Acute hyponatraemia in children admitted to hospital: retrospective analysis of factors contributing to its development and resolutionBMJ 2001; 322 doi: https://doi.org/10.1136/bmj.322.7289.780 (Published 31 March 2001) Cite this as: BMJ 2001;322:780
All rapid responses
"The remainder of the patients [17 or 23]had a decrease in natraemia
that exceeded the decline if the entire volume of electrolyte free water
infused was retained (points below broken line in fig 2). Therefore there
was either another non-recorded input of water or the excretion of a large
volume of hypertonic urine (a desalination of infused isotonic saline"(1).
What of the effects of fluid and electrolyte shifts between intracellular
and extracellular compartments?
In the gut lumen total ionic concentration decreases from its istonic
value of 328 mEq/l as the amount of acid added to it increases for H+ and
HCO3- combine to form CO2 and H20 (2). Furthermore the diffusion of H+
from an acidic solution into cells is accompanied by an equimolar gain of
Na+, K+ and Cl- (3) and presumably the reverse must occur in the presence
of an abnormally elevated pH (4). For practical purposes the net flux of
water between ECF and ICF follows the Na+.
The inference is that, should these changes be generic, plasma
osmolality might fall as the extracellular pH falls and the accompanying
intracellular diffusion of H+ be matched by the appearance in ECF of Na+,
with its osmotic equivalent of water, K+ and Cl-. In other words ICF
volume might decrease and ECF volume increase. Were the extracellular pH
to rise the reverse might occur, ICF volume increasing and ECF volume
decreasing. Were instead the pH changes to occur intracellularly from
unreversed ATP hydrolysis the reverse might occur. In which case the fate
of intravenous fluids, and hence risk of intracranial hypertension and
coning, is likely to be intimately related to the pH in ICF and ECF at the
time of infusion, an increase in ICF volume being favoured by an rise in
pH in ECF or a fall in pH in ICF. In either case clamping the
extracellular pH at an abnormally low level, but keeping the pCO2-gap
normal, might be expected to decrease intracellular volume and thereby
decrease the likelihood of developing intracranial hypertension and
Vasopressin, an antidiretic hormone that if released in abnormal
amounts might have favoured the abnormal retention of water and casued
hyponatraemia, was not measured in this study. In patients undergoing
cardiopulmonary resuscitation, however, circulating endogenous vasopressin
concentrations are significantly higher in successfully resuscitated
patients than in patients who die. Furthermore in the cardiopulmonary
resuscitation laboratory, vasopressin improves vital organ blood flow,
cerebral oxygen delivery, the probability of restoring spontaneous
circulation, and neurologic recovery (6). Should, therefore, the secretion
of vasopressin be impaired as occurs in some head injuries (7)
hyponatraemia per se is an unlikely cause of an adverse outcome.
The most likely cause of hyponatraemia in this study might well have
been an intracellular acidosis accompaning a decline in the Daniel
Atkinson energy charge for any number of reasons. The changes are
unlikely to have been constant and could have fluctuated widely and so
different answers could have been obtained had isolaated rather than
sequential or continuous measurements been made(8). If there is a lesson
to be learned from this report it is that it is very difficult if not
impossible to determine precisely what the cause of coning in these
patients might have been without measurements of regional and systemic
tissue energetics. More importantly the cause is unlikely to be
indentified earlier enough and managed rationally without these
1. Michael Halberthal, Mitchell L Halperin, and Desmond Bohn
Lesson of the week: Acute hyponatraemia in children admitted to hospital:
retrospective analysis of factors contributing to its development and
BMJ 2001; 322: 780-782
2. Fiddian-Green RG, Hobsley M Hypo-acidity of gastric juice in
chronic gastric ulceration caused by neutralisation.
S Afr Med J. 1976 Apr 3;50(15):580-2.
3. Dorricott NJ, Fiddian-Green RG, Silen W. Mechanisms of acid
disposal in canine duodenum.
Am J Physiol. 1975 Jan;228(1):269-75.
4. Fiddian-Green RG, Silen W. Mechanisms of disposal of acid and
alkali in rabbit duodenum.
Am J Physiol. 1975 Dec;229(6):1641-8.
5. Might intracranial pressure be a passive reflection of
Richard G Fiddian-Green (16 November 2004) eLetter re: M Czosnyka and J
Monitoring and interpretation of intracranial pressure
J Neurol Neurosurg Psychiatry 2004; 75: 813-821
6. Krismer AC, Wenzel V, Stadlbauer KH, Mayr VD, Lienhart HG, Arntz
HR, Lindner KH Vasopressin during cardiopulmonary resuscitation: a
Crit Care Med. 2004 Sep;32(9 Suppl):S432-5
7. Gionis D, Ilias I, Moustaki M, Mantzos E, Papadatos I, Koutras DA,
Mastorakos G. Hypothalamic-pituitary-adrenal axis and interleukin-6
activity in children with head trauma and syndrome of inappropriate
secretion of antidiuretic hormone.
J Pediatr Endocrinol Metab. 2003 Jan;16(1):49-54.
8. SUD: product of an abnormally increased amplitude of synchronised
Richard G Fiddian-Green (16 November 2004)eLetter re: A M A Shehab, R J
MacFadyen, M McLaren, R Tavendale, J J F Belch, and A D Struthers
Sudden unexpected death in heart failure may be preceded by short term,
intraindividual increases in inflammation and in autonomic dysfunction: a
Heart 2004; 90: 1263-1268
Patents issued in my name
Competing interests: No competing interests
Electrolyte disturbance is recognised as one of the commonest
problems encountered in hospitalised patients; it may be associated with
significant morbidity and occasionally, mortality.
Statistical surveys in the published literature, (readily accessed by
a Medline search) reveals a continuing and extremely disturbing picture of
a failure by clinicians, irrespective of both their experience and field
of expertise to recognise this problem. The recognition of the clinical
presentation and critical timeous treatment of these abnormalities (which
might appear to be so simple) may even be significantly delayed by the
performance of lung and brain scans, with the consequent progression
during that delay to irreversible neurological injury and even death.
Within a purely surgical context the nature and volume of peri-
operative and post-operative fluid prescriptions and their rate of
infusion may also contribute to these abnormalities. That there is a clear
association between these prescriptions and the pre-operative condition of
the patient and planned procedure is well known, but that the patient’s
sex and age are also important considerations is not as well recognised.
If patients are not to be subject to the potential fatal consequences
of iatrogenic electrolyte disturbance then it behoves all physicians to
maintain a high level of awareness, to recognise the non-specific early
signs, and to immediately take the correct and appropriate action when the
disorder is recognised.
It is however critical and far more important that the problem of
electrolyte disturbance not be precipitated and be added to the existing
burden of hospitalised patients that have placed their lives and trust in
I recently attempted to conduct a postal survey on Peri-operative
Fluid Management within the NHS Consultant Anaesthetic community with the
view to publishing an analysis of the findings and the level of
appreciation (or otherwise) of the problems that have been outlined.
The response thankfully indicated overwhelmingly that less than 1% of
respondents were still routinely using the incorrect fluids, but even then
there was an indication that many of the respondents were not aware of all
the critical associations.
The response rate was only 20%!
This degree of apathy to a single page, postage paid questionnaire
with SIX simple questions that should not take more than a few minutes to
complete about a condition that kills patients, and that could help us all
deliver a level of care that we would expect for our selves and our
families is difficult to understand.
It behoves all of us to strive constantly to advance knowledge, to
improve our level of expertise, and the care of all patients.
I should like to be collect a more representational sample of current
peri-operative fluid usage and to this end a copy of the survey can be
obtained by contacting me on barwin @onetel.com.
Winston D. Shaer
Specialist Plastic and Reconstructive Surgeon
Competing interests: No competing interests
Hyponatraemic nadirs and paradox of the ‘missing’ volumetric
I read this excellent article  with interest. The authors
concluded that: “acute hospital induced hyponatraemaia is caused by
electrolyte-free fluids, or ‘volumetric overload type1 (VO1)’, in the
presence of elevated serum vasopressin. The condition affects men, women
and children, particularly postoperative patients. It is responsible for
far greater morbidity and mortality than generally received.” It concerns
not only physicians and intensive care therapists among all clinicians who
prescribe fluid therapy in the most compelling of clinical emergencies,
but also primarily surgeons.
The authors’ call for a change of the policies on fluid therapy is
fully supported but requires scientific justification. It is interesting
that such revolutionary conclusion is based on a retrospective study and
observations. Had I been gifted with the clarity and authority with which
the conclusion was given, not only hyponatraemia but also the puzzle of
the multiple vital organ dysfunction/ failure (MVOD/F) syndromes should
have been resolved long ago. I commend the Editor and reviewers of BMJ for
considering this study an evidence-based medicine.
I have long recognized these conditions as killers of surgical
patients and have spent most of my career life investigating and
understanding. My initial observations were communicated over 16 years ago
. For resolving giant clinical puzzles such as hyponatraemia and
MVOD/F, one needed to fly high for a bird’s eye view and dive deep for a
close up examination of a piece of evidence that lies at the bottom of the
ocean of knowledge on the subject. In doing so, artificial boundaries of
science and super specialties of medicine and surgery needed crossing for
gathering the scattered pieces of evidence. Missing pieces were either
excavated and rejuvenated or newly discovered. Facts needed segregation
from fallacies, and reorganization, in order to reconstruct the real
Although acute hyponatraemia is ‘iatrogenic complication’ of fluid
therapy, it should not cause any ‘guilt feeling’. It is a complex problem
with wide range of severity and many masks of presentations. It underlies
many variously named but identical clinical syndromes such as the
transurethral prostatctomy (TURP) syndrome and others affecting medical
and surgical patients . It may be confused with many recognized medical
conditions as well as features of MVOD/F . Its primary nadir and
paradox remain overlooked. The key for resolving the puzzles relates to a
century old erroneous physiological law that dictated the ‘faulty rules’
of fluid therapy .
The authors alluded to the ‘missing’ VO1 at the second nadir of
natraemia on tertiary referral. This letter’s main objective is to
identify, locate and quantify the ‘missing’ VO1 and uncover its primary
nadir and paradox. Major surgery in general and TURP in particular are
examples where and when VO1 may induce the condition and its first nadir
. Not only the faulty rules on fluid therapy dictate the infusion of
large VO during surgery but also, invariably and incorrectly, every
hypotension episode is considered synonymous with hypovolaemia . The
observed paradox was this: VO1 of about 5% body weight (BW) gained in one
hour may cause hypotension shock. This misleadingly calls for further
vascular expansion using electrolyte-based fluids (VO2), inducing coma and
anuria among other features of the MVOD/F syndrome.
Dilutional hyponatraemic shock was reported 55 years ago  and
later in patients suffering from the TURP syndrome . It represents VO1
vascular shock. Our prospective study , precisely quantified VO1 by
adding the per-operative infused fluids to the measured volume of absorbed
1.5% Glycine irrigant. After providing anecdotal evidence , our
prospective study also re-juvinated the life-saving therapy of instant
rapid 5% NaCl . Further experience showed that 8.4% sodium bicarbonate
is a good alternative therapy but lower sodium concentrations are less
effective. All VO2 fluids such as isotonic saline are harmful, as it
clouds the serum markers while aggravating VO and establishing the MVOD/F
VO1 dilutes all serum contents and induces the first nadir of
natraemia , manifesting at the immediate post-operative period. The
second nadir of natraemia may appear less seriously later, reflecting much
less VO1 than was actually gained. This is due to the intracellular
osmotic shift of fluid. Cellular oedema manifests with encephalopathic
coma and annuria, among other features of MVOD/F [3,4]. Further delay,
before and after involving the physicians, may make hyponatraemia chronic,
establishing the permanent brain damage. The latter was incorrectly
attributed to hypertonic sodium therapy. The second nadir of natraemia may
also follow another common scenario: any urinary output, that represents a
recovery from VO1, when chassed by fluid input may keep the retained VO1
constant or increased. No pitting oedema occurs because most of the
‘missing’ VO1 resides in the cells.
Time plays a bivious hidden role on the nadirs of natraemia of VO1.
This was the hardest to understand and unravel. “VO versus time” (of fluid
infusion) is a helpful concept to consider in clinical settings requiring
massive fluid therapy or vascular expansion. Contrasting the physiological
effects of a normal daily fluid intake (about 5%BW or 3.5 l of 70 Kg) to
its pathological effects when infused in one hour, should be considered
dead seriously. Mathematical calculation reveals that such VO1 lowers the
serum sodium from 140 to 112 mmol/l (the first natraemic nadir). Assuming
no further input or output occurred, the time (of osmotic equilibrium)
might spontaneously elevate the second nadir to 129 mmol/l. This is the
result of extracellular fluid space dilution by only 1.2 l. The ‘missing’
2.3 l of gained VO1 resides in cells.
Perhaps, a better approach for resolving such complex clinical
problem was to go ‘back to basics and to the future’: to recognize the
error of the physiological law that dictated the faulty rules on fluid
therapy. Physical studies, done in 1984 and reported in 2001 ,
discovered a hydrodynamic phenomenon with physiological and clinical
relevance to the mentioned conditions. This may provide a tenable
alternative hypothesis for the capillary-interstitial fluid transfer, and
the scientific basis for the call to change the policies on fluid therapy.
1. Halberthal M, Halperin ML, Bohn D. Acute hyponatraemia in children
admitted to hospital: retrospective analysis of factors contributing to
its development and resolution. BMJ 2001; 322: 780-782
2. Ghanem AN. Hypoalbuminaemic hyponatraemia: a new syndrome? Br Med Jour
1985; 291: 1502-3
3. Ghanem AN. Monitoring the critically ill patient. J R Coll Surg Edinb
2000; 45 (2): 138-9.
4. Ghanem AN. Magnetic field-like fluid circulation of a porous orifice
tube and relevance to the capillary-interstitial fluid circulation:
Preliminary report. Medical Hypotheses 2001; 56 (3): 325-334.
5. Ghanem AN, Ward JP. Osmotic and metabolic sequelae of volumetric
overload in relation to the TURP syndrome. Br J Uro 1990; 66: 71-78
6. Danowski TS, Winkler AW, Elkington JR. The treatment of shock due to
salt depression; comparison of isotonic, of hypertonic saline and of
isotonic glucose solutions. J. Clin. Invest. 1946; 25: 130.
7. Harrison III RH, Boren JS, Robinson JR. Dilutional hyponatraemic shock:
another concept of the transurethral prostatic reaction. J Urol. 1956; 75
8. Ghanem AN, Wojtlewski JA, Penney MD, Dangers in treating hyponatraemia.
Br Med Jour; 1987; 294: 837.
Competing interests: No competing interests