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“The Science Behind the Art” 
Volume 10 - No.3 2022 

Anesthesia eJournal - Online 
ISSN 2333-2611

Page 1

Negative Pressure Pulmonary Edema 
Christine Nagel, RN, BSN, CCRN

Affiliation:
Texas Christian University 

Grant/Financial Support: 
None 

KEYWORDS:  Negative pressure pulmonary edema, NPPE, Laryngospasm

Abstract
Negative pressure pulmonary edema (NPPE) is a rare but dangerous complication of general anesthesia potentially 
causing anoxic brain injury and a 5% mortality, if not promptly recognized and treated. This case report reviews an 
18-year-old male who developed NPPE after a pilonidal cyst removal under general anesthesia. The purpose of this
poster is to educate professionals on the etiology, signs, symptoms, treatments, risk factors, and preventions of NPPE to
aid in the early recognition and treatment of its occurrence.

AEJ
Volume 10- No. 3 2022

About the Author: Christine Nagel, is a graduate student pursing a Doctorate of Nurse Anesthesia Practice from 
Texas Christian University School of Nurse Anesthesia. 



Texas Christian University 
“The Science Behind the Art” 
Volume 10 - No.3 2022 

Anesthesia eJournal - Online
ISSN 2333-2611 

Page 2

PowerPoint Template ©2009 Texas Christian University, Center for Instructional Services. For Educational Use Only. Content is the property of the presenter and their resources.

Background of NPPE
§ PICOT: In surgical patients, how is negative pressure 

pulmonary edema (NPPE) best prevented and treated 
compared to the traditional methods of intubation and 
mechanical ventilation to provide safer anesthesia care during 
the perioperative period? 

§ NPPE is a rare, life-threatening complication of general 
anesthesia 

§Incidence: 0.01-0.1% of all general anesthetics
• Etiology: non-cardiogenic

•Large negative intrathoracic pressure produced by forceful 
inspiration against a closed glottis
•Increased pulmonary capillary permeability and enhanced 
venous return to the heart leads to fluid accumulation in 
the alveoli from the intravascular system

• Type 1 NPPE: occurs immediately due to obstruction 
• Type 2 NPPE: delayed appearance; due to relief of a 

chronically obstructed airway 
• Characterizations of NPPE: acute hypoxemia, upper airway 

obstruction after removal of endotracheal tube (ETT) or 
laryngeal mask airway (LMA), radiographic evidence of 
pulmonary infiltrates, productive cough of pink frothy sputum

• Common causes: laryngospasm (50%), upper airway
occlusion (11%), residual neuromuscular blockade (NMB) 

•Laryngospasm incidence: 1% of adult general anesthetics, 
2% of pediatric cases, 3% in neonates, and up to 10% in 
the presence of upper respiratory infection or asthma 
•Percent of laryngospasms that result in NPPE: 4%

• NPPE mortality: 5%

Results/Synthesis of Evidence
• Risk factors: age (<35 years), male, ASA I-II classification, 

reactive airway, active smoking, environmental smoke 
exposure, lower BMI (<27), ETT, and emergency operation

• Prevention: limited direct laryngoscopy attempts, LMA, 
magnesium sulfate IV for muscle relaxation, adequate and 
gentle suctioning, deep extubation, oral airway, lidocaine 
topical or IV, and propofol IV

• Most common findings: acute and isolated respiratory failure, 
hypoxemia, productive cough of pink/red frothy sputum, 
auscultation abnormalities (rales, rhonchi), tachypnea, 
tachycardia, and paradoxical breathing 

• Diagnostic measures: chest x-ray, arterial blood gas, physical 
presentation, auscultation abnormalities, bloody bronchoscopy 
and bronchoalveolar lavage 

• Management:
•Treating the cause (obstruction) – PPV via facemask, 
100% oxygen, adequate NMB reversal, gentle chest 
compressions (pediatrics), intubation and mechanical 
ventilation, propofol IV, midazolam IV, succinylcholine 
IV/IM
•Treating NPPE – PPV (BiPAP, CPAP), 100% oxygen, 
albuterol, diuretic (if no improvement in symptoms), 
intubation and mechanical ventilation with PEEP

• Close monitoring in ICU/PACU recommended for 24 hours
• Average time to full resolution: 30 hours 
§ Gaps in the literature: diuretics as treatment, associated 

surgeries, the the use of desflurane and/or sugammadex as a 
possible cause

Negative Pressure Pulmonary Edema
Christine Nagel, BSN, RN, CCRN Texas Christian University

Case Report
Pre-anesthetic:
• 18 y/o male, 102 kg, pilonidal cyst removal 
• ASA II – active marijuana smoking 
• Preop VS: 97.6 F, HR 85 bpm, NSR, RR 20 bpm, BP 142/70

Intraoperative:
• Induction: midazolam 2 mg IV, fentanyl 100 mcg IV, lidocaine 

50 mg IV, propofol 200 mg IV
• Muscle relaxation: rocuronium 50 mg IV
• ETT size 7.5 placed at 21 cm at the teeth 
• Prone position 
• Sevoflurane 2% at 2 L/min used throughout case
• Neuromuscular reversal: 3/4 twitches, sugammadex 200 mg 

IV given, 4/4 twitches after reversal 

Postoperative
• Patient experienced a laryngospasm upon ETT removal 
• Oxygen desaturation to 50%
• Positive pressure ventilation (PPV) and propofol 100 mg IV 

given with no improvement
• Succinylcholine 200 mg IV given and patient re-intubated with 

presence of red, frothy sputum in ETT
• Mechanical ventilation with 100% oxygen given for 20 

minutes
• Furosemide 10 mg IV given for pulmonary edema 
• Patient extubated awake 30 minutes later – placed on 100% 

oxygen via facemask at 15 L/min 
• Monitored for 24 hours in the PACU 
• Discharged after all symptoms had resolved and pulmonary 

infiltrates had cleared on the chest x-ray

References
1. Collins S, Schedler P, Veasey B, Kristofy A. Prevention and treatment of laryngospasm in the pediatric patient: A literature

review. AANA J. 2019;87(2). Accessed October 23, 2021. https://www.aana.com/docs/default-source/aana-journal-web-
documents-1/prevention-and-treatment-of-laryngospasm-in-the-pediatric-patient-a-literature-review-april-
2019.pdf?sfvrsn=de3a986f_8

2. Tsai P, Wang J, Huang S, et al. Characterizing post-extubation negative pressure pulmonary edema in the operating room-a 
retrospective matched case-control study. Perioper Med. 2018;7(2). Accessed October 28, 2021.
https://perioperativemedicinejournal.biomedcentral.com/track/pdf/10.1186/s13741-018-0107-6.pdf

3. Contou D, Voiriot G, Djibré M, Labbé V, Fartoukh M, Parrot A. Clinical features of patients with diffuse alveolar 
hemorrhage due to negative-pressure pulmonary edema. Lung. 2017;195(4):477-487. Accessed October 31, 2021.
https://www.proquest.com/docview/1922264919?accountid=7090&forcedol=true&pq-origsite=summon

4. Silva LA, Guedes AA, Filho MF, et al. Negative pressure pulmonary edema: report of case series and review of literature.
Rev Bras Anestesiol. 2019;69(2).222-226. Accessed October 30, 2021. https://doi.org/10.1016/j.bjane.2018.12.002

5. Furuichi M, Shinhiro T, Akada S, et al. Noninvasive positive pressure ventilation in patients with perioperative negative
pressure pulmonary edema. J Anesth. 2010;24.464-468. Accessed October 30, 2021.
https://link.springer.com/content/pdf/10.1007/s00540-010-0899-0.pdf. 

6. Din-Lovinescu C, et al. Systematic review of negative pressure pulmonary edema in otolaryngology procedures. Ann Oto 
Rhinol Laryngol. 2021;130(3) 245-253. Accessed October 29, 2021. https://journals-sagepub-
com.ezproxy.tcu.edu/doi/pdf/10.1177/0003489420938817

7. Kao CL, Kuo, CY, Su YK, Hung KC. Incidence of negative-pressure pulmonary edema following sugammadex 
administration during anesthesia emergence: A pilot audit of 27,498 general anesthesia patients and literature review. J 
Clin Anesthesia. 2020;62. Accessed October 29, 2021.
https://www.sciencedirect.com/science/article/abs/pii/S0952818020300015?via%3Dihu

8. Lemyze M, Mallat J. Understanding negative pressure pulmonary edema. Intensive Care Med. 2014;40. Accessed 
February 22, 2022. doi: 10.1007/s00134-014-3307-7

9. Choi HL, Min JH, Kang JH, Kim H, Park JS. Postobstructive pulmonary edema that developed immediately after 
emergency surgical cricothyroidotomy. Am J Emerg Med. 2016;34(5):936.e1-936.
http://library.tcu.edu/PURL/EZproxy_link.asp?/login?url=https://www.proquest.com/scholarly-journals/postobstructive-
pulmonary-edema-that-developed/docview/1785128652/se-2?accountid=7090. doi: 
http://dx.doi.org/10.1016/j.ajem.2015.09.018.

Recommendations and Suggestions
• Careful assessment of risk factors for upper airway obstruction
• Prevention and treatment preparation in high-risk patients 
• Prevention with gentle suctioning, LMA if applicable, oral 

airway, and proper medications prior to extubation 
• Treatment sequence: 100% + PPV à Larson’s maneuver à

propofol à succinylcholine à intubation (if unable to 
ventilate) à PEEP/PPV à beta-2 agonist àICU/PACU 
monitoring + 100% oxygen + PPV 

• Non-invasive treatment of NPPE was shown to be a safe 
alternative to intubation and mechanical ventilation 

• More data and experience with NPPE needed to further 
improve outcomes and patient safety

Methods
§ PubMed, PMC, and Frog Scholar
§ Articles dated between 2010 and 2021 were studied
§ Key words: negative pressure pulmonary edema, signs, 

symptoms, causes, treatments, prevention, laryngospasm, 
English-only, meta-analysis, RCT, SR

§ Result: PubMed 10, Frog Scholar 17
§ One systematic review (SR), 5 randomized controlled trials 

(RCT), and 1 case series included

Literature Review
1. SR that analyzed the pathophysiology, prevention, and 

treatment of laryngospasm in pediatric patients to better 
educate providers in preventing NPPE and death.

2. RCT that identified the major risk factors of NPPE.
3. RCT that described the risk factors, features, and outcomes 

of patients with NPPE.
4. Case series that identified the causes, risk factors, signs and 

symptoms, treatments, and preventions of NPPE to increase 
patient safety.

5. RCT that tested the effectiveness of NPPV compared to 
invasive ventilation in the treatment of NPPE.

6. SR of quasi-experimental studies that identified risk factors, 
presentation, management, and outcomes of NPPE after 
otolaryngology procedures.

7. RCT that examined the correlation between sugammadex 
and post-extubation NPPE on emergence.

Differential Diagnoses:
§ Anaphylactic reaction
§ Cardiogenic pulmonary edema
§ Myocardial infarction
§ Volume overload
§ Pneumonia
§ Pulmonary embolism
§ Aspiration 
§ Covid-19 complications 

Risk Factors of Laryngospasm:
Age, lower BMI, male, ASA I-II, reactive airway, smoke exposure, ETT, 

emergency operation, multiple DL attempts

Prevention Strategies:
• LMA versus ETT

• Magnesium sulfate 15-30 mg/kg IV infusion 
• Lidocaine topical or 1-2 mg/kg IV before extubation 

• Sub-hypnotic propofol 0.5 mg/kg IV prior to extubation
• Thorough suctioning

• Deep extubation + oral airway

Treatments:
1. 100% oxygen, PPV, oral airway
2. Larson’s maneuver/jaw thrust

3. Ensure NMB reversal
4. Gentle chest compression (pediatrics)

If no ventilation: 
1. Propofol 0.5 mg/kg IV

2. Midazolam 0.03 mg/kg IV
3. Succinylcholine 1-2 mg/kg IV or 4 mg/kg IM

4. Re-intubation + mechanical ventilation

Symptoms: 
Acute respiratory failure, hypoxemia, productive cough of pink/red frothy 

sputum, auscultation abnormalities, tachycardia, paradoxical breathing

Treatments:
1. Positive pressure (BiPAP, CPAP) + 100% oxygen

a. If re-intubated, give PEEP
2. Beta-2 agonists (albuterol)

3. If no improvement in symptoms, give diuretics

NPPE Prevention/Treatment Algorithm 

IF LARYNGOSPASM OCCURS:

IF NPPE OCCURS:

Figure 2: Chest x-ray of bilateral pulmonary infiltrates immediately after NPPE occurrence versus follow-up x-ray 24 hours after9

Figure 1: Pathophysiology of NPPE8


