Chapter 58. Post-Obstructive Pulmonary Edema

A 43-year-old morbidly obese woman presented for gastroplasty. Her past medical history included treated hypothyroidism and past surgical history was unremarkable. She reported functional Class II to III dyspnea on exertion. Her medications consisted of L-thyroxine, amitriptyline, codeine, and furosemide. Laboratory investigations and ECG were normal. She weighed 340 lb (150 kg) and was 5 ft 6 in (168 cm) tall. Preoperative airway examination revealed normal mouth opening with full teeth, a thyromental span of 7 cm, and good jaw protrusion. She demonstrated a modified Mallampati Score III and had slightly restricted head extension. The rest of her physical examination was unremarkable.

Following appropriate positioning and denitrogenation, a rapid-sequence induction (RSI) was performed using midazolam, fentanyl, propofol, and succinylcholine. Direct laryngoscopy using a Macintosh #3 blade revealed a Cormack/Lehane (C/L)1 Grade 2 view. Although some difficulty with tube passage was encountered, successful tracheal intubation using a styletted 7-mm internal diameter (ID) endotracheal tube (ETT) occurred on the second attempt. General anesthesia was maintained with sevoflurane, further doses of fentanyl, and rocuronium for muscle relaxation. Two liters of Lactated Ringer were given during the 2-hour procedure. On emergence, residual neuromuscular blockade was fully reversed, and she demonstrated a regular pattern of spontaneous respiration, with good tidal volumes.

At this time, the patient vigorously bit down on the ETT. For a period of approximately 90 seconds, no gas exchange occurred, even with attempted assisted manual ventilation via the anesthetic circuit. Although respiratory efforts continued, no CO2 trace was apparent during the episode. Oxygen saturation fell to 78% before her jaw relaxed somewhat, allowing assisted, then spontaneous ventilation to resume. She was subsequently placed in the lateral position until her eyes opened and she was able to obey commands. At this point, she was extubated. Shortly after extubation, she began to cough up frothy, pink fluid without either retching or vomiting. Her oxygen saturation, which had been 97% on a simple oxygen face mask immediately post-extubation, dropped to 85%.

58.2.1 What Is Post-Obstructive Pulmonary Edema?

Post-obstructive pulmonary edema (POPE) is characterized by the sudden onset of pulmonary edema of varying severity following vigorous inspiratory efforts against an obstructed upper airway. It most often occurs in a patient with no intrinsic cardiac, neurologic, or pulmonary disease. POPE usually presents with dyspnea, tachypnea, hypoxemia, and a cough productive of pink, frothy sputum. After confirming that the obstruction has been relieved, treatment of POPE is usually symptomatic, and varies from simple application of supplemental oxygen, to intubation with mechanical ventilation and application of positive end-expiratory pressure (PEEP). The condition usually resolves within 24 to 48 hours and most patients suffer no long-term sequelae.

Pulmonary edema following acute upper airway obstruction was first described in children in 1973.2 A few years later, Oswalt described a number of cases of respiratory distress and pulmonary congestion following episodes of severe acute upper airway obstruction in otherwise healthy patients.3 Since then, numerous case reports and case series have been published on this phenomenon.

58.2.2 What Synonyms Have Been Used to Refer to POPE?

Many synonyms appear in the literature to describe this process. These include the following:

• Negative pressure pulmonary edema4-12
• Post-laryngospasm pulmonary edema13
• Laryngospasm-induced pulmonary edema7,14,15
• Post-extubation pulmonary edema16,17
• Non-cardiogenic pulmonary edema4
• Athletic pulmonary edema7

58.2.3 What Are the Two Types of POPE?

Two types of POPE have been described.18 They present with similar clinical pictures, and most likely have similar pathophysiologies:

• POPE type I: This typically occurs shortly after relief of an episode of acute upper airway obstruction from any cause, for example, laryngospasm.
• POPE type II: POPE type II occurs after relief of a chronic upper airway obstruction, caused by conditions such as chronic tonsillar hypertrophy, laryngeal tumor, goiter, or bilateral vocal cord paralysis.4

The remainder of this chapter refers mainly to POPE type I, as this is most commonly encountered in anesthetic and airway management practice.

58.3.1 What Is the Incidence of POPE?

The incidence of POPE has been estimated at 0.5 to 1.0 case per thousand surgical patients.6,19 Of patients who have experienced, or required intervention for an episode of acute upper airway obstruction, published figures suggest a 5% to 10% incidence of progression to POPE.8,19,20 POPE occurs most often in younger adults and children, most with ASA 1 and 2 status.5,6 Young, athletic males are strongly represented in case series,17,21 possibly because their well-developed musculature enables them to develop stronger inspiratory efforts against the upper airway obstruction, with resultant highly negative intrathoracic pressures. Most cases occur following tracheal extubation.6

58.3.2 What Predisposes to the Occurrence of POPE?

In the adult population, the most common cause of POPE is post-extubation laryngospasm,17,22 while in children younger than 10, most cases follow upper airway obstruction from croup, epiglottitis,5,20 and to a lesser extent, laryngospasm. However, POPE following vigorous attempts to inspire against upper airway obstruction has been reported from many other causes, including biting down and occluding the lumen of ETTs9,23 and laryngeal mask airways (LMAs).11,12 POPE has also been reported following upper airway obstruction from hanging, strangulation,3,9 foreign body aspiration,24,25 laryngeal tumor,5 hematoma, goiter,9,26 obstructive sleep apnea,27 bilateral vocal cord paralysis,28 and direct suctioning of both ETTs29 and chest tubes.30 Unilateral POPE has also been described in a lung occluded by an accidental mainstem bronchus intubation of the contralateral lung.31

58.3.3 What Is the Pathophysiology of POPE?

The variable clinical and laboratory manifestations of POPE probably reflect its multifactorial pathophysiology and various degrees of severity. The two proposed mechanisms of edema formation relate to (a) consequences of the highly negative intrathoracic pressure generated during an episode of complete upper airway obstruction (the Mueller maneuver),20,22,25 and (b) the hyperadrenergic response to airway obstruction and hypoxia5,16,18 (Figure 58-1). The following are probable contributory mechanisms:

1. Negative pressure transfer to the pulmonary alveoli and interstitium affects Starling forces by creating a gradient that favors transudation of fluid out of the pulmonary capillaries to the interstitium.4,24 Once the capacity of pulmonary lymphatics to remove fluid from the interstitium is exceeded, leakage of fluid occurs into the alveolar space.16,32,33

2. Enhanced venous return to the right heart and pulmonary arteries results from the generated negative intrathoracic pressure4-6,22,24 and is compounded by central blood redistribution from the hyperadrenergic state caused by significant hypoxemia, anxiety, and hypercarbia.5,9,16,22,24,32,34 Higher pulmonary arteriole and capillary bed blood volumes and hydrostatic pressures further favor fluid transudation from capillary to interstitium.8

3. Impeded outflow from the pulmonary capillary bed occurs as left-sided pressures rise from (a) decreased stroke volume resulting from increased systemic vascular resistance;6,24,32,34 (b) decreased left ventricular diastolic compliance (from right ventricular distension); and (c) depression of myocardial contractility, from hypoxia and acidosis.9

4. Hypoxic pulmonary vasoconstriction directly contributes to increases in pulmonary capillary pressures.5,16

5. Disruption of the alveolar-capillary membrane (stress failure)35 and its barrier function can eventually occur from damage to the capillary endothelium by increased pulmonary capillary volume and pressures. In addition, particularly with prolonged hypoxia,24 the hyperadrenergic state can directly contribute to further membrane disruption.4,6 Such disruption can be manifested by the leakage of both protein-rich exudative and hemorrhagic fluid.

POPE has a spectrum of clinical presentations. It is likely that in most cases, with intact pulmonary capillaries, simple alteration in Starling forces result in the transudative production of low-protein edema.34 Fremont and his group looked retrospectively at a series of 341 patients intubated for pulmonary edema and identified 10 individuals who had POPE as the etiology. Analysis of the edema fluid of this subset of patients, looking at the edema fluid-plasma protein ratio and its rate of clearance, strongly suggested a transudative, hydrostatic mechanism in most of the patients.36

However, higher negative intrathoracic pressures, coupled with a hyperadrenergic response, may result in ultrastructural changes in the capillary endothelial barrier, allowing the escape of exudative edema, as documented in some case reports.28,37 Extreme cases result in breaks in the alveolar-capillary membrane, allowing red blood cell leakage, and possibly frank hemorrhage. Chest radiographs in this latter situation may show an alveolar pattern of edema, in contrast to the more interstitial pattern typical of transudative edema.7 That case reports differ in their reporting of transudative and exudative edema, or primarily interstitial or alveolar patterns of edema on chest radiography probably reflects the varying degrees of severity of the obstructive episode causing the POPE.

58.3.4 Why Does POPE Appear Only after the Relief of Upper Airway Obstruction?

Type I POPE generally appears shortly after the relief of an acute upper airway obstruction. In many cases, this is a fixed obstruction, such as laryngospasm or an occluded ETT. Profoundly negative intrathoracic pressures generated during attempted inspiration (Mueller maneuvers) may be balanced during attempted expiration against the same fixed obstruction (ie, a Valsalva maneuver), akin to an auto-PEEP phenomenon. It may be that this PEEP-like effect during attempted expiration is somewhat protective by limiting the transcapillary pressure gradient. On relief of the obstruction, pulmonary edema becomes manifest5,6,24 with the sudden transient drop in mean airway pressure,8 together with the increase in venous return and pulmonary hydrostatic pressure.7,32

In type II POPE, chronic, usually variable obstruction favors the Mueller maneuver in that more obstruction occurs during attempted inspiration than expiration. In this situation, the generated negative intrathoracic pressure is counteracted by more modest levels of PEEP. Although still somewhat protective against the development of pulmonary edema,38 published reports document abnormal A-a gradients and radiographic evidence of pulmonary edema before relief of chronic upper airway obstructions.5,6,24 Following the relief of both type I and type II obstructions, it is likely that altered capillary permeability, previously occult interstitial edema38 and LV dysfunction,24 contribute to the development of POPE in spite of now-normal lung volumes and pressures.

58.4.1 What Are the Presenting Symptoms and Signs of POPE?

The patient with POPE often presents within minutes5,22 after the relief of an episode of upper airway obstruction characterized by vigorous inspiratory efforts without significant air movement.16,34 The initial presentation is often with dyspnea,8 tachypnea,24,39,40 agitation,8,21,34 and cough11,21,22 producing pink, frothy fluid.3,4,8,9,22,34,41 In addition to hypoxemia,7,39 the patient is also often tachycardic14,34 and hypertensive.34 Other patients have presented with frank hemoptysis,9,12,19,23,42 although this is less frequent. Residual partial obstruction may be present in this population, manifested by stridor8,11,16,21,43 or intercostal and subcostal retractions.21,24,44 On auscultation, most patients have rales,12,16,22,24,40,41 sometimes with associated rhonchi.3,14,22,25,34,40

58.4.2 What Are the Results of Investigations Typically Performed on the Patient with POPE?

• Invasive monitoring of central venous (CVP) or pulmonary artery pressures (PAP) is rarely undertaken in the patient recognized to have POPE. However, when reported, pressures, including CVP3,22 and pulmonary capillary wedge pressures (PCWP)5,22,45,46 have generally been normal, while PAPs have been normal or only slightly elevated.22
• Chest radiographs of the patient with POPE often show signs of edema with either an alveolar (airspace consolidation)9,16,19,44 or interstitial (perihilar haze, perivascular or peribronchial cuffing, and Kerley lines)3,4,6,25 pattern, or both.7,24,39 Most often the edema distribution is predominantly central and bilateral, although asymmetrical34 or even unilateral distributions have been reported.7,11,19 Heart size is generally normal.7,19,24 Vascular pedicle width in one series was found to be above normal, suggesting an increase in central blood volume.7
• High-resolution CT scans of the chest have shown findings of ground-glass opacities, peribronchial cuffing, and interlobular septal thickening, typical of interstitial pulmonary edema.25,42 Others have shown diffuse patchy lobular airspace disease.24
• Bronchoscopy performed on patients with POPE has shown punctate bleeding lesions in both trachea and mainstem bronchi43 or more generalized blood staining of the tracheobronchial tree.23,34 Bronchial-alveolar lavage (BAL) in one report revealed a progressively bloody return, consistent with alveolar hemorrhage,34 while in a second report, BAL produced clear returns.23
• No specific electrocardiogram (ECG) pattern has been reported in the POPE patient population. When reported, ECG findings have been uniformly normal.

58.4.3 Should the Patient Presenting with POPE Be Referred for Echocardiography?

Most case reports and case series of patients experiencing POPE have documented rapid resolution of the episode with no long-term sequelae and no special cardiac work up performed. Echocardiograms have generally been normal.9,16,19,25,26,34,42,47,48 One exception was a case series of six patients who had experienced POPE, all of whom had echocardiograms. In this small retrospective series, abnormalities were detected in 50% of the cases: one patient had hypertrophic cardiomyopathy, and the other two had pulmonary and tricuspid valvular insufficiency.4 However, in the absence of other recognized indications, the current lack of evidence does not support a recommendation for routine echocardiographic testing of all POPE patients.

58.5.1 What Is the Usual Clinical Course of POPE?

Following relief of the acute upper airway obstruction, the onset of POPE is generally rapid, that is, within minutes, however a minority of case reports document delayed onset of up to 4 to 6 hours,5,38 suggesting that following an episode of acute, severe upper airway obstruction,18 patients should be monitored for 6 to 12 hours. The same recommendation has been made for patients who have had surgical relief of chronic upper airway obstruction.18

In most cases, POPE runs a benign course, with symptoms, and clinical and radiologic signs clearing within 24 to 48 hours.4-6,17,22,38,44,48

58.5.2 How Is POPE Managed?

As the name implies, most cases of POPE present after the upper airway obstruction has been alleviated. After confirming airway patency, supplemental oxygen should be administered, and may be all that is required.3,6,16,22 Continuous positive airway pressure (CPAP) by face mask has also been shown to be an effective intervention,14,19 and the use of noninvasive ventilation has been reported.26 Hypoxemia, or patient fatigue that is unresponsive to noninvasive methods may require reintubation and positive pressure ventilation. The larger case series report re-intubation rates of between 66.5%8 and 85%.5,6,22 Of those patients re-intubated, about half require mechanical ventilation5 with3,4,34 or without PEEP, usually for less than 24 hours.6

Although diuretics are often used in the setting of POPE3,5,6,14,23,24,34,44 this practice has been questioned5,24 based on the finding of normal central filling pressures, and the equally rapid resolution of symptoms when they are not used.9,44 The use of steroids has been reported sporadically,3,14,44 although as with the use of diuretics, their use is controversial18 and without proven benefit. Other case reports make mention of fluid restriction3,18 and the administration of conventional congestive cardiac failure (CCF) medications such as morphine or digoxin.22

The available evidence would suggest that if the diagnosis of POPE is correct, drug therapy is unlikely to be of benefit, particularly in view of the self-limited and rapidly resolving course of the condition. With rare exceptions,4,10 the same can be said of invasive hemodynamic monitoring.16

58.5.3 What Is the Differential Diagnosis of POPE?

The primary alternate diagnosis to POPE is aspiration pneumonitis, which may lead to pulmonary edema even when frank regurgitation has not been noted.5 The initial management of this condition is identical to that of POPE, unless of course the aspirate is suspected to be particulate or contaminated by bacteria. It is more important to rule out other causes of pulmonary edema where management differs from that of POPE, including iatrogenic volume overload, primary cardiogenic causes, or drug reactions.

58.5.4 What Are Risk Factors and Preventive Strategies for the Development of POPE?

A number of factors place the patient at higher risk for the development of POPE. Some are unavoidable, while some can be minimized by employing the principles of good airway management. The early recognition and management of acute, severe upper airway obstruction, and the conditions leading to it, are critical to the prevention of POPE:

• Laryngospasm: Most cases of POPE in adults, and many in children follow an episode of laryngospasm. Many case reports of POPE document laryngospasm following extubation during emergence from anesthesia, before the patient is fully awake.44,49 Therefore, it is recommended that extubation be performed in patients who are either deeply anesthetized or fully awake. The prevention of intra-operative laryngospasm under mask or extraglottic device (EGD) anesthesia requires deep general anesthesia, particularly for highly stimulating surgical procedures. Prior to removing an ETT, suctioning of blood or secretions that may trigger laryngospasm is essential, particularly following upper airway surgery. Should laryngospasm occur, the initial treatment is to relieve any soft tissue obstruction together with gentle application of 10 to 20 cm H2O CPAP by mask. However, the administration of succinylcholine 0.2 mg·kg−1 (or other appropriate neuromuscular blocking agent) may be indicated in patients making vigorous inspiratory efforts against a closed glottis, particularly if it persists for more than 30 seconds.49
• Tube occlusion by biting down: POPE has been described in patients who have bitten down to occlude ETTs41,44 and EGDs (eg, LMA).11,12,50 Most reports have documented this occurring on emergence from anesthesia, although it has also been described during the positioning process.11 Use of a rolled gauze bite block alongside the lumen of an endotracheal tube9,41 or LMA (as recommended by its inventor50) ought to minimize this risk. As with laryngospasm, the administration of a neuromuscular blocking agent may be indicated. Alternatively, deflation of the cuff of the ETT or EGD may permit sufficient alleviation of obstruction to prevent the marked negative intrathoracic pressure that leads to the development of POPE.
• Other soft tissue obstruction: POPE has been described as a complication of obstructive sleep apnea, in patients with obesity and vocal cord paralysis, and in those with other risk factors for upper airway obstruction.16,40 The preoperative identification of patients at risk for these conditions mandates full recovery of neuromuscular function and that they be fully awake prior to extubation.
• Type of surgery: A retrospective study by Deepika et al showed that the majority of POPE cases (63%) occurred following surgery to the aerodigestive tract,6 suggesting that vigilance be exercised in patients suffering from chronic tonsillar hypertrophy, goiter, and other conditions leading to chronic upper airway obstruction. In other published case series, none of the patients was undergoing aerodigestive tract surgery.17
• Patient: In adults, POPE occurs about twice as often in male patients,4-6,8,17 and in those with an average age of 25 to 45 years.4-6,8,17 The male preponderance may be related to well-developed musculature and their ability to generate high negative intrathoracic pressures.21 Early and aggressive treatment of airway obstruction should occur in this population.

POPE is an important cause of morbidity in otherwise young, healthy patients that may lead to an unplanned hospital or ICU admission. With prompt recognition and appropriate therapy, the condition generally resolves inside 24 to 48 hours without long-term sequelae.6,19 However, deaths can occur; a recent review of published adult case series of POPE reported three deaths in 146 patients—a mortality rate of 2%.8

Following extubation in the operating room, the patient exhibited clinical evidence of developing pulmonary edema and increasing respiratory distress. Her oropharynx was suctioned and she was placed in a semi-sitting position. Oxygen, 100%, was administered via a face mask through the anesthetic circuit and CPAP was applied. This failed to improve the SpO2 above 90%, so assisted bag-mask-ventilation (BMV) was attempted. However, agitation and reduced lung compliance made assisted ventilation increasingly difficult, and the SpO2 could not be maintained above 90%. Therefore, the patient was re-intubated using a rapid-sequence intubation technique. Following intubation, her SpO2 returned to 97% with 2 minutes of mechanical ventilation using an Fio2 of 100%; suctioning yielded copious quantities of pink, frothy fluid. Sedation was maintained with midazolam and she received IV furosemide 40 mg. An arterial line was placed, and the patient was admitted to the ICU. A chest x-ray showed signs of pulmonary edema. A 12-lead ECG was normal and troponins were negative. The patient remained sedated, intubated, and ventilated overnight. By the following day, her radiographic findings and arterial blood gases had improved, and she was extubated that evening. There were no further respiratory complications.

Post-obstructive pulmonary edema is an uncommon, yet potentially life-threatening condition. Occurring shortly after the relief of acute or chronic upper airway obstruction of varying cause, POPE presents with dyspnea, cough, progressive oxygen desaturation, tachypnea, and agitation. In most cases, POPE resolves within 24 to 48 hours. Sometimes, nothing more than supportive care with supplemental oxygen administration is required. Mask-delivered CPAP or noninvasive ventilation may also be effective. However, some patients with POPE may require tracheal intubation and mechanical ventilation with PEEP to maintain adequate oxygenation. Although often used, the benefits of diuretics and steroids in managing POPE remain unproven.

Practitioners should be aware of this condition, be able to identify and where possible avoid the predisposing risk factors, and be able to manage it if it occurs. Prompt management of acute upper airway obstruction is crucial in reducing the incidence of POPE and improving outcome, particularly as deaths have been reported.