Chronic Aspiration

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Continuing Education Activity

Chronic aspiration is a common condition that occurs in the elderly population, pediatric patients with certain neurological conditions, and chronically intubated patients. Patients with risk factors for dysphagia should be promptly evaluated by a formal speech and swallow study, and to try to prevent aspiration from occurring. Silent aspiration occurs in everyone, regardless of age, but those with certain co-morbidities are at higher risk for the disease. This activity describes the evaluation and management of chronic aspiration pneumonia and explains the role of the interprofessional team in evaluating and treating patients with this condition.

Objectives:

  • Identify the specific risk factors for chronic aspiration.
  • Summarize the evaluation process for chronic aspiration.
  • Review the treatment of acute aspiration.
  • Describe how the interprofessional team can work together to coordinate care and improve patient outcomes.

Introduction

Aspiration is a common problem that can occur in healthy or sick patients wherein pharyngeal secretions, food material, or gastric secretions enter the larynx and trachea and can descend into the lungs, causing an acute or chronic inflammatory reaction. The term chronic aspiration refers to a common condition in the elderly population, pediatric patients with certain neurological disorders, and chronically intubated patients.

Aspiration can be further classified into microaspiration and macroaspiration by the subjective amount of aspirate. Microaspiration occurs with minuscule amounts of foreign material are inhaled, while macroaspiration occurs when large amounts of foreign material are inhaled. There is not a specific differentiating cut-off. Chronic aspiration is most often secondary to microaspiration.

The consequences of a single episode of aspiration vary from benign to catastrophic depending on the nature and volume of aspirated material. While aspiration can occur in healthy patients, repetitive and, thus, chronic aspiration indicates underlying pathology in the functioning of a healthy individual’s ability to speak, swallow, breathe, or maintain airway protection. Chronic aspiration commonly affects three main demographics with specific comorbidities: children, elderly, and intensive care unit (ICU) patients. It is the cause of significant morbidity and mortality in these populations. In children, chronic pulmonary aspiration is one of the leading causes of death in neurologically impaired patients.[1] Patients with dysphagia have triple the rates of pneumonia and suffer from a 2.9% increase in in-hospital mortality.[2][3][4]

Etiology

Anything contributing to the breakdown of the neuromuscular pathways involved in speaking, swallowing, breathing, and maintaining a patent airway can lead to chronic aspiration and its sequelae. Several main risk factors include neurologic impairment, pulmonary diseases, supraglottic disease, and other conditions.

Neurologic Impairment

This can be cognitive or focal. In children, the most common risk factors are encephalopathy, cranial nerve dysfunction (CHARGE – CN VII, IX, X), neuromuscular disease such as Duchenne muscular dystrophy, congenital muscular dystrophy, myotonic dystrophy, and spinal muscular atrophy as well as vocal fold immobility, and cerebral palsy. The mechanisms of aspiration differ in these. For instance, neuromuscular diseases may cause an overall weakness in swallowing solid foods, while cerebral palsy and other neurologically delaying syndromes cause difficulty with oral secretions and thin liquids.[5] In pediatric patients, there is a strong correlation between recurrent aspiration pneumonia and swallowing dysfunction, specifically penetration, aspiration, reflux, and abnormal esophageal function.[6]

In adults, examples include acute and chronic stroke, dementia, amyotrophic lateral sclerosis, multiple sclerosis, Parkinson disease (PD), and Guillain-Barre syndrome. Adults mostly develop overall swallowing muscle weakness that may become exacerbated by a neurologic decline, such as occurs in dementia or stroke involving certain aspects of the central nervous system (CNS). Dysphagia in these populations often contributes to increased overall morbidity. In PD, for example, the risk of being hospitalized for aspiration pneumonia is over three times higher than in healthy patients. This risk increases as patients advance into later stages of the disease and have a breakdown of their cough and swallowing function.[7][8]

Pulmonary Disease

Patients with poor forced expiratory volume, inadequate cough, or those who require a ventilator are also at increased risk. Critically ill patients with extended stays in the ICU often develop neuromuscular weakness and flaccidity. This, in addition to deconditioning, weak airway muscles, prolonged intubation, and poor airway protection, contribute to an increased risk for significant oropharyngeal dysphagia and aspiration-related pneumonia.[3] Weak respiratory and laryngeal musculature can alter sensitivity to aspiration and decrease the drive and strength of the reflexive cough. Similar insidious frailty and weakness occur in the patients at the end-of-life stage and patients suffering from multisystem chronic diseases such as chronic kidney disease, heart failure, and chronic obstructive pulmonary disease.[9] This often results from generalized cachexia and sarcopenia. Obstructive pulmonary disease specifically causes poor forced expiratory volume and increased aspiration risk.

Supraglottic Disease

Patients with poor dentition, oropharynx abnormalities, impaired swallowing, or esophageal dysmotility also suffer from an increased risk of aspiration. In children, tracheoesophageal fistula, laryngotracheoesphageal fistula, airway obstructive lesions (laryngomalacia), and other laryngeal or craniofacial abnormalities that prevent normal swallowing function can increase the risk.[5][10] Fistulas allow foreign material to bypass the body's airway protective system entirely when swallowing. Congenital masses, including cystic hygromas, lymphovascular malformations, and neuroblastoma, can also contribute to worsening aspiration risk. Obstructive lesions and abnormal facial anatomy can result in lingering food particulate after the swallowing process has completed and normal respiration has resumed leading to potential aspiration.

The most common forms of supraglottic disease in adults include achalasia, Zenker diverticulum (ZD), and head and neck cancers. In achalasia and ZD, food products are not properly transferred to the stomach during the swallowing process by means of progressive ganglion degeneration, causing failed esophageal peristalsis and lower esophageal relaxation and outpouching of the esophageal mucosa and submucosa respectively. The lingering material can then easily be aspirated during normal respiration. Dysphagia also often occurs as a long-term side effect of radiation therapy in head and neck cancers. Esophageal cancer has the added risk of obstruction resulting in lingering foreign material and associated regurgitation and reflux. 

Other Conditions

  • Position changes
  • High volume vomitus
  • Analgesia of the pharynx and/or larynx
  • Oral, esophageal, or airway procedures such as nasogastric (NG) tube, tracheostomy, upper endoscopy, bronchoscopy, gastrostomy feeding tube
  • Trauma
  • Medications: Prolonged intake of proton pump inhibitors can lead to gastric flora overgrowth. Antipsychotics have extrapyramidal motor side effects that can cause impaired function of striated muscles involved in swallowing. Antihistamines and antidepressants decrease oral lubrication. Anticonvulsants alter CNS functioning and can provoke drowsiness and incoordination. These all affect gastric motility, possibly increasing reflux.

Epidemiology

The exact number of patients affected by chronic aspiration is unknown. While this condition can affect any age group, it most commonly affects children, the elderly, and ICU patients, all of whom exhibit a higher incidence of aspiration risk factors. The incidence of aspiration pneumonia hospitalizations in the United States is declining but still represents a significant healthcare burden, especially in patients greater than 65.[11] 

In children, it has been estimated that up to 25% of this population has swallowing and feeding disorders. This statistic increases to 40% in prematurely born infants and up to 78% in developmentally delayed children.[12][13] Developmentally delayed and medically complex children also make up the majority of aspiration-related hospitalizations and ICU admission with an average of 2.4 times the cost of care compared to community-acquired pneumonia (CAP)-related hospitalizations.[14]

Pathophysiology

Aspiration occurs secondary to swallowing dysfunction, reflux, or inability to protect the airway adequately. The presence of foreign material in the lungs subsequently initiates an inflammatory response. There is conflicting evidence concerning the role of acidity in morbidity. A normal airway pH is 7.3, and the presence of acidic gastric fluid has been speculated to reduce surfactant functioning and damage bronchial epithelial cells by a combined mechanism of direct toxicity and digestive enzymes such as bile salts and pepsin.[15] However, preclinic studies in animals demonstrate the presence of foreign material, not acidity, affects the presence and severity of the disease.[16] Releasing inflammatory mediators and vagus-mediated reflexes results in inflammation, edema, mucus production, and smooth muscle contraction. This airway damage can lead to pneumonitis, fibrosis, bronchiolitis, and an increased risk of subsequent infections.

Swallowing Mechanisms and Alterations

The practice of normal swallowing necessitates greater than thirty muscles in the recruitment and coordination of the lips, palate, tongue, pharynx, larynx, and esophagus. The process is separated into four phases and demands exquisite timing. The first two phases, oral preparatory and oral, are voluntary. In the oral preparatory phase, the closed chamber of the mouth receives food, and through chewing and enzyme-rich saliva addition, a bolus is formed. The tongue and palatoglossus muscle work to keep the bolus in place, not spilling out the anterior oral cavity or prematurely entering the pharynx. In the oral phase, the conscious decision to swallow is made, and the bolus is transferred posteriorly into the pharynx by the tongue and muscles on the floor of the mouth. Elevation of the soft palate at this time prevents nasal regurgitation.

The following pharyngeal and esophageal phases are involuntary. The pharyngeal phase is particularly critical in protecting against aspiration. As the bolus is propelled posteriorly, the glossopharyngeal and vagus nerves stimulate the simultaneous laryngeal inlet closure and esophagus opening. As swallowing continues, the body halts respiration, adducts the vocal cords, approximates the false vocal cords, elevates the larynx, and flexes the epiglottis over the larynx.[17] 

This coordinated muscle action ensures the food bolus passes into the pyriform sinus and around the epiglottis and airways. When the larynx lifts, pharyngeal contraction shortens, and the upper esophageal sphincter passively opens, allowing the passage of the bolus into the negatively pressured esophagus. b Normally, swallowing occurs during the expiratory phase of respiration when lung volumes are low. The expiration of air pushes foreign material away from the larynx, further preventing aspiration.[18] The final phase occurs when the bolus traverses the esophagus to the lower esophageal sphincter and into the stomach utilizing peristalsis. Disfunction or discoordination of these phases can result in pulmonary aspiration.

During the pharyngeal phase of swallowing, the food particles may enter the supraglottic area surrounding the vocal cords. If the vocal cords do not approximate fully, or if the ability to force expiration is diminished, there is a propensity for foreign material aspiration into the trachea. Once past the vocal cords, the musculature is controlled by the afferent recurrent laryngeal nerve. Sensory stimulation in the subglottic region elicits a normal cough reflex stimulating laryngeal adduction and a forceful cough, ideally propelling the particulate out of the vocal cords.[19] Failure of either the sensory or motor part of this cough response can result in the particulate continuing to travel down into the tracheobronchial tree, resulting in potentially harmful aspiration syndromes. 

Reflux

Reflux is the retrograde passage of stomach contents. It can also contribute to pulmonary aspiration as foreign material is near the larynx when the body is not undergoing the swallowing process. In the majority of cases, reflux is secondary to impaired functioning of the lower esophageal sphincter or a hiatal hernia. Normally the lower esophageal sphincter acts as a barrier preventing stomach contents from entering the esophagus at the gastroesophageal junction. There is some physiologic reflux after eating because the sphincter transiently relaxes to allow gas ventilation from the stomach. Pathologic reflux occurs when the sphincter is relaxed for extended periods. Several things can cause this relaxation, including obesity, pregnancy, diabetes, scleroderma, and various medications such as cholinergic agonists and calcium channel blockers. Other etiologies of reflux include obstruction and bariatric surgery. In the same way, microaspiration stimulates the vagus nerve, and reflux initiates the same inflammatory response of edema, mucus production, and smooth muscle contraction. Microaspirate and reflux have synergistic effects compounding the diseased state.

History and Physical

Common symptoms include:

  • Wheezing
  • Chronic cough
  • Nocturnal cough
  • Recurrent pneumonia
  • Failure to thrive (in children)

Some of these symptoms may only manifest themselves after the patient eats. In infants, a poor sucking reflex and frequent coughing after feeding may indicate the need to rule out a neuromuscular disease.[5]

On physical exam, early signs can include the above, as well as abnormal lung sounds, including wheezing, rhonchi, or crackles on auscultation. Decreased or lack of breath or sounds can be a finding if a complete obstruction has occurred. Desaturation on pulse oximetry can demonstrate a worsened aspiration syndrome, given that a significant portion of the respiratory tract must be knocked out to cause overall hypoxemia. In ICU patients, especially those who are intubated for an extended period, a sudden worsening of respiratory drive or oxygen saturation can be a key early finding of aspiration and should always be on the differential.

Evaluation

Radiographic Evidence

Plain films demonstrate non-specific findings indicative of bronchial inflammation, such as segmental infiltrates, peribronchial thickening, hyperinflation, and atelectasis. Chest computed tomography (CT) is more sensitive to the presence, location, and severity of the disease.[20] Findings are most often located in dependent areas of the lung and include interstitial thickening, prominent septal lines, diffuse basilar centrilobular nodules, ground-glass opacities, and regions of bronchiectasis.[21]

Sequela of chronic aspiration, such as aspiration bronchiolitis and pneumonia, can also be imaged. The CT evaluation of aspiration bronchiolitis demonstrates increased attenuation, centrilobular nodules, and poorly defined mottled acinar areas. Radiographic features of aspiration pneumonia depend on volume, pH, and chronicity.[20] On plain films, there may be lobar or segmental airspace opacification. Often there is a gravity-dependent predilection. CT shows the involvement of dependent areas of the lung. In a recumbent patient, this is the posterior segment of upper lobes and superior segment of lower lobes. In an erect patient, this is the bilateral basal segments, lingula, and middle lobe.[22]

Further complications of these sequelae include lung abscess and empyema. It is important to differentiate lung abscess and empyema as they are treated drastically differently. Plain films of a lung abscess demonstrate air-fluid levels in a generally round cavity, while empyema is usually lentiform. Distinguishing features are more readily observable on CT. Abscesses have thick irregular walls and form an acute angle with the pleura. In contrast, empyemas have smooth walls and form an obtuse angle with the pleura. In addition, abscesses abruptly interrupt bronchovascular structures, while empyemas compress and distort adjacent lung tissue, often causing separation and thickening of visceral and parietal pleura.[23]

Diagnostic Procedures 

Speech and Swallow Studies

The breakdown of swallowing, breathing, and speaking mechanisms are directly related to the risk of chronic aspiration. Thorough speech and swallow studies are the mainstays of early evaluation of these processes. In children where a formal swallow and speech study is indicated, it may be necessary to place a feeding tube and take stepwise diet progression if the child is unable to perform classic testing.[5] These speech studies are also used for adults and must include physical observation, posture and positioning, cranial nerve functioning, cough and gag reflexes, and observed feedings with progressively thick liquids and solids.

The next step is a formal videofluoroscopic swallow study (VFSS), also known as a barium swallow. In this study, the subject ingests food or liquid mixed with barium. The fluoroscope is then used to observe the ingested material as it descends through the oropharynx, esophagus, and into the stomach. Three key findings are visible on VFSS: penetration, aspiration, and response to aspiration. Penetration is the passage of food or liquid into the epiglottis’ laryngeal surface, sometimes extending to the vocal folds in what is known as deep penetration. Aspiration is indicated by the presence of the barium in the trachea or bronchioles.

Finally, the patient’s response to aspiration is observed. If the patient does not cough when barium is in the pulmonary system, it is considered a silent aspiration. A penetration-aspiration score (PAS) is given on a scale of 1 to 8, with eight being the worst and indicating passage of the material into the tracheobronchial tree without any cough or clearance response. Higher scores are generally associated with worse functional outcomes, but research shows mixed results regarding the predictive morbidity and mortality outcomes of this scoring.[19]

Fiberoptic endoscopic evaluation of swallowing (FEES) is an alternative method to the VFSS. It involves a skilled practitioner passing a scope transnasally into space above the soft palate to observe swallowing. Aspiration and pooling of oral secretions can be observed. It is clearer than VFSS if clefts or physical deformities contribute to the aspirations. VFSS and FEES are often used in conjunction. Both have a strong positive correlation, but FEES has a slight advantage in detecting penetration and aspiration.[24] The requirement of physical tube placement is a drawback of FEES as this is not always feasible when a child is too small or is not cooperating with the procedure.

Another useful adjunct is a radionucleotide salivary scan. A tagged tracer is added to the saliva of the patient’s oropharynx and observed as swallowing occurs. This test is useful in patients that cannot tolerate formal VFSS or FEES. It can also pick up small salivary microaspirations that may be missed on FEES or VFSS. If used in conjunction with these other tests, it can increase the detection of aspiration pneumonia in both children and adults.[25]

Laryngoscopy and Bronchoscopy

Direct observation of the oropharynx and vocal folds using a laryngoscopy, bronchoscopy, or combination can be useful tools to rule out anatomic lesions or abnormalities that may contribute to aspiration risk. Flexible laryngoscopy observes the mobility of the vocal folds and is used to directly identify high-risk anatomical features. The patient must be awake for this procedure. A rigid laryngoscopy with bronchoscopy has the added benefit of being able to distract and probe into the inter arytenoid space and posterior cricoid. This makes it easier to find and identify clefts, fistulas, and other anatomic variances. This method is more sensitive in finding airway lesions than flexible laryngoscopy but does require the patient to undergo heavier sedation and anesthesia.[26] 

Finally, a flexible bronchoscopy with lavage (BAL) allows for assessing aspiration such as laryngomalacia and tracheomalacia. The BAL can differentiate the presence or absence of inflammation and disease, guiding management by determining if a chosen strategy is preventing further aspirations.

Treatment / Management

Conservative Measures

The mainstays of management and treatment involve addressing the underlying speech and swallow abnormalities and preventing further insults. The patient’s diet should be adjusted to match the foods and liquids most tolerable based on the diagnostics. Other conservative measures, such as continued direct observation, adjusting the size of intake, thickening feeds, and drinking water during and after meals to clear residual pharyngeal secretions, can effectively reduce aspiration risk and improve outcomes.[5][27] Further sessions with a therapist may be necessary to practice adequate posture, positioning, and swallowing technique and build muscle strength and coordination. Because aspiration is intermittent in nature, patients with persistent swallowing dysfunction and radiographic evidence of lung injury may require more aggressive management.  

One of the most important causes of aspiration-related mortality is aspiration-related pneumonia. Improving oral care is a simple but effective measure to decrease aspiration-related mortality. Regular oral care has been shown to reduce the bacterial count in the oral cavity.[28]

Pneumonia Management

If the aspiration leads to pneumonia, bacterial cultures should be obtained, and a beta-lactam/lactamase inhibitor combination, clindamycin, or carbapenem should be initiated. The current Infectious Disease Society of America guidelines as of 2019 do not recommend empirically treating gram-negative gut flora unless cultures indicate involvement. If blood cultures are negative and the suspicion is higher for aspiration pneumonitis, antibiotics should be stopped, and appropriate supportive treatment and aspiration prevention should be initiated. This includes oxygen supplementation, intermittent suctioning, elevated head of the bed, small or intermittent feedings or temporary tube placement, and intubation if necessary. In ventilated patients, subglottic secretion drainage effectively reduced the incidence and morbidity associated with early and late-onset ventilator-associated pneumonia.[29]

Data does not support using prophylactic antibiotics to treat recurrent aspiration pneumonia.[30] If a lung abscess develops secondary to acute or chronic pneumonia, treatment includes physiotherapy with postural drainage and prolonged antibiotics. Empyema, in contrast, requires percutaneous drainage.[23]

Feeding Tubes

If a patient fails to progress after multiple attempts or if a patient’s nutritional status is in question, a feeding tube can be considered. The options range from a naso- or orogastric feeding tube to a surgically-placed percutaneous gastrostomy or jejunostomy tube. Importantly in infants, those who were fed thickened oral liquids before surgical interventions had half the number of hospital admissions and less than a tenth of hospital days compared to their counterparts. It is important to note that all types of feeding tubes can be placed temporarily in both infants and adults until a more formal evaluation has been conducted. More definitive surgical options exist for those who fail conservative management. These are often performed by an experienced otorhinolaryngologist or general surgeon. While feeding tubes are an option to fulfill the nutritional needs of a patient who has dysphagia or is chronically aspirating, there are concerns for aspiration even after temporary feeding tubes or surgical feeding tubes are placed; thus, that should be kept in consideration and carefully evaluated.

Surgical Approaches

Laryngeal suspension. It is sometimes combined with an upper esophageal sphincter myotomy and concerns surgically positioning the larynx under the tongue for increased protection. The procedure usually shows good efficacy in reducing the risk in chronically aspirating patients by reducing penetration. It also allows for easier swallowing while protecting normal respiration and speaking function.[31]

Unilateral Vocal cord medialization. It should be considered if there is unilateral vocal cord immobility and the cord does not approximate fully or is relaxed or paralyzed for any reason during the swallowing process. In the procedure, the affected vocal cord is brought medially, either surgically or by the injection of material into the vocal cord itself, in an attempt to restore glottic and subglottic pressure during swallowing. This operation can improve speech, swallowing, and pulmonary function.

Laryngectomy. A final consideration is a laryngectomy, which removes the larynx entirely and reattaches the airway through the neck. This procedure is a last resort because it removes the patient’s ability to speak. It is only used when a life-threatening aspiration risk is present and refractory to all other previous management.

Differential Diagnosis

Chronic aspiration must be differentiated from:

  • Pneumonia (bacterial or viral)
  • Pulmonary embolism
  • Acute respiratory distress syndrome (ARDS)
  • Heart failure
  • Lung cancer
  • Tuberculosis
  • Gastroesophageal reflux disease (GERD)
  • Idiopathic pulmonary fibrosis

Prognosis

Prognosis is varied and depends on many underlying factors, including the cause and duration of the aspiration, the amount and nature of the aspirate, and the use of diagnostic tools to identify the source of the problem. It also relies heavily on modifications to diet and feeding techniques, utilization of adjuncts such as thickened feeds, feeding tubes, and surgical interventions. Better lung function prior to the insults also is associated with a better outcome, while poor cognitive functioning is associated with worse outcomes overall.

Complications

Common sequelae may include:

  • Aspiration pneumonia
  • Aspiration bronchiolitis
  • Obstructive bronchiolitis
  • Lung abscess and empyema

Symptoms indicating disease progression include early signs of infection, such as fever, leukocytosis, tachycardia, tachypnea, hypotension, and elevated lactate, in addition to the aforementioned aspiration symptoms. Chronic aspiration is also associated with interstitial lung disease, idiopathic pulmonary fibrosis, refractory asthma, and lung transplant rejection.[21]

Deterrence and Patient Education

Proper oral care, eating foods cleared by a speech and language professional, and practicing appropriate posture and positioning are all important to educate patients on who is at risk for chronic aspiration. Despite several available treatment options, no perfect options exist. There are concerns for micro and macro aspiration in several treatment options. Thus after carefully evaluating all available treatment options, patients should decide whether or not they should pursue any of those available treatment options.

Patients have a right to choose their treatment and may choose to continue to eat/drink despite the risks of aspiration pneumonia. For pediatric patients, it is essential to inform parents of early signs that their child may be aspirating, especially those at higher risk because of cognitive delay or neuromuscular disorders. In the elderly population, it is important to inform both the patient and those closest to them and who spend the most time involved in their care about the signs and symptoms of aspiration so that they can get appropriate help quickly.

Enhancing Healthcare Team Outcomes

Chronic aspiration is a condition that can be recognized by a primary care provider, including pediatricians, or by a hospitalist or intensivist while inpatient. It is a well-researched, well-understood pathology with established standards of care for each subset of patients. In this context, the nursing staff is vital for early recognition of aspiration syndromes and observing eating in at-risk patients. The evaluation further involves consulting a certified speech-language therapist to do a speech and swallow study. Therefore, care for these patients involves the efforts of a multidisciplinary and interprofessional healthcare team, functioning as a cohesive unit, documenting all interactions, interventions, and findings, and communicating with other team members whenever necessary. This will optimize patient outcomes. [Level 5]

A radiologist may need to be utilized at this point to do a visual fluoroscopic swallow study. A radiologist is also required for imaging as a chest CT scan. Further diagnostic studies, including FEES, laryngoscopy, and bronchoscopy, require an otorhinolaryngologist, a general pediatric surgeon, or a pulmonologist to perform and evaluate the results of these tests. Evaluation of the underlying disorders causing the aspiration may require consultation from a neurologist. This is especially important with pediatric patients that have evidence of persistent dysphagia and may have an underlying neuromuscular disorder or cognitive delay contributing to their aspiration risk. Management may include conservative measures that involve watching and instructing patients on proper feeding techniques.

This may require in-hospital staff or frequent pediatric visits to the speech-language therapist in pediatric patients. In the elderly, nursing home staff or home health nursing care will be instrumental in successfully implementing aspiration prevention and long-term management. In all of these areas, close supervision by physicians or nursing staff is vital to ensure further aspiration events do not occur or that they are rapidly identified and receive immediate intervention. Surgery may be necessary for cases of chronic respiration that do not improve with conservative management. An ear, nose, and throat surgeon, general surgeon, or pediatric specialist will need to be consulted for these operations. This demonstrates the necessity of teamwork in providing care to these patients.


Details

Editor:

Marco Cascella

Updated:

7/4/2023 12:35:32 AM

References


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