1. health and fitness
2. disease

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PULMONARY AND CRITICAL
CARE BULLETIN
Vol. XII, No. 2, April 8, 2006
Website : indiachest.org
(pp. 9-16)
IN THIS ISSUE
THE CRITICALLY ILL PREGNANT PATIENT
1. The Critically ill Pregnant Patient
Dr. A.S. Paul
2. Pathophysiology of Hypercapnic and
While caring for the critically ill pregnant patient the physician is primarily
looking after the mother. It is important, however, for him to be aware of any effects,
diagnostic or therapeutic measures might have on the foetus. This requires an
understanding of the physiological changes in pregnancy.
Hypoxic Respiratory Failure and V/Q’
General changes
Relationships
Alok Nath
Published under the
auspices of
Pulmonary C.M.E. Programme of
The Chest
(Chest Health Care, Education & Research
Trust)
Editorial Board
Dr. D. Behera, Chief Editor
Dr. S.K. Jindal
Dr. D. Gupta
Dr. A.N. Aggarwal
Department of Pulmonary Medicine,
Postgraduate Institute of Medical
Education & Research, Chandigarh
Progesterone causes hyperaemia and oedema of all mucosal surfaces. The resultant
nasal congestion may necessitate use of a small bored nasogastric tube.
The diaphragm ascends 4cm and the chest wall widens by 5-7 cm. Q waves in the
inferior leads may result. Care needs to be taken not to misinterpret these findings as
suggestive of cardiac disease. In case a chest tube is being placed this change in
diaphragmatic position has to be taken into consideration.
Respiratory changes
Spirometry remains normal and so does the FEV1. Asthmatics who are pregnant
show variable changes. It is said about a third improve, a third deteriorate and the
remainder remain unaffected by the pregnant state.
Flow volume loops and peak flow remain unchanged. TLC decreases by 4-5% and the
FRC decreases 20%. These changes are because of the changed diaphragmatic
position. Minute ventilation increases by 50%. This change is mediated mainly by an
increase in tidal volume rather than in rate.
60 % experience dyspnoea of pregnancy. This is primarily an effect of progesterone
on the respiratory centre. Direct respiratory stimulation is also mediated by
progesterone. It also enhances the response to Pa CO 2.
Subcription
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The normal ABG in pregnancy shows a slight respiratory alkalosis with compensatory
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The PaCO2 level can vary between 30-32 mEq/L while the Pa CO2 maybe normal or
slightly increased. Bicarbonate values vary between 18 and 21 mEq/L.
Oxygen consumption
Oxygen consumption increases by about 20%. This is accounted for by the increase
in uterine and fetal requirements and also the increase in cardiac and respiratory
9
Ephedrine is the vasopressor of choice as it does not cause
vasoconstriction in the uterine circulation. All other agents
normally used in the ICU may interfere with foetal circulation.
work. However, the O2 reserve is less. This is because the
FRC is reduced and there is increased consumption. The
practical significance of this fact is that attempts at intubation
can be accompanied by rapid desaturation.
The foetus is capable of high O2 extraction. The foetal
haemoglobin levels are high and a saturation of 80-90% is
obtained at a paO2 of only 30-35 mm Hg ie the level found at
the interface with the maternal circulation in the umbilical veins.
The ductus arteriosus ensures that two ventricles are available
to contribute to the circulation.
Cardiac changes
Cardiac output increases by about 40%. There is an increase
in blood volume by approximately 2 litres. The RBC mass
increases by 20-30%. This explains the relatively well tolerated
loss of blood during a normal delivery or LSCS (0.6l and 1l
respectively). The values for CVP and capillary wedge pressure
remain unchanged. Colloid oncotic pressure is decreased.
The normal albumin level is slightly lower and accounts for
this. There is compression of the IVC on lying down. This is
significant by about 20wks and can cause a drop in the ejection
fraction of about 20-30%. Lateral repositioning is an important
manoeuvre which can correct this haemodynamic
compromise. The normal diastolic BP reading is lower. An
ejection murmur is commonly heard and there often is a third
heart sound. The typical ECHO study shows an increase in
all chamber dimensions and the LV wall thickness.. A small
effusion may be seen and a mild TR/PR is almost universal. A
mild MR is seen in upto 30%.
Oxygen reserve is approximately 42 ml. At a rate of
consumption of 20 ml/min the foetus should be able to survive
only two minutes theoretically. However, the actual value is
about 10 minutes because there is shunting away from nonessential organs and perfusion to essential viscera is preserved.
The practical significance of this fact is that a perimortem
LSCS should be done within 5 minutes of maternal arrest.
The foetus should be viable( ie at least 24 wks gestation and
a weight of 750g.)
ICU Admissions
A few common indications for ICU admission in the pregnant
state are enumerated below. Pre-eclampsia is a fairly common
indication. The aim is to prevent eclampsia and ensure close
observation. Delivery is always in the mother’s best interest.
Renal and GI Changes
The GFR increases by 50% and so does creatinine clearance.
The normal creatinine is lower than 0.8mg%. Values in the
higher “normal” range may indicate significant dysfunction.
Amniotic fluid embolism is rare but catastrophic and treatment
is only supportive.
Reflux is a common complaint and the risk of aspiration is
always present. There is a decrease in albumin (n 3.1 g %)
due to dilution. The serum alk phos values are two to four
times the normal. Appendicitis and cholecystitis are the two
commonest surgical indications besides the usual obstetric
causes.
Tocolytic pulm oedema was common when beta adrenergic
agents were frequently used to prevent labour from progressing.
However, it is not seen that frequently any more, because
these agents are less frequently used now.
Peripartum cardiomyopathy is seen late in pregnancy or in
the post-partum period. It is important to avoid ACE inhibitors
in the pregnant state. Otherwise management is like any
other heart failure.
Foetus and placenta
The placenta serves to provide gas exchange,nutrition and
waste elimination. It works by a mechanism of “Concurrent
exchange”.
Septic shock may occur. Choice of vasopressor should ideally
be ephedrine.
Oxygen delivery depends on the flow in the uterine artery
(increases to 600 ml/min as against a value of 50 ml per minute
in the non-pregnant state), the O2 content of the maternal
blood and its Hb concentration and saturation.
PTE may occur with greater frequency than in the normal
population. Warfarin has to be avoided and IVC filters tend to
slip out of position because the venous system is dilated.
ARDS is often precipitated by conditions related to pregnancy.
These patients have a better prognosis than the normal
population. This maybe because these patients are younger,
relatively fitter and do not have co-morbidities. Asthma may
Hypotension, contractions and vasoconstriction all
compromise flow.
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worsen and need ICU admission. The principles of
management remain the same.
of failed intubation , rapid desaturaturation during intubation,
and aspiration.
Pre-existing cardiac disease worsened by pregnancy may
need ICU care.
Hyerventilation is to be avoided as this adversely affects uterine
blood flow. Plateau pressures of 30-35 cm of water are well
tolerated. A PaCO2 of 60 is acceptable to both mother and
foetus as long as hypoxia is corrected. In case, acidosis is
marked, bicarbonate may be used in a titrated manner. In
most situations delivery may improve the maternal outcome.
Management issues
Conventional vasopressors may impede uterine flow.
Ephedrine is the pressor of choice after giving adequate volume
replacement, and ensuring that the patient has been placed
in the left lateral position.
Further reading
CPR technique remains essentially the same. Defibrillation
should be done after removal of any foetal electrodes placed
for monitoring. The left lateral position should not be forgotten.
In case a perimortem LSCS is being considersd CPR will
probably have to be interrupted to ensure that this is done on
time.
1
Chestnutt AN Physiology of normal pregnancy Crit Care
Clin 20 2004 609-615
2
Cohen R,Talwar A, Efferen L, Exacerbation of underlying
pulmonary disease in pregnancy Crit Care Clin 20 (2004)
713-730
3
Lapinsky SE Cardiopulmonary complications of
pregnancy Crit Care Med 2005 Vol 33 No 7.
Ventilation may be either invasive or non-invasive. Vomiting
and aspiration are real risks in case of non invasive ventilation.
Problems with invasive ventilation include a greater frequency
Dr. A. S. Paul
PATHOPHYSIOLOGY OF HYPERCAPNIC AND HYPOXIC RESPIRATORY
FAILURE AND V/Q RELATIONSHIPS
CONTROL OF VENTILATION
INTRODUCTION
Before going into the details of mechanisms involved
in respiratory failure lets have a brief overview of the pathways
involved in breathing. The process starts from the higher CNS
centers from where neural signals are delivered to respiratory
muscles and chest wall which initiates airflow from airways
into the alveoli, sum total of which is the minute ventilation.
The part of minute ventilation, which takes part in gas exchange, is alveolar ventilation that is responsible for determination of partial pressures of O2 and CO2. Now these values
send feedback signals back to CNS via chemoreceptors (central and peripheral).
The function of respiratory system is divided broadly in two
main groups i.e ventilation which is responsible for removal of
waste carbon dioxide and oxygenation which responsible for
adequate delivery of O2 from atmosphere to blood. Dysfunction
of ventilatory apparatus leads to hypercapnic respiratory failure
and of gas exchange leads to hypoxic respiratory failure.
Respiratory failure is one of the most commonly encountered
clinical condition in specialty of critical care and is defined as
failure of adequate oxygenation or removal of waste carbon
dioxide due to dysfunction of one or the other components of
respiratory system and is characterized by PaO2 < 60mm of
Hg and PaCO2 > 45 mm of Hg dividing it into hypoxic and
hypercapnic respiratory failure respectively. In clinical practice hypoxemic and hypercapnia do not occur in watertight
compartments and mostly coexist. Each of these subtypes
of respiratory failure is further classified into acute which develops in minutes to hours and chronic which can take days
or even longer to develop.
The neural signals from higher centers descend in
the dorsal and ventral respiratory group of neurons in the spinal cord. The dorsal respiratory group is responsible for the
involuntary or the metabolic respiratory control system and
the ventral respiratory group is involved in the voluntary or the
behavioral control system. These neurons descend in the cord
and supply main and accessory respiratory muscles at their
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respective level. The generation of the respiratory rhythm starts
in dorsolateral pons at nucleus parabrachialis. Some authors
have also termed this area as the Bottzinger or the
prebottzinger complex. The inspiratory motoneurons activate
the process of inspiration however expiratory neurons deactivate in inspiratory neurons so that the process of expiration
takes place passively.
3)
Muscular dystrophy, respiratory muscles fatigue
4)
5)
6)
Amount of dead space ventilation
3)
CO2 production
But here we must consider that the mechanisms of hypercapnic respiratory failure obstructive airway disorders like COPD
is much more complex and will be dealt with, later.
INCREASED DEAD SPACE
We know that dead space ventilation is the amount of
air inhaled which does not take part in gas exchange .It is
divided into two parts that is anatomical and alveolar. Again
dead space ventilation can increase and lead to hypercapnia
due to
1)
Increase in RR
2)
Vascular occlusion
3)
Inequalities of ventilation ( physiological and pathological)
INCREASED CO2 PRODUCTION
This is one of the less commonly recognized but clinically significant modes of hypercapnia. This can occur in various conditions like fever, anxiety, stress, sepsis and very high
carbohydrate diet. This usually is taken care by the body but
may become clinically significant in patient s with underlying
obstructive airway disease.
So any factor that causes increase in CO2 production and
amount of dead space ventilation or decreases total minute
ventilation will cause hypercapnic respiratory failure.
DECREASED MINUTE VENTILATION
Described above are the various mechanisms involved
in development of hypercapnia but to under stand the basic
pathophysiology behind hypercapnic respiratory failure an important concept is that of ventilatory supply and ventilatory
demand. As told above that integrity of ventilatory apparatus
is responsible for the removal of excess CO2 produced in the
body. So whenever ventilatory demand increases than ventilatory supply or vice versa ventilatory failure develops.
Minute ventilation is the product of respiratory frequency and inhaled tidal volume. So in condition which causes
decrease in inhaled tidal volume or relative decrease in alveolar ventilation (or increase in dead space) due to increase in
respiratory rate or airway obstruction will lead to hypercapnia.
Various conditions which can lead to hypercapnic respiratory
failure due to this mechanism are;
1)
CNS disorders
Ventilatory supply depends on Respiratory drive, motor neuron/nerve function, muscle strength and respiratory mechanics and this is responsible for the Maximal sustainable
ventilation. Maximal sustainable ventilation is the maximum
amount of ventilation achieved without development of respiratory muscle fatigue. In health ventilatory supply exceeds than
Stroke, brain tumor, spinal cord lesions, drug over
dose
2)
Airway obstruction
Upper airway obstruction, Asthma, COPD
If we look at the alveolar ventilation equation, PaCO2
= K · VCO2 / VA , we can see that the partial pressures of
CO2 depends on three main factors;
2)
Metabolic abnormalities
Myxedema, hypokalemia
HYPERCAPNIC RESPIRATORY FAILURE
Total minute ventilation and alveolar ventilation
Chest wall abnormalities
Scoliosis, kyphosis, obesity
The stimulus for regulation of respiration are the partial pressures of O2 and CO2, pH of blood and CSF and hydrogen ion and bicarbonate ion concentration of blood. The
peripheral chemoreceptors, which are situated in carotid bodies and aortic bodies, respond predominantly to partial pressures of O2 and to some extent to other stimuli however central chemoreceptors mainly respond to hydrogen ion concentration and pH of the extracellular fluid. One point which needs
consideration here is that for the same amount of change in
pH the response to respiratory acidosis is much more than
metabolic acidosis because CO2 crosses the blood brain barrier much more readily than hydrogen and bicarbonate ions.
1)
Muscle disorders
Peripheral nerve disease
Guillain Barre syndrome, botulism, myasthenia gravi
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not be considered as respiratory failure and hence will not be
discussed here.
ventilatory demand so much so that in conditions of physiological stress respiratory failure does not develop. Ventilatory demand on the other hand depends on O2 demand, CO2
production and dead space ventilation.
The major mechanisms involved in development of
hypoxia will now be discussed one by one.
So Ventilatory demand >>> Ventilatory supply = Hypercapnic
respiratory failure.
SHUNT
Shunt is blood pathway that does not allow any contact between alveolar gas and red cells and hence there is no
gas exchange.
One of the prototypes of hypercapnic respiratory failure is COPD but the pathophysiology of hypercapnic respiratory failure in COPD is multifactorial and is due to:
1)
Decreased FEV. But the relationship between FEV1
and CO2 curvilinear and CO2 retention
does not
occur unless FEV1 < 20 – 30 % of normal
2)
Altered lung mechanics
3)
Increased dead space ventilation
4)
Expiratory air trapping due to obstructive physiology
5)
Respiratory muscle fatigue
Shunt can be physiological which comprises of some
of blood from the coronary venous circulation and bronchial
arterial connections. Pathological shunt can be at pulmonary
level or extrapulmonary level. Extrapulmonary shunt is at the
level of heart leading direct mixing of blood from the right side
of heart to the left side and subsequent development of hypoxemia. We are here concerned only with pathological pulmonary shunts and etiologies of shunt development are:
6)
Decreased muscle blood flow
1)
7)
Increased CO2 production
Diffuse alveolar filing diseases like ARDS, Pulmonary
edema
2)
Massive collapse
3)
Abnormal arteriovenous connections at the level of lungs
(PAVM)
So, we can see that many factors come into play
among which the decrease in FEV1 and altered lung mechanics due to flattening of diaphragm and hyperinflation are the
primary abnormalities which contribute to the development of
chronically increase CO2 tensions in blood and lead to development of chronic hypercapnic respiratory failure.
The amount of hypoxemia contributed by development of shunt
depends on shunt fraction, which is the percentage of cardiac
output, which is going from right to left side of the heart without oxygenation. Shunt becomes clinically important when it
is more than 30% of the cardiac output. The hallmark shunt
physiology is poor or no response to increased inspired O 2
concentrations and it usually results in hypoxemic respiratory failure but it can cause hypercapnia when shunt fraction
is more than 60% of the cardiac output. This happens due
failure of ventilatory compensation, increase in dead space
due to tachypnoea, decrease in total alveolar ventilation and
development of respiratory muscle fatigue.
HYPOXIC RESPIRATORY FAILURE
The partial pressure of oxygen in blood depends basically on the concentration of O2 in inspired gas, and alveolar
arterial gradient. The basic mechanisms causing hypoxia can
be easily enumerated as we look on to the alveolar gas equation i.e
PaO2 = [FiO2 (PATM-PH2O) – PaCO2/R] – [A-a gradient].
They are:
1)
Low inhaled FiO2
VENTILATION PERFUSION RATIO (V/Q RATIO)
2)
Conditions which lead to widening of the alveolar arterial gradient viz
a)
Presence or absence of shunt physiology
Now what exactly this V/Q is? To understand this
we must undergo through some simple derivations of equation
b)
Ventilation perfusion mismatch
c)
Diffusion limitation
CO2 lost in alveolar gas from capillary is given by:
VCO2 = Q (Cvco2-Ccco2)
In clinical practice low inspired concentration of oxygen is not encountered but may occur only in situation like
high altitude, which is physiological maladaptation and can
CO2 lost from exhaled gas into air is given by equation; VCO2 =
VA x PACO2 xK
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In steady state CO2 lost from capillary and alveoli is same
So Va x Paco2 x K = Q (Cvco2-Ccco2)
i.e. VA/Q= (Cvco2-ccco2/ PACO2)x K…….(1)
Similarly for O2:
VO2= VI x Fio2 – Va x FAO2
And..
VO2= Q( Cco2 – CvO2)
Now, as Inspired VA = Expired VA
So,
We can see that in low V/Q areas i.e between 10 and 1 there
is significant fall in alveolar and endcapillary O2 levels but
above V/Q of 10 the effect not as significant. For CO 2 the
effects are quite different, In low V/Q areas CO2 levels increase
but only slightly but between V/Q areas 1 and 10 the fall is
clinically significant. Logically speaking there should be actually an increase in the CO2 levels in high V/Q areas because
of creation of large alveolar dead space but this does not happen practically. This is because for CO 2 to rise in high V/Q
areas the V/Q should alter in a magical way so that rest the
parameters and compensatory changes do not take place.
But in practice the disproportionate increase in ventilation is
responsible for the decrease in CO2 levels.
VA/Q = CcO2 - CvO2 / FIO2- FAO2..... (2)
Now we can easily see that gas exchange is determined by
three major factors
1)
V/Q ratio
2)
Composition of inspired gas
3)
Slopes and position of the relevant blood gas dissociation curves
In normal lungs 5-10 mm of Hg difference in alveolar and arterial oxygen partial pressures is due physiological inequality of
ventilation and perfusion, which can be,
1)
Gravitationally based inequality based on “West’s lung
model”
2)
Fractally based inequality
3)
Anatomically based inequality
4)
Collateral ventilation
5)
Reactive vaso and bronchoconstriction
The difference in effects on the levels of O2 and CO2 is
due the difference in slopes and positions of dissociation curves
of O2 and CO2.
Unfortunately neither equation 1 or 2 is amenable for simple
mathematical calculations but results can be derived from
computerized analysis.
Figure 1 shows the effects development low and high V/Q
areas on alveolar and endcapillary O2 and CO2.
Now what is the effect of increase in inspired concentration of
O2 on Alveolar and endcapillary blood O2 levels. Figure 2 demonstrates these effects. We can see in high V/Q areas (more
than 10) that as we go on increasing the FiO 2 the O2 levels
keep on increasing. In areas with very low V/Q areas which
more or less start behaving like shunt there is no effect of
increasing the FiO2. Increase in FiO2 most significantly effects
the areas with V/Q ratios between 1 and 10and this again in
part is due to the position of dissociation curve of O2.
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DIFFUSION LIMITATION
Summarizing, the principal effects V/Q inequality on O2 and
CO2 exchange are
1)
It affects both gases no matter what the pathological
basis of inequality is.
2)
Causes hypoxemia and hypercapnia
3)
Causes more severe hypoxemia and hypercapnia
4)
Affects O2 more than CO2 in low V/Q areas
5)
Affects CO2 more than O2 in very high V/Q areas
6)
Impair total O2 and CO2 exchange by the lungs
7)
Creates alveolar arterial difference for both the gases.
One of less common mechanisms of hypoxemic respiratory
failure is diffusion limitation. Diffusion capacity of a gas depends on:
RESPONSE OF THE BODY TO V/Q MISMATCH
Changes in the mixed venous oxygen saturation
2)
Changes in ventilation
3)
Changes in cardiac output
Thickness of the alveolar basement membrane.
2)
Avidity of the gas to bind to hemoglobin
3)
Hemoglobin concentration
4)
Alveolar partial pressures of O2
5)
Capillary transit time
6)
Lung volumes
Normally diffusion limitation does not cause significant hypoxemia at rest but during exercise the time required
for uploading of O2 to red cells is markedly decreased and
leads to hypoxemia. Only when the diffusion is severely limited (<0.25 normal) or the transit time is markedly shorten
(<0.25 seconds) is it possible to have a PaO2 less than
PAO2.This holds true in conditions like ILDs and to extent in
DPLDs and ARDS.
The body responds to V/Q mismatch by three main
mechanisms in the acute phase:
1)
1)
The only short term compensatory changes are in mixed
venous blood, total ventilation and changes in cardiac output.
If it assumed that there is no limit to how much O2 can be
extracted from arterial blood by the peripheral tissues, it is
evident that V/Q inequality will passively lead to reduced
venous PO2 and increased venous PCO2. If venous PO2 falls
indicates that alveolar PO2 will fall an each V/Q compartment.
The prototype of hypoxemic respiratory failure is acute
respiratory distress syndrome and the major mechanisms involved in its development are the same which have been described above. For the sake of enumeration they are;
Thus a circle of events is set up so that if a single red
cell was followed around the circulation, at each passage
through the lungs and then tissues, PO2 would fall progressively with each circuit of the body.
1)
Maldistribution of ventilation
2)
Shunt physiology
3)
Alveolar hypoventilation
4)
Diffusion limitation
In severe degrees of ARDS hypercapnia ca also supervene
and this due to the imbalance between ventilatory supply and
respiratory demand. Ventilatory supply decreases because
of;
Both arterial and venous PO2 will restabilize at new
lower values (PO2 values will be higher) than were present
immediately after the V/Q insult developed. In doing so VO2
and VCO2 will be restored to normal values.
CHANGES IN VENTILATION
In low V/Q areas increase in ventilation leads to significant
drop in CO2 but O2 is barely affected if at all and in high V/Q
areas both O2 and CO2 usually come to nearly normal levels.
1)
Increased lung compliance
2)
Decreased FRC
3)
Increased air flow resistance
4)
Respiratory muscle fatigue,
And ventilatory demand increases because of;
CHANGES IN CARDIAC OUTPUT
In low V/Q areas increase in cardiac output improves O2 which
may or may not be clinically significant however in high V/Q
areas there is no significant effect.
1)
Increased dead space
2)
Decreased total alveolar ventilation
3)
Increased O2 consumption by lungs
And this contributes to hypercapnia.
So to conclude we can say that the basic pathophysi15
and predominant type of respiratory failure as that is going to
ology of both types of respiratory failure may be different but
actually in practice both hypoxemia and hypercapnia can coexist. It is very important to recognize the main mechanism
decide the mode of therapy and formulation of treatment plan.
Alok Nath
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