Continuing Education Activity

In Curtis Lester Mendelson’s original 1946 description of his namesake syndrome, chemical pneumonitis was described in young and healthy obstetrical patients following aspiration of gastric acid under anesthesia. The standard use of regional anesthesia for most laboring women and increased awareness among anesthesia providers regarding the high risk of aspiration and potential difficult airway management in parturients has increased the safety in this population. This activity reviews the evaluation and management of Mendelson syndrome and highlights the role of the interprofessional team in evaluating and improving care for patients with this condition.

Objectives:

• Review the etiology of Mendelson syndrome.
• Describe the presentation of a patient with Mendelson syndrome.
• Summarize the treatment options for Mendelson syndrome.
• Outline the importance of improving care coordination among interprofessional team members to improve outcomes for patients with Mendelson syndrome.

Introduction

In Curtis Lester Mendelson’s original 1946 description of his namesake syndrome, chemical pneumonitis was described in young and healthy obstetrical patients following aspiration of gastric acid under anesthesia.[1] In the case series by Mendelson, 66 obstetrical patients under anesthesia with ether aspirated gastric contents. Within two hours of the witnessed aspiration, patients developed respiratory distress and cyanosis.[2] Unilateral or bilateral lower lobe infiltrates were present on chest radiography. Although Mendelson’s sample had a positive outcome, subsequent studies have revealed that patients may develop acute respiratory distress syndrome (ARDS) following aspiration pneumonia.[3] Mendelson’s landmark study suggested that chemical pneumonitis was preventable by restricting oral intake during labor, which eventually led to the NPO guidelines we have in place today for parturients. The field of obstetrics and gynecology has come a long way since Mendelson’s time, as the use of general anesthesia is now infrequent for laboring women, and neuraxial analgesia is the standard of care for modern practice. At present, the American College of Obstetricians and Gynecologists encourage the ingestion of clear liquids and the avoidance of solid food during labor.

Mendelson’s study reviewed the aspiration of gastric contents among 44000 pregnancies at the New York Lying-In Hospital from 1932 to 1945. His paper has two parts: a clinical report and an animal model. “Mendelson syndrome” was initially described as aspiration of gastric contents causing a chemical pneumonitis characterized by fever, cyanosis, hypoxia, pulmonary edema, and potential death. Among the patients studied, there were 66 cases of aspiration (0.15%) and two deaths (0.0045%). Both patients tragically died following suffocation from solid food aspiration of full meals that were ingested six and eight hours before delivery, respectively. The remaining 64 patients experienced aspiration of liquid material, and they often went unrecognized with complete recovery.[1]

Mendelson replicated the gastric acid in the respiratory distress syndrome he witnessed in human patients through his animal model. He placed both neutralized and untreated hydrochloric acid and vomitus from pregnant women into the respiratory tracts of rabbits. Mendelson found that during labor, there is prolonged retention of solids and liquids in parturients’ stomachs, and aspiration commonly occurs after abolishing laryngeal reflexes. During Mendelson’s time, the induction of general anesthesia was not limited to parturients undergoing a cesarean section but was also the method for spontaneous or operative vaginal deliveries. 21% of aspiration cases were among women who delivered via cesarean section, while 79% of women were undergoing general anesthesia for vaginal deliveries. The general anesthetic at this time consisted of a nonspecific mixture of gas, oxygen, and ether. The airway was left unsecured during delivery as parturients were subjected to mask induction and maintenance with an opaque black rubber mask. Following aspiration, the initial clinical course was severe including massive atelectasis with cyanosis, dyspnea, mediastinal shift, and radiographic signs of lung injury. Despite this, the 64 nonfatal cases were almost all liquid aspirations with radiographic resolution within seven days and clinical recovery within 36 hours without the use of antibiotic treatment.[1]

Mendelson’s study led to several recommendations that still are in use in the obstetric population to this day. Pregnant women are treated as though they have a “full stomach” regardless of their last meal, and inhalational anesthesia without intubation is strictly avoided. Opaque rubber masks that can conceal regurgitation and vomitus have been replaced with clear plastic masks and ingestion of solid food has been discouraged during labor. Two American anesthesiologists, Paleul Flagg, and James Miller suggested that experienced anesthesiologists could help avoid the complications that Mendelson described. Miller reported over 26000 deliveries at Hartford Hospital with no mortality secondary to asphyxia, partially attributed to expert anesthesiology staff.[1] The argument was that safely administered general anesthesia could reduce the risk of aspiration in parturients.

Although Mendelson’s contributions to obstetric anesthesia should not be understated, modern obstetrics has evolved considerably since then. During the last thirty years, aspiration in pregnant women has markedly declined, primarily due to advances in obstetrical anesthesia. The standard use of regional anesthesia for most laboring women and increased awareness among anesthesia providers regarding the high risk of aspiration and potential difficult airway management in parturients has increased the safety in this population. Care has also improved by advances in difficult airway management devices including video laryngoscopes, endotracheal tube introducers, optical stylets, and flexible endoscopes. The routine utilization of pulse oximetry, capnography, and difficult airway algorithms have also helped to mitigate the risks associated with general anesthesia in parturients.[4]

Etiology

There are specific physiologic changes of pregnancy that increase aspiration risk in this population. Minute ventilation, oxygen consumption, and carbon dioxide production are increased in early pregnancy, while the gravid uterus displaces the diaphragm upward in late pregnancy, substantially reducing functional residual capacity. Cardiac output, heart rate, stroke volume and circulating blood volume are all increased during pregnancy. The gravid uterus increases intra-abdominal pressure, predisposing patients to reflux. Progesterone-mediated relaxation of the lower esophageal sphincter (LES) and prolonged gastric emptying time increase the risk of gastroesophageal reflux disease and aspiration of gastric contents during general anesthesia.[5] The upper esophageal sphincter is made of striated muscle and is not affected by progesterone, but anesthetic induction will reduce its tone. Parturients must be on strict NPO guidelines (two hours for clear liquids, six hours for a light meal, and eight hours for a solid fatty meal).[6]

Chemical pneumonitis is more likely following the aspiration of gastric contents if pH is less than 2.5 and volume is at least 0.3 mL/kg body weight. The basis of these calculations is a 1974 study by Roberts and Shirley following direct placement of acid into a Rhesus monkey’s right mainstem bronchus.[7] Knowledge, medical expertise, and appropriate fasting intervals have made aspiration uncommon today, with an incidence of 1 in 3216 procedures, with a much higher risk in emergency procedures.[8] In most patients following aspiration, clinical and radiographic abnormalities do not develop. In symptomatic patients, pulmonary embarrassment is due to neutrophil recruitment as well as the release of proinflammatory cytokines including tumor necrosis factor-alpha and interleukin 8.[9]

Clear liquids are permissible during labor based on findings by William Beaumont, a military surgeon, who treated an individual with a gunshot wound to the stomach who had developed a gastric fistula. This injury allowed him to discern gastric emptying time for liquids versus solids. Beaumont stated that liquids pass through the stomach shortly after arrival, and gastric emptying of liquids is an exponential process; the rate of emptying is based upon the amount that remains in the stomach. The rate of emptying of solids is constant and starts an hour after the meal: about half reaches the duodenum within a few hours.[10] Factors that most commonly increase aspiration risk include emergency surgical procedures, inadequate depth of anesthesia, gastrointestinal pathology, obesity, concomitant opioid administration, impaired consciousness, lithotomy positioning, difficult airway or intubation, gastrointestinal reflux, and hiatal hernia. The severity of respiratory compromise following aspiration depends upon the amount of material aspirated, its acidity, patient age, and comorbidities. Acute respiratory distress leading to cyanosis and possible death is the result of large objects that obstruct the trachea or larynx. Aspiration of smaller particles can cause unilateral wheezing, dyspnea, cough, and atelectasis.

Epidemiology

Pulmonary aspiration rates have significantly declined over the last 30 years. In a 1990 to 2003 review of closed obstetric anesthesia claims, Davies et al. reported that the incidence of aspiration declined from 4.2% to 0.46%.[11] Subsequently, in 2008, McDonnell reviewed 1095 cesarean deliveries under general anesthesia at 13 institutions and reported 5 cases of aspiration (incidence of 0.4%).[12] In 2014, the Society for Obstetric Anesthesia and Perinatology Serious Complications Registry project published data regarding serious complications of obstetric anesthesia.[13] Data compilation was from more than 30000 deliveries with 250000 regional anesthetics and 5000 general anesthetics, with no aspiration events noted. In contrast, nonobstetric emergency surgery literature suggests pulmonary aspiration rates of 1 to 373 to 1 to 895.[14]

Mhyre et al. used the nationwide inpatient sample from 1998 to 2011 to evaluate the etiology and outcome of maternal cardiac arrest for hospitalization for labor, and their findings implicated aspiration in 7.1% of cases.[15] Among patients with pulmonary aspiration, survival was among the highest at almost 83%, though. Of note, although ingestion of solid food is certainly an important risk factor to consider in pulmonary aspiration, Lock et al. found that anesthetic care by inexperienced anesthesiologists is the leading cause of maternal mortality in this population.[16] Aspiration pneumonia accounts for 5 to 15% of 4.5 million cases of community-acquired pneumonia.[17] Aspiration occurs 3 in every 10000 anesthetics, more commonly during emergency surgery and in patients with higher American Society of Anesthesiologists (ASA) status.[18] A retrospective review concluded the 30-day mortality rate following aspiration pneumonia is 21% overall vs. 29.7% for healthcare-associated pneumonia.[19]

Pathophysiology

Animal models have been used to study the pathophysiology of aspiration pneumonitis - those afflicted with gastric reflux may experience episodes of recurrent pneumonitis, often accompanied by pulmonary fibrosis.[20] Animal models reveal the development of atelectasis, pulmonary edema, and peribronchial hemorrhage within three minutes. Within a few hours, fibrin and leukocytes begin to engulf alveoli which leads to hyaline membrane development and pulmonary alveolar consolidation within 48 hours. Outcome following severe aspiration can vary from complete recovery to pulmonary fibrosis.[21]

During pregnancy, chemical pneumonitis is more likely due to the plethora of anatomic and physiologic changes that are present. Almost all parturients have a gastric pH of less than 2.5, and greater than 60% of them have gastric volumes greater than 25 mL.[22] The lower esophageal sphincter (LES) is displaced cephalad and anteriorly, predisposing to its incompetence. Secretion of gastrin by the placenta causes hypersecretion of gastric acid in parturients. Opioids and anticholinergics reduce LES pressure and also delay gastric emptying, as does labor. Regardless of last oral intake, all parturients are considered to have a full stomach and to be at risk for pulmonary aspiration. Parturients exhibit an increased risk of difficult intubation following induction of general anesthesia. Circulating blood volume is elevated in these patients as a result of increased estrogen levels, leading to pharyngeal and laryngeal mucosal edema. Laryngeal anatomy is subject to distortion, the glottic diameter reduced, and bleeding is more likely during intubation due to friable pharyngeal mucosa. An enlarged tongue and redundant pharyngeal and palatal soft tissue can make glottic visualization with direct laryngoscopy challenging. Furthermore, mask ventilation may be difficult or impossible in these patients. Abdominal panniculus and enlarged breasts can impair mouth opening and laryngoscope introduction.[23]

In a 2009 review by Djabatey et al., 1 in every 150 obstetrical patients is difficult to intubate, and 1 in every 280 patients is a failed intubation, as compared to 1 in 2230 failed intubations in the general population.[24][25] The majority of general anesthetics for the obstetrical population are performed for emergency cesarean sections, subjecting the patient and the medical team to a highly stressful situation. Anesthesiologists must be prepared to induce general anesthesia in this emergent situation where both maternal and fetal lives are potentially at risk. Due to high aspiration risk, pregnant women should undergo rapid sequence induction with cricoid pressure. Aspiration most commonly includes organisms from the oropharynx (Staphylococcus aureus, anaerobic or gram-negative bacteria) particulate matter, liquids, or gastric acid.

History and Physical

Mendelson syndrome may mimic pulmonary edema in its presentation with an acute onset following aspiration. Patients present with dyspnea, cough, fever, and profuse frothy pink sputum. Symptoms may be indolent or can progress to pulmonary necrosis with lung abscess or empyema. On physical examination the patient is tachypneic, having tachycardia and crackles on auscultation of chest mostly on the right lower part which is the most dependant area for the aspirated contents.

Evaluation

The diagnosis of Mendelson syndrome depends upon clinical history, including a witnessed aspiration, risk factors, and characteristic chest radiography findings, although X-rays may initially be negative. Radiographic films may reveal irregular densities in the dependent pulmonary segments, primarily on the right side, which is at greater risk of aspiration due to the larger diameter and more vertical orientation of the right mainstem bronchus. Pulse oximetry can show oxygen desaturation and tachycardia. A computed tomography scan of the chest can reveal consolidation.

Treatment / Management

Although the best treatment should be primarily preventative, aspiration should be recognized and managed swiftly to curb dangerous sequelae. The patient should be in the Trendelenburg position, and the oropharynx suctioned. If the patient exhibits signs of hypoxia and diminished airway reflexes, swift intubation should follow. After an endotracheal tube is secured, a soft suction catheter should be passed to prevent the dislodgement of aspirated material further into the lung with positive pressure ventilation. In the case of aspiration of particulate matter, bronchoscopy and pulmonary lavage may prove useful. Mechanical ventilation and intensive care unit admission may be appropriate depending on the patient’s clinical status. Prophylactic antibiotics should not be utilized even in patients with radiographic findings of an infiltrate until the patient’s clinical condition warrants their use.

Prevention is via specific recommendations from the American society of anesthesiology (ASA). A modest amount of oral intake of clear liquids may be allowed for uncomplicated laboring patients up to two hours before anesthetic induction. While the volume of liquid ingested is unimportant, the presence of particulate matter is of significance in terms of aspiration risk. Solid foods are to be avoided in laboring patients and those with additional risk factors including diabetes, morbid obesity, and a difficult airway. For patients undergoing elective surgery, patients should fast for 6 or 8 hours depending on the fat content of the meal. Excessive sedation and some antipsychotic medications should be avoided as they can increase aspiration risk.[26]

Medication prophylaxis is used routinely for parturients to mitigate the risks of aspiration pneumonitis. Clear nonparticulate antacids such as sodium citrate 15 to 30 mL orally every 3 hours maintain gastric pH greater than 2.5. Histamine receptor-2 antagonists such as ranitidine aid in reducing gastric acid volume and increasing pH. Prokinetic agents such as metoclopramide reduce gastric volume, increase LES tone and reduce peripartum nausea and vomiting.[26] Antiacid therapy has been shown to reduce the risk of chemical pneumonitis by neutralization of gastric pH.[27] Paranjothy et al. concluded that histamine receptor-2 antagonists in addition to nonparticulate antacids, such as sodium citrate, significantly increased gastric pH above 2.5 at intubation as compared to placebo.[28]

Differential Diagnosis

Mendelson syndrome mimics the presentation of many other disorders which should be ruled out. These include:

• Foreign body aspiration
• Near drowning
• Barium aspiration
• Acute exogenous lipoid pneumonia
• Chronic exogenous lipoid pneumonia
• Necrotizing pneumonia      
• Aspiration pneumonia secondary to periodontal disease
• Pulmonary abscess status post laryngectomy
• Aspiration bronchiolitis
• Obliterative bronchiolitis
• Bronchitis
• Tuberculosis
• COPD/emphysema
• Adult epiglottitis
• Mycoplasma pneumonia
• Viral pneumonia

Prognosis

The prognosis of Mendelson syndrome depends upon the comorbid disease, the severity of aspiration, complications, and the patient's underlying health status. In Mendelson's 1946 original series, 66 obstetric patients aspirated gastric acid during their anesthetic, and almost all had a complete clinical recovery. Subsequent studies have included elderly patients with the comorbid disease, with a reported mortality rate of 30 to 62%, as chemical pneumonitis can lead to ARDS. The mortality rate for chemical pneumonitis can be up to 70%. If pneumonia develops and does not receive prompt treatment, it can lead to the development of a lung abscess or a bronchopleural fistula. The mortality rate for empyema that complicates aspiration pneumonia is approximately 20%, while that of uncomplicated pneumonia is about 5%. An animal model of mice with aspiration pneumonitis suggested that they are more susceptible to subsequent respiratory infections.[29]

Complications

Mendelson syndrome can lead to serious complications and these include:

• Bacterial pneumonia
• Lung abscess
• Airway obstruction
• Bronchopleural fistula
• Respiratory failure
• Acute respiratory distress syndrome
• Pleural effusion
• Empyema
• Shock
• Sepsis

Deterrence and Patient Education

A modest amount of oral intake of clear liquids may be allowed for uncomplicated laboring patients up to two hours before anesthetic induction. While the volume of liquid ingested is unimportant, the presence of particulate matter is of significance in terms of aspiration risk. Laboring patients are to avoid solid foods, especially those with additional risk factors including diabetes, morbid obesity, and a difficult airway. Patients should fast for 6 or 8 hours before undergoing elective surgery depending on the meal's fat content. Excessive sedation and some antipsychotic medications should be avoided as they can increase aspiration risk.

Enhancing Healthcare Team Outcomes

Mendelson syndrome is best managed and prevented by an interprofessional team that includes an anesthesiologist, anesthesia nurse, intensivist, pulmonologist, obstetrician, and a nursing team with specialized pulmonary and obstetric training. Because the disorder has high morbidity and mortality, it is best prevented. Prevention is via specific recommendations from the ASA. A modest amount of oral intake of clear liquids may be allowed for uncomplicated laboring patients up to two hours before anesthetic induction. While the volume of liquid ingested is unimportant, the presence of particulate matter is of significance in terms of aspiration risk. Laboring patients are to avoid solid foods, and those with additional risk factors including diabetes, morbid obesity, and a difficult airway. Patients should fast for 6 or 8 hours before undergoing elective surgery depending on the meal's fat content. Excessive sedation and some antipsychotic medications should be avoided as they can increase aspiration risk. The nurses and pharmacists should work with the providers to carefully manage sedation to avoid this disease process and improve outcomes. A cooperative team environment of double-checking doses and careful monitoring will minimize the risk.

The outlook for patients with Mendelson syndrome remains guarded. Despite optimal treatment, there are still reports of mortality rates of close to 30%.[30](Level V)