A 26-year-old man presented with a fractured tibia and fibula, sustained during a collision with two other players while playing recreational hockey. He was scheduled for open reduction and internal fixation of the fractures. Significant past medical history was limited to a 5 pack-year history of smoking. He had previously undergone reconstruction of an anterior cruciate ligament without incident. He was on no medications pre-morbidly and laboratory investigations were normal. He weighed 220 lb (100 kg) and was 6′0″ (183 cm) tall. Preoperative airway examination revealed normal mouth opening with full teeth, a thyromental span of 4 cm, and good jaw protrusion. He demonstrated a modified Mallampati score¹ of II and had a normal cervical range of motion. The rest of his physical examination was unremarkable. He had been fasted for 8 hours preoperatively.

Following appropriate positioning and denitrogenation, general anesthesia was induced using midazolam, fentanyl, and propofol. Rocuronium was administered to facilitate tracheal intubation. Direct laryngoscopy using a Macintosh #4 blade revealed a Cormack–Lehane (C/L)² Grade 2 view, and successful tracheal intubation using an 8.0-mm internal diameter (ID) endotracheal tube (ETT) followed. General anesthesia was maintained with sevoflurane in air and oxygen. After the airway was secured, three 4 × 8 inch gauze flats were rolled up and inserted into the mouth as a bite block. Over the course of the 2-hour case, several doses of hydromorphone were given for analgesia. Additional doses of rocuronium were also given for muscle relaxation, with monitoring by a nerve stimulator. Two liters of Ringer’s lactate were given during the procedure. Estimated blood loss was 150 mL. On emergence, residual neuromuscular blockade was fully reversed.

At this time, the patient started to cough and buck on the ventilator. He then proceeded to spit out the gauze bite block and subsequently bit down on the ETT. For a period of approximately 60 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 his jaw relaxed somewhat, allowing assisted, then spontaneous ventilation to resume. Once conscious, with his oxygen saturation recovered to >90% and a regular pattern of respiration, the patient was extubated. Shortly after extubation, he began to cough up frothy, pink fluid without either retching or vomiting. His oxygen saturation, which had been 97% on a simple oxygen face mask immediately after extubation, dropped to 85%.

What Is Post-Obstructive Pulmonary Edema (POPE)?

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 airway is patent with relief of any obstruction, treatment of POPE is usually symptomatic, varying 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 1973.³ A few years later, Oswalt et al.⁴ described a number of cases of respiratory distress and pulmonary congestion following episodes of severe acute upper airway obstruction in otherwise healthy patients. Since then, numerous case reports and case series have been published on this phenomenon.

What Synonyms Have Been Used to Refer to POPE?

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

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  Negative pressure pulmonary edema^5–13;

  
  
• 
  

  Post-laryngospasm pulmonary edema¹⁴;

  
  
• 
  

  Laryngospasm-induced pulmonary edema^8,15,16;

  
  
• 
  

  Post-extubation pulmonary edema^17,18;

  
  
• 
  

  Non-cardiogenic pulmonary edema⁵;

  
  
• 
  

  Athletic pulmonary edema⁸;

  
  
• 
  

  Negative pressure pulmonary hemorrhage.¹⁹

What Are the Two Types of POPE?

Two types of POPE have been described.²⁰ 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 obstructing nasal pathology,²¹ chronic tonsillar hypertrophy, laryngeal tumor, goiter,²¹ or bilateral vocal cord paralysis.⁵

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

What Is the Incidence of POPE?

The incidence of POPE has been estimated at 0.5 to 1.0 case per thousand surgical patients.^7,22 Of patients who have experienced upper airway obstruction, or required intervention for an episode, published figures suggest a 5% to 10% incidence of progression to POPE.^9,22–24 POPE occurs most often in younger adults and children, most with ASA 1 and 2 physical status.^6,7 Young, athletic males are strongly represented in case series,^18,25 possibly because their well-developed musculature enables them to develop stronger inspiratory efforts against the upper airway obstruction, with resultant highly negative intrathoracic pressure. Most cases occur after tracheal extubation.⁷

What Predisposes to the Occurrence of POPE?

In the adult population, the most common cause of POPE is post-extubation laryngospasm,^18,26 while in children younger than 10, most cases follow upper airway obstruction from croup, epiglottitis,^6,23 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 ETTs^10,27,28 and laryngeal mask airways (LMAs).^12,13,29,30 POPE has also been reported following upper airway obstruction from hanging,³¹ strangulation,^4,10 supraglottic occlusion by³² or aspiration of a foreign body,^33–37 laryngeal tumor,⁶ hematoma, goiter,^10,38 obstructive sleep apnea,³⁹ bilateral vocal cord paralysis,⁴⁰ and direct suctioning of both ETTs⁴¹ and chest tubes.⁴² POPE can occur unilaterally, for diverse reasons.^43,44 Medications such as sugammadex⁴⁵ and naloxone⁴⁶ have been implicated in case reports of POPE, though upper airway obstruction has generally also been involved.

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 attempted inspiration against complete upper airway obstruction (the Mueller maneuver),^23,26,34 and (b) the hyperadrenergic response to airway obstruction and hypoxemia (Figure 61–1).^6,17,20 The following are probable contributory mechanisms:

1. 
   

   Negative pressure transfer from the intrapleural space to the pulmonary interstitium creates a gradient that favors transudation of fluid out of the pulmonary capillaries to the interstitium.^5,33 Once the capacity of pulmonary lymphatics to remove fluid from the interstitium is exceeded, leakage of fluid occurs into the alveolar space.^17,47,48

   
   
2. 
   

   Enhanced venous return to the right heart and pulmonary arteries results from the generated negative intrathoracic pressure^5–7,26,33 and is compounded by central blood redistribution from peripheral vasoconstriction due to the hyperadrenergic state caused by significant hypoxemia, anxiety, and hypercarbia.^{6,10,17,26,33,47,49} Higher pulmonary arteriolar and capillary bed blood volumes and hydrostatic pressure further favor fluid transudation from capillaries to the interstitium.⁹

   
   
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^7,33,49,47; (b) decreased left ventricular (LV) diastolic compliance (from right ventricular distension); and (c) depression of myocardial contractility, from hypoxemia and acidosis.¹⁰

   
   
4. 
   

   Hypoxic pulmonary vasoconstriction contributes directly to increases in pulmonary capillary pressure.^6,17

   
   
5. 
   

   Disruption of the alveolar-capillary membrane (“stress failure”)⁵⁰ and its barrier function can eventually occur from damage to the capillary endothelium by increased pulmonary capillary volume and pressure. In addition, the hyperadrenergic state associated with prolonged hypoxemia,³³ can directly contribute to further membrane disruption.^5,7 This 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.⁴⁹ 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.⁵¹

However, higher negative intrathoracic pressure, 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.^40,52,53 Extreme cases result in breaks in the alveolar-capillary membrane, allowing red blood cell leakage, and occasionally frank hemorrhage.^19,53 Chest radiographs in this latter situation may show an alveolar pattern of edema, in contrast to the more interstitial pattern typical of transudative edema.⁸ 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.

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 pressure generated during attempted inspiration (Mueller maneuvers) may be balanced during attempted expiration against the same fixed obstruction (i.e., 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 manifest^6,7,33 with the sudden transient drop in mean airway pressure,⁹ together with the increase in venous return and pulmonary hydrostatic pressure.^8,47

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,⁵⁴ published reports document abnormal A-a gradients and radiographic evidence of pulmonary edema before relief of chronic upper airway obstructions.^6,7,33 Following the relief of both Type I and Type II obstructions, it is likely that altered capillary permeability, previously occult interstitial edema,⁵⁴ and LV dysfunction³³ contribute to the development of POPE in spite of now-normal lung volumes and pressures.

What Are the Presenting Symptoms and Signs of POPE?

The patient with POPE often presents within minutes^6,26 after the relief of an episode of upper airway obstruction characterized by vigorous inspiratory efforts without significant air movement.^17,49 The initial presentation is often with dyspnea,⁹ tachypnea,^33,55,56 agitation,^9,25,49 and cough^12,25,26 producing pink, frothy fluid.^{4,5,9,10,26,49,57} In addition to hypoxemia,^8,55 the patient is also often tachycardic^15,49 and hypertensive.⁴⁹ Other patients have presented with frank hemoptysis,^{10,13,22,27,53,58} although this is less frequent. Residual partial obstruction may be present in this population, manifested by stridor^{9,12,17,25,59} or intercostal and subcostal retractions.^25,33,60 On auscultation, most patients have rales,^{13,17,26,33,56,57} sometimes with associated rhonchi.^{4,15,26,34,49,56}

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

• 
  

  Invasive monitoring of central venous pressure (CVP) or pulmonary artery pressures (PAP) is rarely undertaken in the patient recognized to have POPE. However, when reported, pressures, including CVP^4,26 and pulmonary capillary wedge pressures (PCWP)^6,26,61,62 have generally been normal, while PAPs have been normal or only slightly elevated.²⁶

  
  
• 
  

  Chest radiographs of the patient with POPE often show signs of edema with either an alveolar (airspace consolidation)^10,17,22,60 or interstitial (perihilar haze, perivascular or peribronchial cuffing, and Kerley lines)^{4,5,7,34,63,64} pattern, or both.^8,33,55 Most often the edema distribution is predominantly central and bilateral, although asymmetrical^31,49 or even unilateral distributions have been reported.^8,12,22 Heart size is generally normal.^8,22,33 Vascular pedicle width in one series was found to be above normal, suggesting an increase in central blood volume.⁸

  
  
• 
  

  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.^34,58 Others have shown diffuse patchy lobular airspace disease.³³

  
  
• 
  

  Bronchoscopy performed on patients with POPE has shown punctate bleeding lesions in both trachea and mainstem bronchi⁵⁹ or more generalized blood staining of the tracheobronchial tree.^27,49 Bronchial-alveolar lavage (BAL) in one report revealed a progressively bloody return, consistent with alveolar hemorrhage,⁴⁹ while in a second report, BAL produced clear returns.²⁷

  
  
• 
  

  No specific electrocardiogram (ECG) pattern has been reported in the POPE patient population. When reported, ECG findings have been uniformly normal.

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 workup performed. Echocardiograms have generally been normal.^{10,17,22,34,38,49,58,65,66} 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.⁵ However, in the absence of other recognized indications, the current evidence does not support a recommendation for routine echocardiographic testing of all POPE patients.

What Is the Usual Clinical Course of POPE?