Is it Aspiration Pneumonia or Aspiration Pneumonitis?

Aspiration of any content is one of those nebulous things we tend to treat, no matter what. The idea is that aspiration of any oropharyngeal contents into the lungs represents an establishment of a new infection and, thus, it needs to be treated. I think the term aspiration pneumonia is actually misunderstood, and it may be better to think of “aspiration syndromes” as an umbrella term to understand that it is not one disease. Indeed, aspiration of gastric contents into the lungs is a common thing and how many community acquired pneumonias get their start (so, my little nerds, argue how all “pneumonias are aspiration pneumonia, actually”). One can argue that any pneumonia is an aspiration pneumonia, but that is not what is meant in the general clinical arena. The term “aspiration pneumonia” I think, is used for frank aspiration events of gastric contents that are witnessed. Or at least, that is what Id like to think. To be fair, i think it means “hey, this altered person who maybe had a seizure is now intubated and we did an CXR and there is an infiltrate. That’s aspiration pneumonia.” Of course, that is too much of a simple explanation here. 

Pathophysiology

I am a fan of pathophysiology (at least in the simple terms sans all the cytokines people make up to justify a specialty. All those glaucomflecken fans will know what I mean) as it allows me to understand what is going on. While the general thought is that lungs were sterile, it seems to be that this is not the case. For instance, one review noted that patients with acute stroke had 103 different bacterial phylotypes after aspiration of their oropharyngeal contents (1). This suggests that the pathogenesis of pneumonia may involve other mechanisms. The stability of the lung microbiome is probably maintained by a balance of immigration and elimination of bacteria and by feedback loops (1). Very complex stuff, but it seems that as long as the microbiome and the normal daily aspiration events are kept in check, one does not get ill. In the event of a macroaspiration event that is large enough to disrupt this balance, it could lead to possible acute infection. Of course macro aspiration of stomach contents and this is what I will focus on. There are several animal studies that lend some insight into what goes in aspiration pneumonitis. There seems to be an interplay between both pH and volume of aspirate. For instance, an animal study demonstrated that gas exchange was significantly altered when the aspirate material had a pH of 1.7 but not with a pH of 3.0. Furthermore, vascular resistance was noted to have tripled in the lobes with the acidic aspirate in comparison with controls (2):

When evaluating the gross pathology, administration of steroids (in this case, pro decadron) diminished the amount of weight gained by the affected lobes by around half, which demonstrates decreased inflammatory infiltrate. Further, severe congestion and parenchymal hemorrhage was seen to have developed within an hour of gastric juice installation, suggesting the pathophysiology of chemical pneumonitis is largely driven by chemical injury and the subsequent inflammatory response. Similarly, another animal study evaluated the permeability index at different pH levels and volumes (3). As seen below, lung permeability index (or degree of lung injury) increased with lower pH, decreasing significantly once reaching a pH of around 2.5, and tapering off in contrast to control pH of 5.3. Further, volume of 1.2cc/kg also resulted in an increase in PI, though not to the extent as that of pH <1.5 though comparable to a pH of ~2.5:

This suggests that both acidity and volume play a role in the pathogenesis here. When looking at the PI of an infusion of 1.2cc of a solution with a pH of 1.5, there is an initial peak at around 1hr, with subsequent increase in PI at around hour 3:

This could represent a subacute worsening, with progression in lung injury at around 3-4 hours after aspiration event with subsequent improvement. Of course, this is conjecture based on animals rather than clinical data. Nevertheless, there seems to be an interplay between pH and volume; namely that at lower pH (lower than 2.5), you need a lower volume to cause some degree of injury to affect oxygenation. This was seen in another animal study (4), where mortality was 90% in rats who got at least 0.3cc/kg of aspirate fluid whose pH was 1. When pH was 1.4, 1cc/kg of aspirate yielded a mortality of 90%. In the mythical 70kg person, this represents 70cc of aspirate fluid if the pH is 1.0. With a slightly higher pH of 1.8, the mythical 70kg person would require 280cc of aspiration material to ] yield a predicted mortality of 38%, though the same volume would yield a 100% predicted mortality if pH was lowered to 1.4. 

This suggests that low pH may play a bigger role in the mortality underlying aspiration pneumonitis. 

When looking at specific types of aspirate (composed of either dairy, meat, vegetable, or alcohol) consumed by healthy volunteers and placed on rabbit lungs (5), only the alcohol aspirate had a pH lower than 2.5. Despite this, aspirated material of the unfiltered dairy (with a pH of 3.78) elicited a more severe response when compared to the more acidic, filtered vegetable material. This suggests that solid matter may also play a role in the inflammatory response seen in the lungs. 

Clinical Presentation:

Long story short, it looks like respiratory distress. The original paper that described the syndrome of aspiration pneumonitis by Mendelson (6) reviews 61 patients with witnessed aspiration after obstetrical anesthesia and was marked by acute respiratory distress, cyanosis, and lower lobe infiltrates occurring within 2 hours of the aspiration event. These were resolved within 7 days without antibiotic therapy. These findings were confirmed in two other retrospective studies. In one study of 60 patients, aspiration pneumonitis was characterized as sudden onset tachypnea, dyspnea, cough, cyanosis, wheezing, and fever with 41 of these having uncomplicated recoveries following the aspiration event within 2 weeks (7). Imaging was a bit more complicated. 54 had abnormalities on their first radiograph, with findings being divided into 2 major patterns; one consisting of perihilar concentric circle from the hilus and the other being a superior or inferior distribution. One interesting tidbit was that those who had worsening infiltrates after initial improvement were noted to either have ARDS or bacterial pneumonia, suggesting that while the initial pathophysiology may not involve bacteria, the lungs may be more susceptible to superimposed infection. Similarly, a retrospective analysis that was limited to 50 patients who had witnessed aspiration of gastric contents found a latency period of around an hour, followed by fever (94%), tachypnea (78%), rales (72%), wheezing and cyanosis (32%), apnea (30%), and shock (24%) with a reported mortality of around 14% (8). Steroids were used in 33 patients, but neither this or the administration of antibiotics influenced the outcome. 

A cohort of 47 patients where aspiration was clearly documented described the clinical course, with mortality being 62% (9). The right lower lobe was involved in the majority of presentation, with more lobe involvement equating to higher mortality. Furthermore, despite using antibiotics or steroids, mortality remained fairly high:

An early review on aspiration syndromes found that aspiration bacterial pneumonia tended to have a less fulminant process than aspiration pneumonitis with the aspiration even being seldom observed, with late stages demonstrating cavitation on CXR (10). This suggests that aspiration pneumonitis has a more dramatic course over a short period of time (usually within hours), and even when an aspiration event is not observed, in the right setting (i.e someone with a stroke with sudden onset worsening hypoxia and new infiltrate) pneumonitis is the more likely event. 

Aspiration Pneumonitis vs Aspiration Pneumonia

There is a difference between these two entities. In general, it can be assumed that any pneumonia in some way is due to aspiration. Paul Marik’s NEJM paper (11) highlights that aspiration pneumonia occurs after inhalation of colonized oropharyngeal material, rather than gastric contents. Common organisms that are responsible for CAP tend to colonize the oropharynx, and those who are at risk of oropharyngeal aspiration tend to present more commonly with community acquired pneumonia. This is higlighted in several retrospective studies on patients at high risk of oropharyngeal aspiration. In a small retrospective study, 10 controls were compared with 5 patients who had aspiration pneumonia and found that the threshold for cough when nebulized citric acid was delivered was significantly higher in those who had aspiration pneumonia, suggesting a role for cough reflex in the development of pneumonia (12):

Another study used propensity score matching to evaluate the risk factors for pneumonia in institutionalized elderly patients (13). 259 subjects were matched, and multivariate analysis found that dehydration, dementia, decreased swallowing function, and sputum suctioning were associated with increased risk for pneumonia:

In a clever study (14) using a radioactive tracer fixed to subjects’ teeth, silent aspiration was noted to be significantly higher in a cohort of patients who were diagnosed with pneumonia (10/14, 71%) when compared to age-matched controls with no prior diagnosis of pneumonia (10%). Similarly, in a cohort of 143 post-stroke patients, those who had reduced swallow reflex had higher incidence of pneumonia the year following their initial stroke (15). Further, those who had swallow latency >5 seconds and lack of cough with citric acid infusion were more likely to have pneumonia:

This highlights a few things: first, all these patients presented with community acquired pneumonia and had risk factors for aspiration, which yielded higher rates of pneumonia overall. Second, the presentation is markedly different from the pneumonitis previously described. Third, it highlights that perhaps, the main pathophysiology behind pneumonia is actually some degree of aspiration. Indeed, one review noted that small amount of aspiration occurs in healthy patients, usually between 0.01 to 0.2ml without clinical consequence (16). Below is a table from the Merik review article highlighting the main differences between these 2 entities:

What is the role of antibiotics?

The thought in settings of aspiration pneumonitis is to cover with antibiotics, with a particular focus on anaerobic organisms. In an aforementioned animal study using several aspirates (5), cultures from rabbit lung cultures grew several organisms, including staphylococcus aureus, E. coli, serratia marcescens, and micrococci. There were not a lot of anaerobes present. A multi-center, retrospective study of 187 patients who had aspiration events noted that no patient grew any anaerobic organism (17). Another prospective study evaluated 143 specimens from patients with suspected VAP and 25 from patients with AP (18). Bacterial pneumonia was confirmed in 34% of the VAP episodes as well as in 48% in aspiration pneumonia. In the episodes where organisms were isolated, only one grew an anaerobe that was deemed non-pathogenic. Rather, the most commonly isolated organisms included enteric gram negatives and H. influenza/streptococcus. Given that many anaerobes are fastidious organisms that take a while to grow it should not be a surprise these studies did not isolate any. So do antibiotics play a role here? The data seems to suggest they do not. In the aforementioned study of 187 patients with aspiration events (17), the administration of antibiotics did not impact hospital survival. One of the largest and most well known studies on the topic was a retrospective cohort study of 200 patients (19). Here, the authors evaluated the utility of receiving antibiotics within 2 days of the witnessed aspiration event. Multivariate analysis did not find that the receipt of antibiotics was associated with improvement in 30-day mortality:

One response to the authors noted the lack of anaerobic coverage in most of the regimens used, however as noted above this may have not played a big role in the end. In a Japanese retrospective cohort of 146 patients, prophylactic antibiotics started within 8hrs of an aspiration event (namely, aspiration pneumonitis) did not yield an improvement in in-hospital mortality in both univariate and multivariate analysis (20):

This was similar after excluding those who died within 48 hours:

In a prospective study of surgical ICUs in France, the frequency of pneumonia following 48 hours of mechanical ventilation was evaluated (21). 98 patients with suspected BAP (based on new infiltrates on imaging among other criteria, which included SIRS criteria) were enrolled as were 152 with no suspected BAP. In the cohort of 98 patients with suspected BAP (all who received empiric antibiotics), only 43 were diagnosed with bacterial pneumonia after undergoing bronchoscopy. ICU mortality did not differ between patients diagnosed with BAP or not, though those without BAP spent less time on mechanical ventilation, in the ICU, and in the hospital. Notably, however, when looking at the 98 patients with suspected BAP, there was no difference in ICU mortality or Hospital mortality in those diagnosed with aspiration pneumonitis or bacterial pneumonia:

This suggests that routine bronchoscopy could reduce the amount of antibiotic given, and elucidates that all that is infiltrated is not bacterial.

Utility of Steroids

Given the pathophysiology behind pneumonitis, it stands to reason that steroids or other antiinflammatories may actually have a role here. Indeed, animal studies have suggested some degree of benefit at least in gross pathology however clinical data is quite scant. For instance, a pair of studies found that radiographically evident lung injury improved more rapidly in those who were given steroids, but there was no difference in overall mortality (22, 23). In one, 60 patients with aspiration pneumonitis were given either 15mg/kg/day of methylprednisolone for 3 days or placebo. The patients were divided into 2 groups; a younger group with drug overdose and an older group with neurological disorders. While the younger cohort who received steroids had shorter number ventilator and intensive care unit days, this did not pan out for the older cohort. Another retrospective study of 43 patients (24) with witnessed aspiration event found no difference in mortality (32% in the steroid group vs 28% in the non-steroid group), however there was a higher risk for gram-negative pneumonia in the steroid group (7/20 vs 0/13, p <0.05).

A more recent study (25) evaluated 73 stroke patients who had aspiration-related ARDS. Steroids were used in 47 of these, with the median time to initiation being 6.5 days, with doses ranging from 20mg/day to 160mg/day, lasting from 2 to 17 days. Multivariate analysis found that steroid use was associated with reduced mortality (OR 0.5, 95% CI 0.35-0.70. Unfortunately, the high degree of variability in the dosing makes it difficult to interpret these data.

So what to do in these situations? Some reviews (1, 11) recommend withholding antibiotics if the patient is hemodynamically stable and imaging is clear. Further, if there is any abnormal radiography, the authors recommend antibiotic therapy with the decision to continue to be guided by the clinical course after the first 48hrs. Further, antibiotics are recommended to be started if the patient has small-bowel obstruction or taking PPIs/acid suppressants. 

Steroids, in general, are not recommended however a case can be made for those who have full blown ARDS, with the knowledge that the data is quite sparse and dosing/length of therapy is otherwise unclear. 

TL;DR

• Aspiration pneumonitis refers to the aspiration of gastric contents into the lung parenchyma; this is marked by a dramatic and progressive course which can progress to full-blown ARDS
• Aspiration pneumonia refers to a pneumonia caused by bacteria such as H. flu and Strep pneumo that colonize the oropharynx, in patients who are at high risk of aspiration of oropharyngeal contents. This is more akin to community acquired pneumonia. 
• When it comes to aspiration events/pneumonia, anaerobes may actually not play a big role
• Antibiotics have no role in pneumonitis, however some authors recommend their use if there is a new infiltrate on imaging and poor dentition. Despite this, data does not support benefit
• Corticosteroids can be used in severe cases of pneumonitis that leads to ARDS, however the data is unclear as to the benefit or the dosing/regimen.

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