59 Aspiration Pneumonitis and Pneumonia
Aspiration is defined as the misdirection of oropharyngeal or gastric contents into the larynx and lower respiratory tract.1 The pulmonary syndromes that commonly follow depend on the quantity and nature of the aspirated material, frequency of aspiration, and the nature of the host’s defense mechanisms and response. The most important syndromes include aspiration pneumonitis, or Mendelson syndrome, a chemical pneumonitis caused by the aspiration of gastric contents; and aspiration pneumonia, an infectious process caused by the aspiration of oropharyngeal secretions colonized by pathogenic bacteria.1 There is some overlap between these two syndromes, but they are distinct clinical entities (Table 59-1). Other aspiration syndromes include airway obstruction, lung abscess, exogenous lipoid pneumonia, chronic interstitial fibrosis, and Mycobacterium fortuitum pneumonia.
TABLE 59-1 Contrasting Features of Aspiration Pneumonitis and Aspiration Pneumonia
| Feature | Aspiration Pneumonitis | Aspiration Pneumonia |
|---|---|---|
| Mechanism | Aspiration of sterile gastric contents | Aspiration of colonized oropharyngeal material |
| Pathophysiologic process | Acute lung injury from acidic and particulate matter | Acute pulmonary inflammatory response to bacteria and bacterial products |
| Bacteriologic findings | Initially sterile, with subsequent bacterial infection possible | Gram-negative rods, gram-positive cocci, and (rarely) anaerobic bacteria |
| Major predisposing factors | Depressed level of consciousness | Dysphagia and gastric dysmotility |
| Age group affected | Any age group, but usually young persons | Usually elderly persons |
| Aspiration event | May be witnessed | Usually not witnessed |
| Typical presentation | Patient with a history of depressed level of consciousness in whom a pulmonary infiltrate and respiratory symptoms develop | Institutionalized patient who presents with features of a “community-acquired pneumonia” with an infiltrate in a dependent bronchopulmonary segment |
| Clinical features | No symptoms; or symptoms ranging from a nonproductive cough to tachypnea, bronchospasm, bloody or frothy sputum, and respiratory distress 2 to 5 hours after aspiration | Tachypnea, cough, fever, and signs of pneumonia |
Reproduced with permission from Marik PE. Aspiration pneumonitis and pneumonia: a clinical review. N Engl J Med. 2001;344(9):665-672.
Aspiration Pneumonitis
Aspiration pneumonitis is best defined as acute lung injury (ALI) following the aspiration of regurgitated gastric contents.1 This syndrome occurs in patients with a marked disturbance of consciousness such as drug overdose, seizures, massive cerebrovascular accident, following head trauma, and after or during anesthesia. Drug overdose is the most common cause of aspiration pneumonitis, occurring in approximately 10% of patients hospitalized following a drug overdosage. Adnet and Baut demonstrated that the risk of aspiration increases with the degree of unconscious (as measured by the Glasgow Coma Scale).2 Historically, the syndrome most commonly associated with aspiration pneumonitis is Mendelson syndrome, reported in 1946 in obstetric patients who aspirated while receiving general anesthesia.3 Mendelson’s original report consisted of 44,016 non-fasted obstetric patients he studied between 1932 and 1945. Of these, more than half received an “operative intervention” with ether by mask without endotracheal intubation. He described aspiration in 66 patients (1:667). Although several became critically ill from their aspiration, “recovery was usually complete” within 24 to 36 hours, and only 2 patients died (1:22,008).
Epidemiology and Risk Factors
Although aspiration is a widely feared complication of general anesthesia, clinically apparent aspiration in modern anesthesia practice is exceptionally rare, and in healthy patients the overall morbidity and mortality are low. The risk of aspiration with modern anesthesia is about 1 in 3000 anesthetics, with a mortality of approximately 1 : 125,000 and accounting for between 10% and 30% of all anesthetic deaths.4,5 The risk of aspiration is greatly increased in patients intubated emergently in the field, emergency room, or intensive care unit (ICU). The risk factors for aspiration are listed in Table 59-2. In these patients, every effort should be made to reduce the risk of aspiration; this includes removing dentures, clearing the airway, and (in certain circumstances) placing a nasogastric tube to empty the stomach prior to intubation. If there is an immediate risk of airway compromise, endotracheal intubation should be performed prior to placement of a nasogastric tube. However, if the patient is likely to have a full stomach (upper-gastrointestinal bleed, small-bowel obstruction, ileus, etc.), it may be prudent to place a nasogastric tube prior to endotracheal intubation. When intubating emergently, suction equipment must be immediately available and rapid-sequence induction using cricoid pressure should be performed.
TABLE 59-2 Factors That Increase Risk of Aspiration During Endotracheal Intubation
Pathophysiology
Mendelson emphasized the importance of acid when he showed that unneutralized gastric contents introduced into the lungs of rabbits caused severe pneumonitis indistinguishable from that caused by an equal amount of 0.1 N hydrochloric acid.3 However, if the pH of the vomitus was neutralized before aspiration, pulmonary injury was minimal. Experimental studies have demonstrated that the severity of lung injury increases significantly with the volume of aspirate and indirectly with its pH, with a pH of less than 2.5 being required to cause aspiration pneumonitis. However, the stomach contains a variety of other substances in addition to acid. Several experimental studies have revealed that aspiration of small particulate food matter from the stomach may cause severe pulmonary damage, even if the pH of the aspirate is above 2.5.
Aspiration of gastric contents results in a chemical burn of the tracheobronchial tree and pulmonary parenchyma, with an intense parenchymal inflammatory reaction. Proinflammatory cytokines, including tumor necrosis factor α (TNF-α) and CXC chemokines such as interleukin 8 (IL-8), are crucial to the development of aspiration pneumonitis by mediating neutrophil recruitment. Once localized to the lung, neutrophils play a key role in the development of lung injury through release of oxygen radicals and proteases. Gastric acid prevents the growth of bacteria, so stomach contents are normally sterile. Bacterial infection, therefore, does not play a significant role in the early stages of acute lung injury following aspiration of gastric contents. However, acid aspiration pneumonitis reduces host defenses against infection, increasing the risk of superinfection.6 The incidence of this complication has not been well studied, but experimental models suggest that acid-aspiration pneumonitis “primes the lung,” making secondary infection more severe.6,7 Colonization of gastric contents by potentially pathogenic organisms may occur when the gastric pH is increased by the use of antacids, H2 blockers, or proton pump inhibitors. In addition, gastric colonization by gram-negative bacteria occurs in patients receiving gastric enteral feedings, as well as in patients with gastroparesis and small-bowel obstruction. In these circumstances, the pulmonary inflammatory response is likely to result from both bacterial infection and the inflammatory response of the gastric particulate matter. It is also important to note that atrophic gastritis and gastric colonization is common in elderly patients; aspiration of vomitus by these patients is likely to result in an inflammatory response due to bacteria and particulate matter.
Clinical Presentation
Aspiration of gastric contents can present dramatically with a full-blown picture that includes gastric contents in the oropharynx, wheezing, coughing, shortness of breath, cyanosis, pulmonary edema, hypotension, and hypoxemia, which may progress rapidly to severe acute respiratory distress syndrome (ARDS) and death. Many patients may not develop signs or symptoms associated with aspiration, whereas others may develop a cough or wheeze. In some patients, aspiration may be clinically silent, manifesting only as arterial desaturation, with radiologic evidence of aspiration. Warner and colleagues studied 67 patients who aspirated while undergoing anesthesia.4 Forty-two (64%) of these patients were totally asymptomatic, 13 required mechanical ventilatory support for more than 6 hours, and 4 died.
Management
The upper airway should be suctioned following a witnessed aspiration. Endotracheal intubation should be considered in patients who are unable to protect their airway. While common practice, the prophylactic use of antibiotics in patients with suspected or witnessed aspiration is not recommended. Similarly, the use of antibiotics shortly after an aspiration episode in a patient who develops fever, leukocytosis, and a pulmonary infiltrate is discouraged, because it may select for more resistant organisms in a patient with an uncomplicated chemical pneumonitis. However, empirical antimicrobial therapy is appropriate in patients who aspirate gastric contents in the setting of small-bowel obstruction or in other circumstances associated with colonization of the stomach. Antimicrobial therapy should be considered in patients with an aspiration pneumonitis that fails to resolve within 48 hours. Empirical therapy with broad-spectrum agents is recommended. Antimicrobials with anaerobic activity are not routinely required. Lower respiratory tract sampling (protected specimen brush/bronchoalveolar lavage) and quantitative culture in intubated patients may allow targeted antimicrobial therapy and discontinuation of antibiotics in culture-negative patients.8
Immunomodulating Agents
Corticosteroids have been used in the management of aspiration pneumonitis since 1955.9 However, limited data exist for evaluating the role of these agents, with only a single prospective placebo-controlled study having been performed. In that study, Sukumaran et al. randomized 60 patients with “aspiration pneumonitis” to methylprednisolone (15 mg/kg/day for 3 days) or placebo.10 The patients were subdivided into two groups: a younger group with drug overdose as the predominant diagnosis and an older group with neurologic disorders. In the overdose group, 87% had an initial gastric pH below 2.5, compared to 12.8% in the neurologic group; 77.6 patients in the overdose group were admitted from the community, compared to 12.8% of patients in the neurologic group. Radiographic changes improved more rapidly in the steroid group, as did oxygenation. The number of ventilator and ICU days was significantly shorter in the overdose patients who received corticosteroids; however, these variables were longer in the neurologic group. There was no significant difference in the incidence of complications or outcome. The results of this study are somewhat difficult to interpret, as it is likely that the patients in the overdose group had true aspiration pneumonitis, whereas many patients in the neurologic group probably developed aspiration pneumonia. In addition, patients received a short course of high-dose corticosteroids. Current evidence suggests that patients with ARDS may benefit from a prolonged course of low-dose corticosteroids, but a short course of high-dose corticosteroids may be harmful.11,12 Wolfe and colleagues performed a case-controlled study of 43 patients with aspiration pneumonitis, of whom 25 received high-dose corticosteroids (approximately 600 mg prednisolone/day for 4 days).13 There was no difference in mortality, but secondary gram-negative pneumonia was reported to be more frequent in the steroid group (7/20 versus 0/13); however, ventilator days tended to be fewer in this group (4.3 versus 9.8 days). Based on these limited data, it is not possible to make evidence-based recommendations on the use of corticosteroids in patients with acid-aspiration pneumonia. However, more recent literature suggests that patients with ARDS may benefit from a prolonged course of low dose corticosteroids, so this approach should be considered.11,12
In animal models, a number of pharmacologic interventions (e.g., inhaled β2-agonists, pentoxifylline, antiplatelet drugs, omega-3 fatty acids) have been shown to attenuate acute lung injury following acid aspiration,14–19 but the role of these interventions in humans remains to be tested. Because of their inherent safety, these agents should at least be considered in patients with severe acid-aspiration pneumonitis.
Aspiration Pneumonia
Aspiration pneumonia develops after the aspiration of colonized oropharyngeal contents. Aspiration of pathogens from a previously colonized oropharynx is the primary pathway by which bacteria gain entrance to the lungs. Indeed, Hemophilus influenzae and Streptococcus pneumoniae first colonize the naso/oropharynx before being aspirated and causing community-acquired pneumonia (CAP).20 However, when the term aspiration pneumonia is used, it refers to the development of a radiographic infiltrate in the setting of patients with risk factors for increased oropharyngeal aspiration. Approximately half of all healthy adults aspirate small amounts of oropharyngeal secretions during sleep. Presumably, the low virulent bacterial burden of normal pharyngeal secretions together with forceful coughing, active ciliary transport, and normal humoral and cellular immune mechanisms result in clearance of the inoculum without sequelae. If mechanical, humoral, or cellular mechanisms are impaired or if the aspirated inoculum is large enough, pneumonia may follow. Any condition that increases the volume and/or bacterial burden of oropharyngeal secretions in the setting of impaired host defense mechanisms may lead to aspiration pneumonia. Indeed, in stroke patients undergoing swallow evaluation, there is a strong correlation between the volume of aspirate and the development of pneumonia.21 Factors that increase oropharyngeal colonization with potentially pathogenic organisms and that increase the bacterial load may augment the risk of aspiration pneumonia. The clinical setting in which pneumonia develops largely distinguishes aspiration pneumonia from other forms of pneumonia, but there is much overlap. For example, otherwise healthy elderly patients with CAP have been demonstrated to have a significantly higher incidence of silent aspiration when compared with age-matched controls.22
Epidemiology
Two principal factors make the epidemiologic study of aspiration syndromes difficult: (1) lack of specific and sensitive markers of aspiration and (2) the failure of most studies to make the distinction between aspiration pneumonitis and aspiration pneumonia. Nevertheless, several studies list “aspiration pneumonia” as the cause of CAP in 5% to 15% of cases.23,24 CAP is a major cause of morbidity and mortality in the elderly, and it is likely aspiration is the major cause of pneumonia in these cases. Epidemiological studies have demonstrated that the incidence of pneumonia increases with aging, with the risk being almost six times higher in those older than 75 compared to those younger than 60 years of age.25,26 The attack rate for pneumonia is highest among those in nursing homes, where pneumonia is the most common cause of death.27
Dysphagia and the Cough Reflex
Swallowing is a complex and coordinated neuromuscular process that consists of both volitional and involuntary activity. Oropharyngeal aspiration due to abnormalities in swallowing and upper-airway protective reflexes is an important pathogenic mechanism leading to CAP. It has been estimated that in the United States, approximately 300,000 to 600,000 people each year are affected by dysphagia resulting from neurologic disorders.28 These include patients with cerebrovascular accidents, Parkinson’s disease, and dementia. Aspiration pneumonia is the major cause of death in these patients. In addition, the efficiency of the swallow mechanism decreases with aging, thereby increasing the risk of aspiration in the elderly. Kikuchi et al. evaluated the occurrence of silent aspiration in otherwise “healthy elderly patients” with CAP and age-matched control subjects using indium-111 chloride scanning.22 Silent aspiration was demonstrated in 71% of patients with CAP, compared to10% in control subjects.
An intact cough reflex is an important respiratory defense mechanism. Sekizawa and coworkers demonstrated a marked depression of the cough reflex in elderly patients with pneumonia.29 Furthermore, the greater the derangement of the cough reflex, the greater the risk of pneumonia.30 Nakazawa and colleagues demonstrated impairment of the swallow and the cough reflex in elderly patients with aspiration pneumonia but not in patients with dementia who had no prior history of aspiration pneumonia.31
Risk Factors for Dysphagia
The major risk factors for dysphagia are listed in Table 59-3. In patients with an acute stroke, the incidence of dysphagia ranges from 40% to 70%.32 Dysphagic patients who aspirate are at an increased risk of developing pneumonia. Although dysphagia improves in most patients following a stroke, in many the swallowing difficulties follow a fluctuating course, with 10% to 30% continuing to have dysphagia with aspiration.33,34
TABLE 59-3 Risk Factors for Dysphagia and Aspiration Pneumonia
| Cerebrovascular Disease |
Risk Factors for Pneumonia In Patients Who Aspirate
Although the presence of dysphagia and the volume of aspirate are key factors that predispose patients to aspiration pneumonia, a number of other factors also play an important role.21 As noted earlier, colonization of the oropharynx is an important step in the pathogenesis of aspiration pneumonia. The elderly have increased oropharyngeal colonization with pathogens such as Staphylococcus aureus and aerobic gram-negative bacilli (e.g., Klebsiella pneumoniae and Escherichia coli). Although the increased colonization may be transient, it underlies the increased risk in the elderly of pneumonia with these pathogens. The defects in host defenses that predispose to enhanced colonization with these organisms are uncertain, but dysphagia with a decrease in salivary clearance and poor oral hygiene may be major risk factors.35 Edentulous patients appear to have a lower risk of aspiration pneumonia than dentate patients.36
Diagnosis and Management of Aspiration Pneumonia
There is no gold standard test to diagnose aspiration pneumonia, and unlike the case with aspiration pneumonitis, aspiration that leads to pneumonia is generally not witnessed. The diagnosis is therefore inferred when a patient with known risk factors for aspiration has a radiographic infiltrate in a characteristic bronchopulmonary segment. In patients who aspirate in the recumbent position, the most common sites of involvement are the posterior segments of the upper lobes and the apical segments of the lower lobes. In patients who aspirate in the upright or semirecumbent position, the basal segments of the lower lobes are favored. The usual picture is that of an acute pneumonic process, which runs a course similar to that of a typical CAP. Untreated, however, these patients appear to have a higher incidence of cavitation and lung abscess formation.37 Gram-negative pathogens and S. aureus are the likely pathogens in patients with CAP due to aspiration pneumonia.38,39 El-Sohl and colleagues performed quantitative bronchial sampling in 95 institutionalized elderly with severe aspiration pneumonia.40 Out of the 67 pathogens identified, gram-negative enteric bacilli were the predominant organisms isolated (49%), followed by anaerobic bacteria (16%) and S. aureus. Anaerobic isolates were recovered in conjunction with aerobic gram-negatives; in these patients clinical response was not related to the use of antibiotics with anaerobic activity.
Antimicrobial therapy is indicated in patients with aspiration pneumonia. The choice of antibiotics depends on the setting in which the aspiration occurs as well as the patient’s premorbid condition. However, antimicrobial agents with gram-negative activity, such as third-generation cephalosporins, fluoroquinolones, piperacillin, and carbapenems, are usually required.38–41 Antibiotics with activity against methicillin-resistant S. aureus (MRSA) may also be required. Antimicrobials with specific anaerobic activity are not routinely warranted and may only be indicated in patients with severe periodontal disease, patients expectorating putrid sputum, and patients with a necrotizing pneumonia or lung abscess on chest radiograph.1,38–41
Assessment and Management of Dysphagia
All elderly patients with CAP, patients with a recent cerebrovascular accident, and patients with degenerative neurologic diseases should be referred to a speech and language pathologist (SLP) for a formal swallow evaluation and for the development and implementation of a management program; this may include dietary modifications as well as various swallow maneuvers.42,43 A clinician’s bedside assessment of the cough and gag reflex is unreliable in screening for patients at risk of aspiration.
Tube Feeding
Nutritional supplementation, as determined by the clinical dietitian, may be required. Tube feeding is not essential in all patients who aspirate. The practice of tube feeding in the end stages of degenerative illnesses in the elderly should be carefully considered. Finucane et al. found no data to suggest that tube feeding of patients with advanced dementia prevented aspiration pneumonia, prolonged survival, reduced the risk of pressure sores or infections, improved function, or provided palliation.44 Short-term tube feeding, however, may be indicated in elderly patients with severe dysphagia and aspiration in whom improvement of swallowing is likely to occur. Nakajoh and colleagues demonstrated that the incidence of pneumonia was significantly higher in stroke patients with dysphagia who were fed orally, compared to those who received tube feeding (54.3% versus 13.2%, P <0.001), despite the fact that the orally fed patients had a higher functional status (higher Barthel index).30 The FOOD trials consisted of two large randomized studies that enrolled dysphagic stroke patients.45 In the first trial, patients enrolled within 7 days of admission were randomly allocated to early tube feeding or no tube feeding for more than 7 days. Early tube feeding was associated with an absolute reduction in risk of death of 5.8%. The second trial allocated patients to early nasogastric feeding or early feeding via a percutaneous endoscopic gastrostomy (PEG) tube. PEG feeding was associated with an absolute increase in the risk of death of 1% and an increased risk of death or poor outcome of 7.8%. Patients with a PEG were less likely to be transitioned to oral feeding than the NG group and were more likely to be living in an institution, perhaps explaining the higher mortality of the PEG fed patients. It was interesting to note that PEG-fed patients were more likely to develop pressure sores, suggesting that these patients may have been cared for differently. The results of the FOOD trials suggest that dysphagic stroke patients should be fed early via nasogastric or feeding tube and transitioned to oral feeding as their dysphagia resolves. Those patients whose dysphagia does not resolve may be candidates for placement of a PEG tube.
Colonized oral secretions are a serious threat to dysphagic patients, and feeding tubes offer no clear protection. There are no data to suggest that patients fed with gastrostomy tubes have a lower incidence of pneumonia than patients fed with nasogastric tubes.46 The incidence of aspiration pneumonia has been shown to be similar in stroke patients with postpyloric as compared to intragastric feeding tubes.47 Over the long term, aspiration pneumonia is the most common cause of death in gastrostomy tube–fed patients.48
Oral Hygiene
Institutionalized patients have been shown to have poor oral hygiene and rarely receive treatment from dentists and oral hygienists.49 An aggressive protocol of oral care will reduce colonization with potentially pathogenic organisms and decrease the bacterial load—measures likely to reduce the risk of pneumonia.50
Pharmacologic Management
The neurotransmitter, substance P, is believed to play a major role in both the cough and swallow sensory pathways. Angiotensin-converting enzyme (ACE) inhibitors prevent the breakdown of substance P and may theoretically be useful in the management of patients with aspiration pneumonia. A number of studies have demonstrated a lower risk of aspiration pneumonia in stroke patients treated with an ACE inhibitor compared to other antihypertensive agents.51,52
Sedative medication has been demonstrated to increase the risk of pneumonia in residents of long-term care facilities and should therefore be avoided.53 The prescription of phenothiazines and haloperidol should be very carefully considered, because they reduce oropharyngeal swallow coordination, causing dysphagia.54,55 Medications that dry secretions, including antihistamines and drugs with anticholinergic activity, make it more difficult for patients to swallow and should therefore also be avoided.54,56
ConclusionsKey Points
Marik PE. Aspiration pneumonitis and pneumonia: a clinical review. N Engl J Med. 2001;344(9):665-672.
Classic review paper on aspiration syndrome.
Mendelson CL. The aspiration of stomach contents into the lungs during obstetric anesthesia. Am J Obstet Gynecol. 1946;52(27):191-205.
Classic paper on aspiration pneumonitis.
El-Sohl AA, Pietrantoni C, Bhat A, et al. Microbiology of severe aspiration pneumonia in institutionalized elderly. Am J Respir Crit Care Med. 2003;167(12):1650-1654.
American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171(4):388-416.
Dennis MS, Lewis SC, Warlow C. FOOD Trial Collaboration. Effect of timing and method of enteral tube feeding for dysphagic stroke patients (FOOD): a multicentre randomised controlled trial. Lancet. 2005;365(9461):764-772.
Finucane TE, Christmas C, Travis K. Tube feeding in patients with advanced dementia: a review of the evidence. JAMA. 1999;282(14):1365-1370.
This paper evaluates the role of PEG tubes in patients with dementia
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2 Adnet F, Baud F. Relation between Glasgow Coma Scale and aspiration pneumonia (letter). Lancet. 1996;348:123-124.
3 Mendelson CL. The aspiration of stomach contents into the lungs during obstetric anesthesia. Am J Obstet Gynecol. 1946;52:191-205.
4 Warner MA, Warner ME, Weber JG. Clinical significance of pulmonary aspiration during the perioperative period. Anesthesiology. 1993;78:56-62.
5 Olsson GL, Hallen B, Hambraeus-Jonzon K. Aspiration during anaesthesia: a computer-aided study of 185,358 anaesthetics. Acta Anaesthesiol Scand. 1986;30:84-92.
6 Rotta AT, Shiley KT, Davidson BA, et al. Gastric acid and particulate aspiration injury inhibits pulmonary bacterial clearance. Crit Care Med. 2004;32:747-754.
7 van Westerloo DJ, Knapp S, van’t Veer C, et al. Aspiration pneumonitis primes the host for an exaggerated inflammatory response during pneumonia. Crit Care Med. 2005;33:1770-1778.
8 Marik PE. An evidence-based approach to the diagnosis of ventilator-associated pneumonia. Resp Care. 2009;54:1446-1448.
9 Haussmann W, Lunt RL. Problem of treatment of peptic aspiration pneumonia following obstetric anesthesia (Mendelson’s syndrome). J Obstet Gynaecol Br Commonw. 1955;62:509-512.
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11 Marik PE. Critical illness related corticosteroid insufficiency. Chest. 2009;135:181-193.
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