pathologically and
clinically distinct: (1) Foreign body aspiration (FBA),
Pulmonary aspiration syndromes (2) Aspiration pneumonitis, (3) Aspiration pneumonia
(Paintal and Kuschner 2007).
Pulmonary aspiration, which is defined as the

Table 1. Aspiration syndromes (adapted from Sun et al. 2017).

Infectious
Volume Acuity of onset
inoculum

AIRWAY SYNDROMES
• Chronic cough No Micro Chronic
• Exacerbation of asthma/bronchospasm No Micro Acute/subacute
• Bronchiolitis obliterans in lung transplantation No Micro Chronic
LUNG PARENCHYMAL SYNDROMES
• Exacerbation of fibrotic lung disease No Micro Chronic
• Aspiration pneumonitis No Macro Acute
BACTERIAL PNEUMONIA
• Community-acquired Yes Micro Acute
• Hospital-acquired Yes Variable Acute
• Ventilator-associated Yes Micro Acute
• Aspiration pneumonia Yes Macro Acute
2021 Aspiration Syndromes and Associated Lung Injury S569

Foreign body aspiration Aspiration pneumonitis

Infants and toddlers are most likely to suffer Aspiration pneumonitis is defined as an acute
from the foreign body aspiration (FBA) which lung injury (ALI) caused by macroaspiration of refluxed
mechanically blocks the airways and causes asphyxiation gastric contents (Son et al. 2017). Aspiration of gastric
(Marraro et al. 2007, Paintal and Kuschner 2007). In contents causing a chemical pneumonitis characterized by
adults, higher risk of foreign body asphyxiation syndrome fever, cyanosis, hypoxia, pulmonary oedema, and
may be observed in patients with impaired sensory potential death was initially described as “Mendelson
capacities, craniofacial trauma, loose teeth, or dental syndrome” (Salik and Doherty 2021). However, the
appliances (Umesan et al. 2012). The typical presentation contents of the stomach include not only acidic fluid but
of tracheobronchial blockage resulting from aspiration also food particles. Animal experiments showed that
includes a history of eating or swallowing followed by administration of small non-acidified gastric particles
an abrupt onset of difficult speaking or breathing. (SNAP) into the trachea induced acute neutrophilic lung
Common signs and symptoms of FBA include inflammation r within 4 to 6 hours, without any direct
tachypnoea, tachycardia, wheezing, cough, and cyanosis lung injury in the early phases (Knight et al. 1993).
(Paintal and Kuschner 2007). The Heimlich manoeuvre is However, the combination of SNAP and acid was found
used to manage foreign object asphyxiation (Montana et to be in close resemblance to the gastric aspiration, with
al. 2020) or the other procedures should be rapidly used more severe changes observed in comparison with lung
to clear the airways. This is an urgent situation because in injuries due to acid or SNAP alone (Davidson et al. 2005,
complete blockade of the trachea, there are only 3 to 5 Son et al. 2017).
minutes to restore the airway, otherwise there is a risk of The gastric contents are sterile under normal
ischemia damage to the brain, heart, and other essential conditions. However, the change in gastric fluid pH
organs that cannot be reversed (Stubington and Kamani creates an environment in which the potentially
2021). Treatment options represent an extraction of the pathogenic microorganisms become viable. For instance,
foreign object using a rigid bronchoscope or flexible gram-negative bacteria may cause a gastric colonization
fiberoptic laryngoscope (Ibrahim Sersar et al. 2005, in patients who are fed enterally, in patients with
Rafanan and Mehta 2001). gastroparesis or with small-bowel blockage [47, 48].
FBA is a rare but potentially fatal complication that When gastric aspiration occurs in those circumstances,
occurs in 0.16–0.33 % of adult bronchoscopic procedures a lung infection may develop as a result of the bacteria
(Sehgal et al. 2015), and is slightly more common in males present in the gastric contents, indicating how
(Limper and Prakash, 1990, Sehgal et al. 2015). The vast pneumonitis can overlap with aspiration pneumonia (Son
majority of adult patients with FBA has obvious risk factors et al. 2017).
for aspiration including neurological deficits with The pathophysiology of aspiration pneumonitis.
swallowing difficulties or altered mental status, The majority of aspirates in the clinical scenarios are
neuromuscular disease, intoxication, or has an iatrogenic liquid whereas the extent and progression of the injury to
cause. Adult FBA typically presents with choking followed the pulmonary parenchyma are determined by the nature
by persistent coughing, but when the first event goes of the aspirate. The inflammation is a result of the
unnoticed, it might mimic more chronic diseases such as chemical burn assuring to the mucosa of the trachea,
COPD, asthma, and obstructive pneumonia (Boyd et al. bronchi and parenchyma of the lungs, due to the toxicity
2009, Limper and Prakash 1990, Lin et al. 2014, Sehgal et of pH of the gastric aspirate (Hunt et al. 2018). While in
al. 2015). Wheezing, dyspnea, hemoptysis, chest discomfort, normal conditions, macrophages are important in the first
and recurrent pneumonia are some of the less common defence line, the acidic environment of the stomach
symptoms. The size of the FB and the area in which it decreases activity of the macrophages. This further
becomes lodged define the symptoms. Impaction in the reduces a bacterial destruction and increases a risk of
trachea leads to a more dramatic presentation of inspiratory developing aseptic respiratory tract infections after
stridor with frequent coughing, while occlusion of the lower gastric content aspiration, (Heming et al. 2001).
bronchi can result in coughing, wheezing, dyspnea, or Generally, two clinical phases of pneumonitis
hemoptysis, and may be mistaken with an alternative can be distinguished (Raghavendran et al. 2011). The
diagnosis (Dikensoy et al. 2002). first phase is defined by intense coughing or
S570 Košutová and Mikolka Vol. 70

bronchospasm that occur immediately after the aspiration Aspiration pneumonia

incident, characterized by stimulation of capsaicin-
sensitive neurons and direct caustic actions of low pH on Aspiration pneumonia is a process of
airway epithelium. The second phase is characterized by proliferation and invasion of pulmonary parenchyma
the onset of neutrophil-induced pulmonary inflammation caused by the inhalation of oropharyngeal secretions that
during the next 4–6 hours (Kennedy et al. 1989). The are colonized by pathogenic bacteria (Almirall et al.
longer is the acidic content in contact with the respiratory 2021). Pneumonia can be induced by aspiration of
tract, the more potent is the alteration of the immune infectious content from the upper airways orthe oral
system (Hackett et al. 2016). Exposure to low pH of cavity, or in more serious cases the bacteria can enter the
gastric content leads to a loss of pulmonary lungs via hematogenous spread from other locations
microvascular integrity, resulting in fluid and protein (Cabre et al. 2010).
extravasation into the airways and alveoli (Raghavendran While previously the most prominent types of
et al. 2011). Plasma proteins and other components of bacteria present in aspiration pneumonia were the
oedema fluid can directly interfere with the function of anaerobic bacteria (Mandell and Niederman 2019),
alveolar surfactantwhat increases the breathing effort due nowadays there has been a shift in the observed types of
to increased airway resistance and decreases a diffusion microorganisms (Bartlett, 2013). Main types of bacteria
of oxygen. in a community-acquired pneumonia are Streptococcus
Gastric aspiration triggers an inflammatory Pneumoniae, Staphylococcus Aureus, Haemophilus
cellular response. Low pH-mobilized and activated Influenza, and Enterobacteria, whereas a hospital-
neutrophils release histamine, leukotrienes and TGF-β acquired pneumonia is usually caused by gram-negative
which affect the surfactant integrity of the alveoli and enteric bacteria, such as Pseudomonas Aeruginosa
contribute to respiratory insufficiency (Reeves et al. (Rotstein et al. 2008). In patients suffering from
2002). There have been several local and systemic gastrointestinal disorders, the gram-negative Enterococci
inflammatory mediators identified to have a role in acid- are often detected (Mandell and Niederman 2019).
induced lung injury (Goldman et al. 1993). Specifically However, in small burden of bacteria in the
levels of proximal proinflammatory cytokine, tumor oropharyngeal secretion, good coughing mechanisms
necrosis factor (TNF)-α (Davidson et al. 1999), along with the patient’s cellular and humoral immune
neutrophil chemotactic chemokine interleukin (IL)-8 systems, and active ciliary clearance, may prevent
(Folkesson et al. 1995), macrophage inflammatory an infection of the lung after the aspiration. Nevertheless,
protein-2 (MIP-2) (Shanley et al. 2000) and cytokine- any impairment of these mechanisms accompanied by
inducted neutrophil chemoattractant-1 (CINC-1) are abundant aspiration may result in aspiration pneumonia
elevated in the bronchoalveolar lavage (BAL) fluid (Dickson et al. 2013).
(Knight et al. 2004). In addition, increases in leukocyte- The pathophysiology of aspiration pneumonia
derived oxidants and proteinases (Raghavendran et al. cannot be understood in the absence of bacteriological
2011) and activation of complement participate in the investigation. It's critical to distinguish aseptic aspiration
systemic response of acid-induced lung injury (Nishizawa pneumonitis, in which the damage to the pulmonary
et al. 1996). Besides epithelial damage, neutrophils tissue is caused by acidic gastric material rather than
themselves cause endothelial cell injury via inhibition of bacteria, from bacterial aspiration pneumonia (Mandell
NADPH oxidase. Both pepsin and bile salts also activate and Niederman 2019). In addition, varying frequency,
the effect of IL-8 causing a direct damage, and via volume, and particle size result into a wide array of
stimulation of neutrophilic influx induce an endothelial changes, which are similar to the pathophysiology of
cell injury (Brinkmann et al. 2004). ARDS (Neill and Dean 2019).
Dysfunction of pulmonary surfactant in acid The microbiological aetiology of aspiration
aspiration pneumonia was confirmed in experiments pneumonia may depend on different aspects. For
where treatment with exogenous surfactant improved instance, the type of pathogen in community-acquired
a pulmonary function, but only when inhibitory plasma pneumonia is influenced by age, smoking habits, alcohol
proteins were removed by a lavage (Davidson et al. 2005, abuse, and comorbidities such as COPD, diabetes
Eijking et al. 1993). mellitus, liver disease, renal failure, and neurological
illness (Almirall et al. 2021, Liapikou et al. 2014).
2021 Aspiration Syndromes and Associated Lung Injury S571

Chronic and frequent aspiration contributes to pneumonia Risk factors of aspiration syndromes
because of denuded epithelium and increased pool of
bacteria in the lungs (Neill and Dean, 2019). When aspiration occurs, two specific factors
The pathophysiology of aspiration pneumonia have been identified as causal: (1) lost or reduced
can be explained as the combination of risk factors that protective reflexes when the individual’s consciousness
alter swallowing function, cause aspiration, and has undergone ageing-related alteration, (2) impairments
predispose the oropharynx to bacterial colonization of neuromuscular function (Marik and Kaplan, 2003).
(Ortega Fernández and Clavé 2013). The pathological There are additional contributing factors that put the older
changes occur when the normal defense mechanisms, i.e. adult at risk for aspiration, including use of sedatives,
the mucociliary transport and alveolar macrophages drug abuse, dementia, use of alcohol, metabolic disorders,
acting in clearing microaspirations, fail in a predisposed traumatic brain injury, stroke, seizures and any type of
individual. Entrance of aspirate with common flora therapeutic or diagnostic procedures that involve the
organisms from the oropharynx and oesophagus into the upper thorax or the oesophagus (Huxley et al. 1978,
bronchi and alveolar space triggers the production of Langmore et al. 1998, Marik and Kaplan 2003).
proinflammatory cytokines, TNF-α, and interleukins The clinical signs of an aspiration incident range
(Sanivarapu and Gibson 2021). from subclinical symptoms like dry cough or dysphonia
Aspiration syndromes are recognized as to life-threatening disorders such as ARDS. Secondary
an independent risk factor for the subsequent infection, lung abscess, airway obstruction, exogenous
development of ARDS (Mokrá, 2020, Raghavendran et lipoid pneumonia, and progression into chronic
al. 2011, Son et al. 2017). Macrophages, alveolar cells, interstitial fibrosis can all aggravate the pathogenic
immune effector cells, and neutrophils, as well as process (Marik 2001). Patients with low gastric pH,
platelets and monocytes are critical in defending the lung decreased gastroesophageal sphincter tone, or elevated
and play key roles in acute lung injury (ALI) induced by gastric pressure are also at risk, as well as the other
aspiration syndromes (Matthay et al. 2019). predisposing factors such as sepsis, pregnancy, and
nutrition (Raghavendran et al. 2011).
The lung injury is associated with
The risk factors for aspiration of a large volume
an accumulation of protein-rich oedema fluid in the
are: (1) altered state of consciousness: sedation, traumatic
interstitium and the distal air spaces (Fanelli et al. 2013).
brain injury, encephalopathy, seizure disorder, poisoning,
Conceptually, increasing lung vascular permeability can
alcohol/drug intoxication, (2) gastrointestinal disorders:
occur because of a breakdown of endothelial junctions or
gastroesophageal reflux, gastroparesis, bowel
a death of endothelial cells. Endothelial cell activation
obstruction/ileus, oesophagal motility disorders: primary
results to generation of mediators, such as angiopoietin-2,
– achalasia, oesophagal stricture, secondary –
and leukocyte accumulation. Endothelial cell activation
scleroderma, polymyositis, (3) compromised gag reflex:
results into neutrophil-platelet interaction. Neutrophil-
endotracheal intubation, bulbar paralysis, enteral tube
platelet aggregates seem to play a synergistic role in
feeding, (4) dysphagia/swallowing dysfunction: stroke,
causing an increase in lung vascular permeability to
dementia, chronic obstructive pulmonary disease
protein (Huppert et al. 2019, Kosutova et al. 2019).
(COPD), Parkinson’s disease, (5) obesity, and (6) labor
Migration and activation of neutrophils into the lung lead
(Raghavendran and Napolitano 2011, Son et al. 2017).
to subsequent degranulation and release of toxic
Risk factors for aspiration syndromes are listed in
mediators, such as proteases, reactive oxygen and
Table 2.
nitrogen species, pro-inflammatory cytokines, and
pro-coagulant molecules (Mikolka et al. 2021, 2019).
Microaspiration and macroaspiration
This causes diffuse inflammatory reaction, pulmonary
surfactant inactivation, and reduced lung compliance.
The amount of aspirated material also belongs to the risk
Ventilation‐perfusion mismatch and increased
factors for aspiration. Microaspiration represents smaller
physiological dead space give rise to hypoxemia, which amounts of reflux material when the microbes are seeded
further affects a lung function in the early phase after into the lower airways most often in the form of
aspiration (Kane-Gill et al. 2007). oropharyngeal secretions. It occurs even in healthy
individuals and to cause a disease, it requires
S572 Košutová and Mikolka Vol. 70

a compromise in the defensive systems (Segal et al. macroaspiration have been also linked to dementia and
2014). Higher prevalence of microaspiration may be taking of sleeping pills (Mandell and Niederman 2019).
found in asthma, COPD, sleep apnea of the obstructive Development of aspiration pneumonia is a frequent
type, atypical lung infections and cystic fibrosis (CF) consequence of cardiopulmonary resuscitation due to
where along with an acid reflux the coordination of cardiac arrest, in which the gastric content may enter the
breathing and swallowing (Miller et al. 2005) and lungs. Pneumonia developed within 3 days after the event
clearance of microorganisms from the lower airways in 65 % of the patients (Perbet et al. 2011). In addition,
(Randell and Boucher 2006) are reduced. larger volume aspiration can occur when a patient has
cancer of the neck, head, or oesophagus, dysphagia, or
Table 2. Risk factors for aspiration syndromes limited motility of the oesophagus, or in COPD or
seizures (Mandell and Niederman 2019).
ALTERED STATE OF CONSCIOUSNESS Macroaspiration could result into ALI (Mokrá,
2020). The severity of clinical presentation of
• Sedation
macroaspiration and microaspiration differs according to
• Traumatic brain injury
aspirated volume so that higher is the volume of the
• Encephalopathy
aspiration, the greater is the injury to the patient and the
• Seizure disorder
more serious are the health consequences (Neill and Dean
• Poisoning
2019). Bacterial pneumonia as a secondary impact was
• Alcohol/drug intoxication
developed in 25 % of patients who had macroaspiration
GASTROINTESTINAL DISORDERS and pneumonitis. However, only some therapies can be
• Gastroesophageal reflux used for treating macroaspiration. Antibiotic therapy
• Gastroparesis given when aspiration pneumonia is apparent after
• Bowel obstruction/ileus a macroaspiration event was found to be more efficacious
• Oesophagal motility disorders than prophylactic antimicrobial therapy in individuals
- Prim: Achalasia, Esophageal stricture with acute aspiration pneumonitis (Dragan et al. 2018,
- Sec: Scleroderma, Polymyositis Kane-Gill et al. 2007). This knowledge allow the
specialists to spend less time implementing the wrong
COMPROMISED GAG REFLEX treatment based on the situation being assessed (Grieco et
• Presence of endotracheal intubation al. 2021).
• Bulbar paralysis
• Enteral tube feeding
Incidence and epidemiology of aspiration
syndromes
DYSPHAGIA / SWALLOWING DYSFUNCTION

• Stroke Most aspiration events go undetected or

• Parkinson’s disease unnoticed, as it is difficult to suggest commonness and
• Dementia abundance of pneumonia caused by aspiration, both
• Chronic obstructive pulmonary disease micro and macro-aspiration. In up to 64 % of aspirations
during anaesthesia, clinical or abnormal radiological
OBESITY signs were not detected (Raghavendran et al. 2011).
LABOUR There are a few studies available describing an aspiration
as a cause of community-acquired pneumonia. Aspiration
pneumonia accounts for 5 to 15 % of cases of
Macroaspiration occurs when a large volume of community-acquired pneumonia (Marik 2001), however,
particles is inhaled into the lungs, most commonly after data on hospital-acquired pneumonia is unavailable
impairment of protective reflexes, e.g., in (Mandell and Niederman 2019). Aspiration was found in
neurodegenerative diseases or drug overdose (Son et al. 4 to 26 % of pneumonia episodes in a survey of more
2017). Macroaspiration can also occur as a result of than 1 million patients in more than 4200 hospitals.
aberrant swallowing mechanics or when swallowing is Patients with aspiration pneumonia have higher
hampered by CNS dysfunction, allowing stomach or predicted mortality than those with other types of
oesophagal contents to enter the lungs. Increased risk of pneumonia, and a risk-adjusted mortality, used as
2021 Aspiration Syndromes and Associated Lung Injury S573

a quality metric, is lower in hospitals reporting a high deaths (Nason 2015). Aspiration is also associated with
frequency of aspiration than in hospitals reporting a low dysphagia, a common and major risk factor that raises
frequency of aspiration (Lindenauer et al. 2018). General mortality rates by 4.69 times in stroke patients (Feng et
anesthesia is a well-known reason for gastric aspiration al. 2019).
that affects one out of every two to three thousand
patients (Marik 2001, Raghavendran et al. 2011, Warner Clinical presentation, diagnosis and
et al. 1993). In reality, it has been observed assessment of aspiration syndromes
that aspiration occurs in roughly 3 out of every
10,000 anaesthetized patients, more frequently in special While macroaspiration is an important feature in
groups and emergency settings (Abdulla, 2013), such as aspiration pneumonia and chemical pneumonitis, it is
trauma and/or intensive care unit (ICU) patients with almost impossible to estimate the degree of the exposure
altered states of consciousness (e.g., head trauma, alcohol because are so uncommon. There is a wide variety of
or drug-induced sensoric alterations, cerebrovascular clinical presenting features, from no symptoms to severe
accidents) and/or disabled patients (Aldridge and Taylor, discomfort and respiratory failure (Calkovska et al. 2019,
n.d.) and/or elderly patients, and nursing home residents Mandell and Niederman 2019) which can develop as
(Mylotte et al. 2003a). According to a prospective study acute or subacute, and may follow in a progressive or
that used the level of pepsin in BAL as a surrogate even more progressive manner. Pulmonary aspiration
marker of aspiration in ICU patients, 88.9 % of the may impact the airway and/or the lung parenchyma.
patients had at least one aspiration episode (Metheny et Aspiration pneumonia is usually acute, and symptoms
al. 2006). appear fastly, usually within hours or just a few days after
Unwitnessed gastric aspiration may explain the event (Hollaar et al. 2016). However, in less
many cases of perioperative pulmonary dysfunction aggressive bacteria, anaerobic aspiration can be subacute,
(Marik 2001, Mylotte et al. 2003b). The ability to and clinical symptoms might be difficult to identify from
distinguish between the two most common presentations those of other bacterial pneumonia (Mandell and
of aspiration syndromes, inflammatory lung injury with Niederman 2019). It is important to note that when there
aspiration pneumonitis and bacterial aspiration is a pulmonary aspiration, patients can also have
pneumonia, is a challenging task. In addition, the severity a chronic cough, asthma attack, or bronchospasm. It is
of lung injury after aspiration varies according to the problematic to distinguish between chemical aspiration
amount, composition, and acidity of aspirate, as well as and other types of aspiration (aspiration pneumonia and
patient-specific features (Son et al. 2017). aspiration of bland material) because of the event being
The severity of a lung injury following gastric unwitnessed (Mandell and Niederman 2019). A solid FB
aspiration ranges from a mild, subclinical pneumonitis to may block the airways, resulting in pneumonia and
a progressive respiratory failure with significant making it difficult to distinguish from bacterial
morbidity and mortality. Larger aspirated volume can pneumonia. In a study of patients over 65 years of age, it
lead to severe complications and a third of patients with was reported that only around 29 % of patients had large
aspiration pneumonitis develop a more severe and FB obstructions with a delaying diagnosis of between
protracted course that is subsequently linked to ARDS 1 and 3 months while in more than 80 % of the aspiration
(Raghavendran et al. 2011, Warner et al. 1993). Patients episodes the foreign object was food (Lin et al. 2014).
who present with several risk factors, such as higher age, A considerable proportion of aspirations
have an increased risk of aspirating and developing syndrome cases is caused by noninfectious
pneumonia or pneumonitis. When other forms of microaspiration, which is frequently caused by gastric
community-acquired pneumonia are compared to reflux disease. Chronic microaspiration is also considered
aspiration pneumonia, the mortality rate in aspiration as a factor in the development of pulmonary fibrosis.
pneumonia is substantially higher, with 29.4 % versus Microaspirations of foreign substances, such as chronic
11.6 %, a finding that could imply hospitals that fail to lipoid pneumonia, provide the most compelling evidence
correctly register its presence (Lindenauer et al. 2018, (DiBardino and Wunderink 2015, Miller et al. 2005,
Mandell and Niederman 2019). ARDS linked with Tobin et al. 1998).
aspiration pneumonitis has a 30 % mortality rate and is The diagnosis of aspiration pneumonia depends
responsible for up to 20 % of all anaesthesia-related mainly on the history of disease, medical history, vital
S574 Košutová and Mikolka Vol. 70

signs and chest radiography. Most often, x-ray common in critically ill patients and, as a result, it is not
investigation reveals a new infiltration in a dependency well understood or treated (A. Matthay et al. 2019). The
pulmonary segment. In bed-bound patients, the reverse study involving a multicenter treatment and the
segments of upper lobes and upper segments of the lower evaluation of the outcomes among critically ill patients
lobes are the dependent pulmonary segments, while lower with aspiration syndromes was conducted (Kane-Gill et
lobes, especially right, are traditionally affected in al. 2007). The risk factors in critically ill patients include
ambulatory patients (Bartlett and Gorbach 1975, Marik impaired consciousness, nasogastric and endotracheal
2001). Dyspnea with a quick onset, hypoxemia, fever and intubation, improper positioning, anesthesia, neurological
radiological identification of any bilateral infiltrates or disorder, alcoholism, the overdose of drugs, and
lung auscultation crackles in a hospitalized patient are the dysfunction of gastrointestinal motility (Kane-Gill et al.
most common clinical variables in the diagnosis of 2007, Miller et al. 2005). The results showed that patients
aspiration pneumonia (Sanivarapu and Gibson 2021). with severe illnesses are more likely to develop aspiration
Clinical features can help to differentiate pneumonia, and patients with multilobular aspiration
aspiration from pneumonitis and pneumonia. In contrast pneumonia have a 90 % mortality rate compared to only
with chemical pneumonitis, the suction event is rarely one lobe aspiration. Complications related to aspiration
seen in aspiration pneumonia (Bartlett and Gorbach infections are not typical, and patients who do not have
1975). Usually, the large amount of gastric content the symptoms within two hours following the aspiration
needed for chemical pneumonitis makes it more apparent. are not likely to develop further respiratory problems
Furthermore, hyperacute hypoxemia occurs almost (Kane-Gill et al. 2007).
immediately (within hours) as a clinical course of The treatment involved a prescription of
chemical pneumonitis and results in either devastating antimicrobial therapy for 97 % of the aspiration-
lung injury or resolution within 48 hours. Patients also suspected patients, and for 100 % of the confirmed
have bronchospasm, a frothy sputum, and infiltrates on pneumonia patients, while 38 % of the patients with
chest x-ray, including non-dependent areas (Bartlett and suspected suction and 52 % of the patients with aspiration
Gorbach 1975, Doyle et al. 1995, Marik 2001, pneumonia were given combination of antibiotics
Mendelson 1946). However, there is no gold standard for (Huppert et al. 2019, Kane-Gill et al. 2007). However,
distinguishing between these two aspiration events. One antimicrobial therapy for aspiration pneumonia should be
option to differentiate aspiration pneumonia and carefully considered depending on the aspiration site and
aspiration pneumonitis is to evaluate the level of serum type of hospital- or community-acquired pneumonia
procalcitonin as an appropriate biomarker. Indeed, the (Lionel et al. 2003). Inappropriate use of antimicrobials
serum concentration of procalcitonin increases under includes an increased risk of resistant pathogens being
various bacterial and viral infections (El-Solh et al. 2011, acquired, causing secondary infections, such as
Son et al. 2017). vancomycin-resistant Enterococci and Clostridium
On the chest x-ray, the changes in the right difficile-associated disease, and elevates drug-related
lower lobe are most frequently involved. Patients who costs (Kane-Gill et al. 2007, Muto et al. 2005).
have aspirated while upright may have bilateral lower Antimicrobial prescribing is often unnecessarily broad,
lobe involvement while patients lying in the left lateral what raises a concern for the development of bacterial
decubitus position tend to have left-sided infiltrates. The resistance.
involvement of the right upper lobe is more common in Other complication in critically-ill patients is
patients who aspirate in the prone position and those with a post-extubation dysphagia (Brodsky et al. 2020).
alcohol use disorder (Sanivarapu and Gibson 2021). Identification of patients at risk of swallowing
Bronchoscopy can identify the aspirated food particles impairments and implementation of screening tools for
and also enables the retrieval of aspirate sample to be dysphagia and aspiration should be the top priority in
used for microbiological investigation. ICU patients (Brodsky et al. 2016, O’Horo et al. 2015).

Pulmonary aspiration in critically ill patients Treatment and management of aspiration

syndromes
Recognition of ARDS is quite low, with slightly
more than half of those with mild ARDS and almost Prior to attempting to discern between aspiration
80 % of those with severe ARDS. ARDS is exceedingly pneumonitis and pneumonia, it is critical to provide
2021 Aspiration Syndromes and Associated Lung Injury S575

a prompt care depending on the symptomatology and et al. 2012, Raghavendran and Napolitano 2011).
course of the disease. However, the treatment is distinct In addition, the role of empirical antibiotics for
for the two aspiration events and consists of supportive aspiration management is examined. It was shown that
management for aspiration pneumonitis and antimicrobial the first-time aspiration occurs as a type of acute
therapy for aspiration pneumonia (Raghavendran et al. pneumonitis, a typical episode of inflammation
2011, Son et al. 2017). accompanied by leukocytosis and fever. Although the
Although the data from randomized clinical treatment of aspiration pneumonitis does not require the
trials concerning a certain therapy for aspiration are use of antibiotics, pneumonia can hardly be distinguished
limited, there are some recommended guidelines in the (Marik 2001). Although there are no randomized clinical
handling of those patients If an aspiration occurs, the trials in the context of treating ventilator-associated
patient should be positioned so that the aspiration for any pneumonia (VAP), a short course of antibiotics has not
gastric content is reduced (Raghavendran and Napolitano been shown to have adverse effects as long as the
2011). The head should be turned laterally to allow antibiotics are de-escalated or discontinued based on
a suction from the pharyngeal and oral cavity for patients quantitative microbiology (Raghavendran et al. 2011,
who are awake. The patient's bed can also be raised with Rebuck et al. 2001). As a rational strategy in VAP,
the head upward by a 45-degree angle. Any decision on antibiotics administration may begin and then with the
intubation shall be based on the hypoxia level, ICU duration it may be reduced. Emphasis is placed on
neurological status and hemodynamic stability of the the equal importance of antibiotics elimination, where the
patient (Matthay et al. 2012, Raghavendran and culture does not demonstrate a bacterial growth that is
Napolitano 2011). However, intubation may be required significant or that the aspirated material was
for those patients who have high volume particulate contaminated (Matthay et al. 2012). There should also be
aspiration to facilitate future bronchoscopy (Moore et al. considerations to the use of antibiotics in those patients
2002). Nebulized bronchodilators may be given in the with the aspiration event and simultaneously with the
case of bronchospasm. Mechanical ventilation must obstruction of the bowel or colonized gastric content
continue following the current standards for lung (Matthay et al. 2019).
protection strategies. Other interventions to prevent The antibiotic therapy is concentrated on the
recurring gastric aspiration events, such as placing possible pathogens aspirated by a patient, determining
nasogastric tubes and connecting gastronomic tubes with that the site was acquired and considering resistant
suction or gravity drainage, should be introduced pathogens. However, seriously ill patients get treatment
(Raghavendran and Napolitano 2011). for the risks of dental health and multidrug resistance
The role of the bronchoscopy is significant, (Mandell and Niederman 2019). Patients with poor dental
however, aspirated material is often liquid and disperses health should be considered and clindamycin specifically
rapidly. Hence, routine bronchoscopy with lavage is recommended for patients with pulmonary abscess or
unlikely to prove useful. Contrary, if the aspirate is lung necrotization should be given (Matthay et al. 2019).
predominantly particulate, with clear radiographic Application of amoxicillin-clavulanate, moxifloxacin,
evidence of lobar collapse or major atelectasis, levofloxacin or clindamycin may be given orally,
a therapeutic bronchoscopy may prove helpful specifically it is recommended for community-acquired
(Raghavendran et al. 2011). If a large amount of gastric pneumonia (Mandell and Niederman 2019). However,
content is aspirated, bronchoscopy can be used to remove intravenous linezolid or vancomycin administration is
the aspirated gastric fluid and solid material from the recommended in hospitalized patients. Oral
central airways, minimizing the inflammatory reaction, administration may be used in some patients with
preventing atelectasis, and lowering the risk of infection methicillin-resistant S. aureus respiratory or nasal
(Marik 2001). In addition, bronchoscopy has the benefit colonization (Constantin et al. 2019). Routine antibiotic
of being able to take a sample of material from the lower therapy is suggested only when suspected bacterial
part of the respiratory tract. Bacteriological investigation infection is present and when bronchoscopic cultures are
of BAL sample can help to guide a definitive therapy, as negative, discontinuation is recommended. There is
well as can allow a discontinuation of antibiotics a number of antibiotic therapy management strategies.
administration if the cultures do not demonstrate Medications for antibiotic treatment of aspiration
significant bacterial growth (Kollef et al. 1995, Matthay pneumonia are listed in Table 3.
S576 Košutová and Mikolka Vol. 70

Table 3. Antibiotics (dose, schedule, administration route) used in the treatment of aspiration pneumonia for patients with normal renal
function (adjusted according to Mandall and Niederman 2019).

Antibiotic Dose, Schedule, Administration route

Ampicillin–sulbactam 1.5–3 g every 6 h, intravenous

Amoxicillin–clavulanate 875 mg twice daily, oral
Piperacillin–tazobactam 4.5 g every 8 h or 3.375 g every 6 h, intravenous
Ceftriaxone 1–2 g once daily, intravenous
Cefepime 2 g every 8–12 h, intravenous
Ertapenem 1 g once daily, intravenous
Imipenem 500 mg every 6 h or 1 g every 8 h, intravenous
Meropenem 1 g every 8 h, intravenous
Levofloxacin 750 mg once daily, intravenous or oral
Moxifloxacin 400 mg once daily, intravenous or oral
Clindamycin 450 mg 3/4 times daily, oral; or 600 mg every 8 h, i.v.
Gentamicin or tobramycin† 5–7 mg/kg once daily, intravenous
Amikacin† 15 mg/kg once daily, intravenous
Colistin‡ 9 million IU per day in 2/3 divided doses, i.v.
Vancomycin† 15 mg/kg every 12 h, intravenous
Linezolid 600 mg every 12 h, intravenous or oral

† For gentamicin and tobramycin, the dose should be adjusted to a trough level of less than 1 mg per litre, less than 4 mg per litre for
amikacin, and 10 to 15 g per millilitre for vancomycin. ‡ The loading dose is 6 million to 9 million IU.

Steroids are not recommended as they show no (Constantin et al. 2019). The patients should receive
benefits. Moreover, one study revealed gram-negative an enteral feeding in a semirecumbent position to
pneumonia occurred at a higher rate in patients receiving decrease a gastric aspiration risk. Patient with
steroids (Raghavendran et al. 2011, Wolfe et al. 1977). oropharyngeal dysphagia should be positioned with chin
down and head turned to one side while feeding and to
Prevention of aspiration pneumonia and encourage swallowing of small volumes, multiple
pneumonitis swallows, and coughing after each swallow (Macht et al.
2014).
The risk for chemical pneumonitis postoperative There is no certainty about the use of nasogastric
procedures can be minimized if patients are required not tubes for the prevention of aspiration pneumonia.
to eat anything for at least eight hours and not to drink Furthermore, research has indicated that gastric feeding is
any clear liquids for at least two hours before the surgical superior to postpyloric feeding (Mandell and Niederman
procedure (Mandell and Niederman 2019). Preventive 2019). Further, a meta-analysis of five randomized
effect may also has an avoidance of medications that may controlled trials involving nonventilated patients at risk
disrupt swallowing or that promote aspiration, including for pneumonia showed that oral care with chlorhexidine
antipsychotic agents, sedatives, and antihistamines in or mechanical oral cleaning was effective in preventing
high-risk patients (Herzig et al. 2017). pneumonia. However, chlorhexidine use is controversial
Patients who have swallowing disorders, such as and may be associated with increased mortality among
those who have had a stroke, should be evaluated for ventilated patients, possibly as a result of the toxic effects
swallowing and talking, oral, rather than enteric tube of chlorhexidine in the lungs (Klompas et al. 2014,
feeding, and be in the form of mechanical supplementary Mandell and Niederman 2019). The prevention for
meals with thickened fluids instead of purified foods and aspiration pneumonia can be also used for aspiration
thin liquids (Momosaki 2017). It is recommended that the pneumonitis, but the differences between the two are
patients with swallowing difficulty and dysphagia receive indicated in terms of prevention because while there are
nutritional rehabilitation as well as early mobilization to the same steps, additional steps can be used for each.
ensure that aspiration pneumonia does not reoccur
2021 Aspiration Syndromes and Associated Lung Injury S577

Conclusion in the appropriate clinical settings in patients with known

risk factors for aspiration and characteristic clinical and
Aspiration syndromes and associated lung injury radiographic findings. There are various clinical
represent a complex health problem. Gross aspiration of manifestations of microaspiration and macroaspiration,
liquid or particulate matter into lungs can result in severe with larger aspiration volume causing more serious
lung injury and respiratory failure leading to hypoxemia. repercussions. Aspiration pneumonia is more frequent in
The initial lung injury is primarily caused by hospitalized patients with dysphagia. Initial therapy for
inflammatory mediators rather than bacterial infection. acute aspiration depends on a prompt recognition that
There is no gold standard for distinguishing between the aspiration has occurred and involves a treatment of acute
aspiration syndromes. In general, aspiration pneumonitis hypoxemia and bronchospasm (Johnson and Hirsch,
is witnessed event caused by aspiration of sterile gastric 2003). Prophylactic antimicrobial therapy is not effective
content, whereas aspiration pneumonia is characterized in patients with acute aspiration pneumonitis, and instead,
by aspiration of colonized oropharyngeal material. Short escalated antibiotic therapy is needed when
summary of the differences in aspiration syndromes can macroaspiration occurs. Current treatment guidelines for
be found in Table 4. The diagnosis should be considered aspiration pneumonia support an initial empirical

Table 4. Aspiration pneumonitis and aspiration pneumonia

ASPIRATION PNEUMONITIS ASPIRATION PNEUMONIA

Primary mechanism Aspiration of sterile gastric contents Aspiration of colonized

oropharyngeal material
Pathophysiology Acute lung injury Acute pulmonary inflammatory
response
Bacteriology Initially sterile, potential subsequent Gram-positive, gram-negative, and
bacterial infection rarely anaerobic bacteria
Main risk factors Depressed level of consciousness Dysphagia and gastric dysmotility
Age group affected Regardless of age, usually young Usually older people
people
Aspiration event Witnessed Usually not witnessed
Typical demonstration History of depressed level of Institutionalized patient with
consciousness, and pulmonary dysphagia; clinical features of
infiltrate and respiratory symptoms pneumonia and an infiltrate in a
develop dependent bronchopulmonary
segment develop
Clinical features No symptoms or symptoms ranging Tachypnoea, cough, and pneumonia
from a non-productive cough to symptoms
tachypnoea, bronchospasm, bloody
or frothy sputum, and respiratory
distress 2 or 5 h after aspiration

antibiotic therapy pending culture results. As Conflict of Interest

demonstrated in this review article, aspiration syndromes There is no conflict of interest.
with rather high morbidity and mortality are still an
important clinical issue. Therefore, the research in this Acknowledgements
field should continue to further elucidate the This work was supported by projects APVV-15-0075 and
pathophysiology, and to improve the screening and VEGA 1/0004/21. Thanks to Daniela Mokra for
treatment of aspiration syndromes. proofreading the article.
S578 Košutová and Mikolka Vol. 70

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