Negative
Pressure
Pulmonary
Edema
ARTHURA MOORE M.D.
STAFF ANESTHESIOLOGIST
ST JUDE CHILDREN’S RESEARCH HOSPITAL
Objectives

Understand the pathophysiological mechanism of the development
and resolution of the condition.

Recognize and diagnose a patient with NPPE

Provide swift treatment for its resolution
ALIASES

Post-obstructive Pulmonary Edema

Laryngospasm-induced Pulmonary Edema
What is negative pressure
pulmonary edema?

NPPE is a manifestation of upper airway obstruction, a markedly low
intrathoracic pressure generated by forced inspiration against an
obstructed airway which leads to exudation of fluid and red blood
cells in the interstitium.

Example of non-cardiogenic edema

Seen during emergence from anesthesia
Medical Myths

Sugar makes children hyperactive

You lose most of your body heat
from your head

You need to drink 8 glasses of
water a day
Myths associated with NPPE

Only occurs with patients who have been intubated

Cannot occur with patients using an LMA

Does not occur in pediatrics

It is always a bilateral presentation.
History of NPPE
1927- Moore and Binger- first to
demonstrate in spontaneously
breathing dogs
1942- Warren- first description of
pathophysiological correlation
between the creation of negative
pressure and pulmonary edema
1973- Capitanio- described
relationship between pulmonary
edema and upper airway
obstruction in 2 children with croup
and epiglottis
1977- Oswalt – first to show the clinical
significance in 3 adults after severe
acute upper airway obstruction
Pathophysiology
3 Major Mechanisms

1: Creation of marked intrathoracic negative pressures of -50 to 100cm H20 provides the stimulus for NPPE

Intrapleural pressure decreases to -50 to -100cm H2O when inspiration is
attempted against a closed glottis.

Muller maneuver
Mechanism #1
Marked Negative
Pressure
Pulmonary
Edema
Sudden increase
of pulmonary
microvascular
pressure
Increase of
Venous Return
LV to afterload
stress to increase
LVEDP
Mechanism #1
Hydrostatic pressure-favors movement of fluid from the capillary into the
interstitium
Oncotic pressure-favors movement of fluid into the vessel
Mechanism #2

Hypoxia and hyperadrenergic state that accompany upper airway
obstruction also contributes to the development of pulmonary
edema.
Mechanism #2
Hypoxia and metabolic
acidosis increases
vasoconstriction at the
precapillary level
Elevates pulmonary
microvascular pressure,
alters pulmonary capillary
membrane permability,
and depresses the
myocardium
Pulmonary Edema
Mechanism #3

In chronic upper airway obstruction- modest level of AutoPEEP with
an increase of end expiratory lung volumes.

Relief of obstruction leads to edema formation
Mechanism #3
Acute relief of
chronic
obstruction
Negative
intrapulmonary
pressure
AutoPEEP
disappears
Pulmonary
Edema
“Type II”
Lung volumes
and pressures
normalize
NPPE Types
Studies have shown that most of the pts
who develop Type I are young.
Whereas, Type II NPPE occurs in extremes
of ages.
Clinical Manifestations

Usually present immediately

S/S of respiratory distress due to acute airway obstruction

Stridor

Suprasternal/Supraclavicular retractions

Use of accessory muscles of inspiration

Decrease of oxygen saturation
Clinical Manifestations
Coarse, rales

Auscultation of lungs
Rhonchi
Wheeze
Clinical Manifestation
Typical CXR
Kerley A lines- caused by
distension of channels between
peripheral and central
lymphatics of lungs
Kerley B lines- represent
interlobular septa, peripherally
located
Peribronchial cuffing
(thickening)- occurs with excess
fluid or mucus build-up in small
airways causes patches of
atelectasis
Clinical Manifestations

Hallmark sign of NPPE is the frothy
pink, sputum
Onset

Time onset of pulmonary edema
after relief of obstruction

30-150 minutes

Lungs can accommodate
increased fluid: lymphatic flow
can increase 3-10X before edema
forms
Stages of Pulmonary Edema

Stage 1: Only interstitial pulmonary edema is present

Stage 2: Fluid fills the interstitium and begins to fill the alveoli

Stage 3: Alveolar flooding occurs, many alveoli are completely
flooded with no air

Stage 4: Marked alveolar flooding spills over into the airway as froth
Diagnosis

Based on history of a precipitating incident and symptoms

Symptoms usually develop within one hour of the event but may be
delayed

CXR findings support diagnosis
Incidence
Reported to be 0.05%-0.1% of all
anesthetic procedures; however
suggested to occur more
commonly than is generally
documented
According to one estimate,
NPPE develops in 11% of all pts
requiring active intervention for
acute upper airway obstruction
for example laryngospasm
The m/m of an unrecognized
event of NPPE is as high as 40%
Anesthetic Procedures
0.1
Uneventful
99.9
NPPE
Case Reports of Postoperative
Pulmonary Edema
Incidence of Cases Reported
12.00%
Type I
44.00%
Type II
44.00%
Other
Laryngospasm

The occlusion of the glottis secondary to contraction of the
laryngeal constrictors.

Defensive system of the upper airway and lungs mediated by the
vagus nerve

Olsen and Hallen reported that the overall incidence of
laryngospasm in the adult and pediatric practice is just under 1%.


The incidence doubles in children and triples in the very young ( birth to
3mths)
Cause in >50% of the cases of NPPE
Risk Factors

Pt with airway lesions

Upper airway surgeries

Obesity

H/o OSA

Young age

Male sex

Short neck

Difficult intubation

Acromegaly
Differential Diagnosis

Other causes:

Cardiogenic edema

Neurogenic edema

ARDS

Anaphylaxis

Drug-induced non-cardiogenic
Management

First treatment priority is relief of the airway obstruction and
correction of the hypoxemia.

Treatment is primarily supportive.


Maintenance of patent airway

Administration of supplemental oxygen
Diuretics are often administered
Persistent airway obstruction may
necessitate an artificial airway

Administration of succinylcholine
(0.1-0.2mg/kg)

Relax the jaw muscles

Break the laryngospasm
Invasive vs. Non-Invasive
Airway Support
50.00%
40.00%
30.00%
1980-2000
20.00%
2000-now
10.00%
2000-now
0.00%
1980-2000
Invasive
Non-invasive
PEEP


Auto (intrinsic) PEEP

Incomplete expiration

Progressive air-trapping
(hyperinflation)

Common in high MV, expiratory
flow limitations, and expiratory
resistance
Applied (extrinsic) PEEP

Small amounts ( 4-5cmH20) used to
mitigate alveolar collapse

Higher levels(>5 cmH20) used to
improve hypoxemia
Purpose of CPAP

Partially compensate respiratory
function by reducing the WOB

Improve alveolar recruitment

Reduce left ventricular afterload
and increase CO which leads to
improved hemodynamics
Non-invasive

Reduce intubation rates

Reduce ICU admissions

Reduce hospital length of stay

Reduce morbidity/mortality rates
Case #1
Presentation

7 y/o, 23kg, girl presented for tonsilloadenoidecotomy.

History of mild OSA

Premedicated with 7.5mg PO midazolam

To OR with standard ASA monitors applied. An uneventful mask
induction with 70% nitrous oxide, 30% oxygen, and 8% sevoflurane

22-gauge PIV inserted

Intubated with 5.5cm uncuffed ETT- atraumatic on 1st attempt with
airleak at 18cm H2O pressure.

Pt returned to spontaneous repiration, maintained with 1.5%
sevoflurane, and 50/50 nitrous oxide and oxygen

She was given 6mg dexamethasone, 2mg morphine, and 2mg zofran
intraoperatively
Case #1
Emergence

While emerging from GA, the SpOs
declined from 98%-100% to 84%87%.

Attempts made to assist ventilation
were unsuccessful

Pt biting on tube

Repeated strenuous inspiratory
efforts
Case #1
Treatment


Pt given 20mg IV Succinycholine

Controlled ventilation resumed,
saturations remained in low 90s.

Frothy pink sputum suctioned from ETT.

5mg Lasix given with improvement of
sats to mid 90s
Over next 20mins, pt’s condition
improved.

Extubation uneventful.

To PACU with simple facemask at
6L/min of oxygen.

Postop CXR revealed:

Pt remained under observation for a few
hours.

Later discharged that evening.
Case #1
Presentation

7 y/o, 23kg, girl presented for tonsilloadenoidecotomy.

History of mild OSA

Premedicated with 7.5mg PO midazolam

To OR with standard ASA monitors applied. An uneventful mask
induction with 70% nitrous oxide, 30% oxygen, and 8% sevoflurane

22-gauge PIV inserted

Intubated with 5.5cm uncuffed ETT- atraumatic on 1st attempt with
airleak at 18cm H2O pressure.

Pt returned to spontaneous repiration, maintained with 1.5%
sevoflurane, and 50/50 nitrous oxide and oxygen

She was given 6mg dexamethasone, 2mg morphine, and 2mg zofran
intraoperatively
Pediatric pts are at risk because of
their extremely compliant chest
walls that can generate large
negative intrapleural pressure.
Myth #1:
NPPE does not occur in pediatrics
Case #2
Presentation

58 y/o 90kg man presented to ED with 3-day h/o fever, worsening
perineal erythema, and pain.

Appropriately NPO

To OR for emergency surgical debridement of the Fournier’s
gangrene.

Premedicated with 2mg IV midazolam

Anesthesia induced with 200mg IV Propofol and 100mcg IV fentanyl

LMA was placed w/o difficulty

Anesthesia maintained with 2-3% sevoflurane with 50/50 oxygen/air

500mcg fentanyl and 1mg dilaudid for intraoperative analgesia
Case #2
Emergence

Conclusion of surgery, sevoflurane
discontinued, before removal of
LMA, pt bit LMA.

LMA removed followed by
laryngospasm

Application of positive pressure via
face mask unsuccessful.
Case #2
Treatment

IV propofol and succinylcholine
and intubated with 7.5ETT

SpO2 remained 85-88% despite
100% FiO2.

Placed on the vent in SIMV mode
with PS of 10 and PEEP 10, PEEP
later increased to 12 with sats
>90%

Admitted to ICU and CXR
revealed

12hrs later FiO2 was weaned and
pt extubated. F/u CXR revealed
Case #2
Presentation

58 y/o 90kg man presented to ED with 3-day h/o fever, worsening
perineal erythema, and pain.

Appropriately NPO

To OR for emergency surgical debridement of the Fournier’s
gangrene.

Premedicated with 2mg IV midazolam

Anesthesia induced with 200mg IV Propofol and 100mcg IV fentanyl

LMA was placed w/o difficulty

Anesthesia maintained with 2-3% sevoflurane with 50/50 oxygen/air

500mcg fentanyl and 1mg dilaudid for intraoperative analgesia
Majority of cases of NPPE in the literature are in
associaton with ETT use. Although the increasing
use of LMAs in the administration of anesthetics
will provide more scenarios where NPPE can
manifest.
Myth #2 and 3:
It only occurs in pts who were intubated.
Cannot occur with pts using an LMA.
Case #3
Presentation

21y/o young male, previous h/o multiple trauma victim, presented
for elective removal of a right intramedullarly femoral nail.

Medical h/o mild asthma

No premedication

To OR routine monitors applied. Anesthesia induced with 200mcg
fentanyl and 200mg propofol IV

#4 LMA placed.

Pt moved into the left lateral position

During positioning, pt began to cough and clenched his teeth upon
the LMA.
Case #3
Treatment

He was given 100mg Propfol and 60mg Sux.

Ventilation reestablished.

Oxygen saturations dropped to the low 80s

100% oxygen administered with attempts to assist ventilation and
provide PEEP. Despite these measures, the SpO2 remained 84-86%

Auscultation revealed coarse BS, L>R, no wheeze, and no notable
prolongation of the expiratory phase. No material found with
suctioning of the LMA.

Procedure abandoned, pt returned to supine with improvement of
sats to 92-93%. LMA removed continued to breath 100% oxygen
with sats 91%

Pt to PACU – received high-flow oxygen and nebulized albuterol
Case #3

CXR- marked left-sided
extravascular lung water and
normal right side.

Pt improved rapidly, w/I 2hrs sats
were 90%RA and 95%on 3L.

Monitored overnight with
complete resolution of CXR in
24hrs.
Case #3
Presentation

21y/o young male, previous h/o multiple trauma victim, presented
for elective removal of a right intramedullarly femoral nail.

Medical h/o mild asthma

No premedication

To OR routine monitors applied. Anesthesia induced with 200mcg
fentanyl and 200mg propofol IV

#4 LMA placed.

Pt moved into the left lateral position

During positioning, pt began to cough and clenched his teeth upon
the LMA.
If airway obstruction occurs in the lateral
position, development of NPPE in the
dependent lung is favored by hydrostatic
forces and possibly the elevated resting
position of the dependent diaphragm.
Myth #4:
It is always a bilateral presentation
Prevention


Avoid airway irritation

Administer topical lidocaine to the laryngotracheal area

Careful suction of the oropharynx
Extubation of trachea in Stage 1
Stages of Anesthesia




Stage 1

From administration of anesthesia to loss of
consciousness

Dizziness, exaggerated hearing and feeling
Stage 2

From Loss of consciousness to loss of eyelid
reflex

Any kind of stimulation intensifies the pt’s
excitement

May vomit, hold breath, or struggle

Increased muscle tone and involuntary muscle
activity
Stage 3

Surgical anesthesia

Spinal reflexes dulled and relaxation of skeletal
muscles obtained

Further divided into 4 planes ( 1-lightest, 4deepest)
Stage 4

Medullary Paralysis

Anoxia

Cardiac/respiratory paralysis and death
Conclusion

Prompt diagnosis and therapeutic action
w/I 24hrs.
NPPE resolution

Early recognition crucial to morbidity

High index of suspicion for NPPE in pts who experienced
postextubation laryngospasm.

Those who have experienced postanesthetic laryngospasm – monitored
longer in PACU

Recommended monitoring period ranges from 2-12 hrs.
References

Rasheed, Asim; Urmila Palaria, Dolly Rani, and Shatrunjay Sharm. A case of negative pressure pulmonary edema in an
asthmatic patient after laproscopic cholecystectomy: Anesthesia Essays and Researches, 2014 Jan-Apr;8(1):88-86

Bhaskar, Balu and John F. Fraser. Negative pressure pulmonary edema revisited: Pathophysiology and review of
management: Saudi Journal of Anesthesia. 2011 Jul-Sep; 5(3):308-313

Vandse, Rashmi, Deven Kothari, Ravi Tripathi, Luis Lopez, Stanislow Stawicki, and Thomas Papadimos. Negative pressure
pulmonary edema with laryngeal mask airway use: Recognition, pathophysiology, and treatment modalities: International
Journal of Critical Illness & Injury Science. 2012 May-Aug; 2(2):98-103

Saqib, Muhammad, Maqsood Ahmad, Raheel Azhar Khan. Development of negative pressure pulmonary edema
secondary to postextubation laryngospasm. Anesthesia, Pain & Intensive Care. 2011;15(1)June 2011

Davidson, Susan, Cherry Guinn, Daniel Gacharna. Diagnosis and Treatment of negative pressure pulmonary edema in a
pediatric patient: A case report. AANA Journal, October 2004/Vol 72, No 5

Sullivan, Michael. Unilateral negative pressure pulmonary edema during anesthesia with a laryngeal mask airway.
Canadian Journal of Anesthesia 1999/46:11/1053-1056

Massad, Islam, Sami Abu Halawa, Izdiad Badran, and Bassam Al-barzangi. MEJ Anesthesia 18(5), 2006, 977-982

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
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