Noncardiogenic pulmonary edema (NCPE) is caused by one of 2 basic mechanisms:

• An imbalance of Starling forces
• Lymphatic insufficiency

• Starling forces: NCPE can result from increased negative interstitial pressure, increased alveolar–capillary membrane permeability, or decreased plasma oncotic pressure.
  • Increased negative interstitial pressure (Ppmv): Imbalances between intra-alveolar pressure and interstitial or intrapleural pressure can lead to an increased transcapillary pressure gradient causing fluid shift from the microvessels (Pmv) to the perimicrovascular interstitium (Ppmv) with resultant pulmonary edema.
  • Increased alveolar–capillary membrane permeability (K): Endothelial injury is believed to result from inflammatory processes or sympathetic discharge. It can result in an influx of water, solutes, and macromolecules into the alveoli.
  • Decreased plasma oncotic pressure (mv): Occurs in low-protein states such as with hypoalbuminemia in liver disease or critical illness, nephrotic syndrome, or protein-losing enteropathy. Pulmonary edema from decreased oncotic pressure usually involves other exacerbating factors since low-oncotic states alone are typically not sufficient to cause clinically significant presentations.
  • Increased hydrostatic pressures (Pmv): Involved in the pathogenesis of cardiogenic pulmonary edema. Not commonly a cause of NCPE states. Involved in the pathogenesis of cardiogenic pulmonary edema. However, it may possibly play a role in neurogenic pulmonary edema (NPE) and negative pressure pulmonary edema (NPPE).
• Lymphatic insufficiency: NCPE can occur from blockage of lymphatic drainage, which is usually related to either fibrotic disease or inflammatory disease but can also be seen after lung transplantation.

• NCPE results in:
  • Increased interstitial hydrostatic pressure
  • Increased interstitial oncotic pressure
  • Atelectasis with decreased functional residual capacity
  • Decreased PaO₂, with an increased A-a gradient and a/A ratio
  • Decreased pulmonary compliance
  • Increased work of breathing (in the spontaneously ventilating patient)
• NPPE or postobstructive pulmonary edema has been shown to occur in up to 1/1,000 patients receiving general anesthesia. It requires 2 entities: A negative intrathoracic pressure and a pathological state that prevents the intra-alveolar pressure to accommodate the gradient (obstruction). The increased intrapleural pressure transmits to the alveoli which draw fluid from the pulmonary capillaries into the interstitial space and ultimately the alveoli. On a more global scale, this acute derangement increases venous return and left ventricular afterload, which can potentially favor edema secondary to hydrostatic forces. It can occur:
  • Post-extubation: Accounts for approximately 74% of all perioperative NPPE. It can result from either laryngospasm or occlusion of the endotracheal tube (e.g., biting the airway conduit), as well as bronchospastic disease.
  • Initial airway management: Usually seen in patients with head and neck tumors, but also with laryngospasm and epiglottis-induced obstruction.
  • Airway collapse: Seen with obesity and obstructive sleep apnea; can cause ongoing airway obstruction and subacute or chronic NPPE.
  • Surgical procedures: An airway procedure such as tracheal dilation can result in complete airway obstruction while the patient remains spontaneously breathing.
  • Pneumothorax: A sudden release can generate sufficient negative interstitial pressure to generate pulmonary edema (usually unilaterally).
• Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): These entities are the end-result of a multitude of disease processes that result in alveolar–capillary membrane injury from inflammatory processes. They are often classified as direct or indirect.
  • ALI is determined by a chest radiograph with bilateral infiltrates, a normal capillary wedge pressure or lack of evidence for cardiogenic failure, and a PaO₂/FiO₂ (P/F) ratio <300. ARDS is a more severe form of ALI with a P/F <200.
  • Direct lung injury can result from pneumonia/pneumonitis, inhaled toxins, and aspiration. Ventilator-induced lung injury (VILI) must also be considered.
  • Indirect lung injury can result from shock, sepsis, trauma, and transfusion-related ALI. Although a component of pulmonary edema seen after cardiopulmonary bypass may be due to alveolar–capillary membrane injury, the mechanism and etiology are not completely understood.
• Lymphatic insufficiency: In the perioperative period, NCPE may be seen in patients after lung transplant.
• Neurogenic pulmonary edema: The pathogenesis is not completely understood. Theories include:
  • Massive sympathetic discharge that increases hydrostatic pressures secondary to systemic hypertension, peripheral vasoconstriction, increased pulmonary artery pressure, and pulmonary vasoconstriction.
  • Increased pulmonary artery permeability from direct or indirect effects of epinephrine and norepinephrine: Indirect effects may involve the secondary release of histamine or bradykinin.
• Drug-induced: Pathogenesis is not completely understood.
  • Narcotic overdose with heroin is the most frequent offending agent; however, parenteral and intravenous forms of other legal preparations have also been associated with NCPE.
  • Cocaine
  • Chemotherapeutic agents including cytarabine, recombinant IL-2, all-trans-retinoic acid, arsenic trioxide, mitomycin plus vinblastine, and intrathecal methotrexate (1)
• Anaphylaxis can result in increased alveolar–capillary membrane injury. Common perioperative offenders include neuromuscular blocking agents, antibiotics, latex, and anesthetics.

Pregnancy Considerations

• Pulmonary edema in the perioperative period can present with hypoxia, rales, frothy sputum, and increased peak and plateau airway pressures. The clinical scenario must always be taken into account, and cardiogenic pulmonary edema should be excluded (acute left heart dysfunction, arrhythmias).
• NPPE: The clinical scenario is usually airway obstruction (stridor, wheezing, and inability to ventilate) in a patient who is able to generate high-negative intrathoracic pressure (e.g., young, healthy, athletes who are American Society of Anesthesiologists physical status categories I and II).
  • Obstruction can also occur in patients with foreign body aspiration, oropharyngeal tumors, and postoperative residual curarization leading to upper airway obstruction.
  • Intubation may be required but simple measures, such as the application of positive pressure in laryngospasm and bronchodilator therapy in patients with acute asthma exacerbations, may alleviate the underlying process.
  • After establishing a patent airway, treatment is largely supportive as symptoms usually resolve within 24 hours.
  • Diuretic therapy is controversial since the primary offense is not intravascular hypervolemia. Additionally, these patients may be intravascularly euvolemic or hypovolemic, and diuretic therapy could lead to further deterioration via hypovolemic shock.
• Anaphylaxis may present as wheezing, hypotension, and shock.
  • Treatment is supportive and aimed at removing the offending agent.
  • Epinephrine is the primary pharmacologic agent for anaphylactic shock (0.2–0.5 mg every 5 minutes as needed). Histamine blockers (diphenhydramine, famotidine, ranitidine) are also beneficial.
  • Measurement of tryptase and histamine levels can help in the diagnosis of an anaphylactic process; however, its clinical effects are not immediate.
• ALI/ARDS: Compared with NPPE and anaphylaxis, ALI tends to develop over hours to days but progresses rapidly.
  • Of all treatment options studied, the only modality that has been demonstrated to reduce mortality is ventilation with low-tidal volumes of 6 mL/kg predicted body weight (3). Other lung protective ventilation strategies include low inspiratory pressures (goal plateau pressure <30 cmH₂O), moderate positive end-expiratory pressure, and permissive hypercapnia in addition to lower tidal volumes (5).
  • In the absence of shock, a fluid-conservative strategy is favored (5).
  • Perioperatively, inhaled nitric oxide, inhaled epoprostenol, glucocorticoids, high-frequency oscillatory ventilation, and extracorporeal life support offer strategies to improve oxygenation (5).
• Neurogenic pulmonary edema treatment is aimed at decreasing intracranial pressure in addition to supportive therapy. Diuretic therapy could be deleterious if it results in hypotension and impaired cerebral perfusion pressures.
• Opioid overdose: Naloxone has not been shown to hasten recovery, and supportive therapy remains the mainstay of treatment.

Starling equation: Q = K [(P_mv – P_pmv) – (_mv – _pmv)], where

• Q = Net transcapillary flow of fluid
• K = Transcapillary permeability
• P_mv = Hydrostatic pressure in microvessels
• P_pmv = Perimicrovascular interstitium
• _mv = Plasma protein oncotic pressure in the peripheral vessels
• _pmv = Protein oncotic pressure in the perimicrovascular interstitium

• Alveoli
• Acute Respiratory Distress Syndrome (Ards)
• Negative Pressure Pulmonary Edema
• Neurogenic Pulmonary Edema
• Anaphylaxis

514 Pulmonary congestion and hypostasis

J81.1 Chronic pulmonary edema

Ravi S. Tripathi , MD

Erik E. Abel , PharmD, BCPS