CASE BASED DISCUSSION

CASE
• 51 year old gentleman was BIBA to A&E after his wife found him collapsed and
unconscious at home on the early hours of Wednesday
• He had a background history of obesity, epistaxis and trismus, but was otherwise
independent and well.
• On admission at 9.00am, the patient’s GCS was 3/15
• Observations:
• Apyrexial, BP 213/120, HR 45, Sats 92% (air), RR 18
• Blood gases (on admission):
• FiO2 21%, pH 7.216, pO2 8.11, pCO2 6.46, Hb 101, SO2 76.4, k 3.5, Na 143, Glu 14, Lact
2.7, BE -2.2, HCO3 20.4
• The ITU registrar was called to assist with the patient’s airway upon admission to A&E.
She noted he was producing copious amounts of pink fluid which required
suctioning, but managed to intubate and ventilate him.
• WHAT IS THE PATIENT COUGHING UP?
• WHAT ARE THE POSSIBLE CAUSES?
• WHAT WOULD YOU DO NEXT?
 PULMONARY OEDEMA
• Definition: an increase in extravascular fluid in the lungs, which occurs when
transudation or exudation exceeds the capacity of lymphatic drainage
• Key pathophysiological mechanisms:
• Imbalance of Starling’s forces of fluid movement across a capillary membrane
• Increased permeability of the capillary-alveolar barrier
• Impaired lymphatic clearance mechanisms
• Clinical consequences: Fick’s law of gas exchange
 PHYSIOLOGY: STRUCTURE OF THE
ALVEOLAR-CAPILLARY UNIT
• Pulmonary capillary endothelial cells
abut one another in a fairly loose
fashion
• gap junctions are ~ 5 nm wide, and
permit the passage of moderately
large protein molecules
• However, alveolar epithelial cells
meet at tight junctions ~ 1 nm wide,
and are virtually impermeable to
protein (DeFouw 1983)
• Epithelial Na & Cl ion channels on the
apical membrane of alveolar
epithelial cells – facilitate water
reabsorption from alveolar airspace
into interstitium
 PHYSIOLOGY: THE STARLING’S LAW
OF THE CAPILLARY
• Starling’s Law of the Capillary:
• Flow = (Pc – Pif) – (πc-πif)
• P = hydrostatic pressure
• Π = oncotic pressure
• Under normal conditions:
• Flow = (15- -4) – (30-15) = 19 – 15 = 4mmHg
• Overall, there is small balance favouring
transudation of fluid into the interstitium (this is
greater in most dependent area of the lung)
• Lymphatics drain fluid from the interstitium into the
systemic circulation at a rate of ~10ml/hr
• The interstitial space and lymphatics can
accommodate an increase in fluid of ~ 500 ml
with an increase of pressure of only ~ 1.5 mmHg
• Arteriolar vasomotor tone can regulates the
transmission of flow & pressures to the capillary
bed
• However, pulmonary venous capillaries lack this
protective system  any increase in left ventricular
pressure will be easily transmitted to the pulmonary
capillaries
 BALANCE OF OEDEMA PROMOTING VS SUPPRESSING
PHYSIOLGOICAL MECHANISMS
SUPPRESSING PROMOTING
Alveolar epithelial gap junctions are narrow and Pulmonary capillary gap junctions are fairly wide
impenetrable to proteins through which proteins can leak through

Epithelial Na & Cl ion channels on the apical Overall, there is small balance favouring
membrane of alveolar epithelial cells facilitate water transudation of fluid into the interstitium
reabsorption from alveolar spaces

Pulmonary lymphatics drain fluid from the interstitium

into the systemic circulation at a rate of ~10ml/hr,
and have significant capacity to drain excess
insterstitial fluid
Arteriolar vasomotor tone can regulates the Pulmonary venous capillaries lack this protective
transmission of flow & pressures to the capillary bed system  increaess in left ventricular pressure will be
easily transmitted to the pulmonary capillaries
 aO2
usually lasts ~ 24/24
2. arterial hypoxaemia develops
PaCO2 remains normal, or subnormal

PATHOPHYSIOLOGICAL CAUSES OF
there are only minor abnormalities on CXR
the is an increase in lung water & QT
usually lasts ~ 24-48/24

PULMONARY OEDEMA 3.* the above diagnostic criteria are present

severe arterial hypoxaemia & a large PA-aO2 gradient develops
• Imbalance of Starling’s Forces [Flow = (Pc – Pif) – (πc-πif) ] PaCO2 becomes slightly elevated
CXR shows characteristic bilateral infiltrates
• Increased Pc hydrostatic pressures (Haemodynamic pulmonary oedema)
CT decreases, the lungs are stiff and PAWP increases
• Absolute hypervolaemia – overtransfusion, renal failure artificial ventilation is usually instituted if not already present
• Relative pulmonary hypervolaemia – postural effects, vasopressors
4. usually terminal
• Increased pulmonary blood flow - left/right shunt, anaemia, exercise (rarely)
massive bilateral consolidation with unremitting hypoxaemia
• PaO2 is usually £ 50 mmHg
Raised pulmonary venous pressures - Cardiogenic (LV failure, dysrhythmias, MVwith disease),
a FIO2 = 1.0drugs (histamine)

• Reduced Pc oncotic pressures VD increases and normocapnia can only be maintained by a large VM,
often 10-20 l/min
• Critically ill patients
• Cirrhosis not all patients progress through all of these stages and the disease may resolve at any stage
serial observations of the CXR and PA-aO2 gradient are the best indicators
• Nephrotic syndrome
• Increased permeability of the capillary-alveolar barrier (non-cardiogenic pulmonary oedema or ARDS )
• Direct injury Predisposing Conditions
• Indirect injury Direct injury Indirect injury
• Impaired lymphatic clearance mechanisms Pulmonary contusion Septicaemia

• Tumour Gastric / other aspiration Shock / prolonged hypotension

• Infection Near-drowning Non-thoracic major trauma

Toxic gas / vapour inhalation Cardiopulmonary bypass
• Surgery Certain infections Head injury
• Miscellaneous: Neurogenic, High altitude Fat embolus Pancreatitis
Amniotic fluid embolus Diabetic coma
Radiation Massive blood transfusion
Bleomycin DIC
Nunn 3rd Ed.
 CLINICAL MANIFESTATIONS OF
diffusion of air within this region of the lungs is very rapid occurring
of this dramatic reduction in air velocity is that inhaled dust and poll
alveoli.
PULMONARY OEDEMA
LUNG STRUCTURE FACILITATES GAS-EXCHANG GAS DIFFUSION ACROSS THE ALVEOLI
DIFFUSION OF OXYGEN AND CARBON DIOXIDE
In our earlier discussion of the structure and function of the
Oxygen and carbon dioxide move
exchanging between
unit of thetoair
the lung is designed and
facilitate theofblO
diffusion
driving force for this diffusion being the pressure gradient across
area available for diffusion and by having a thin membrane separati
blood in the pulmonary capillaries. This is denoted thei
schematically
Fick’s law of diffusion statesanalysis thattha
net d
o

tissue is proportional to the area o

• FICK’S LAW
1) Diffu
proportional to the thickness of th 2) Diffu

• diffusion of gas across a sheet of contains 300-500 million alveoli a

between 50 and 100 square meter
tissue is proportional to the area of membranes in the body! In additi
the sheet and inversely proportional close association between the alve
to the thickness of the tissue. further improves the efficiency of
• C = concentration lung. The intimate association be
vasculature can bring the blood to
• D = Diffusion co-efficient for a gas alveoli, further facilitating flow in
minimizing the thickness of the ti
Alveolar number and surface
adolescence (See Table below). A
Therefore, net gas exchange is dependent upon;
remains constant an
1) Length of the diffusion path (thickness)
2) Surface Area have a limited capac
3) Concentration Gradient
• Alveolar Ventilation
• Pulmonary Blood Flow
4) Diffusion Coefficient for O 2 and CO2
 diffusion of air within this region of the lun
of this dramatic reduction in air velocity is
STAGES OF PULMONARY OEDEMA alveoli.

• Stage 1: Interstitial pulmonary oedema LUNG STRUCTURE FACILITAT

• Excessive fluid enters into the interstitium Oxygen and carbon dioxide move b
•  increases ”thickness” in Fick’s equation driving force for this diffusion being the pr
• Lymphatic system becomes distended and tries Fick’s la
to compensate but fails to completely drain tissue is
excess interstitial fluid proporti
• Increased interstitial pressures can cause contains
capillary narrowing between
•  increases ”thickness” in Fick’s equation membra
• Lung compensates by recruiting more alveolar- close ass
capillary units further i
• Increase in interstitial fluid  reduced lung lung. Th
compliance vasculat
• This results in increased work of breathing , to alveoli,
maintain alveolar ventilation minimiz
• Clinical sign: Increased work of breathing/ Alve
Dyspnoea adolesce
 STAGES OF PULMONARY OEDEMA
• Stage 2: Crescenteric alveolar filling
• Interstitial oedema increases further and there is
passage of fluid into the alveoli
• This first appears as crescents in the angles
between adjacent septa
• The centre of the alveoli and most of the
alveolar walls remain clear
• So gas exchange remains little affected and the
PA-aO2 gradient remains small
• Clinical manifestation: Tachypnoea, relatively
normal gases
• Mechanism: Stimulation of J-receptors
• sensory nerve endings of the vagus nerve which
are present in the alveolar walls and are in close
contact with pulmonary capillaries.
• When stimulated they result in a reflex comprising
of hyperventilation, bradycardia and hypotension
 mem
close
furth
STAGES OF PULMONARY OEDEMA lung.
vascu
• Stage 3: Alveolar flooding alveo
minim
• some alveoli become totally flooded with fluid, while A
others, frequently adjacent show only crescentic filling
adole
• No gas exchange can occur in completed flooded alveoli
•  Further increase in ”thickness” in Fick’s equation
•  Reduced “area” in Fick’s equation – as functioning
alveolar membranes are reduced
•  this results in alveolar shunting causing venous admixture
i.e. the venous flow to the lung goes past alveoli without
coming into contact with alveolar air
• Clinical manifestations:
• Hypoxia, normo or hypocapnea,
• Coarse inspiratory crackles
• X-ray: Kerley-B lines, Pleural effusions, perihilar haze, b/l
fluffy air-space shadowing, ”bat wing” oedema, pulmonary
vascular congestion, large cardiac sillhouette,

THE GENERATION OF A PRE

 STAGES OF PULMONARY OEDEMA
• Why is there normocapnoea/hypocapnea despite chemore
hypoxia? more do
respons
• CO2 is 23 times more soluble than O2 in plasma and for any chemore
given partial pressure gradient, it will diffuse 23 x 0.85 (diffusion ventilati
bodies a
coefficient) = 20 times faster than O2. chemore
These c
• If PaO2 become severe (<60mmHg or 8kPa), then hypoxic changes
ventilatory drive kicks in stimulated by peripheral 500 mm
chemoreceptors (located in carotid bodies) between
• if patients with severe oedema are treated with a high hypoxia
FI O2 , hypercapnia may result from interference with gas
I 2
subsequ
exchange effect o
unmask
• Tachypneoa also stimulated by J-receptor reflex a typica
left. Alv
the insp
 STAGES OF PULMONARY OEDEMA
• Stage 4: Airway flooding
• Fluid floods the alveolar spaces and extends to the airways  effectively blocks air
passages preventing any meaningful gas exchange and is rapidly fatal unless treated
 SYSTEMIC EFFECTS OF
PULMONARY OEDEMA
 NEUROGENIC PULMONARY
OEDEMA
• Definition: The rapid onset (mins-hours) of pulmonary oedema secondary to
an injury to the central nervous system (CNS) and typically associated with
raised intracranial pressure (ICP)
• It is a diagnosis of exclusion
• Causes:
• Cerebral haemorrhage (SAH – most common cause)
• TBI
• Epileptic seizures
• Embolic stroke
• Blocked VP shunt
 NEUROGENIC PULMONARY OEDEMA
• Pathophysiology:
• CNS injury  excessive stimulation of sympathetic nervous system
• Anatomical site of CNS discharge not exactly known: Animal data suggest that the presence of blood and
inflammatory mediators in the hypothalamus and medulla oblongata is pivotal, particularly when
associated with ischaemia.
• Pulmonary effects: pulmonary venous vasoconstriction  rapid elevation in pulmonary capillary
hydrostatic pressure
•  imbalance of Starling’s forces  transudation of fluid into interstitium
•  mechanical stress injury to endothelium (when Pc pressures >24mmHg)  inflammatory response +
exudation of fluid
• Cardiovascular effects:
•  increased systemic arterial resistance
•  tachycardia
•  increased venous return
•  increased CO & SVR  HTN
•  these can all precipitate cardiac stunning  superadded cardiogenic oedema
•  hypovolaemia can arise through the lung and third spaces due to the raised systemic capillary pressure
• Other effects: Neurogenic diabetes insipidus can arise secondary to TBI or less commonly cerebral
haemorrhage
•  can worsen hypovolaemia
RAISED ICP  CUSHING REFLEX
• Raised ICP  Cerebral areteriolar
compression when ICP > MAP  cerebral
ischaemia
• Stage 1:
• RICP  Sympathetic nervous sytem 
vasoconstriction + tachycardia +
increased venous return  increased
CO & SVR  hypertension
• Stage 2:
• HTN  Baroreceptors in aortic arch 
stimulate vagus nerve in response to
HTN  bradycardia
 INVESTIGATIONS & MANAGEMENT
• AIRWAYS
• The presence of pink frothy sputum indicates severe acute pulmonary oedema.
• Suction secretions
• BREATHING
• Position the patient e.g. sit the patient up
• Patient positioning should be considered as an early intervention since it can have an
immediate effect on oxygenation and symptoms of breathlessness (O’Driscoll et al 2008).
• Supplementary high-flow oxygen - to achieve SaO2 94-98%
• NIV
• RCEM recommend NIV should be considered in all patients with cardiogenic pulmonary
oedema, especially if pH <7.35 & RR>20/min
• Non-Invasive Positive Pressure Ventilation (NIPPV) is the NIV of choice in pulmonary
oedema (especially if cardiogenic)
• Can use either BiPAP or CPAP – no signfiicant differences in efficacy
• But there is a reluctance to recommend BiPAP as standard treatment because a previous study
indicated an increased incidence of myocardial infarction during treatment when compared
with CPAP (Mehta et al 1997).
• Commence PEEP at 5-7cmH20 and increase to 10 as tolerated – be weary of increasing
PEEP too much
 INVESTIGATIONS &
MANAGEMENT
• Beneficial effects of NIPPV:
• Recruits alveoli
• Increases Functional Residual Capacity
• Allows breathing to be on more compliant part of the lung’s
pressure-volume curve
•  decreases work of breathing, improves ventilation-perfusion
relationships, corrects hypoxia and hypercapnia
• Positive intrathoracic pressure  decreased pre-load and
afterload (but be careful not to increase afterload)
 INVESTIGATIONS & MANAGEMENT
• BREATHING: Invasive ventilation in the setting of pulmonary oedema
• Ventilation should prevent hypoxaemia and avoid iatrogenic lung injury which
patients with ARDS are at higher risk of developing.
• Lung-protective strategies include: smaller VTs, permissive hypercapnia, pressure-limited
ventilation, inverse-ratio ventilation
• Initial tidal volumes should be 6–7 ml kg−1 utilising PEEP to aid clearance of the
oedema and maintain alveolar recruitment.
• Care should be taken, however, that high PEEP does not impair cardiac function. Also in
setting of CNS injury, high PEEP can increase ICP further.
• Any patient with raised ICP should be ventilated according to neuroprotective
parameters which may conflict with optimal ventilation for pulmonary oedema.
• Permissive hypercapnia should not be used in the presence of raised ICP or only
permitted if ICP monitoring is in place, as it can cause cerebral vasodilatation and further
worsen ICP.
• But hypocapnia can also be harmful “Early, prophylactic hyperventilation in traumatic
brain injury associated with worse outcomes” (Muizelaar et al 1991)
• So aim for eucappnia
• High-frequency oscillation ventilation may aid the treatment of refractory
hypoxaemia.
 INVESTIGATIONS & MANAGEMENT

• CIRCULATION
• ECG, Bedside echocardiogram, CXR
• Vascular access
• Blood tests: FBC, U&Es, Blood gas, CRP, LFTs, Coag, Troponin, BNP, Blood cultures
• Catheterisation and careful fluid input-output monitoring
• Pharmacological management
 INVESTIGATIONS & MANAGEMENT
• CIRCULATION
• Pharmacological management:
• Vasodilators - reduces systemic venous and arteriolar vascular resistance and hence both
pre-load and afterload  reduces cardiac workload
• Nitrate infusion commence at a rate of 10-20mcg/min increasing every 3-5min by 5-10 mcg/min
as needed and as BP allows
• Contraindications: aortic stenosis, systolic BP <90mmHg
• Loop Diuretics – reduces pre-load by increases diuresis + venodilator effect
• Theoretically, counteracts increased effects of RAAS in cardiogenic pulmonary oedema
• But limited benefits in RCTs
• Also, evidence of harmful effects (hypotension, hyponatraemia, dehydradation) at high doses
• The ESC Guidelines advocate small intravenous boluses of furosemide at 20-40mg for patients with
CPO and symptoms of fluid overload or congestion
• High dose diuretics should be used with caution and only in those with evidence of fluid overload
and a history of long term diuretic use
• Note diuretics should be avoided in neurogenic pulmonary oedema where DI can arise post-
cerebral injury. Also can worsen cerebral vasospasm, so should be avoided in patients with SAH
• Inotropes (e.g. IV dobutamine at 2-3mcg/kg/min)
• not routinely recommended in cardiogenic pulmonary oedema as lack of evidence but may be
required if cardiogenic shock develops OR signs of end-organ failure OR in neurogenic pulmonary
oedema where myocardial stunning may develop
 INVESTIGATIONS & MANAGEMENT
• DISABILITY
• People with acute pulmonary oedema will be distressed
• Small doses of opiates (e.g. 2.5mg IV morphine) can be given to reduce anxiety
+ reduce pre-load + can produce mild vasodilatation (and thus reduce
afterload)
• Although opiate analgesia may be required to control pain or distress, the risks of
depressing an already compromised respiratory system should be considered
(Skinner and McKinney 2011)
• NICE (2014) recommended that opiates should not be routinely given to people
in acute cardiogenic pulmonary oedema

• E: Treat underlying cause

 USEFUL RESOURCES
• Nunn’s Applied Respiratory Physiology: Chapter 29
• Neurogenic pulmonary oedema:
https://academic.oup.com/bjaed/article/11/3/87/257170
• http://www.derangedphysiology.com/main/required-
reading/cardiology/Chapter%205.1.5/pulmonary-oedema
• http://www.oxfordmedicaleducation.com/cardiology/acute-pulmonary-
oedema/
• http://adultemergencymedicine.blogspot.co.uk/2015/04/pulmonary-
oedema.html
• https://www.rcemlearning.co.uk/references/cardiogenic-pulmonary-
oedema/