Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3080_Библиотеки_им_академика_М_И_Перельмана
.pdf
Clinical Cases in Critical Care, First Edition. Alice Myers and Theophilus Samuels.
© 2023 John Wiley & Sons Ltd. Published 2023 by John Wiley & Sons Ltd.
11
A
t morning handover, you are informed about Gladys. She is an 80- year- old
patient who has just arrived at your HDU for management of severe
hyponatraemia. She had been prescribed furosemide 7 days prior to admission for
symptoms of heart failure, including pedal oedema. She lives with her
husband
and can walk around her bungalow with the aid of a Zimmer frame, but rarely
leaves her home for fear of falling. She is mildly confused, and the laboratory
has called to conrm that her serum sodium concentration is 105 mmol/L.
The Patient
with Hyponatraemia
Dene hyponatraemia
Hyponatraemia is defined as a serum sodium concentration less than
135 mmol/L. It is the most common disorder of electrolytes seen in hospital-
ised patients.
Classify hyponatraemia according to serum sodium
concentration, time of development, symptoms,
serum osmolality and
volume status
See Table11.1.
Discuss and describe hyponatraemia according
to severity of symptoms
See Table11.2.
Some patients with profound biochemical hyponatraemia may have clini-
cally mild symptoms, while others with moderate biochemical hyponatraemia
may present with signicant neurological symptoms. Elderly patients are prone
to non-
specic symptoms (e.g. nausea, malaise, anorexia), and it is worth
https://t.me/medicina_free
Clinical Cases in Critical Care
140
Table 11.2: Hyponatraemia classied according to the severity of symptoms.
Severity Symptoms
Mild Non- specic or may be absent
Moderately severe Nausea without vomiting
Headache
Confusion
Severe (unlikely with serum
sodium
>130 mmol/L)
Cardiorespiratory arrest
Vomiting
Reduced consciousness (Glasgow Coma Score
≤8)
Seizures
Abnormal and deep somnolence
Table 11.1: Classication of hyponatraemia. Classifying hyponatraemia using volume
status can be considered ambiguous. It is often not clear in this context whether
volume status refers to extracellular uid volume (ECF), to the effective circulating
volume (ECV) or to the total body water. A potential workaround to reduce ambiguity is
to use the terms ECV and ECF.
Classication
based on
Categories Parameters/cut- off values
Serum sodium
concentration
Mild 130–135
mmol/L
Moderate 125–129
mmol/L
Profound <125
mmol/L
Time of
development
Acute <48
h
Chronic >48
h
Symptoms ‘Moderately
symptomatic’
Any biochemical degree of
hyponatraemia in the presence of
moderately severe symptoms of
hyponatraemia
‘Severely
symptomatic’
Any biochemical degree of
hyponatraemia in the presence of
severe symptoms of hyponatraemia
Serum osmolality Hypotonic <275
mOsm/kg
Non-
hypotonic 275 mOsm/kg
Volume status
Hypervolaemic
Clinical assessment
Euvolaemic
Hypovalaemic
considering hyponatraemia if they are present. It is recommended that the
management of hyponatraemia is guided by the presenting clinical symptoms
and signs rather than the degree of hyponatraemia. The clinician should con-
sider all symptoms that can be associated with cerebral oedema as symptoms
that can occur with moderately severe or severe symptomatic hyponatraemia.
https://t.me/medicina_free
The Patient with Hyponatraemia
141
What is the pathophysiology behind disturbances
in sodium homeostasis and what is the likely cause
in this case?
The underlying principle that explains most sodium disorders centres
around the imbalance that occurs between water intake and water excre-
tion. Serum osmolality is maintained at a near-
constant level through the
tightly regulated homeostatic mechanisms involving water intake and the
excretion of water (e.g. via increased or decreased antidiuretic hormone
[ADH] release).
In this case, the profound hyponatraemia is most probably due to her
furosemide therapy for hypertension (although thiazide diuretics are more
commonly the culprit). Furosemide acts by blocking the sodium-
potassium-
chloride co- transport mechanisms in the luminal membrane of the loop of
Henle (thick ascending limb). By blocking this receptor, furosemide increases
urine output of water, sodium, potassium, chloride and other electrolytes by
two mechanisms:
Greater delivery of solutes to the distal nephrons. These solutes then act
as osmotic agents which prevent the reabsorption of water.
An increase in the osmolality of the medullary interstitial fluid
reduces the absorption of ions from the loop of Henle into the
medullary interstitium. This in turn disrupts the countercurrent
multiplier system.
Both eects also reduce the ability of the kidney to dilute or concentrate
the urine.
What is normal serum osmolality?
A standard reference range for serum osmolality is 280–296 mOsm/kg. Normal
serum osmolality is tightly controlled, and it varies less than 0.5% throughout
the day in healthy individuals. Serum osmolality (P
osm
) can be estimated by
the following formula:
osm
2
From this relationship, it becomes apparent that in health, the major
determinant for serum osmolality is serum sodium concentration (repre-
senting approximately 94% of the extracellular osmoles). However, in the
presence of renal disease, the contributions of urea and glucose should be
considered.
Before reviewing Gladys, you review her medical clerking and results of the
blood tests that have been ordered.
https://t.me/medicina_free
Clinical Cases in Critical Care
142
Dene osmolality and osmolarity.
What is the difference?
Osmolarity refers to the number of dissolved particles per 1 L of solvent and is
expressed as Osm/L. Osmolality is the number of dissolved particles in 1
kg of
solvent and is expressed as Osm/kg.
The dierence between the two is insignicant for dilute solutions such
as when considering the physiology of body uids. However, as the volume
of a solvent changes with temperature, osmolarity is considered temperature
dependent. Therefore, since osmolality is temperature independent as it is
based on the mass of the solvent, it is the preferred term in biological systems.
Why is it important to establish whether
hyponatraemia is hypotonic?
Hypotonic hyponatraemia is managed differently from non- hypotonic
hyponatraemia. Cerebral oedema does not occur with non- hypotonic
hyponatraemia.
Excluding hyperglycaemic hyponatraemia is also important in these
patients. Several formulae can be used to correct the measured serum sodium
concentration in the presence of a raised measured serum glucose concentration.
Hyponatraemia can be hypotonic, isotonic or hypertonic when estimating
the serum osmolality. This is because the estimate depends upon which osmot-
ically active agents are present and whether they are incorporated into the
calculation. Conversely, a measured serum osmolality <275 mOsm/kg always
conrms that the hyponatraemia is hypotonic.
How is normal serum osmolality physiologically
maintained?
There are two basic principles for maintaining serum osmolality that should
be borne in mind when considering how changes in intracellular and extra-
cellular uid volumes are handled by the body.
The number of osmoles (the amount of a substance that is fully dis-
sociated and dissolved in water) in the intracellular and extracellular
compartments remains relatively constant due to cell membranes pos-
sessing almost complete impermeability to many solutes (e.g. sodium
and chloride).
The osmotic equilibrium between the two compartments remains almost
exactly equal due to water being able to rapidly move across cell mem-
branes, so no osmotic gradients exist among the body’s uid compartments.
The exception to this is the renal medulla due to its need to concentrate
urine, hence the osmolality is much larger than in other parts of the body.
Bearing these principles in mind, the physiological changes that occur to
maintain normal serum osmolality can be summarised as follows:
https://t.me/medicina_free
The Patient with Hyponatraemia
143
Changes in plasma osmolality are sensed by specialised cells called
osmoreceptors located in the anterior hypothalamus near the supra-
optic nuclei (increased osmolality causes them to shrink). These hypo-
thalamic osmoreceptors then proportionately stimulate cells located in
the supraoptic and paraventricular nuclei.
Both the supraoptic and paraventricular nuclei have axonal extensions
that project into the posterior pituitary. Membrane permeability to
calcium ions increases following stimulation. This results in an increase
in the release of stored ADH into the circulation.
Circulating levels of ADH then affect the proportion of aquaporins
(water channels) that are inserted into the collecting duct of the kidney,
thus altering its permeability to free water resulting in the ability of the
kidney to excrete concentrated/low-
volume or dilute/high- volume urine.
Osmoreceptors can detect changes in osmolality rapidly, which results in a
signicant increase in ADH within minutes. In addition, they induce thirst in
response to an increased extracellular uid osmolality.
Describe how ADH works
Antidiuretic hormone (also known as arginine vasopressin) binds to type 2
vasopressin receptors (V2R), resulting in an increase in intracellular cyclic
adenosine monophosphate (cAMP) levels and protein kinase A activity through
a stimulatory G- protein- coupled mechanism. This then increases water perme-
ability of the collecting ducts in the kidney through the actions of aquaporin-
2water channels (Figure11.1).
AC
Gs
cAMP
ATP
Protein
Kinase A
Protein
Phosphorylation
H
2
O
H
2
O
Tubular cells
Figure 11.1: Effect of antidiuretic hormone on renal tubular cells. Aquaporin 3 and 4
channels allow passage of water out of the cell. Regulation of these aquaporins appears
to be independent of AVP. AC, adenylate cyclase; AQP- 3/AQP- 4, aquaporin 3 and 4
channels; AVP, arginine vasopressin or ADH; cAMP, cyclic adenosine triphosphate;
Gs, G stimulatory protein; V2, vasopressin- 2 receptors.
Source: Theophilus Samuels.
https://t.me/medicina_free
Clinical Cases in Critical Care
144
In the absence of disease, the kidney can vary urine concentration
dramatically, ranging from an osmolality of 1200 mOsm/kg at maximal activity
to as low as 50
mOsm/kg. However, in a diseased state, as in critically unwell
patients, this range can be considerably smaller. This is important as when
daily solute load is increased or decreased, the ability of the kidneys to react to
these changes to maintain serum sodium concentration within normal limits
is diminished.
What other factors inuence the synthesis
and
release of ADH?
While plasma osmolality plays an important role as described above, an equally
if not more powerful stimulation of ADH release occurs in the setting of low
arterial blood pressure and low eective arterial volume. It is therefore plausible
for a hypotensive patient to have low plasma osmolality but high circulating
levels of ADH. Other factors that can increase ADH levels include pain, stress,
hypoxia, hypercapnia, nausea and medications (e.g. adrenaline).
Describe the management of severe symptomatic
hyponatraemia
Irrespective of the cause or whether it is acute or chronic, severe symptom-
atic hyponatraemia requires immediate treatment with the appropriate clinical
monitoring in place (Figure11.2).
The current recommended guidance aims to increase serum sodium
concentration by 5 mmol/L within the rst hour of treatment. This threshold
ideally minimises the immediate risk of cerebral oedema and reduces the risk
of osmotic demyelination and over-
rapid correction.
This can be accomplished by infusing 150
mL 3% hypertonic saline solution
(or equivalent) intravenously over 20 minutes. After this rst infusion has n-
ished, it is recommended that a second 150 mL 3% hypertonic saline infusion
is started while the serum sodium level is measured. This entire process can be
repeated twice until the serum sodium concentration increases by 5 mmol/L
or until the symptoms improve, whichever comes rst. If successful, then the
3% hypertonic saline solution is stopped and the smallest feasible volume of
0.9% saline is given to keep the IV line patent until cause- specic treatment
is started.
Increases in serum sodium concentration should be limited to less than
10 mmol/L within the rst 24 hours of treatment (including the initial 5 mmol/L).
Subsequently, increases in serum sodium concentration should be limited to
8 mmol/L every 24 hours until it reaches 130 mmol/L.
Following review of the notes and results, you go to review Gladys. Her mea-
sured serum osmolality is 233 mOsm/kg. She is now drowsy, and her GCS
has reduced to 11 (E3, V3, M5) so you assess her to be severely symptomatic
from the hypotonic hyponatraemia.
https://t.me/medicina_free
The Patient with Hyponatraemia
145
Check serum sodium concentration
WHILE
repeating another IV infusion of
150 ml 3% hypertonic saline
(or equivalent) over 20 minutes
Promptly commence an IV infusion of
150 ml 3% hypertonic saline
(or equivalent) over 20 minutes
Continue IV infusion of
3% hypertonic saline
(or equivalent) aiming for
an additional 1 mmol/L
per hour increase in
serum Na
+
concentration
STOP infusion of 3% hypertonic saline
(or equivalent)
AND
Keep IV line patent using smallest
feasible volume of 0.9% saline
AND
Start diagnosis-specific
treatment if possible
YES
NO
Check serum Na
+
concentration after
6 and 12 hours and then daily until
serum Na
+
concentration has stabilised
Check
serum Na
+
every 4 hours
with infusion
*10 mmol/L
includes the
initial 5 mmol/L
Figure 11.2: Management algorithm for severe symptomatic hyponatraemia. Ideally,
pre- prepared 150 mL bags of 3% hypertonic saline should be readily available.
Preparing a solution of 3% hypertonic saline solution is time- consuming and prone to
errors in calculating the correct amount of NaCl required. See text for symptoms of
severe hyponatraemia.
Source: Theophilus Samuels.
Gladys receives the treatment as outline above, and her serum sodium
increases by 5 mmol/L within the rst hour of treatment. However, her
clinical symptoms do not improve. Through clinical assessment, you have
not found any other obvious cause for a low GCS.
https://t.me/medicina_free
Clinical Cases in Critical Care
146
What do you do next with regard to her
symptomatic severe hyponatraemia?
Bear in mind that patients with severe symptoms may not improve immedi-
ately, as it may take time for the brain to recover.
Nevertheless, as Gladys has not clinically improved, despite the increase in
serum sodium concentration by 5 mmol/L, an infusion of 150 mL 3% hypertonic
saline (or equivalent) should be continued. The aim is to increase the serum
sodium concentration by 1
mmol/L per hour until the symptoms improve,
the serum sodium concentration increases 10
mmol/L in total, or it reaches
130
mmol/L, whichever occurs rst. The serum sodium concentration should
ideally be measured every 4 hours while the 3% hypertonic saline infusion is
continued (see Figure11.2).
Should her symptoms still fail to improve after a 10
mmol/L increase in
serum sodium concentration (including the rst 5
mmol/L), then it is likely that
her symptoms are not due to hyponatraemia and other causes should be sought.
What are the concerns surrounding delayed
and overly rapid correction of hyponatraemia?
Delayed correction of profound hyponatraemia from a rapid decrease in sodium
level can surpass the brain’s ability to osmotically adapt. This can lead to irre-
versible brain damage and death from persistent cerebral oedema. Overly rapid
correction without considering the need to protect the patient from the neu-
rological sequelae of cerebral oedema can result in osmotic demyelination
syndrome (OMS) approximately 3–10 days after treatment. Hence, this can
occur following discharge from critical care. OMS is characterised by specic
abnormalities in the brainstem seen on magnetic resonance imaging (MRI)
and indicated clinically by:
Fluctuating levels of consciousness
Pseudobulbar palsy
Dysarthria
Ataxia
Dysphagia.
OMS can be devastating for the patient and their families and is often
irreversible.
List risk factors for developing osmotic
demyelination syndrome
The acronym CCHASM can be used as dened below:
Chronic hyponatraemia
Cirrhosis
Hypokalaemia
Alcoholism
https://t.me/medicina_free
The Patient with Hyponatraemia
147
Serum sodium <105 mmol/L
Malnutrition
What can be done if the serum sodium
concentration rises too rapidly (i.e. rapid
overcorrection)?
Evidence is lacking with regard to managing the rapid overcorrection of serum
sodium concentration. The use of electrolyte-
free water (e.g. 5% glucose solu-
tions) and/or desmopressin can reduce serum sodium concentration in cases
of rapid overcorrection.
However, it is strongly recommended that expert advice is sought before any
attempt is made to re-
lower serum sodium concentration in the presence of a
rapid overcorrection. In addition, overcorrection may indicate the presence of
a complex case. Therefore, the eect of further treatment may be even more
dicult to predict, and these cases should be discussed with medical profes-
sionals experienced in managing these patients.
Explain how serum and urinary concentration
of electrolytes can help clinically in determining
the aetiology of sodium disorders
First, it is important to understand that it is the concentration of the electro-
lytes within the urine and not its osmolality that ultimately determines the
net excretion of water. So, for example, a net loss of free water may still occur
in the presence of a high urine osmolality, which itself is the result of excess
solutes (e.g. urea) with few electrolytes present. Therefore, if the concentration
of electrolytes within the urine is less than that of the serum, it suggests that
free water is being excreted. Conversely, when free water is not excreted in
the urine, it will tend to have a concentration of electrolytes (e.g. sodium and
potassium) greater than that in the serum.
Which urinary tests can aid in diagnosing the causes
of hyponatraemia?
The urine osmolality and urine sodium concentration can be used for this
purpose (Figure11.3). Performing these tests must not take precedence over
treating patients with symptomatic hyponatraemia and can be requested once
the patient has stabilised.
Within 3 hours of ongoing treatment, Gladys's level of consciousness
improves and she becomes much more alert and responsive. Over
the next 24
hours, her serum sodium concentration continues to rise
accordingly. Your consultant asks you to investigate the cause of her
hyponatraemia.
https://t.me/medicina_free
Clinical Cases in Critical Care
148
Urine osmolality
As a simple method, it can be easily and rapidly used to conrm an excess
of uid intake relative to solute intake.
It is recommended as a first step in the diagnostic work- up of
hyponatraemia.
A urine osmolality 100 mOsm/kg on a spot urine sample always
indicates maximally dilute urine (e.g. excess water intake or beer
potomania).
If the urine osmolality is >100 mOsm/kg then determining the urine
sodium concentration on a spot urine sample is the next step in identi-
fying the underlying cause.
Urine sodium concentration
Both the urine and serum samples should be collected around the same
time to allow correct interpretation of the value.
A urine sodium concentration threshold of 30 mmol/L provides good
sensitivity and acceptable specicity in determining volume status.
A value less than or equal to 30 mmol/L suggests that, even in patients
on diuretics, the eective arterial blood volume is low.
YES
NO
Consider
Diuretics
Kidney disease
Also consider all
other causes listed
If ECF normal consider
SIAD
Secondary adrenal insufficiency
If ECF reduced consider
Vomiting
Primary adrenal insufficiency
Renal salt wasting
Cerebral salt wasting
Low effective
arterial
blood volume
If ECF expanded consider
Cardiac failure
Cirrhosis
Nephrotic syndrome
If ECF reduced consider
Diarrhoea and vomiting
Third spacing
Consider
Primary polydipsia
Low solute intake
Beer potomania
Figure 11.3: Diagnostic algorithm for hyponatraemia. ECF, extracellular uid; SIAD,
syndrome of inappropriate antidiuresis.
Source: Adapted from Spasovski, G., et al. (2014). Clinical practice guideline on diagnosis and treatment
of hyponatraemia. Eur. J. Endo. 170: G1-G47.
https://t.me/medicina_free
Соседние файлы в папке Библиотека им академика М.И. Перельмана